- A condition resulted by the action of antibodies or immunologically competent cells.
- Cause structural or functional damage of the normal components of the body.
- Literally means ‘protection against self’ but means ‘injury to self’ in actual.
- Ehrlich postulated the concept of horror auto-toxicus.
- Was proposed while observing goats producing antibodies against erythrocytes from other goats.
- But not against own erythrocytes.
- Various criteria proposed to prove authenticity of putative autoimmune disease.
- It could also be proper to restrict the term ‘autoimmune diseases’ to those where autoimmune processes, humoral or cellular are shown to be liable for the pathogenesis, instead of merely associated.
- Following features are associated with diseases of autoimmune origin.
a) Elevated Immunoglobulins level
b) Incidence higher in females
c) Non-reversible chronicity
d) Genetic predisposition towards autoimmunity
e) More than one type of autoimmune lesion occurring in an individual
f) Corticosteroid or other immunosuppressive therapy providing benefits
g) Demonstrable autoantibodies
h) Sites of lesion with high level of lymphocytes and plasma cells.
i) Sites of election (such as renal glomeruli) with deposition of immunoglobulins or their derivatives.
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Mechanism of auto-immunity
i) Antigenic alterations
- Physical, chemical or biological influences may put cells or tissues to undergo antigenic alteration.
- Immune response may be elicited by such altered or neo-antigens.
- Irradiation, photosensitivity and cold allergy can arise neo-antigens.
- Leucopenias, thrombocytopenias and drug-induced anemias often have an autoimmune basis.
- Cell antigens alteration may also be induced by infectious organisms like viruses and other intracellular pathogens.
- Mononucleosis, a viral infection, often precedes autoimmune disease.
- Enzymes produced by bacteria also alter the cell antigens.
- Myxo-viruses and many bacteria produce neuraminidases that act on erythrocyte releasing T antigen.
- Mutation also may produce neo-antigens which are called mutant cells.
- Such cells may be immunogenic.
ii) Sequestered antigens
- Due to presence of certain self-antigens in closed systems, they become non-accessible to the immune apparatus.
- Thus, they are known as sequestered antigens.
- Lens antigen of the eye is one of the examples.
- Protein making lens of eye remains surrounded by its capsule.
- They do not circulate in blood.
- Hence, during fetal life, no immunological tolerance arises against this protein.
- Leaking of antigen resulted by penetrating injury may induce immune response.
- This results in the damage to the lens of other eyes.
- Sperm antigens can be one of the examples where sequestration of time is noticed.
- Development of spermatozoa that begins at puberty cannot induce tolerance at fetal life.
- Thus, sperms cannot be recognized as self which if enters the circulation, can be immunogenic.
- This explains the pathogenesis of orchitis following mumps.
- The basement membrane of the seminiferous tubules damages causing leakage of sperms.
- This damage is caused by the virus which later on initiates an immune response.
- This, finally results to orchitis.
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iii) Cross-reacting foreign antigen
- Cross-reacting antigen theory of autoimmunity explains the similarity of some foreign and self-antigens.
- Several species bear organ-specific antigens.
- Immune response is induced when heterologous organ specific antigens get injected.
- This cause damage to the particular organ or tissue in the host.
- In neurological injury i.e., the complication of antirabic immunization in humans with the neural vaccine of infected sheep brain tissue it can be understood well.
- Injection elicits an immune response against sheep brain antigens.
- This response damages the individual’s nerve tissue.
- Damage is the result of cross-reaction between human and sheep brain antigens.
- Likewise M proteins in Streptococcus and heart muscle show similarity in antigenic characteristics.
- The immune response thus induced damages the heart when streptococcal infection occurs repeatedly.
- Renal glomeruli and nephritogenic strains of streptococci also possess similar antigens.
- This similarity leads to glomerulonephritis when infection by these strains occurs.
iv) Molecular mimicry
- Molecular mimicry is a related type of autoimmunization.
- Its presence is due to some infecting microorganisms and self-antigens.
- They have epitopes with identical peptide sequences.
- Arthritogenic Shigella flexneri and HLA-B27, Mycobacterium tuberculosis and joint membranes, etc. are the best examples having homologous sequences.
v) Polyclonal B cell activation
- It is also one of the hypothesis of autoimmunity’s mechanism.
- According to it, an antigen generally activates only its corresponding B cells.
- But sometimes certain stimuli turn on multiple B cell clones non-specifically.
- Such stimuli include chemicals like 2- mercaptoethanol, bacterial products (PPD and lipopolysaccharides), enzymes(trypsin), antibiotics(nystatin).
- Infections with some bacteria, viruses and parasites also act as non-specific stimuli.
- Multiple non-specific antibodies are thus produced during infectious diseases.
- Anti-human erythrocyte cold antibodies in Mycoplasma pneumonia and anti-sheep erythrocyte antibodies in infectious mononucleosis are best studied diseases.
- These are polyclonal antibodies which are IgM in nature.
- Thus, they are similar to the natural antibodies produced by CD5 + Bcells.
vi) Forbidden clones
- Cessation of tolerance results when there is breakdown of immunological homeostasis.
- Along with it, emergence of forbidden clones of immune-competent cells occurs.
- These cells are capable of mounting immune response against self-antigens.
- Autoimmunization may result when tolerance to self-antigens is abrogated.
- This can be studied by injecting self-antigen with Freund’s adjuvant.
vii) Altered T or B cell function
- There are many causes of autoimmunity.
- Sometime the cause may be the enhanced and decreased functions of helper and suppressor T cells respectively.
- Some other causes are defects in thymus, in stem cell development and macrophage function.
- Autoimmunity may also result by defect in idiotype-anti-idiotype network.
- Defective Ir or immunoglobulin genes as genetic factors also act as causes.
- Though many mechanisms have been proposed, their actual role in autoimmunity has not been established well.
Auto immunity: Introduction and Mechanism