HYPERSENSITIVITY REACTIONS TYPES class.pptx

It explains the classification and in detail description of hypersensitivity reactions.

1. HYPERSENSITIVITY REACTIONS PRESENTER : DR.A.SHAMILI MODERATOR : DR.ARUNDATHI

2. Hypersensitivity : Refers to the undesirable injurious consequences in a sensitised host following contact with specific antigens Allergy refers to all immune processes harmful to the host such as hypersensitivity and autoimmunity

3. Two French scientists, Paul portier and Charles Richet were first to recognise and describe hypersensitivity reaction Richet coined the term anaphylaxis

4. CLASSIFICATION

5. Causes of Hypersensitivity Diseases Reactions against self antigens: autoimmunity Reactions against microbes. Reactions against nonmicrobial environmental antigens

6. Immediate Hypersensitivity Reactions Occur immediately, within few minutes to few hours of antigen contact, as a result of abnormal exaggerated humoral response ( antibody mediated ). Further classified into three types: Type- I hypersensitivity reaction Type- II hypersensitivity reaction Type- III hypersensitivity reaction

7. Delayed Hypersensitivity Reaction Occurs after few days of antigen contact, as a result of abnormal cell mediated immune response. Also called as type- IV hypersensitivity reaction

8. TYPE I HYPERSENSITIVITY REACTION A type I hypersensitive reaction is induced by certain types of antigens referred to as allergens Within minutes after exposure to the antigen Mediated by IgE and involves degranulation of mast cells or basophils.

9. Allergens The term allergen refers specifically to nonparasitic antigens capable of stimulating type I hypersensitive responses in allergic individual Atopy , a hereditary predisposition to the development of immediate hypersensitivity reactions against common environmental antigens.

10. Experiments to demonstrate type 1 P–K Reaction : K Prausnitz and H Kustner (1921) - first to demonstrate that antibody in the serum responsible for the allergy. Named it as P-K antibody or reaginic antibody . Later - known as IgE (in 1960), after its discovery.

11. Schultz dale phenomenon To demonstrate anaphylaxis in vitro By exposing isolated tissues such as intestine or muscle segments of guinea pig to the allergens Theobald smith phenomenon To demonstrate anaphylaxis in vivo by injecting allergen into guinea pigs

12. Mechanism of Type I Hypersensitivity

13. Sensitization phase Allergen is processed by the APC and are presented to the CD4 helper T cells Activated T H cells are differentiated into T H 2 cells which in turn secrete IL4 Induces the B cells to differentiate into IgE producing plasma cells and memory cells Secreted IgE migrate to the target sites, and coat on the surface of mast cells and basophils Such sensitized mast cells will be waiting for interaction with the subsequent antigenic challenge

14. Effector phase Shocking dose - directly encounters with the Fab region of IgE coated on mast cells Degranulation-Allergen bound to IgE triggers the mast cells (and basophils) activation and degranulation Primary mediators- Secondary mediators-

15. Primary Mediators Action Histamine, Heparin and Serotonin ↑Vascular permeability ↑Smooth-muscle contraction Eosinophil chemotactic factor (ECF-A) Eosinophil chemotaxis Neutrophil chemotactic factor (NCF-A) Neutrophil chemotaxis Proteases Bronchial mucus secretion; Degradation of blood-vessel basement membrane

16. Secondary Mediators Action Platelet-activating factor Platelet aggregation and degranulation; Contraction of pulmonary smooth muscles Leukotrienes ↑ Vascular permeability; Contraction of pulmonary smooth muscles Prostaglandins ↑Vasodilation; Contraction of pulmonary smooth muscles; Platelet aggregation Bradykinin ↑Vascular permeability; Smooth-muscle contraction Cytokines (IL-1 and TNF-α) Systemic anaphylaxis; ↑ Expression of cell adhesion molecules (CAMs) on venular endothelial cells

17. MANIFESTATION OF TYPE 1 REACTION

18. IMMEDIATE REACTIONS SYSTEMIC ANAPHYLAXIS : Acute medical emergency condition, characterized by severe dyspnoea, hypotension, and vascular collapse leading to death Occurs within minutes of exposure to allergen and unless treated promptly, may lead to fatality.

19. LOCALISED REACTIONS : Allergic rhinitis (or hay fever) Asthma Food allergy Atopic dermatitis (allergic eczema) Drug allergy

20. LATE REACTIONS Immediate phase of type 1 reaction is followed, 4–6 hours later, by an inflammatory response. This phase lasts for 1–2 days and leads to tissue damage.

21. Factors Influencing Type I Hypersensitivity Genetic makeup Allergen dose Dose of the allergen has a definite impact on the type of immune response produced. T H 1 vs T H 2 response

22. Detection of Type I Hypersensitivity Skin prick test : Small amounts of suspected potential allergens are introduced at different skin sites either by intradermal injection or by superficial scratching

23. Advantage: relatively inexpensive and allows screening of a large number of allergens at one time Disadvantage: sometimes sensitizes the allergic individual to new allergens and in some rare cases may induce systemic anaphylactic shock

24. Treatment Avoidance of contact with known allergens Hyposensitization Monoclonal anti- IgE Drugs Antihistamine Epinephrine Steroids

25. TYPE II HYPERSENSITIVITY REACTION

26. TYPE II HYPERSENSITIVITY REACTION Type II hypersensitive reactions involve antibody-mediated destruction of cells by IgM and IgG Antibody bound to cell surface antigens can induce death by three mechanism : Complement-dependent Reactions Antibody-Dependent Cellular Cytotoxicity (ADCC) Antibody dependent cellular dysfunction

27. Complement-dependent Reactions Fc region of antibody can activate Classical pathway of complement system Complement dependant cytolysis Complement dependant inflammation Opsonisation EX: ABO incompatability Rh incompatability Drug induced hemolytic anaemia

28. Transfusion Reactions Are Type II Reactions RBC from an incompatible donor are destroyed after being coated with recipient antibody directed against the donors blood group antigens

29. Hemolytic Disease of the Newborn

30. Antibody-Dependent Cellular Cytotoxicity ADCC is involved in destruction of the targets that are too large to be phagocytosed, e.g. parasites, tumors or graft rejection

31. Antibody dependent cellular dysfunction Host produces certain autoantibodies which bind and disturb the normal function of human self-antigens. Antibodies may be directed against human receptors, resulting in: Activation of receptor; e.g. Grave’s disease Inhibition of receptor; e.g. Myasthenia gravis

32. EX: Goodpasture syndrome (antibody produced against type IV collagen) Pernicious anemia (antibody directed against intrinsic factor) Rheumatic fever (antibody against streptococcal antigens cross reacting with heart)

33. TYPE III HYPERSENSITIVITY REACTION

34. TYPE III HYPERSENSITIVITY REACTION Occurs as a result of excess formation of immune complexes (Ag-Ab complexes) which initiate an inflammatory response through activation of complement system leading to tissue injury SOLUBLE & INSOLUBLE IMMUNOCOMPLEXES :

35. MECHANISM OF TISSUE INJURY Classical complement activation Platelet activation Activation of Hageman factor

36. Classical complement activation Antibody dependent pathway. Pathway is triggered by the antigen antibody complex formation

37. Platelet activation Immunocomplexes bind to the Fc receptors on platelets leading to their activation. Platelet aggregation (leads to microthrombi formation) and vasoactive amines released from activated platelets. Cause tissue ischemia leading to further tissue damage.

38. Types of type 3 hypersensitivity Localised or arthus reaction Generalised or systemic type 3 reaction Serum sickness

39. Localised or arthus reaction Defined as localized area of tissue necrosis due to vasculitis resulting from acute immune complex deposition at the site of inoculation of antigen In skin In lungs

40. Generalised reaction Formation of small sized soluble Ag-Ab complexes Deposition of the immune complexes in various tissues, thus initiating an inflammatory reaction in various sites throughout the body such as: Blood vessels (vasculitis) Glomerular basement membrane (glomerulonephritis), Synovial membrane (arthritis).

41. Serum sickness Seen following serum therapy i.e. administration of foreign serum e.g., horse anti-tetanus serum, to treat tetanus cases. Horse serum proteins being foreign  induce antibody formation in the host, leading to formation of large number of immune complexes Typically, after 7-8 days, the individuals begin to show various manifestations which are collectively called as serum sickness

42. Example Connective tissue disorders : Result due to autoantibodies forming immune complexes with self-antigens SLE (systemic lupus erythematosus): Anti-DNA Ab Rheumatoid arthritis: Ab against human immunoglobulin Parasitic diseases : Resulting from immune complex deposition Nephrotic syndrome in Plasmodium malariae Katayama fever in schistosomiasis African trypanosomiasis Bacterial diseases : Resulting from immune complex deposition Streptococcus pyogenes : Post-streptococcal glomerulonephritis Mycobacterium leprae (Lepra reaction type 2)

43. Viral diseases : With immune complex deposition Hepatitis B (arthritis) Hepatitis C (arthritis) Infectious mononucleosis (Epstein-Barr virus) Dengue (arthritis) Others: Hyperacute graft rejection Subacute bacterial endocarditis Serum sickness

44. TYPE IV HYPERSENSITIVITY REACTION

45. TYPE IV HYPERSENSITIVITY REACTION DTH is an injurious cytokine-mediated inflammatory reaction resulting from the activation of T cells, particularly CD4 + T cells. The reaction is called delayed because it typically develops 24 to 48 hours after antigen challenge in a previously immunized (sensitized) individual

46. MECHANISM OF INJURY

47. SENSITIZATION PHASE

48. EFFECTOR PHASE

49. Role of DTH Protective response Under normal circumstances, the pathogens are usually cleared with little tissue damage; mediated by the enhanced microbicidal potency of activated macrophages Tissue damage response When the intracellular microbes escape the macrophage killing mechanisms  e nhanced phagocytic activity and release of various lytic enzymes by the activated macrophages in an attempt to kill the pathogen leads to non specific tissue destruction

50. Pathology of DTH Reaction (Granuloma Formation)

51. Types Tuberculin Prior infection or immunisation shows - positive tuberculin test 2. Contact dermatitis: C ontact with chemicals such as nickel and chromium, dyes, drugs such as penicillin, plant allergen

52. Contact dermatitis Detection using ‘patch test’ - Allergen is applied to the skin - Itchiness in 4–5 hours, and local reaction - F rom erythema to vesicle or blister formation, after 24–48 hours

53. stimulatory hypersensitivity (“type V”) Similar to type II hypersensitivity Antibodies to cell surface antigens, but in this case the antibodies do not mediate their effect via cytotoxicity but rather are directed to a cell surface receptor and act as an agonist leading to stimulation of the cell. EX: When thyroid‐ stimulating hormone (TSH) binds to its receptor on the thyroid epithelial cells to stimulate thyroid hormone production. Once sufficient levels of the hormones are produced, a negative feedback loop shuts off the production of TSH.

54. The thyroid‐stimulating antibody present in patients with Graves’ disease is an autoantibody against the TSH receptor and mimics the effect of TSH Except in this case there is continuous secretion of the autoantibody by plasma cells that provides a constant stimulation of the thyroid leading to hyperthyroidism

55. Innate hypersensitivity reactions Excessive activation of pattern recognition receptors (PRR) Many infections provoke a toxic shock syndrome Characterized by hypotension, hypoxia, oliguria, and microvascular abnormalities and mediated by elements of the innate immune system independently of the operation of acquired immune responses.

56. Stimulation of pattern recognition receptors on macrophages by microbial products Results in excessive release of TNF, IL‐1β, and IL‐6 The excess of circulating LPS, and the cytokines released in response to its presence, lead to unwanted pathophysiology at distant sites

57. EX: Acute respiratory distress syndrome associated with Gram‐negative bacteria is primarily due to the lipopolysaccharide (LPS) endotoxin provoking a massive invasion of the lung by neutrophils.

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