Nasal- or nasopharynx- associated lymphoid tissue (NALT) represents immune system of nasal mucosa and is a part of

mucosa-associated lymphoid tissue The mucosa-associated lymphoid tissue (MALT), also called mucosa-associated lymphatic tissue, is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal trac ...

(MALT) in mammals. It protects body from airborne viruses and other infectious agents. In humans, NALT is considered analogous to

Waldeyer's ring Waldeyer's tonsillar ring (pharyngeal lymphoid ring, Waldeyer's lymphatic ring, or tonsillar ring) is a ringed arrangement of Lymphatic system, lymphoid organs in the human pharynx, pharynx. Waldeyer's ring surrounds the nasopharynx, naso- and orop ...

Structure

NALT in mice is localized on cartilaginous soft palate of upper jaw, it is situated bilaterally on the posterior side of the palate. It consists mainly of

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

s, T cell and B cell enriched zones, follicle-associated epithelium (FAE) with epithelial M cells and some

erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

. M cells are typical for antigen intake from mucosa. In some areas of NALT, there are

lymphatic vessel The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vess ...

s and HEVs (high endothelial venule). Dendritic cells and macrophages are also present. NALT contains about same amount of

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s and

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s. The T-cell population contains about 3–4 times more CD4⁺ T cells than CD8⁺ T cells. Most of T cells are with αβ

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 b ...

(TCR) and only few are with γδ TCR. CD4⁺ T cells are in naive state, marked by high expression of CD45RB. B cells are mostly in unswitched state, with sIgM⁺ IgD⁺ phenotype.

Development

Formation of NALT starts early after birth, it is not present during embrygenesis or in newborn mice. First signs of NALT (HEV with associated lymphocytes) occurs one week after birth, but full formation is established after 5–8 weeks. In contrast to

Peyer's patch Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (clu ...

es and

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s, NALT formation is independent of IL-7R, LT-βR and ROR-γ signalling. It requires ''

Id2 DNA-binding protein inhibitor ID-2 is a protein that in humans is encoded by the ''ID2'' gene. Function The protein encoded by this gene belongs to the inhibitor of DNA binding (ID) family, members of which are transcriptional regulators that ...

'' gene, which induce genesis of CD3⁻CD4⁺CD45⁺ cells. These cells accumulates on the site of NALT after birth and induce NALT formation.

Function

NALT in mice has strategic position for incoming

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

s and it is the first site of recognition and elimination of inhaled pathogens. It has a key role in inducing mucosal and systemic

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 different microorganisms including viruses, bacteria, parasites, and fungi which could ...

. NALT is inductive site of

MALT Malt is germinated cereal grain that has been dried in a process known as " malting". The grain is made to germinate by soaking in water and is then halted from germinating further by drying with hot air. Malted grain is used to make beer, wh ...

similarly to Peyer's patches in a small intestine. After intranasal

immunization Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen). When this system is exposed to molecules that are foreign to the body, called ''non-sel ...

or pathogen recognition, lymphocytes in NALT proliferate and differentiate. They start to produce

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s, such as

IFN-γ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

, type I interferons,

IL-2 The Ilyushin Il-2 (Russian language, Russian: Илью́шин Ил-2) is a Ground attack aircraft, ground-attack plane that was produced by the Soviet Union in large numbers during the World War II, Second World War. The word ''shturmovík'' (C ...

, IL-4,

IL-5 IL 5 or IL-5 may refer to: * Interleukin 5 * Illinois's 5th congressional district * Illinois Route 5 Illinois Route 5 (IL 5) is a four-lane road in Rock Island County, Illinois, United States, that runs from U.S. Route 67 (US 67) in ...

, IL-6 or IL-10 (amount depend on used immunizating agent or adjuvans). B cells go through

isotype switching Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the ...

and produce antigen-specific

IgM Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...

and mainly IgA. Activated B cells can migrate through body to

respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...

and genito-uritary tract, because they express

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

receptors

CCR10 C-C chemokine receptor type 10 is a protein that in humans is encoded by the ''CCR10'' gene. Function Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of va ...

and α₄β₁-integrin. Memory T and

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

are established and last for long time after immunization.

Vaccination

Intranasal (i.n.)

vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity 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 ...

is an effective way to stimulate respiratory immune system. This way of immunization can provoke both the cell-mediated and humoral immune responses and is capable of stimulating both the mucosal and systemic immune systems. A dose of i.n. administered antigen can be much smaller than of oral administered

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

, because antigens are not exposed to

digestive enzyme Digestive enzymes are a group of enzymes that break down polymeric macromolecules into their smaller building blocks, in order to facilitate their absorption into the cells of the body. Digestive enzymes are found in the digestive tracts of anim ...

s. Thus, it would be a suitable way of vaccination against airborne viruses and bacteria. In 1997, nasal-spray vaccine containing inactivated

influenza virus ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ...

with nLT (

heat-labile enterotoxin In molecular biology, the heat-labile enterotoxin family includes ''Escherichia coli'' heat-labile enterotoxin (Elt or LT) and cholera toxin (Ctx) secreted by ''Vibrio cholerae''. lt is so named because it is inactivated at high temperatures. ...

) as

adjuvants In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy#Pharmacology, efficacy or Potency (pharmacology), potency of certain drugs. Specifically, the term can refer to: * Adju ...

was used in

Switzerland ). Swiss law does not designate a ''capital'' as such, but the federal parliament and government are installed in Bern, while other federal institutions, such as the federal courts, are in other cities (Bellinzona, Lausanne, Luzern, Neuchâtel ...

, but it had to be withdrawn from the market, because it caused

Bell's palsy Bell's palsy is a type of facial paralysis that results in a temporary inability to control the facial muscles on the affected side of the face. In most cases, the weakness is temporary and significantly improves over weeks. Symptoms can vary fr ...

in some patients. Thus, scientists are looking for more suitable and safe adjuvants, for expamle, Masafumi Yamamoto et al. in 1998 on mice model proved safe and efficient i.n. vaccination against ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They are ...

'' and in 2002 also against influenza virus.{{Cite journal, last=Kweon, first=Mi-Na, last2=Yamamoto, first2=Masafumi, last3=Watanabe, first3=Fumiko, last4=Tamura, first4=Shinichi, last5=Ginkel, first5=Frederik W. van, last6=Miyauchi, first6=Akira, last7=Takagi, first7=Hiroaki, last8=Takeda, first8=Yoshifumi, last9=Hamabata, first9=Takashi, date=2002-11-01, title=A Nontoxic Chimeric Enterotoxin Adjuvant Induces Protective Immunity in Both Mucosal and Systemic Compartments with Reduced IgE Antibodies, journal=Journal of Infectious Diseases, language=en, volume=186, issue=9, pages=1261–1269, doi=10.1086/344526, issn=0022-1899, pmid=12402195, doi-access=free

References

Immune system