Autoimmunity

 Autoimmunity

•       autoimmune disease -  is immune responses of an organism against its own healthy cells, tissues and other body normal constituents

•       Resulting disease - Autoimmunity means presence of antibodies or T cells that react with self-protein and is present in all individuals, even in normal health state.

•       It causes autoimmune diseases if self-reactivity can lead to tissue damage

•       Autoimmune diseases is a group of disorders in which tissue injury is caused by Ab (by auto-antibodies) or CMI (by auto-reactive T cells) to self-antigens.•

•       An autoimmune disorder may result in:–

v The destruction of one or more types of body tissue–

v Abnormal growth of an organ

v Changes in organ function

Autoimmunity causes:

1)     is caused by abnormal and excessive activity of one or both of the immune system effector cells. in case of excessive activity of B-cells, we have excess antibodies and excess activity of T – cells, leads to infiltration of tissues by T-lymphocytes and macrophages 

2.             Failure of immune system to discriminate between self and non-self antigens

3.    Exposure to hidden antigen

4.    Immunization to cross-reacting antigens that share immunogenic determinants with autoantigens

5.  Intense stimulation of lymphocytes due to use of adjuvants for immunization-leads to overproliferation of lymhpocytes leading to attack of self antigens

 

6. The immune system is under regulation and the regulation involves receiving signals from regulatory system. The regulatory signals may become abundant due to interference of the control system. This results to abnormal response that leads to autoimmunity. The net effect of this abnormal activity leads to injury to self tissues.

•       So autoimmunity in effect is a reflection of loss of immunological tolerance to self tissues antigens through a number of processes

 

•       Auto –immune Diseases

1)    Haemolytic autoimmune diseases

2)    Localised autoimmune diseases

3)    Systemic autoimmune diseases

 

I. Haemolytic autoimmune diseases•

•       Clinical disorder due to destructions of RBC by autoantibodies

•       Auto Ab attack RBCs, Platelets or Leucocytes .•

 E.g.

•       Haemolytic anaemia,

•       Leucopenia,

•       Thrombocytopenia

2. Localized autoimmune disease

A particular organ is affected due to auto Abs.-

}  Eg:–

1)    Thyroiditis (attacks the thyroid)–

2)    Myasthenia gravis (attacks nerve-muscle  junction)–

3)    Juvenile diabetes or Type I DM (attacks insulin-producing cells)

}  Hashimoto’s thyroiditis•

}   Hypothyroidism & destruction of thyroid cells

}  Characterised by Goitre, enlarged thyroid gland

}  Characterized by Type IV hypersensitive reactions

}  It is a T-cell associated auto immune disease .

}  Myasthenia Gravis• Caused by auto antibody against muscle antigen & acetylcholine receptor antigen.•

Type I diabetes• β cells produce little or no insulin. Heritable, Symptoms are like being very thirsty, hungry, tired or fatigued, urinating more often.

3. Systemic autoimmune disease

v  Non organ-specific autoimmune diseases

v Immune complexes accumulate in many tissues and cause inflammation and damage.

E.g.: Harms kidneys, heart, brain, lungs, skin

 

I .Systemic Lupus Erythematosus (SLE): Skin disease due to the production of anti-nuclear factor (ANF) .  In these patients, SLE cell (a mature neutrophil) appears in blood & bone marrow–

Function – Phagocytosis in the presence of ANF.

2.  Rheumatoid Arthritis

}  Disease of the joints

}   Caused by the auto Antibody of IgM type, called rheumatoid factors.

}  The synovial fluid of these patients contain increased no. of T-cells & macrophages.

}   Marked by inflammatory changes in the synovial membrane.• In later stage, deformity develops.

 

HLA, Genetics and Disease

1.    This group of genes resides on chromosome 6.

•       Certain individuals are genetically susceptible to developing autoimmune diseases.

•        This susceptibility is associated with multiple genes plus other risk factors.

•       Genetically predisposed individuals do not always develop autoimmune diseases.

•       Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:

v Immunoglobulins

v T-cell receptors

v The major histocompatibility complexes  (MHC).

Genetic factors

•         The first two (Ig &TCR), which are involved in the recognition of antigens, are inherently variable and susceptible to recombination.

•          These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocytes capable of self-reactivity.

•         HLA DR2 is strongly positively correlated with systemic lupus erythematosus  and multiple sclerosis, and negatively correlated with DM Type 1.

 

•  HLA DR3 is correlated strongly with  myasthenia gravis, SLE, and DM Type 1.

•       HLA DR4 is correlated with the genesis of rheumatoid arthritis, Type 1 diabetes mellitus,

•       Fewer correlations exist with MHC class I molecules.

•       The most notable and consistent is the association between HLA B27 and ankylosing spondylitis and reactive arthritis.

•       Recently, PTPN22 locus is one of the strongest risk factors outside of the MHC that associates with autoimmune diseases.

•       PTPN22-(Protein tyrosine phosphatase, non-receptor type 22)

•       PTPN22 encodes lymphoid protein tyrosine phosphatase (Lyp) which is expressed exclusively in immune cells.

•       PTPN22 plays roles in lymphocyte dev’t and activation, establishment of tolerance, and innate immune cell–mediated host defense and immunoregulation

•        

•       A single base change in the coding region of this gene resulting in an arginine to tryptophan AA substitution (within a polyproline binding motif) associates with type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosis, Hashimotos thyroiditis, Graves disease, Myasthenia Gravis

•       Treatment

•       immunomodulation

•       Some autoimmune diseases are treated with medications that Target specific symptoms

•       Haemolytic anaemia: Treated with Vit B12, iron

•       SLE : Treated with NSAIDS such as ibuprofen or naproxen, antimalarial drugs, and corticosteroids

•       In more aggressive cases, immunosuppressive drugs maybe used.

 

Immunosuppressive drugs

Drugs that inhibit or prevent activity of the immune system

1.    Immunosuppressive drugs can be classified into four groups:

v  Glucocorticoids (suppress allergic, inflammatory and autoimmune disorders) .

v  Cytostatics (inhibit cell division) .

v  Antibodies (prevent the acute rejection and targeted treatment of autoimmune disorders) .

v Drugs acting on immunophilins (Cyclosporin A,Tacrolimus)

 

Reference

v Hussain Y, Khan H. Immunosuppressive Drugs. Encyclopedia of Infection and Immunity. 2022:726–40. doi: 10.1016/B978-0-12-818731-9.00068-9. Epub 2022 Apr 8. PMCID: PMC8987166.

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