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16 autoimmune (And 17?) [7] (1-Mechs (1.1 Disease examples. Know: (Type IV…
16 autoimmune (And 17?) [7]
1-Mechs
( not type 1, this is anaphylais?)
Type III
IgG, IgM and complement
Type II
IgG & complement
IgG, NK cells, eosinophils (ADCC)
Type IV autoreactive T Cells
Th1 CD4 cells
CD8 T cells
1.1 Disease examples. Know:
Type IV
: autoreactive T Cells
MS: target myelin, etc.
Psoriasis: some skin antigen
Chrones: Intestine microbiota
Type 1 Diab: pancreatic b cell
Rheumatoid Arthritis: some synovial joint antigen
Type III:
Autoantibodies against
soluble
antigens.
Rheum arthritis: rheum factorr IgG complexes
Mixed essential cryoglobulinemia: rheum factorr IgG complexes
Outcome: vasculitis
Type II:
autoantibodies against cell surface
Autoimmune hemolytic anemia: Rh group antigens, I antigen
Purpura: platelet integrin
Goodpasture's: basem. membrane collagen
Pemphigus vulgaris: epiderm cadherin
Acute rheumatic fever: cross rxn with cardiac
2- Prevention of autoimmune rxn
Eliminate Self-reactive T Cells
Kill in thymus
Anergy (t cell inactivation) through binding to Ag+MHC on non-antigen-presenting cell
Regulatory T Cells ("suppressor"?)
Eliminate self-reactive B cells
Kill in bone marrow
Check in germinal centers (in lymph node and spleen). If
not
(?) binding to self-antigen, is destroyed
Regulation by T cells
3- Risk Factors
Exposure fo antigen
Female gender
Age
Old age: Thymic shrinkage, failure
Genetics
IDDM
HLA Class II heterodimers
Cytokine deficincies
4: Mechanisms of autoimmune
Molec. mimicry: path antigen and self antigen
E.g., Rheum fever
Similar antigens can bind to
same MHC
Similar to neo-antigen mech
Drug-induced hemolytic anemia
Lost ability to suppress immune
E.g. lupus: ageing causes t cell reg deline, allowing autoantibodies to act on DNA, RNA, histones etc.
Sequestered antigens released erroniously
Sympathetic Opthalmia
E.g. due to tissue trauma
Antigen presentation altered
E,.g. Autoimmune thyroiditis
APCs infected
5 Infections assoc with autoimmune (LIST)
6: Indirect symptom causation, E.g GRAVES disease
1) Antibodies attack TSH receptor, stimulates TH production
2) TH -> dcrease TSH production in hypothal and pituitary
3) Antibody creation not affected, therefore TH continues to be produced excessively
E.g. Myasthenia Gravis: Ach receptors tagged with Abs, internalized and degraded
7: Therapy
Plasmaphoresis: neonate graves' disease
Immunosuppressives
Monoclonal antibodies against certain T cells
Soluble factor antagonists
Induction of tolerance to a certain antigen
Rheum. arthritis is III
and
IV