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The immune system is a network of
biological process Biological processes are those processes that are vital for an organism to live, and that shape its capacities for interacting with its environment. Biological processes are made of many chemical reactions or other events that are involved in th ...
es that protects an
organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological ...

organism
from
diseases A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. Diseases are often known to be medical ...
. It detects and responds to a wide variety of
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory ...
s, from
virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecu ...

virus
es to
parasitic worm Parasitic worms, also known as helminths, are large macroparasites; adults can generally be seen with the naked eye. Many are intestinal worms An intestinal parasite infection is a condition in which a parasite Parasitism is a symbi ...
s, as well as
cancer cells Cancer cells are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division Cell division is the process by which a parent Cell (biology), cell divides into two or more daughter cells. Cell div ...
and objects such as wood
splinter A splinter (also known as a sliver) is a fragment of a larger object, or a foreign body#REDIRECT Foreign body A foreign body (FB) is any object originating outside the body of an organism In biology, an organism (from Ancient Greek, Gre ...

splinter
s, distinguishing them from the organism's own healthy
tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubitata'', a species of geometer mot ...
. Many species have two major subsystems of the immune system. The
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the d ...

innate immune system
provides a preconfigured response to broad groups of situations and stimuli. The
adaptive immune system The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, ...
provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use
molecules A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position In physics, motion is the phenomenon ...
and
cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Closed spaces * Monastic cell, a small room, hut, or cave in which a monk or religious recluse lives * Prison cell, a room used to hold peopl ...
to perform their functions. Nearly all organisms have some kind of immune system.
Bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

Bacteria
have a rudimentary immune system in the form of
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s that protect against
virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecu ...

virus
infections. Other basic immune mechanisms evolved in ancient
plants and animals Plants and Animals are a Canadian indie-rock band from Montreal Montreal ( ; officially Montréal, , Tio'tia:ke in Mohawk language, Mohawk) is the List of the 100 largest municipalities in Canada by population, second-most populous city in Ca ...

plants and animals
and remain in their modern descendants. These mechanisms include
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis Endocytosis is a cellular process i ...

phagocytosis
,
antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between Prokaryote, prokaryotic and eukaryota, eukaryotic cells that may r ...
called
defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct Antimicrobial peptides, antimicrobial ...
s, and the
complement system The complement system, also known as complement cascade, is a part of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργαν ...

complement system
.
Jawed vertebrate Gnathostomata are the jawed vertebrates. The term derives from Greek language, Greek: (') "jaw" + (') "mouth". Gnathostome diversity comprises roughly 60,000 species, which accounts for 99% of all living vertebrates. In addition to opposing ja ...
s, including humans, have even more sophisticated defense mechanisms, including the ability to adapt to recognize pathogens more efficiently. Adaptive (or acquired) immunity creates an
immunological memory Immunological memory is the ability of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any i ...
leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of
vaccination Vaccination is the administration of a vaccine to help the immune system develop protection from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

vaccination
. Dysfunction of the immune system can cause
autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of differe ...

autoimmune disease
s,
inflammatory diseases Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen In biology Biology is the natural science that studies life and living organisms, including their anatom ...
and
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most often refers to: * Cell (biolo ...
.
Immunodeficiency Immunodeficiency, also known as immunocompromisation, is a state in which the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργα ...
occurs when the immune system is less active than normal, resulting in recurring and life-threatening infections. In humans, immunodeficiency can be the result of a
genetic disease A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology and genetics, a genome is all genetic information of an organism. It consists of nucleotide sequences of DNA ( ...
such as
severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a sin ...
, acquired conditions such as
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus ''Lentivirus'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, inc ...

HIV
/
AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of ...
, or the use of
immunosuppressive medication Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications are drugs Uncoated tablets, consisting of about 90% acetylsalicylic acid, along with a minor amount of inert fillers and binde ...
.
Autoimmunity Autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other body normal constituents. Any disease that results from such an aberrant immune response is termed an "autoimmune disease An autoimmu ...
results from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...
,
diabetes mellitus type 1 Type 1 diabetes (T1D), previously known as juvenile diabetes, is an autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response An immune response is a reaction which occurs within an organism for the purp ...
, and
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary between people and may be mild to severe. Co ...
.
Immunology Immunology is a branch of biology and Medicine that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in states of both health and ...
covers the study of all aspects of the immune system.


Layered defense

The immune system protects its host from
infection An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host A host is a person responsible for guests at an event or for providing hospitality during it. Host may ...

infection
with layered defenses of increasing specificity. Physical barriers prevent pathogens such as
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
and
virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecu ...

virus
es from entering the organism. If a pathogen breaches these barriers, the
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the d ...

innate immune system
provides an immediate, but non-specific response. Innate immune systems are found in all
animal Animals (also called Metazoa) are multicellular A multicellular organism is an organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells ...

animal
s. If pathogens successfully evade the innate response, vertebrates possess a second layer of protection, the
adaptive immune system The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, ...
, which is activated by the innate response. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an
immunological memory Immunological memory is the ability of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any i ...
, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered. Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self
molecule A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position In physics, motion is the phenomenon ...

molecule
s. In immunology, ''self'' molecules are components of an organism's body that can be distinguished from foreign substances by the immune system. Conversely, ''non-self'' molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (originally named for being ''anti''body ''gen''erators) and are defined as substances that bind to specific
immune receptor An immune receptor (or immunologic receptor) is a receptor, usually on a cell membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmale ...
s and elicit an immune response.


Surface barriers

Several barriers protect organisms from infection, including mechanical, chemical, and biological barriers. The waxy
cuticle A cuticle (), or cuticula, is any of a variety of tough but flexible, non-mineral outer coverings of an organism, or parts of an organism, that provide protection. Various types of "cuticle" are non-homology (biology), homologous, differing in the ...
of most leaves, the
exoskeleton An exoskeleton (from Greek έξω, ''éxō'' "outer" and σκελετός, ''skeletós'' "skeleton") is the external skeleton A skeleton is a structural frame that supports an animal Animals (also called Metazoa) are multicellular ...

exoskeleton
of insects, the
shells Shell may refer to: Architecture and design * Shell (structure), a thin structure **Concrete shell, a thin shell of concrete, usually with no interior columns or exterior buttresses **Thin-shell structure, **Oil company Science Biology * Seashell ...
and membranes of externally deposited eggs, and
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have differ ...

skin
are examples of mechanical barriers that are the first line of defense against infection. Organisms cannot be completely sealed from their environments, so systems act to protect body openings such as the
lung The lungs are the primary organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma ...

lung
s,
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, d ...

intestine
s, and the
genitourinary tract The genitourinary system, or urogenital system, are the organ (anatomy), organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, Development of the urinary and reproductive orga ...
. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the
respiratory tract The respiratory tract is the subdivision of the respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system A biological system is a complex network which connects several biologically re ...

respiratory tract
. The flushing action of
tears Tears are a clear liquid secreted by the lacrimal glands (tear gland) found in the eyes of all Mammal, land mammals (except for goats and rabbits). Their functions include lubricating the eyes (basal tears), removing irritants (reflex tears), and ...

tears
and
urine Urine is a liquid by-product A by-product or byproduct is a secondary product derived from a production process, process or ; it is not the primary product or service being produced. A by-product can be useful and marketable or it can be cons ...

urine
also mechanically expels pathogens, while
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists o ...
secreted by the respiratory and
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system The human digestive system consists of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, d ...
serves to trap and entangle
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes ...
s. Chemical barriers also protect against infection. The skin and respiratory tract secrete
antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between Prokaryote, prokaryotic and eukaryota, eukaryotic cells that may r ...
such as the β-
defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct Antimicrobial peptides, antimicrobial ...
s.
Enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

Enzyme
s such as
lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, is an antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an ...

lysozyme
and
phospholipase A2 Phospholipases A2 (PLA2s) are enzymes that cleave fatty acid In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, str ...
in
saliva Saliva (commonly referred to as spit) is an extracellular fluid In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including t ...
, tears, and
breast milk . Breast milk or mother's milk is milk Milk is a nutrient-rich liquid food produced by the mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their nam ...
are also
antibacterials
antibacterials
.
Vagina In mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), and characterized by the presence of mammary glands which in Female#Mammalian female, femal ...

Vagina
l secretions serve as a chemical barrier following
menarche Menarche ( ; ) is the first menstrual cycle, or first Menstruation, menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fe ...
, when they become slightly
acid An acid is a or capable of donating a (hydrogen ion H+) (a ), or, alternatively, capable of forming a with an (a ). The first category of acids are the proton donors, or s. In the special case of , proton donors form the H3O+ and are ...
ic, while
semen Semen, also known as seminal fluid, is an organic fluid created to contain spermatozoon, spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphrodite, hermaphroditic animals and can fertilization, f ...

semen
contains defensins and
zinc Zinc is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical element ...

zinc
to kill pathogens. In the
stomach The stomach is a muscular, in the of humans and many other animals, including several s. The stomach has a dilated structure and functions as a vital organ. In the digestive system the stomach is involved in the second phase of digestion, ...

stomach
,
gastric acid Gastric acid, gastric juice, or stomach acid, is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid An acid is a or capable of donating a (hydrogen ion H+) (a ), or, alternatively, capable of for ...
serves as a chemical defense against ingested pathogens. Within the genitourinary and gastrointestinal tracts,
commensal Commensalism is a long-term biological interaction In ecology Ecology (from el, οἶκος, "house" and el, -λογία, label=none, "study of") is the study of the relationships between living organisms, including humans, and their phy ...

commensal
flora Flora is all the plant Plants are predominantly photosynthetic Photosynthesis is a process used by plants and other organisms to Energy transformation, convert light energy into chemical energy that, through cellular respiration, ca ...
serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, changing the conditions in their environment, such as
pH
pH
or available iron. As a result, the probability that pathogens will reach sufficient numbers to cause illness is reduced.


Innate immune system

Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by
pattern recognition receptorsPattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system The innate immune system is one of the two main immunity strategies found in vertebrates (the other being the adaptive immune system). The ...
, which recognize components that are conserved among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm signals, many of which are recognized by the same receptors as those that recognize pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens in a generic way. This system does not confer long-lasting
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * Immunity (journal), ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequ ...
against a pathogen. The innate immune system is the dominant system of host defense in most organisms, and the only one in plants.


Immune sensing

Cells in the innate immune system use
pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of t ...
s to recognize molecular structures that are produced by pathogens. They are
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
s expressed, mainly, by cells of the
innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the d ...

innate immune system
, such as dendritic cells, macrophages, monocytes, neutrophils and epithelial cells to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial
pathogens In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, ...
, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or cell death. Recognition of extracellular or endosomal PAMPs is mediated by
transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein An integral membrane protein (IMP) is a type of membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane protei ...
s known as
toll-like receptor Toll-like receptors (TLRs) are a class of protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John ...
s (TLRs). TLRs share a typical structural motif, the leucine rich repeats (LRR), which give them a curved shape. Toll-like receptors were first discovered in ''
Drosophila ''Drosophila'' () is a genus of fly, flies, belonging to the family (biology), family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the character ...

Drosophila
'' and trigger the synthesis and secretion of
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and ...

cytokine
s and activation of other host defense programs that are necessary for both innate or adaptive immune responses. Ten toll-like receptors have been described in humans. Cells in the innate immune system have pattern recognition receptors, which detect infection or cell damage, inside. Three major classes of these "cytosolic" receptors are NOD–like receptors, RIG (retinoic acid-inducible gene)-like receptors, and cytosolic DNA sensors.


Innate immune cells

Some
leukocytes White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
(white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system. The innate leukocytes include the "professional" phagocytes (
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s,
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They are also called po ...

neutrophil
s, and
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), an ...

dendritic cell
s). These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. The other cells involved in the innate response include
innate lymphoid cell Innate lymphoid cells (ILCs) are the most recently discovered family of Innate immune system, innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretio ...
s,
mast cell#REDIRECT Mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem ...

mast cell
s,
eosinophils Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of ...
,
basophils Basophils are a type of white blood cells, white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsib ...
, and
natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic Cytotoxicity is the quality of being toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances c ...

natural killer cell
s.
Phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis Endocytosis is a cellular process i ...

Phagocytosis
is an important feature of cellular innate immunity performed by cells called phagocytes that engulf pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines. Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular
vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and liv ...
called a
phagosome In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, M ...
, which subsequently fuses with another vesicle called a
lysosome A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...

lysosome
to form a
phagolysosome In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanisms, D ...
. The pathogen is killed by the activity of digestive enzymes or following a
respiratory burst Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen (O2) produce ...
that releases
free radicals In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structure, properties, behavior and the changes they un ...
into the phagolysosome. Phagocytosis evolved as a means of acquiring
nutrient A nutrient is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance, a material with a definite chemical composition * Matter, anything that has mass and t ...
s, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism. Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals. Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens. Neutrophils are normally found in the
bloodstream The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a biological system A biological system is a complex biological network, network which connects several biological ...
and are the most abundant type of phagocyte, representing 50% to 60% of total circulating leukocytes. During the acute phase of inflammation, neutrophils migrate toward the site of inflammation in a process called
chemotaxis Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism in response to a chemical stimulus. Somatic cells, bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They ...

chemotaxis
, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce an array of chemicals including enzymes, , and cytokines, while they can also act as scavengers that rid the body of worn-out cells and other debris, and as
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen In immunology, an antigen (Ag) is a molecule or molecular structure, such as may be present on the outside of a pathogen, that can be bound by an antigen-speci ...
s (APC) that activate the adaptive immune system. Dendritic cells are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have differ ...

skin
,
nose A nose is a protuberance in vertebrate Vertebrates () comprise all species of animal Animals (also called Metazoa) are multicellular A multicellular organism is an organism In biology, an organism () is any organic, l ...
, lungs, stomach, and intestines. They are named for their resemblance to
neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapse In the nervous system In biology Biology is the natural science that studies life and living ...

neuron
al
dendrite Dendrites (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approx ...

dendrite
s, as both have many spine-like projections. Dendritic cells serve as a link between the bodily tissues and the innate and adaptive immune systems, as they to
T cell A T cell is a type of lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
s, one of the key cell types of the adaptive immune system.
Granulocyte Granulocytes are cells in the innate immune system The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutiona ...
s are leukocytes that have granules in their cytoplasm. In this category are neutrophils, mast cells, basophils, and eosinophils. Mast cells reside in
connective tissue Connective tissue is one of the many basic types of animal Animals (also called Metazoa) are multicellular A multicellular organism is an organism In biology, an organism () is any organic, life, living system that functions ...
s and
mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists of one or more layers of Epithelium, epithelial cells overlying a layer of loose connect ...
s, and regulate the inflammatory response. They are most often associated with
allergy Allergies, also known as allergic diseases, are a number of conditions caused by hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, ...

allergy
and
anaphylaxis Anaphylaxis is a serious allergic reaction Allergies, also known as allergic diseases, are a number of conditions caused by hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable rea ...
.
Basophil Basophils are a type of white blood cells, white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsib ...

Basophil
s and
eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network o ...

eosinophil
s are related to neutrophils. They secrete chemical mediators that are involved in defending against
parasites Parasitism is a Symbiosis, close relationship between species, where one organism, the parasite, lives on or inside another organism, the Host (biology), host, causing it some harm, and is adaptation (biology), adapted structurally to this w ...

parasites
and play a role in allergic reactions, such as
asthma Asthma is a long-term Long-Term Capital Management L.P. (LTCM) was a hedge fund''A financial History of the United States Volume II: 1970–2001'', Jerry W. Markham, Chapter 5: "Bank Consolidation", M. E. Sharpe, Inc., 2002 based in Greenwich, ...

asthma
. Innate lymphoid cells (ILCs) are a group of cells that are derived from
common lymphoid progenitorLymphopoiesis (lĭm'fō-poi-ē'sĭs) (or lymphocytopoiesis) is the generation of lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that protects an organism ...

common lymphoid progenitor
and belong to the lymphoid lineage. These cells are defined by absence of antigen specific B or
T cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding be ...
(TCR) because of the lack of recombination activating gene. ILCs do not express myeloid or dendritic cell markers.
Natural killer cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that ...
(NK) are lymphocytes and a component of the innate immune system which does not directly attack invading microbes. Rather, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells, recognizing such cells by a condition known as "missing self." This term describes cells with low levels of a cell-surface marker called MHC I (
major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are ca ...
)—a situation that can arise in viral infections of host cells. Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens are recognized by killer cell immunoglobulin receptors which essentially put the brakes on NK cells.


Inflammation

Inflammation is one of the first responses of the immune system to infection. The symptoms of inflammation are redness, swelling, heat, and pain, which are caused by increased blood flow into tissue. Inflammation is produced by
eicosanoid Eicosanoids are signaling molecules In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cell (biology), cells and coordinates multiple-cell actions. A signal is an entity th ...
s and
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and ...

cytokine
s, which are released by injured or infected cells. Eicosanoids include
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid In and , a lipid is a macro that is soluble in solvents. are typically s used to dissolve other naturally occurring hydrocarbon lipid s that do not (or do not easily) ...
s that produce
fever Fever, also referred to as pyrexia, is defined as having a temperature Temperature ( ) is a physical quantity that expresses hot and cold. It is the manifestation of thermal energy Thermal radiation in visible light can be seen on th ...

fever
and the dilation of
blood vessel The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a biological system A biological system is a comp ...
s associated with inflammation, and
leukotriene Note the four double bonds, three of them conjugated. This is a common property of A4, B4, C4, D4, and E4. is a cysteinyl leukotriene, as are D4 and E4. Leukotrienes are a family of eicosanoid Eicosanoids are signaling molecules made by t ...
s that attract certain
white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
s (leukocytes). Common cytokines include
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system ...
s that are responsible for communication between white blood cells;
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the firs ...
s that promote
chemotaxis Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism in response to a chemical stimulus. Somatic cells, bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They ...

chemotaxis
; and
interferon Interferons (IFNs, ) are a group of signaling protein In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, mo ...

interferon
s that have anti-viral effects, such as shutting down
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
in the host cell.
Growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential gro ...
s and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens. The pattern-recognition receptors called
inflammasome Inflammasomes are cytosolic multiprotein oligomer In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions: their composition, structu ...
s are multiprotein complexes (consisting of an NLR, the adaptor protein ASC, and the effector molecule pro-caspase-1) that form in response to cytosolic PAMPs and DAMPs, whose function is to generate active forms of the inflammatory cytokines IL-1β and IL-18.


Humoral defenses

The complement system is a
biochemical cascade A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions that occur within a biological cell when initiated by a stimulus. This stimulus, known as a first messenger, acts on a receptor that ...
that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to "complement" the killing of pathogens by
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique mo ...

antibodies
. Complement is the major humoral component of the innate immune response. Many species have complement systems, including non-
mammal Mammals (from Latin Latin (, or , ) is a classical language A classical language is a language A language is a structured system of communication Communication (from Latin ''communicare'', meaning "to share" or "to be i ...
s like plants, fish, and some
invertebrate Invertebrates are animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This includes all animals apart from the chordata, chordate subphylum vertebrate, Vertebra ...
s. In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to
carbohydrate A carbohydrate () is a biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a ...
s on the surfaces of
microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes ...
s. This recognition
signal In signal processing Signal processing is an electrical engineering subfield that focuses on analysing, modifying, and synthesizing signals such as audio signal processing, sound, image processing, images, and scientific measurements. Sig ...
triggers a rapid killing response. The speed of the response is a result of signal amplification that occurs after sequential
proteolytic Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, bu ...

proteolytic
activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a
catalytic that utilizes a low-temperature oxidation catalyst to convert carbon monoxide to less toxic carbon dioxide Carbon dioxide (chemical formula ) is a colorless gas with a density about 53% higher than that of dry air. Carbon dioxide molecules ...

catalytic
cascade that amplifies the initial signal by controlled
positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop Feedback occurs when outputs of a system are routed back as inputs as part of a chain Image:Kettenvergleich.jpg, Roller c ...
. The cascade results in the production of peptides that attract immune cells, increase
vascular permeability Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells (lympho ...
, and
opsonize Opsonins are proteins of the innate and adaptive immune system The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system The immune system is a network of biological processes that protects an ...

opsonize
(coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their
plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

plasma membrane
.


Adaptive immune system

The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as
immunological memory Immunological memory is the ability of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any i ...
, where each pathogen is "remembered" by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called
antigen presentationImage:Antigen presentation.svg, 240px, Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Be ...

antigen presentation
. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.


Recognition of antigen

The cells of the adaptive immune system are special types of leukocytes, called lymphocytes.
B cell #REDIRECT B cell 3D rendering of a B cell B cells, also known as B lymphocytes, are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a ne ...
s and T cells are the major types of lymphocytes and are derived from
hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cell In multicellular organisms Multicellular organisms are organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguo ...

hematopoietic stem cell
s in the
bone marrow Bone marrow is a semi-solid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphos ...
. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response. Killer T cells only recognize antigens coupled to
Class I MHC MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on ...
molecules, while helper T cells and regulatory T cells only recognize antigens coupled to
Class II MHC MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on antigen-presenting cell#Types and functions, professional antigen-presenting cells such as dendritic cells, monocyte, mononuclear phagocyte ...
molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the
γδ T cellsGamma delta T cells (γδ T cells) are T cells that have a distinctive T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In cont ...
that recognize intact antigens that are not bound to MHC receptors. The double-positive T cells are exposed to a wide variety of self-antigens in the
thymus The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ad ...

thymus
, in which
iodine Iodine is a chemical element In chemistry, an element is a pure Chemical substance, substance consisting only of atoms that all have the same numbers of protons in their atomic nucleus, nuclei. Unlike chemical compounds, chemical ele ...

iodine
is necessary for its thymus development and activity. In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface and recognizes native (unprocessed) antigen without any need for
antigen processingAntigen processing, or the cytosolic pathway, is an immunological process that prepares antigen In immunology, an antigen (Ag) is a molecule or molecular structure, such as may be present on the outside of a pathogen, that can be bound by an an ...
. Such antigens may be large molecules found on the surfaces of pathogens, but can also be small
haptenHaptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself (in general, only large molecules, infectious agents, ...

hapten
s (such as penicillin) attached to carrier molecule. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture. When B or T cells encounter their related antigens they multiply and many "clones" of the cells are produced that target the same antigen. This is called
clonal selection Image:Clonal selection.svg, 200px, Clonal selection theory of lymphocytes: 1) A hematopoietic stem cell undergoes differentiation and genetic rearrangement to produce 2) immature lymphocytes with many different antigen receptors. Those that bind to ...

clonal selection
.


Antigen presentation to T lymphocytes

Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a "non-self" target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a "self" receptor called a major histocompatibility complex (MHC) molecule.


Cell mediated immunity

There are two major subtypes of T cells: the
killer T cell . A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T cell, T lymphocyte (a type of white blood cell White blood cells (WBCs), also called leukocytes or leuc ...
and the
helper T cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity of ...
. In addition there are
regulatory T cells The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain immune tolerance, tolerance to self-antigens, and prevent autoimmune disease. Treg ce ...
which have a role in modulating immune response.


Killer T cells

Killer T cells are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. As with B cells, each type of T cell recognizes a different antigen. Killer T cells are activated when their
T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding be ...
binds to this specific antigen in a complex with the MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a
co-receptor A co-receptor is a cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane cell membrane vs. Prokaryotes The cell membrane (also known as the plasma me ...
on the T cell, called
CD8 CD8 (cluster of differentiation The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecule ...

CD8
. The T cell then travels throughout the body in search of cells where the MHC I receptors bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins, such as
perforin Perforin-1 is a protein that in humans is encoded by the ''PRF1'' gene and the ''Prf1'' gene in mice. Function Perforin is a pore forming cytolysis, cytolytic protein found in the granules of cytotoxic T cell, cytotoxic T lymphocytes (CTLs) and Nat ...

perforin
, which form pores in the target cell's
plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

plasma membrane
, allowing
ion An ion () is an atom An atom is the smallest unit of ordinary matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ...
s, water and toxins to enter. The entry of another toxin called granulysin (a protease) induces the target cell to undergo
apoptosis Apoptosis (from Ancient Greek Ancient Greek includes the forms of the Greek language Greek ( el, label=Modern Greek Modern Greek (, , or , ''Kiní Neoellinikí Glóssa''), generally referred to by speakers simply as Greek (, ) ...

apoptosis
. T cell killing of host cells is particularly important in preventing the replication of viruses. T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T cells (see below).


Helper T cells

Helper T cells The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity of ...
regulate both the innate and adaptive immune responses and help determine which immune responses the body makes to a particular pathogen. These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. They instead control the immune response by directing other cells to perform these tasks. Helper T cells express T cell receptors that recognize antigen bound to Class II MHC molecules. The MHC:antigen complex is also recognized by the helper cell's
CD4 #REDIRECT CD4 In molecular biology, CD4 (cluster of differentiation#REDIRECT Cluster of differentiation {{Redirect category shell, 1= {{R from other capitalisation ... 4) is a glycoprotein Glycoproteins are protein Proteins are large ...
co-receptor, which recruits molecules inside the T cell (such as
Lck Lck (or lymphocyte-specific protein tyrosine kinase) is a 56 Atomic mass unit, kDa protein that is found inside specialized Cell (biology), cells of the immune system called lymphocytes. Lck is a tyrosine kinase, which phosphorylates tyrosine r ...
) that are responsible for the T cell's activation. Helper T cells have a weaker association with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on the helper T cell must be bound by an MHC:antigen to activate the helper cell, while killer T cells can be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also called
CD154 CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the Tumor necrosis factors, TNF superfamily of molecules. It binds to CD40 (protein) on antigen-presenting cells (APC), which ...
), which provide extra stimulatory signals typically required to activate antibody-producing B cells.


Gamma delta T cells

Gamma delta T cell Gamma delta T cells (γδ T cells) are T cell A T cell is a type of lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that protects an organism In bio ...
s (γδ T cells) possess an alternative T-cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T cells and share the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as
CD1d #REDIRECT CD1D CD1D is the human gene that encodes the protein CD1d, a member of the CD1 (cluster of differentiation 1) family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are non-classical Major histoco ...
-restricted
natural killer T cell Natural killer T (NKT) cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the Polymorphism (biology), non-polymorphic CD1d molecule, an antigen-presenting molecu ...
s, γδ T cells straddle the border between innate and adaptive immunity. On one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the innate immune system, as restricted TCR or NK receptors may be used as
pattern recognition receptor Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed, mainly, by cells of t ...
s. For example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by microbes, and highly restricted Vδ1+ T cells in epithelium, epithelia respond to stressed epithelial cells.


Humoral immune response

A
B cell #REDIRECT B cell 3D rendering of a B cell B cells, also known as B lymphocytes, are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a ne ...
identifies pathogens when antibodies on its surface bind to a specific foreign antigen. This antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides. The B cell then displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen attracts a matching helper T cell, which releases lymphokines and activates the B cell. As the activated B cell then begins to cell division, divide, its offspring (plasma cells) secretion, secrete millions of copies of the antibody that recognizes this antigen. These antibodies circulate in blood plasma and lymphatic system, lymph, bind to pathogens expressing the antigen and mark them for destruction by Complement system, complement activation or for uptake and destruction by phagocytes. Antibodies can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that viruses and bacteria use to infect cells. Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called Immunoglobulin G, IgG, is transported from mother to baby directly through the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother. Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies. This is passive immunization, passive immunity because the fetus does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be intravenous immunoglobulin, transferred artificially from one individual to another.


Immunological memory

When B cells and T cells are activated and begin to replicate, some of their offspring become long-lived memory cells. Throughout the lifetime of an animal, these memory cells remember each specific pathogen encountered and can mount a strong response if the pathogen is detected again. This is "adaptive" because it occurs during the lifetime of an individual as an adaptation to infection with that pathogen and prepares the immune system for future challenges. Immunological memory can be in the form of either passive short-term memory or active long-term memory.


Physiological regulation

The immune system is involved in many aspects of physiological regulation in the body. The immune system interacts intimately with other systems, such as the Endocrine system, endocrine and the Nervous system, nervous systems. The immune system also plays a crucial role in embryogenesis (development of the embryo), as well as in Tissue (biology), tissue repair and Regeneration (biology), regeneration.


Hormones

Hormones can act as immunomodulators, altering the sensitivity of the immune system. For example, female sex hormones are known immunostimulators of both adaptive and innate immune responses. Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty. By contrast, androgen, male sex hormones such as testosterone seem to be immunosuppressive. Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D.


Vitamin D

When a T-cell encounters a foreign
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory ...
, it extends a vitamin D receptor. This is essentially a signaling device that allows the T-cell to bind to the active form of vitamin D, the steroid hormone calcitriol. T-cells have a symbiotic relationship with vitamin D. Not only does the T-cell extend a vitamin D receptor, in essence asking to bind to the steroid hormone version of vitamin D, calcitriol, but the T-cell expresses the gene CYP27B1, which is the gene responsible for converting the pre-hormone version of vitamin D, calcidiol into calcitriol. Only after binding to calcitriol can T-cells perform their intended function. Other immune system cells that are known to express CYP27B1 and thus activate vitamin D calcidiol, are
dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammal Mammals (from Latin language, Latin , 'breast') are a group of vertebrate animals constituting the class (biology), class Mammalia (), an ...

dendritic cell
s, keratinocytes and
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s.


Sleep and rest

The immune system is affected by sleep and rest, and sleep deprivation is detrimental to immune function. Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement (REM sleep, REM) sleep. Thus the immune response to infection may result in changes to the sleep cycle, including an increase in slow-wave sleep relative to REM sleep. In people suffering from sleep deprivation, active immunizations may have a diminished effect and may result in lower antibody production, and a lower immune response, than would be noted in a well-rested individual. Additionally, proteins such as NFIL3, which have been shown to be closely intertwined with both T-cell differentiation and circadian rhythms, can be affected through the disturbance of natural light and dark cycles through instances of sleep deprivation. These disruptions can lead to an increase in chronic conditions such as heart disease, chronic pain, and asthma. In addition to the negative consequences of sleep deprivation, sleep and the intertwined circadian system have been shown to have strong regulatory effects on immunological functions affecting both innate and adaptive immunity. First, during the early slow-wave-sleep stage, a sudden drop in blood levels of cortisol, epinephrine, and norepinephrine causes increased blood levels of the hormones leptin, Growth hormone 1, pituitary growth hormone, and prolactin. These signals induce a pro-inflammatory state through the production of the pro-inflammatory cytokines interleukin-1, interleukin-12, TNF-alpha and IFN-gamma. These cytokines then stimulate immune functions such as immune cell activation, proliferation, and Cell differentiation, differentiation. During this time of a slowly evolving adaptive immune response, there is a peak in undifferentiated or less differentiated cells, like naïve and central memory T cells. In addition to these effects, the milieu of hormones produced at this time (leptin, pituitary growth hormone, and prolactin) supports the interactions between APCs and T-cells, a shift of the Th1 cell, Th1/Th2 cytokine balance towards one that supports Th1, an increase in overall Th cell proliferation, and naïve T cell migration to lymph nodes. This is also thought to support the formation of long-lasting immune memory through the initiation of Th1 immune responses. During wake periods, differentiated effector cells, such as cytotoxic natural killer cells and cytotoxic T lymphocytes, peak to elicit an effective response against any intruding pathogens. Anti-inflammatory molecules, such as cortisol and catecholamines, also peak during awake active times. Inflammation would cause serious cognitive and physical impairments if it were to occur during wake times, and inflammation may occur during sleep times due to the presence of melatonin. Inflammation causes a great deal of oxidative stress and the presence of melatonin during sleep times could actively counteract free radical production during this time.


Repair and regeneration

The immune system, particularly the innate component, plays a decisive role in tissue repair after an Insult (medical), insult. Key actors include
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s and
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They are also called po ...

neutrophil
s, but other cellular actors, including γδ T cells,
innate lymphoid cell Innate lymphoid cells (ILCs) are the most recently discovered family of Innate immune system, innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretio ...
s (ILCs), and regulatory T cells (Tregs), are also important. The plasticity of immune cells and the balance between pro-inflammatory and anti-inflammatory signals are crucial aspects of efficient tissue repair. Immune components and pathways are involved in regeneration as well, for example in amphibians such as in Axolotl#Regeneration, axolotl limb regeneration. According to one hypothesis, organisms that can regenerate (''e.g.'', axolotls) could be less immunocompetent than organisms that cannot regenerate.


Disorders of human immunity

Failures of host defense occur and fall into three broad categories: immunodeficiencies, autoimmunity, and hypersensitivities.


Immunodeficiencies

Immunodeficiency, Immunodeficiencies occur when one or more of the components of the immune system are inactive. The ability of the immune system to respond to pathogens is diminished in both the young and the old age, elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence. In developed country, developed countries, obesity, alcohol abuse, alcoholism, and drug use are common causes of poor immune function, while malnutrition is the most common cause of immunodeficiency in developing country, developing countries. Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, immunoglobulin A, IgA antibody concentrations, and cytokine production. Additionally, the loss of the
thymus The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ad ...

thymus
at an early age through Mutation, genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection. Immunodeficiencies can also be inherited or 'Immunodeficiency#Acquired immune deficiency, acquired'. Severe combined immunodeficiency is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations. Chronic granulomatous disease, where phagocytes have a reduced ability to destroy pathogens, is an example of an inherited, or Primary immunodeficiency, congenital, immunodeficiency.
AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of ...
and some types of cancer cause acquired immunodeficiency.


Autoimmunity

Overactive immune responses form the other end of immune dysfunction, particularly the autoimmunity, autoimmune disorders. Here, the immune system fails to properly distinguish between Self-protein, self and non-self, and attacks part of the body. Under normal circumstances, many T cells and antibodies react with "self" peptides. One of the functions of specialized cells (located in the
thymus The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ad ...

thymus
and bone marrow) is to present young lymphocytes with Self-protein, self antigens produced throughout the body and to eliminate those cells that recognize self-antigens, preventing autoimmunity. Common autoimmune diseases include
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid, thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid m ...

Hashimoto's thyroiditis
,
rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and ...
,
diabetes mellitus type 1 Type 1 diabetes (T1D), previously known as juvenile diabetes, is an autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response An immune response is a reaction which occurs within an organism for the purp ...
, and
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary between people and may be mild to severe. Co ...
.


Hypersensitivity

Hypersensitivity is an immune response that damages the body's own tissues. It is divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction. Type I hypersensitivity is an immediate or anaphylaxis, anaphylactic reaction, often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by immunoglobulin E, IgE, which triggers degranulation of
mast cell#REDIRECT Mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem ...

mast cell
s and
basophils Basophils are a type of white blood cells, white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsib ...
when cross-linked by antigen. Type II hypersensitivity occurs when antibodies bind to antigens on the individual's own cells, marking them for destruction. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by immunoglobulin G, IgG and immunoglobulin M, IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or ''delayed type hypersensitivity'') usually takes between two and three days to develop. Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis. These reactions are mediated by
T cell A T cell is a type of lymphocyte A lymphocyte is a type of white blood cell in the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
s, monocytes, and
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s.


Idiopathic inflammation

Inflammation is one of the first responses of the immune system to infection, but it can appear without known cause. Inflammation is produced by
eicosanoid Eicosanoids are signaling molecules In biology, cell signaling (cell signalling in British English), or cell-cell communication, governs the basic activities of cell (biology), cells and coordinates multiple-cell actions. A signal is an entity th ...
s and
cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and ...

cytokine
s, which are released by injured or infected cells. Eicosanoids include
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid In and , a lipid is a macro that is soluble in solvents. are typically s used to dissolve other naturally occurring hydrocarbon lipid s that do not (or do not easily) ...
s that produce fever and the Vasodilation, dilation of blood vessels associated with inflammation, and
leukotriene Note the four double bonds, three of them conjugated. This is a common property of A4, B4, C4, D4, and E4. is a cysteinyl leukotriene, as are D4 and E4. Leukotrienes are a family of eicosanoid Eicosanoids are signaling molecules made by t ...
s that attract certain white blood cells (leukocytes). Common cytokines include
interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system ...
s that are responsible for communication between white blood cells;
chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokine Cytokines are a broad and loose category of small protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the firs ...
s that promote
chemotaxis Chemotaxis (from '' chemo-'' + '' taxis'') is the movement of an organism in response to a chemical stimulus. Somatic cells, bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They ...

chemotaxis
; and
interferon Interferons (IFNs, ) are a group of signaling protein In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, mo ...

interferon
s that have anti-viral effects, such as shutting down
protein synthesis Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
in the host cell.
Growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential gro ...
s and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.


Manipulation in medicine

The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy, and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system (see #Active memory and immunization, immunization) or cancer.


Immunosuppression

Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent rejection after an organ transplant. Anti-inflammatory drugs are often used to control the effects of inflammation. Glucocorticoids are the most powerful of these drugs and can have many undesirable adverse effect, side effects, such as central obesity, hyperglycemia, and osteoporosis. Their use is tightly controlled. Lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine. Chemotherapy, Cytotoxic drugs inhibit the immune response by killing dividing cells such as activated T cells. This killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects. Immunosuppressive drugs such as cyclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.


Immunostimulation

Claims made by marketers of various products and Alternative medicine, alternative health providers, such as Chiropractic, chiropractors, Homeopathy, homeopaths, and Acupuncture, acupuncturists to be able to stimulate or "boost" the immune system generally lack meaningful explanation and evidence of effectiveness.


Vaccination

Long-term ''active'' memory is acquired following infection by activation of B and T cells. Active immunity can also be generated artificially, through
vaccination Vaccination is the administration of a vaccine to help the immune system develop protection from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

vaccination
. The principle behind vaccination (also called immunization) is to introduce an antigen from a pathogen to stimulate the immune system and develop specific immunity against that particular pathogen without causing disease associated with that organism. This deliberate induction of an immune response is successful because it exploits the natural specificity of the immune system, as well as its inducibility. With infectious disease remaining one of the leading causes of death in the human population, vaccination represents the most effective manipulation of the immune system mankind has developed. Many vaccines are based on non-cellular life, acellular components of micro-organisms, including harmless toxin components. Since many antigens derived from acellular vaccines do not strongly induce the adaptive response, most bacterial vaccines are provided with additional Immunologic adjuvant, adjuvants that activate the
antigen-presenting cell An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen In immunology, an antigen (Ag) is a molecule or molecular structure, such as may be present on the outside of a pathogen, that can be bound by an antigen-speci ...
s of the innate immune system and maximize immunogenicity.


Tumor immunology

Another important role of the immune system is to identify and eliminate tumors. This is called immune surveillance. The ''transformed cells'' of tumors express antigen#Tumor antigens, antigens that are not found on normal cells. To the immune system, these antigens appear foreign, and their presence causes immune cells to attack the transformed tumor cells. The antigens expressed by tumors have several sources; some are derived from oncogenic viruses like human papillomavirus, which causes cancer of the cervical cancer, cervix, vulva cancer, vulva, vaginal cancer, vagina, penis cancer, penis, anal cancer, anus, oropharynx, mouth, and throat, while others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells. One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (for example, melanocytes) into tumors called melanomas. A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival, that commonly mutate into cancer inducing molecules called oncogenes. The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells. Tumor antigens are presented on MHC class I molecules in a similar way to viral antigens. This allows killer T cells to recognize the tumor cell as abnormal. NK cells also kill tumorous cells in a similar way, especially if the tumor cells have fewer MHC class I molecules on their surface than normal; this is a common phenomenon with tumors. Sometimes antibodies are generated against tumor cells allowing for their destruction by the
complement system The complement system, also known as complement cascade, is a part of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργαν ...

complement system
. Some tumors evade the immune system and go on to become cancers. Tumor cells often have a reduced number of MHC class I molecules on their surface, thus avoiding detection by killer T cells. Some tumor cells also release products that inhibit the immune response; for example by secreting the cytokine TGF beta, TGF-β, which suppresses the activity of
macrophage Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...

macrophage
s and lymphocytes. In addition, immune tolerance, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells. Paradoxically, macrophages can promote tumor growth when tumor cells send out cytokines that attract macrophages, which then generate cytokines and growth factors such as Tumor necrosis factor alpha, tumor-necrosis factor alpha that nurture tumor development or promote stem-cell-like plasticity. In addition, a combination of hypoxia in the tumor and a cytokine produced by macrophages induces tumor cells to decrease production of a protein that blocks metastasis and thereby assists spread of cancer cells. Anti-tumor M1 macrophages are recruited in early phases to tumor development but are progressively differentiated to M2 with pro-tumor effect, an immunosuppressor switch. The hypoxia reduces the cytokine production for the anti-tumor response and progressively macrophages acquire pro-tumor M2 functions driven by the tumor microenvironment, including IL-4 and IL-10. Cancer immunotherapy covers the medical ways to stimulate the immune system to attack cancer tumors.


Predicting immunogenicity

Some drugs can cause a neutralizing immune response, meaning that the immune system produces neutralizing antibodies that counteract the action of the drugs, particularly if the drugs are administered repeatedly, or in larger doses. This limits the effectiveness of drugs based on larger peptides and proteins (which are typically larger than 6000 Dalton (unit), Da). In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for paclitaxel, Taxol. Computational methods have been developed to predict the immunogenicity of peptides and proteins, which are particularly useful in designing therapeutic antibodies, assessing likely virulence of mutations in viral coat particles, and validation of proposed peptide-based drug treatments. Early techniques relied mainly on the observation that hydrophile, hydrophilic amino acids are overrepresented in epitope regions than hydrophobe, hydrophobic amino acids; however, more recent developments rely on machine learning techniques using databases of existing known epitopes, usually on well-studied virus proteins, as a training set. A publicly accessible database has been established for the cataloguing of epitopes from pathogens known to be recognizable by B cells. The emerging field of bioinformatics-based studies of immunogenicity is referred to as ''immunoinformatics''. Immunoproteomics is the study of large sets of proteins (proteomics) involved in the immune response.


Evolution and other mechanisms


Evolution of the immune system

It is likely that a multicomponent, adaptive immune system arose with the first vertebrates, as
invertebrate Invertebrates are animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This includes all animals apart from the chordata, chordate subphylum vertebrate, Vertebra ...
s do not generate lymphocytes or an antibody-based humoral response. Many species, however, use mechanisms that appear to be precursors of these aspects of vertebrate immunity. Immune systems appear even in the structurally simplest forms of life, with bacteria using a unique defense mechanism, called the restriction modification system to protect themselves from viral pathogens, called bacteriophages. Prokaryotes (
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
and archea) also possess acquired immunity, through a system that uses CRISPR sequences to retain fragments of the genomes of phage that they have come into contact with in the past, which allows them to block virus replication through a form of RNA interference. Prokaryotes also possess other defense mechanisms. Offensive elements of the immune systems are also present in protist, unicellular eukaryotes, but studies of their roles in defense are few. Pattern recognition receptors are proteins used by nearly all organisms to identify molecules associated with pathogens. Antimicrobial peptides called
defensin Defensins are small cysteine-rich cationic proteins across cellular life, including vertebrate and invertebrate animals, plants, and fungi. They are host defense peptides, with members displaying either direct Antimicrobial peptides, antimicrobial ...
s are an evolutionarily conserved component of the innate immune response found in all animals and plants, and represent the main form of invertebrate systemic immunity. The
complement system The complement system, also known as complement cascade, is a part of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ὀργαν ...

complement system
and phagocytic cells are also used by most forms of invertebrate life. Ribonucleases and the RNA interference pathway are conserved across all eukaryotes, and are thought to play a role in the immune response to viruses. Unlike animals, plants lack phagocytic cells, but many plant immune responses involve systemic chemical signals that are sent through a plant. Individual plant cells respond to molecules associated with pathogens known as pathogen-associated molecular patterns or PAMPs. When a part of a plant becomes infected, the plant produces a localized hypersensitive response, whereby cells at the site of infection undergo rapid
apoptosis Apoptosis (from Ancient Greek Ancient Greek includes the forms of the Greek language Greek ( el, label=Modern Greek Modern Greek (, , or , ''Kiní Neoellinikí Glóssa''), generally referred to by speakers simply as Greek (, ) ...

apoptosis
to prevent the spread of the disease to other parts of the plant. Systemic acquired resistance is a type of defensive response used by plants that renders the entire plant Disease resistance in fruit and vegetables, resistant to a particular infectious agent. RNA interference, RNA silencing mechanisms are particularly important in this systemic response as they can block virus replication.


Alternative adaptive immune system

adaptive immune system#Evolution, Evolution of the adaptive immune system occurred in an ancestor of the jawed vertebrates. Many of the classical molecules of the adaptive immune system (for example, immunoglobulins and
T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding be ...
s) exist only in jawed vertebrates. A distinct lymphocyte-derived molecule has been discovered in primitive agnatha, jawless vertebrates, such as the lamprey and hagfish. These animals possess a large array of molecules called Variable lymphocyte receptors (VLRs) that, like the antigen receptors of jawed vertebrates, are produced from only a small number (one or two) of genes. These molecules are believed to bind pathogenic antigens in a similar way to
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and Viral disease, viruses. The antibody recognizes a unique mo ...

antibodies
, and with the same degree of specificity.


Manipulation by pathogens

The success of any pathogen depends on its ability to elude host immune responses. Therefore, pathogens evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system. Bacteria often overcome physical barriers by secreting enzymes that digest the barrier, for example, by using a type II secretion system. Alternatively, using a type III secretion system, they may insert a hollow tube into the host cell, providing a direct route for proteins to move from the pathogen to the host. These proteins are often used to shut down host defenses. An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called intracellular pathogenesis). Here, a pathogen spends most of its Biological life cycle, life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement. Some examples of intracellular pathogens include viruses, the foodborne illness, food poisoning bacterium ''Salmonella'' and the eukaryote, eukaryotic parasites that cause malaria (''Plasmodium spp.'') and leishmaniasis (''Leishmania spp.''). Other bacteria, such as ''Mycobacterium tuberculosis'', live inside a protective capsule that prevents lysis by complement. Many pathogens secrete compounds that diminish or misdirect the host's immune response. Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system. Such biofilms are present in many successful infections, such as the chronic ''Pseudomonas aeruginosa'' and ''Burkholderia cenocepacia'' infections characteristic of cystic fibrosis. Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include ''Streptococcus'' (protein G), ''Staphylococcus aureus'' (protein A), and ''Peptostreptococcus magnus'' (protein L). The mechanisms used to evade the adaptive immune system are more complicated. The simplest approach is to rapidly change non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed. This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus. The parasite ''Trypanosoma brucei'' uses a similar strategy, constantly switching one type of surface protein for another, allowing it to stay one step ahead of the antibody response. Masking antigens with host molecules is another common strategy for avoiding detection by the immune system. In HIV, the envelope that covers the virus, virion is formed from the outermost membrane of the host cell; such "self-cloaked" viruses make it difficult for the immune system to identify them as "non-self" structures.


History of immunology

Immunology Immunology is a branch of biology and Medicine that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the Physiology, physiological functioning of the immune system in states of both health and ...
is a science that examines the structure and function of the immune system. It originates from medicine and early studies on the causes of immunity to disease. The earliest known reference to immunity was during the plague of Athens in 430 BC. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. In the 18th century, Pierre Louis Maupertuis, Pierre-Louis Moreau de Maupertuis experimented with scorpion venom and observed that certain dogs and mice were immune to this venom. In the 10th century, Persian physician Muhammad ibn Zakariya al-Razi, al-Razi (also known as Rhazes) wrote the first recorded theory of acquired immunity, noting that a smallpox bout protected its survivors from future infections. Although he explained the immunity in terms of "excess moisture" being expelled from the blood—therefore preventing a second occurrence of the disease—this theory explained many observations about smallpox known during this time. These and other observations of acquired immunity were later exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease. Pasteur's theory was in direct opposition to contemporary theories of disease, such as the miasma theory of disease, miasma theory. It was not until Robert Koch's 1891 Koch's postulates, proofs, for which he was awarded a Nobel Prize in Physiology or Medicine, Nobel Prize in 1905, that microorganisms were confirmed as the cause of infectious disease. Viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. Immunology made a great advance towards the end of the 19th century, through rapid developments in the study of humoral immunity and Cell-mediated immunity, cellular immunity. Particularly important was the work of Paul Ehrlich, who proposed the side-chain theory to explain the specificity of the antigen-antibody reaction; his contributions to the understanding of humoral immunity were recognized by the award of a joint Nobel Prize in 1908, along with the founder of cellular immunology, Elie Metchnikoff. In 1974, Niels Kaj Jerne developed the immune network theory; he shared a Nobel Prize in 1984 with Georges J. F. Köhler and César Milstein for theories related to the immune system.


See also

* Fc receptor * Immune system receptors * Immunostimulator * Neuroimmune system * Original antigenic sin – when the immune system uses immunological memory upon encountering a slightly different pathogen * Plant disease resistance * Polyclonal response * Antigen#Tumor antigens, Tumor antigens


References


Bibliography

* * * * * * * * * * * * * *


External links


Microbiology and Immunology On-Line Textbook
– from the University of South Carolina School of Medicine (undergraduate level) {{Authority control Immune system,