What are the Common Defects in Immune System?

Defects in lymphoid organs, mutations in lymphocytes or defective function of lymphocytes could result in autoimmune reactions.

Thymus atrophy is often encountered with systemic lupus erythmatosis (SLE). If elimination of self reacting lymphocytes is not properly done during their development in primary lymphoid organs and released in to the circulation, they may induce autoimmune problems.

Since proper antigen presentation is essential for proper action of immune cells, defects in antigen presenting cells could result in auto immune reactions.

Cytokine imbalances or defective immune regulatory circuits may also contribute to the emergence of autoimmunity.

For example, decreased apoptosis, diminished production of tumor necrosis factor (TNF) and interleukin-10 (IL-10) has been reported to be associated with the development of autoimmunity.

Intense stimulation of T lymphocytes can produce nonspecific signals that bypass the need for antigen-specific helper T cells and lead to polyclonal B cell activation with the formation of multiple auto antibodies. For example, antinuclear, anti erythrocyte and anti lymphocyte antibodies are produced during the chronic graft-versus-host reaction.

Anti-Idiotype Antibodies:

One of the mechanisms that regulate normal humoral immune responses is production of anti-idiotype antibodies. These are immunoglobulin molecules directed against antigen-binding determinants of the specific antibodies originally elicited by the immunogen.

Even the initial immunogen is T cell independent, production of anti-idiotype antibodies may depend on TH cells activity.

Therefore, it is possible that abnormalities in the synthesis of appropriate anti-idiotype antibodies, either at the B or T cell level are responsible for the development of autoimmunity in certain circumstances.

Genetic Factors:

Since genes influence overall reactivity of the immune system, they may predispose an individual to autoimmunity. Three main sets of genes are suspected in many autoimmune diseases they are genes for immunoglobulins, T-cell receptors and the major histocompatibility complexes (MHC).

The first two are concerned in the recognition of antigens and are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but some times the variation may result in the production of self reactive lymphocytes.

Some of the MHC class II allotypes are strongly correlated with specific autoimmune diseases. Other allotypes may affect the ability of the target tissue to resist or modify immune attack.

Lack of Regulatory T Cells:

Regulatory T-cells are important for the maintenance of peripheral tolerance. Fundamentally regulatory T cells have a suppressive effect on the neighboring immune cells, thus contributing to the local modulation and control of immune response. There are fewer regulatory T-cells in many autoimmune diseases, In the IPEX syndrome (immunodysregulation, poly endocrinopathy and enteropathy, X-linked), which is caused by mutation in Foxp3 gene.

The Foxp3 gene influences the development and function of regulatory T cells. Mutations in the gene results in severe autoimmune reactions that may produce the following auto immune problems;

Autoimmune endocrine disorders eg. Type 1 diabetes, thyroiditis etc.,

I. Respiratory and nutritive allergies.

II. Eczema and severe infections.

III. Different types of allergies eg. Allergy for pollen grains, dust mites, nutritive allergens.

IV. Autoimmune diseases eg. Rheumatoid arthritis, multiple sclerosis type 1 diabetes

V. Lower number or decreased functional capability of regulatory T cells.

It is clear that no single mechanism can explain all the varied manifestations of autoimmunity. Indeed, it appears clearly in systemic autoimmune diseases, where a number of abnormalities converge to induce the complete syndrome.

Moreover, one abnormality may cause a second, which, in concert with the first, facilitates the expression of autoimmunity.