Self-protein refers to all proteins endogenously produced by DNA-level transcription and translation within an organism of interest. This does not include proteins synthesized due to viral infection, but may include those synthesized by commensal bacteria within the intestines. Proteins that are not created within the body of the organism of interest, but nevertheless enter through the bloodstream, a breach in the skin, or a mucous membrane, may be designated as “non-self” and subsequently targeted and attacked by the immune system. Tolerance to self-protein is crucial for overall wellbeing; when the body erroneously identifies self-proteins as “non-self”, the subsequent immune response against endogenous proteins may lead to the development of an

autoimmune disease An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...

Examples

Of note, the list provided above is not exhaustive; the list does not mention all possible proteins targeted by the provided autoimmune diseases.

Identification by the immune system

Autoimmune responses and diseases are primarily instigated by T lymphocytes that are incorrectly screened for reactivity to self-protein during cell development. During T-cell development, early T-cell

progenitors In genealogy, the progenitor (rarer: primogenitor; german: Stammvater or ''Ahnherr'') is the – sometimes legendary – founder of a family, line of descent, clan or tribe, noble house, or ethnic group.. Ebenda''Ahnherr:''"Stammvater eines ...

first move via chemokine gradients from the bone marrow into the thymus, where T-cell receptors are randomly rearranged at the gene level to allow for T-cell receptor generation. These T-cells have the potential to bind to anything, including self-proteins. The immune system must differentiate the T-cells that have receptors capable of binding to self versus non-self proteins; T-cells that can bind to self-proteins must be destroyed to prevent development of an autoimmune disorder. In a process known as “ Central Tolerance”, T-cells are exposed to cortical epithelial cells that express a variety of different major histocompatibility complexes (MHC) of both class 1 and

class 2 Class 2 may refer to: * BR Standard Class 2 2-6-0, British steam locomotive * BR Standard Class 2 2-6-2T, British steam locomotive * Class 2 Touring Cars, FIA classification for cars in auto racing * Classes of U.S. Senators * L&YR Class 2, Bri ...

, which have the ability to bind to T-cell receptors of CD8+

cytotoxic T-cells 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 lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

, and CD4+ helper T-cells, respectively. The T-cells that display affinity for these MHC are positively selected to continue to the second stage of development, while those that cannot bind to MHC undergo

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. In the second stage, immature T-cells are exposed to a variety of

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s, and medullary epithelial cells that express self-protein on MHC class 1 and

. These epithelial cells also express the transcription factor labelled autoimmune regulator (AIRE) - this crucial transcription factor allows the medullary epithelial cells of the thymus to express proteins would normally be present in peripheral tissue rather than in an epithelial cell, such as

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

-like peptides, myelin-like peptides, and more. As these epithelial cells now present a large variety of self-proteins that could be encountered across the body, the immature T-cells are tested for affinity to self-protein and self-MHC. If any T-cell has strong affinity for self-protein and self-MHC, the cell undergoes apoptosis to prevent autoimmune function. T-cells that display low/medium affinity are allowed to leave the thymus and circulate throughout the body to react to novel non-self antigen. In this manner, the body attempts to systematically destroy T-cells that could lead to autoimmunity.

References

{{Reflist, 30em Immunology