IMMUNITY

IMMUNITY III

Immune mediated mechanism of the disease: Type I Hypersensitivity Reaction-Antibody mediated : Type I anaphylactic reaction is mediated by IgE antibodies, the production of which depends on TH2 cytokines that bind to high affinity receptors on mast cells & basophils. Subsequent cross linking of these receptors by antigen triggers degranulation & the release of range of mediators (e.g. histamine, prostaglandin & leucotriens) , which produce

the immediate symptoms as increased vascular permeability & smooth muscle constriction, the release of cytokine leads to eosinophil recruitment, the site of mast cell activation determines whether there's a local response (e.g. allergic rhinitis, anaphylaxis and asthma).

Type II Hypersensitivity Reaction - Antibody mediated Cytotoxity: Antibodies against circulating or fixed cells are involved in the pathogenesis of a variety of diseases including: 1.Autoimmune haemolytic anemia 2.Autoimmune thrombocytopenia 3.GoodPasteur's syndrome 4.Pemphigus & Pemphigoid 5.Pernicious Anemia 6.Mysthenia gravis 7.Grave's disease

Pathogenic antibodies cause tissue damage by variety of mechanisms including lyses by complement & phagocytosis of opsonized cells, in addition inflammatory cells are recruited to tissues by antibody deposition & complement activation. Antibody also binds to receptors& alter the cellular function without damaging the cells. Antibody can be present but not involved in disease pathogenesis, which likely is the case in rheumatoid arthritis.

Type III Hypersensitivity Reaction - Immune complex mediated disease: Should the antigen be soluble, circulating aggregates of antibody & antigen (immune complex) may arise, the deposition of immune complexes in tissues such as blood vessels wall may directly cause inflammation & tissue damage, in addition, immune complex resulting from repeated exposure to antigen in the presence of pre-existing anti-IgG antibodies may activate complement leading to increase vascular permeability & the recruitment of polymophonuclear leucocytes termed the Arthus reaction .

Immune complex disease can also occur in response to a single immunization with pre-formed antibody as acute serum sickness until the foreign serum proteins are cleared. Examples of immune complex disease include: 1. Systemic Lupus Erythematous 2. Poly arteritis nodosa 3. Post streptococcal glomerulonephritis 4. Farmer's lung

Type IV Hypersensitivity Reaction Delayed type hypersensitivity: Is mediated by antigen - specific T - cells with the appearance of a local inflammatory reaction 24 - 48 hours after a sensitized individual is challenged with antigen. Inflammatory TH 1 cells migrate to the site of injection, recognize peptide / MHC class II complexes on APCs & release cytokines such as IL-2 , IFN-sigma, TNF and other chemo attractants. These leads to increase vascular permeability and the recruitment as well as activation of macrophages & CD 8 cytotoxic cells.

Examples: 1.Graft rejection 2.Contact Dermatitis 3.Immune response to mycobacterial antigen (purified protein derivative skin test)