Hypersensitivity ()Qingqing WangInstitute of ImmunologyZhejiang University School Of Medicinewqq@zju.edu.cn
Type II hypersensitivity(cytotoxic type)Type II hypersensitivity reactions are mediated by IgG and IgM antibody binding to specific cells or tissues. The damage caused is thus restricted to the specific cells or tissues bearing the antigen.The antibodies damage cells and tissues by activating complement, and by binding and activating effector cells carrying FcR.
I. Pathogenic mechanisms Ags on the surface of target cells bodyIgG, IgM 1. damage the target cell 1) activation of complement 2) opsonization: FcR, C3bR 3) ADCC: NK cells, M 2. target cell dysfunction
Effector mechanisms of Ab-mediated diseasesGraves diseaseIn myasthenia gravis the Abs against Ach receptor inhibit neuromuscular transmission and cause paralysis
II. Clinical disease1. Transfusion reactions
2. Hemolytic disease of the newbornMainly occurs when an Rh- mother gives birth to an Rh+ infant.Prevention: The administration of anti-Rh Ab to an Rh- mother within 72 hours of delivering an Rh+ infant will prevent sensitization and problems with subsequent pregnancies.
3. Autoimmune hemolytic disease Some drugs or viruses stimulate Ab formation by changing the erythrocyte surface components to form new epitopes. The resulting Abs can cross react with epitopes on unmodified RBCs.
Human antibody-mediated diseases
4. Drug-induced reaction to blood components These diseases have been associated with many different chemotherapeutics, such as penicillin, the sulfonamides. These drugs stimulate Ab formation by forming new epitopes with serum proteins, which then adsorb nonspecifically to the red blood cell surface so that its new epitopes are expressed.
5. Graves disease
The patients produce antibodies to thyrotropin (thyroid stimulating hormone, TSH) receptor. The end result is overproduction of thyroid hormone and hyperthyroidism.
Type III hypersensitivity(immune complex type)Immune complexes (IC) deposit in basement membranes of small blood vessels in various organs.
I. Pathogenic mechanisms AgbodyIgG, IgM, IgA immune complexes (IC) soluble IC ICs are deposited from the circulation into vascular basement membranes FcRactivation of complement plat. and basophils C3a, C5a mast cell release of vasoactive amines basophils Neutrophils vasodilation lysosomal edema enzymesdamage the tissueaggravate
IC are capable of triggering a variety of inflammatory processesICs interact with the complement system to generate C3a and C5a. These complement fragments stimulate the release of vasoactive amines and are chemotactic factors for mast cells and basophils, eosinophils and neutrophils.ICs interact directly with basophils and platelets (via FcR) to induce the release of vasoactive amines.Neutrophils exocytose their lysosomal enzymes onto the site of IC deposition and damage the underlying tissue.
Deposition of IC in tissuesAn increase in vascular permeability In general, complement, mast cells, basophils and platelets must all be considered as potential producers of vasoactive amines.Local high blood pressure and turbulence The blood pressure in the glomerular capillaries is approximately four times that of most other capillaries.
II. Clinical diseases1. Arthus reaction An animal is immunized repeatedly until it has appreciable levels of serum Ab (mainly IgG). Following subcutaneous or intradermal injection of the antigen a reaction develops at the injection site, sometimes with marked edema and hemorrhage.
Nicolas Arthus 1862-1945
Arthuss reaction 1903,
2. Serum sickness Serum sickness is a complication of serum therapy, in which massive doses of anti-serum are given in conditions such as snake bite.
Serum sicknessClemens Pirquet 1874-1929
3. Postinfectious glomerulonephritisA2-3
Human immune complex disease
4. Rheumatoid arthritisRheumatoid factor (RF): an immunoglobulin (mainly IgM but also IgG and IgA) with antibody specificity for the Fc portion of IgG.The joint synovial fluid contains IC consisting of RF-IgG-complement.Many patients with rheumatoid arthritis also have antinuclear antibodies.5. Systemic lupus erythematosus (SLE)antinuclear antibodieshypergammaglobulinemia
Type IV hypersensitivity(Delayed type hypersensitivity)Delayed type hypersensitivity is initiated by sensitized T cells reacting with specific antigens. The reactions are manifest as inflammation at the site of antigen exposure, which usually peaks 24-72 hours after exposure.This reaction is independent of antibody and complement.
I. Pathogenic mechanisms Ag-MHC AntigenAPCT cells co-stimulating factors sensitized T cell effector and memory cells CD4+T cell (Th1 type) CD8+T cell (CTL) release of cytokines killing target cells by the release of inducing the inflammatory perforin and granzymesresponse or by the FasL-Fas pathway(primarily M and T cells)
Mechanisms of T cell-mediated tissue injury
II. Clinical diseases1. Infectious DTH In the infective process, intracellular parasitical bacteria (Mycobacterium tuberculosis, Mycobacterium leprae, Brucella), viruses and fungi cause T cell-mediated immune responses, which are referred to as infectious delayed type hypersensitivity.
Tuberculin-type hypersensitivityThe tuberculin skin test (OT) reaction principally involves M
tuberculinbodyT cells are activated IFN-MTNF, IL-1 endothelial cells in dermal blood vessels express CAM: E-selectin, ICAM-1, VCAM-1 recruiting monocytes and T cells (Monocytes constitute 80-90% of the total cellular infiltrate)
Tuberculin-like delayed type hypersensitivity reaction are used practically in two ways.1) To confirm past infection with M. tuberculosis, but not necessarily active disease.2) To be a general measure of cell-mediated immunity.
2. Contact dermatitisLangerhans cells and keratinocytes acting as APCs have key roles in contact hypersensitivity.Keratinocytes produce a range of cytokines.A contact hypersensitivity reaction has two stages: sensitization and elicitation. Sensitization produces a population of memory T cells and elicitation involves recruitment of CD4+ lymphocytes and macrophages.
Many important sensitizing allergens are organic chemicals, and some are metals such as nickel, chromate. It is assumed that they function as haptens.When allergen again penetrates the skin, these memory cells rapidly evolve into effectors that mediate a delayed-type hypersensitivity reaction at the site of penetration.
T cell-mediated diseases
Comparison of 4 types of hypersensitivity
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