Aeitology of autoimmune disease – Multifactorial (Abbas 179)

So what is the cause of autoimmune disease?

Basically, the cause is many.

1. Some proteins/cells and other components in the body are sequestered. This means, under normal circumstances the immune system is unaware of their existence (i.e.: Think of security guards and you hiding somewhere, they cant see you!). Sometimes, infectious agents damage the tissues that sequester them, therefore now you have antigen released. For example: sperm inside testes, proteins inside eye, or DNA inside cells can be seen by T cells. Therefore an autoimmune reaction is set in motion.

2. Sometimes a self antigen is not recognised by the immune system, but it is modified so that new epitopes are formed – now it is recognisable as foreign so immune system activated. (i.e.: RBCs, IgG following antigen binding. 3) Molecular mimicry (Robbins pp 215) – Some infectious agents have the same epitopes as self antigens. So an immune reaction against the microbes, means tissue damaging reactions against self antigens. Removal of microbe will still cause an immune response. An example is rheumatic fever post-strep infections. This is because an antibody against streptococcal M protein cross reacts with cardiac glycoproteins≫ Rheumatic fever.

3. T suppressor cells (regulatory cells) suppress themselves and regulate the inactivation of other potential autoreactive cells. If the no. of these cells decreases, then auto-immunity can occur. Some antigen specific CD4+ T cells can suppress antigen specific proliferation of other T cells ≫ prevent autoimmune colitis (mouse model).
   

4. Viruses: interfere with immunological control,
   

5. Excess of autoreaction T helper cells

6. Polyclonal lymphocyte activation: Clonal anergy is maintained because antigen specific 2^nd signal is not present. Sometimes, microbes can cause B cells to get activated even though the 2^nd signal is antigen non-specific (i.e.: activated by 1 type of antigen ≫ 1^st signal, activation by 2^nd type of antigen ≫ 2^nd signal),

7. Genetic predisposition: there is an associated familial risk, many autoimmune diseases in humans are linked to particular MHC alleles ≫ i.e.: inheritance of particular alleles of HLA means increased risk of autoimmune disease.

Sex ration & autoimmune disease

Generally, females are predisposed to autoimmune diseases when compared to males.

Signs of autoimmune disease

Just remember: GACIL (gamma globulins, autoantibodies, ↓ serum complement, immune complexes in serum, lesions found in biopsy).

Category: Pathology Notes