Autoimmune Diseases
the failure of self-tolerance; and is a specific immunological reaction against self-structuresTolerance is the state of specific immunological unresponsiveness .
C. Phagocytic Cells ToleranceAntigens or immune complexes which cannot be cleared up from the body result in tolerance.
B. Peripheral tolerance
deal with escaped self-reactive B- and T- cells after leaving the bone marrowby:
1. Excessive cross-linking of B-cells receptors for antigens (clonal anergy/ignorance).
2. Inadequate co-stimulatory signals
3. Role of T-reg cells and their cytokines
4. Idiotype-Anti-idiotype network
A. Central tolerance
Clones of B- and T-cells reactive to self-antigens are deleted in the bone marrow and the thymus respectively by a process called negative selection
Tolerogenic antigens lead to apoptosis or a state of anergy of lymphocyte response.
Immunogenic antigens lead to the stimulation and proliferation of lymphocytesPromotion or break of tolerance
1. High doses of antigens leading to excessive cross-linking of B-cell antigen receptors.
2. Failure of clearance of the antigen or immune complexes3. Low levels of co-stimulatory signals
4. Intravenous or oral administration of the antigens.
5. Sequestered antigens
6. Molecular mimicry (cross-reactivity),
7. Infective agents may provide excessive T-cell stimulation, tissue destruction and antigenic modification .
8. Superantigens that activate numerous T-cell clones.
9. Age and gender
10. Life style (smoking )
11. Complement deficiencies
Classification of autoimmune diseases
Systemic autoimmune diseases- SLE
- Systemic sclerosis
- Mixed connective tissue disease
Organ-specific autoimmune diseases
- Insulin-dependent DM (type-I)- Rheumatoid arthritis
- Grave's disease
- Goodpasture's syndrome
- Myasthenia gravis
Aetiology of Autoimmune Diseases
I. Release of sequestrated antigens
II. Infectious microbes may produce peptide antigens that are similar to self antigens, this is called “molecular mimicry”
Example one: Antibodies formed against M protein of Streptococcus pyogenes cross react with cardiac myosin leading to rheumatic fever.
Example two: Rubella and diabetes type I
III. Alteration of self antigens or appearance of new antigens under effects
IV. defects in immune regulatory mechanisms.
V. T-Cell Bypass
VI. Genetic predisposition
1. There is a familial incidence of autoimmune diseases. Certain diseases run in families
2. There is a concordance rate of susceptibility to development of diseases
3. Most of autoimmune diseases appear to be associated with certain HLA antigens/ genes
4. Females are more prone to develop autoimmune diseases than males
Mechanisms of Tissue Damage in Autoimmune Diseases
Can be due to any type of hypersensitivity except type 13. DHS (type IV) by T cells as in ulcerative colitis, coeliac disease
2. Immune complex deposition (type III) in blood vessel walls, skin, joints, glomeruli
1. Cytotoxic reactions (type II) as occurs in autoimmune haemolytic anaemias ,
Symptoms of autoimmune diseases
Symptoms that often occur with autoimmune diseases include fatigue, malaise, and fever. When symptoms get worse, it is called a flare-up. Most autoimmune diseases are chronic, but many can be controlled with treatment.
4. Complement levels may be decreased in particular C3 and C4.
5. Immune complexes may be detected in serum6. HLA typing
7. General laboratory tests .
Management of autoimmune diseases
relieve symptoms, preserve organ function, and target disease mechanisms.
1. Anti-inflammatory drugs
2. Immunosuppressive agents
3. Biological agents
4. Plasmapheresis
5. Some patients may need supplements to replace a hormone or vitamin that the body is lacking
6. Surgery sometimes is required to correct or preserve functions
Laboratory Diagnosis of Autoimmune Diseases
1. Autoantibodies
2. Total immunoglobulin concentration may be increased
3. Cryoglobulins are antibodies directed against other immunoglobulins that form immune complexes which precipitate in cold.
- Type I: Monoclonal IgM paraprotein with no particular specificity, e.g. lymphoproliferative diseases , normal complement level
- Type II: Monoclonal IgM against IgG constant region, e.g. hepatitis C or B; decreased C4
- Type II: Polyclonal IgM or IgG against IgG constant region, e.g. hepatitis C or B, SLE decreased C4