Autoimmune disorders – An agent capable of stimulating immune response is known as antigen. It may be a protein, polysaccharide or a complex lipid. There are two kinds of immune responses.
Humoral immune response involved in the production of antibodies and cellular immunity in which incompetent cells react directly against the foreign material. T and B- lymphocytes are involved in these responses.
Although each antibody is specific for a particular surface antigen (epitope) but more than one antigen may be present with the result that antibodies raised against the antigen may react with corresponding epitope (Cross-reactivity).
Antibody production is governed by lymphocytes, macrophages and proliferation of T and B cells which produce plasma cells for B lymphocytes (synthesizing of antibody). T helper cells (cooperate with plasma cells in the synthesis of certain antibodies) and T suppressor cells (regulation of antibody synthesis).
On exposure to antigen, an individual responds by synthesizing specific antibodies that subsequently may interact with inciting antigens to form antigen antibody complexes. This immune response is designed to eliminate and br neutrialize the antigen thus benefiting the host.
In most instances this is largely achieved but if it sometimes fails, it is because of altered host response to foreign antigens. Immune complexes formed by binding of foreign antigen to specific atuologus antibodies could produce inury in host.
Thus in certain infectious autoimmune diseases the immune complexes formed may cause greater injury than the microbes themselves especially if microbial antigens are produced in large amounts over prolonged periods. Evidence of immune complex lesions accompany many infectious diseases.
Auto antibodies are of greater threat to immune complex injury because their supply of auto-antigens is continuous and essentially limitless. Exogenous or endogenous agents leading to immune complex disease may react with antibody locally at the site of antigen production to produce local immune complex disease or they may reach and react with antibody in circulation to form circulating immune complexes that cause multisystem immune complex disease.
The activity and fate of immune complexes is influenced by various factors such as nature, amount and ratio of antigen and antibody in immune complexes. Between antibody excess and mild antigen excess, the complexes are rapidly precipitated and tend to be localized to the site of introduction of antigen. In moderate to gross antigen excess, soluble complexes are formed which circulate and may cause systemic reactions.
Immune complexes which are formed in slight antigen excess are usually of small and intermediate size, circulate largely in blood, bind less avidly to phagocytic cells and are the one, which are most pathogenic.
Auto immunity is the loss of tolerance to auto-antigens. There is production of either antibodies that react with host tissue or immune effector T cells. The production of auto-antibodies is an inherent property of the normal immune system and this is done by a feed back network of T and B cells. ‘Wide variety of antigens produce a number of auto-antibodies which may be organ specific or non oigan specific.
Mechanisms involved in the pathogeness of autoimmunity shall be:
(a) Immune complex disease where elevated levels of circulating immune complexes are correlated with clinical variety of a number of auto immune diseases such as rheumatid arthritis, systemic lupus erythematosis and glomerulonephritis.
The main mechanism for the tissue injury due to immune complexes is attributed to complement activating antibodies primarily of the class IgG. Immune complexes may affect multiple cells (neutrophils, eosinophils, basophils, monocytes and lymphocytes) modulating immune response.
(b) Defects in cell mediated immunity generally results in injury to cells directly or indirectly. Antibodies deficiencies result in recurrent bacterial infections.
(c) Clonal selection therapy. As per this the contact of antibody forming cells with their respective antigens during intra uterine life leads to their elemination. In later life by somatic mutation. Sell reacting antibodies are produced. Thus production of auto antibodies is an inherent property of normal immune system.
(d) Suppressor cells deficiency. When suppressor cells (Ts) are deficient, their activity is not sufficient for immune stimulation with the result that inappropriate immune reaction is produced.
(e) Genetic factors also play important role in the genesis of autoimmune disease. There is association of several genetic markers with auto immune disorders. Genes of HLA types (HLA B8, HLA B21) are associated with Type 1 diabetes mellitus while HLB B 8 (class I) and DR3 (Class II) are associated with Myasthenia gravis, thyrotoxicosis and pemicious anaemia.
In addition to the above factors, auto immune diseases are governed by factor of sex linked predilaction, environmental factors, infections (viral, bacterial) and hormonal influences.
Classification of Autoimmune disorders
(a) Organ specific. Autoimmune disorders includes diseases where auto antibodies are directed against specific organ. This includes autoimmune thyroiditis (Hashimoto’s disease), pernicious anemia, type I diabetes mellitus and various endocrinal disorders.
(b) Non-organ specific. Here multiple organs are involved and a large variety of auto antibodies are directed against various structures. The diseases in this group include Rheumatoid arthritis, dermatomyositis and connective tissue diseases.
Very often a patient may have auto-antibodies both organ specific and non-organ specific in the circulation. This happens in auto immune chronic active. Hepatitis, myasthemia gravis, autoimmune haemolytic anaemia, idiopathic thrombocytopenia and systemic lupus erythematosis etc.
Thus autoimmune diseases have number of factors operative and these include genetic and neuro endocrine ones where self antigens drive an auto immune response leading to disease. Mechanism of tissue damage in auto immune diseases is mainly of two types.
Firstly there is direct injury by the autoantibody (Type II reaction) and secondly where tissue damage occurs through type III mechanism (Immune complex mediated).
COMMON AUTOIMMUNE DISEASES
1. Hashimoto’s thyroiditis
2. Pernicious anaemia
3. Myasthenia gravis
4. Autoimmune haemolytic anaemia
5. Idiopathic thrombocytopenic purpura
6. Chronic active hepatitis
7. Rheumatid arthritis
8, Systemic lupus erythematosis
12. Goodpasture’s syndrome
14. Sjogren’s disease
15. Primary biliary cirrhosis