Saturday, June 22, 2013

Autoimmune Diseases and Some Important Immunological Disorders


The auto-immune diseases result from immunologically mediated tissue destruction where the antigens involved are autologous. Several mechanisms have been proposed to explain the pathogenesis of auto-immune diseases.

Forbidden clone theory: All the clones which react with self antigens are destroyed during intra-uterine life but such a clone may be generated by somatic mutation in later life.

Sequestrated antigen theory: Antigens exposed to lymphoid system during intra-uterine life are recognized as self. But some tissues (e.g, lens, thyroid, CNS) are anatomically sequestered or guarded from the lymphocytes. In adult life, when such antigens are exposed the immune system reacts against them.

Suppressor cell (TS) deficiency: Small quantities of thyroglobulin (and other auto-antigens) are seen in circulation even in normal persons, but they are below the threshold level for immuno-stimulation. The suppressor cells also inhibit sensitization. In persons with deficient TS activity, inappropriate immune reactions are produced.

genetic effect: Auto-immune diseases show a familial distribution and female preponderance. Many of them are associated with particular HLA types. These suggest that genetic predisposition may play a role in their pathogenesis.

Modified antigenic structure: Normal tissues may be altered by micro-organisms, making them antigenic. Drugs such as methyl-DOPA may act as haptens combining with cellular proteins. These altered proteins can elicit immunological responses. Antibodies once produced will attack not only the hapten, but also the carrier molecules.

Cross reacting antibodies: Antibodies produced against exogenous antigens can cross react with tissue proteins e.g post-rabies vaccine encephalitis, and post-streptococcal rheumatic fever. In any given instance one or more of the above mechanisms may be operative.

Some Important immunological disorders

1. Organ specific diseases
a. Pernicious anemia: auto-antigen are Parietal cells of stomach (Diagnostic test- Immunoflourescence test) and Intrinsic factor (Neutralization test).
b. Ulcerative colitis: Auto-antigens are Lipopolysaccharides of mucous membrane of colon Immunoflourescence test)
c. Acute post-streptococcal Nephritis: Auto-antigen is the streptococcal antigen (Complement fixation test and Immunoflourescence test).
d. Sympathetic Pphthalmia: Auto-antigen is the Uveal protein Skin test).
e. Bullous pemphigoid: Auto-antigen is the basement membrane (Immunoflourescence tests).
f. Pemphigus Vulgaris; Auto-antigens are the Desmosomes (Immunoflourescence tests).
g. Thyrotoxicosis by LATS (Long acting thyroid stimulator): Cell surface receptor proteins (Bioassay).
h. Hashimoto's thyroiditis: Thyroglobulin microsomes (Passive hemagglutination and Complement fixation test).

2. Affecting two or more organ systems
a. Goodpasture's syndrome: Glomerular and lung basement membrane (Immunoflourescence test).
b. Auto-immune hemolytic anemia: Membrane proteins of RBC (Coomb's test).
c. Immune-thrombocytopenia: Platelet components (Demonstration of antibody)
d. Myasthenia gravis: Skeletal, heart and thymus myoid cells (Immunoflourescence tests).
e. Primary biliary cirrhosis: Liver and Kidney mitochondria (Immunoflourescence tests).
f. Rheumatic fever: Streptococcal antigen cross reacting with heart and joint tissues (Immunoflourescence).

3. systemic or generalized diseases
a. Rheumatoid arthritis: Immunoglobulins, especially IgG (Latex agglutination)
b. Sjogren's disease: Ductus mitochondria of glands (Immunoflourescence tests).
c. Systemic Lupus erythematosus: Nuclear DNA and nucleo-proteins (Immunofloresence tests).
d. Systemic sclerosis (scleroderma): Nuclear proteins (Immunoflorescence tests).

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