Hypersensitivity is the term used when an immune response results in exaggerated or inappropriate reactions harmful to the host.

Transcription

1

2

3 Hypersensitivity is the term used when an immune response results in exaggerated or inappropriate reactions harmful to the host. Hypersensitivity vs. allergy Hypersensitivity reactions require a pre-sensitized (immune) state of the host. The first contact of the individual with the antigen sensitizes, i.e., induces the antibody, and the subsequent contacts elicit the allergic response. A substance that causes a reaction is called an allergen

4

5 Overview of Hypersensitivity Reactions ANTIBODY MEDIATED CELL MEDIATED

6

7 occurs when an antigen (allergen) binds to IgE on the surface of mast cells with the consequent release of several mediators pollens, animal danders, foods (nuts, shellfish, eggs) Drugs Pathophysiology: Acute (immediate) phase response Late phase response

8 an allergen encountered for the first time presented by an Antigen-Presenting Cell to T H 2 lymphocytes IL-4 IL-13 B cells switching to produce IgE IgE circulates in the blood and binds to an IgE-specific receptor mast cells and basophils. The IgE-coated cells, at this stage are sensitized to the allergen. ( sensitization ) If the 2 nd exposure for the same allergen occurs, the allergen bind to the IgE molecules held on the surface of the mast cells or basophils Cross-linking of the IgE and Fc receptors cell degranulation of the preformed mediators vasodilation, mucous secretion, nerve stimulation, and smooth muscle contraction.

9

10 Histamine: from mast cells and basophils and acts on (H1) and (H2) receptors. causes vasodilation, increased capillary permeability, and smooth-muscle contraction. Serotonin (hydroxytryptamine) is preformed in mast cells and blood platelets. When released during anaphylaxis, it causes capillary dilation, increased vascular permeability, and smoothmuscle contraction. Tryptase: protease released by mast cells; its exact role is uncertain. It is a good marker of mast cell activation.

11 Proteoglycans: Proteoglycans include heparin and chondroitin sulfate. heparin seems is important in storing the preformed proteases and may play a role in the production of alphatryptase. Chemotactic factors: An eosinophilic chemotactic factor of anaphylaxis causes eosinophil chemotaxis; an inflammatory factor of anaphylaxis results in neutrophil chemotaxis. Eosinophils release major basic protein and, together with the activity of neutrophils, can cause significant tissue damage in the later phases of allergic reactions.

12 Mast Cell Activation by antigen (allergen) cross-linking of FcεRIbound IgE

13 occurs approximately 6 hours after exposure to the antigen and is due to mediators that are synthesized after the cell degranulates influx of inflammatory cells, such as neutrophils and eosinophils, erythema and induration. Complement is not involved with either the immediate or late reactions because IgE does not activate complement.

14 Slow-reacting substance of anaphylaxis (SRS-A) consists of several leukotrienes, which do not exist in a preformed state. This accounts for the slow onset of the effect of SRS-A. Leukotrienes are formed from arachidonic acid by the lipoxygenase pathway and cause increased vascular permeability and smooth-muscle contraction. They are the principal mediators in the bronchoconstriction of asthma and are not influenced by antihistamines. Prostaglandins and thromboxanes are related to leukotrienes. They are derived from arachidonic acid via the cyclooxygenase pathway. Prostaglandins cause dilation and increased permeability of capillaries and bronchoconstriction. Thromboxanes aggregate platelets.

15 Normal people respond by IgG, no receptors for IgG on mast cells. Genetic factors, environmental factors Hygiene hypothesis

16 Atopic disorders, such as hay fever, asthma, eczema, and urticaria, are immediate-hypersensitivity reactions that exhibit a strong familial predisposition and are associated with elevated IgE levels. Several processes seem likely to play a role in atopy, for example, failure of regulation at the T-cell level, enhanced uptake and presentation of environmental antigens, and hyperreactivity of target tissues. Target tissues often contain large numbers of Th-2 cells, and these are thought to play a major role in the pathogenesis of atopic reactions.

17 -oid??

18 Anaphylaxis and Shock Contraction of vasculature smooth muscle & dilatation of capillary endothelium

19

20 antibody directed at antigens of the cell membrane activates complement membrane attack complex damages the cell membrane. As a result, there is complementmediated lysis. In addition to causing lysis, complement activation attracts phagocytes to the site, with consequent release of enzymes that damage cell membranes. IgG-mediated Antigens involved are: mainly endogenous (autoantibodies) sometimes exogenous chemicals (haptens) e.g., immune response to certain drugs (e.g., penicillin) where drug binds to cell surface and antibody causes removal of the cells(usually by macrophages).

21 The antibody (IgG or IgM) attaches to the antigen via its Fab region and acts as a bridge to complement via its Fc region.

22 Type V This is an additional type that is sometimes used as a distinction from Type 2. Instead of binding to cell surface components, the antibodies recognise and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling. Some clinical examples: Graves' disease Myasthenia gravis

23

24

25

26

27 occurs when antigen antibody complexes induce an inflammatory response in tissues. Normally, immune complexes are promptly removed by the reticuloendothelial system, but occasionally they persist and are deposited in tissues. Wherever immune complexes are deposited, they activate the complement system. Polymorphonuclear cells are attracted to the site, and inflammation and tissue injury occur. Two types: (1) Local (individual organs): Arthus: hypersensitivity pneumonitis (2) General: serum sickness (or generalized Arthus reaction)

28

29

30

31 is a function of T lymphocytes, not antibody. The response is "delayed"; i.e., it starts hours (or days) after contact with the antigen and often lasts for days. (36 to 48 hours) In certain contact hypersensitivities, such as poison oak, the pruritic, vesicular skin rash is caused by CD8-positive cytotoxic T cells that attack skin cells that display the plant oil as a foreign antigen. In the tuberculin skin test, the indurated skin rash is caused by CD4-positive helper T cells and macrophages that are attracted to the injection site.

32 It is a major mechanism of defense against various intracellular pathogens, including mycobacteria, fungi, and certain parasites, and it occurs in transplant rejection and tumor immunity. The central role of CD4 + T cells in delayed hypersensitivity is illustrated in patients with AIDS. Because of the loss of CD4 + cells, the host response against intracellular pathogens such as Mycobacterium tuberculosis is markedly impaired. The bacteria are engulfed by macrophages but are not killed.

33 The recruited macrophages can form giant cells. The characteristic histologic appearance of the macrophage T-cell infiltrate is a granuloma. This type of infiltrate in the tissue is called granulomatous inflammation.

34

35

36 type mediator reaction I (immediate, anaphylactic) II (cytotoxic) III (immune complex) IV (delayed) Antibody (IgE) Antibody (IgG) Antibody (IgG) Cell IgE antibody is induced by allergen and binds to mast cells and basophils. When exposed to the allergen again, the allergen cross-links the bound IgE, which induces degranulation and release of mediators, e.g., histamine. Antigens on a cell surface combine with antibody; this leads to complement-mediated lysis, e.g., tranfusion or Rh reactions, or autoimmune hemolytic anemia. Antigen antibody immune complexes are deposited in tissues, complement is activated, and polymorphonuclear cells are attracted to the site. They release lysosomal enzymes, causing tissue damage. Helper T lymphocytes sensitized by an antigen release lymphokines upon second contact with the same antigen. The lymphokines induce inflammation and activate macrophages, which, in turn, release various mediators.

37 Review of Medical Microbiology & Immunology, Tenth Edition, by Levinson E-medicine: Wikipedia : overview#showall overview#showall

38

39 Abdulaziz Al-Roshodi