Hypersensitivity- types of hypersensitivity.pptx

This presentation contains knowledge on 4 types of hypersensitivity

1. Hypersensitivity

2. Objectives Types of hypersensitivity reactions Anaphylactic shock Describe Immunological basis Clinical examples Principles of management

3. Immune response Protective Damage to host tissue Hypersensitivity Autoimmunity

4. Hypersensitivity reactions – ‘over reaction’ of the immune system to harmless environmental antigens – exaggerated immune response

5. Hypersensitivity reaction depends on: 1) chemical nature of allergen 2) route involved in sensitization i.e. - inhalation, ingestion, injection etc. 3) physiological state of individual / genetic potential

6. CLASSIFICATION https://www.youtube.com/watch?v=jXTW4F-8jd4

7. Original classification by Gell and Coombs Type Immune mechanism Time of onset I IgE mediated 2-30 mins (immediately) II Ab & complement 5-8 hrs (intermediate) III Ag/ab complexes 2-8hrs (intermediate) IV T cell mediated 24-72 hrs (delayed)

8. Type I- IgE mediated- immediate type hypersensitivity Commonest type Mild reaction to fatal Atopic individuals have a genetic predisposition to make high levels of IgE Occur with harmless antigens (eg. Pollen, food) and microbial antigens (fungal, bacterial, parasitic)

9. Atopy Atopy is the term for the genetic trait to have a predisposition for localized anaphylaxis. Atopic individuals have higher levels of IgE and eosinophils.

10. FIGURE 14.7. Wheal-and-flare reaction (atopic urticaria).

11. Type I - Mechanism 1 st exposure to allergen antigen stimulation of TH2 cells stimulate IgE class switching in B cells production of IgE Binding of IgE to Fc e receptor on mast cells Repeat exposure to allergen allergen binding to IgE on mast cells activation of mast cell & basophils

12. Activation of mast cells Degranulation of preformed metabolites ex. Histamin, proteases Produts of cell membrane lipids Cytokines ex. Leukotrines, PG ex. IL4, IL5, TNF a Late phase acute phase Mast cell IgE allergen

13. Type I- examples Allergy Rhinitis Asthma Urticaria- acute/chronic Angioedma Anaphylaxis

14. Dignosis History Specific IgE for different allergens Skin prick test Food elimination and challenge

15. https://www.mountsinai.org/health-library/tests/allergy-testing-skin

16. Skin prick test

17. Treatment Avoidance of allergen Antihistamines Adrenalin Corticosteroids Mast cell stabilizers – Cromolyn Leukotriene receptor antogoists

18. Type II – Cytotoxic hypersensitivity IgG and IgM mediated Antibodies are directed to cellular antigens (eg. on erythrocytes) or surface of autoantigens Causes damage by Opsonization and phagocytosis complement mediated lysis ADCC ( antibody dependent cellular cytotoxicity)

19. Type II - examples Rhesus incompatibility / haemolytic disease of new born IgG against Rh antigen Tranfusion reactions (miss-matched transfusions) Isohaemaglutinins against major blood grp antigens (A &B) Autoantigens Basement membranes of lungs and kidney – Goodpasture’s synd Acetylcholine receptor – Myesthenia gravis Erythrocytes – haemolytic anaemias Drugs Infections- Mycoplsma-----> h’lytic anaemia - Grp. A Strep ------- > Rheumatic fever

20. Treatment Exchage transfusion Plasmapheresis Immunosupressives/ cytotoxic drugs

21. Type III – Immune complex mediated Mainly IgG (uncommonly IGM also) against self and non-self antigens – eg. Microbes, drugs, antisera, autoantigens Deposition of soluble immune complexes (Ag-Ab) Activation of complement cascade and activation of inflammatory cells Local damage- Arthus reaction Eg. Farmer’s lung- inhalation of spores Bird fancier’s lung – avian serum/ faeces Systemic damage Serum sickness vasculitis

22. Mechanism of Type III Small immune complexes (usually cleared by RES) deposited in tissues on the basement membrane of blood vessels Then activate the classical complement pathway This may cause: a. Massive inflammation , due to complement protein C5a triggering mast cells to release inflammatory mediators; b. Influx of neutrophils due to complement protein C5a , resulting in neutrophils discharging their lysosomes and causing tissue destruction and furthes inflammation c. MAC lysis of surrounding tissue cells, due to the membrane attack complex, C5b6789n; d. Aggregation of platelets , resulting in more inflammation and the formation of microthrombi that block capillaries; and

23. Clinical examples of type III 1. Arthus reaction (local reaction) 2. Serum sickness ( systemically ) 3. Schick test 4. Polyarteritis Nodosa ( PAN ) 5. Rheumatoid arthritis ( RA ) 6. Systemic lupus erythematosus ( SLE ) 7. Acute viral hepatitis 8. Pencillamine toxicity 9. Hyperacute graft rejection  10. Type 2 lepra reaction ( ENL )  

24. Treatment Corticasteroids Immunosupressives/ cytotoxic drugs Plasmapheresis Monoclonal antibodies

25. Type IV – delayed type Mediated by cells TH1 cells Macrophages main cells Dendritic cells CTL + Cytokines Persistent presence of antigen leads to chronic inflammation and granuloma formation Antibody-independent

26. Mechanism In chronic diseases : T.B., Leprosy, Schistosomiasis Intracellular organisms resist destruction by macs Macs present intracellular antigens to TH1 cells with MHC II molecules TH 1 cells are activated -  produce cytokines  activate macrophages to kill the intracellular org. Continuous release of cytokines by Th1 cells lead to accumulation of macrophages which form in to epithelioid and giant cells-  granuloma

27. Type IV- Examples Contact dermatitis- Nickel, silica Post primary TB, Leprosy Mantoux test

28. Treatment Removal of antigen Corticosteroids Immunosuppressives

29. What is anaphylaxis? An exaggerated response to a substance to which the subject has become sensitised which histamine, serotonin and other vasoactive substances are released

30. Why does it occur ? IgE mediated/ non IgE mediated Release of vasoactive substances from the basophils and mast cells Such as Histamine Serotonin Leukotrienes Other vasoactive agents

31. What happens? ( Clinical features) Pruritus Erythema and flushing Urticaria Angio- oedema – laryngeal oedema Nausea and diarrhoea Brochospasm Hypotension Cardiovascular collapse and Death.

32. Anaphylaxis An acute allergic reaction with one or more life threatening features Hypotension Respiratory difficulty Incidence 1- 3 per 10,000 population

33. Common causes Foods ( nuts, shellfish) Drugs ( antibiotics, NSAIDs) Insect venom Latex Radio contrast solutions

34. Clinical Features Skin, Respiratory, Cardiovascular and GIT systems commonly affected Onset often rapid For those who are highly sensitive even the smell/ touch of the food can cause a reaction

35. Clinical Features Generalized pruritus and urticaria Swelling of the lips and face ( angioneurotic oedema) Feeling unwell Sense of doom

36. Clinical Features- life threatening features Stridor – laryngeal oedema Severe bronchospasm – hypoxia and hypercarbia Hypotension – vasodilatation and increased vascular permeability Arrythmia Cardiovascular collapse Diziness and loss of consciousness

37. Diagnosis Clinical History P/H Exposure to allergens Elevated mast cell tryptase levels ( between 1 -5 hours after the reaction )

38. Management of Anaphylactic shock Initial therapy Stop the drug Lie the patient flat and elevate the feet Loosen clothes Deliver O 2 Establish IV access FIRST LINE THERAPY – ADRENALINE IV fluids – crystalloid / colloid

39. Adrenaline 1 : 1000 ( 1mg/ ml) 0.5 – 1 ml IM / SC repeated every 10 min according to BP !: 10,000 ( diluted to 10 ml) 0.5 – 1ml repeated every 1 minute IV till response is obtained.

40. Management of Anaphylactic shock Secondary therapy Antihistamines ( clopheniramine 10 -20mg IV) Corticosteroids Hydrocortisone 100 – 3—mg IV Bronchodilators Catecholamine infusions

41. Before discharge Advice to the patient regarding anaphylaxis and prevention of future exposure Diagnosis card – red flag Refer to an allergy specialist Prepare for accidental exposure – preloaded syringe of adrenaline

42. Treatment of severe allergic reaction without life threatening features Gen urticaria, bronchospasm Antihistamine Hydrocortisone Observe

43. Summary Types of hypersensitivity reactions Immunopathogenesis Examples Principles of management Anaphylactic shock