23 - Hypersensitivity reaction1q11111.ppt

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1. Hypersensitivity reaction

2. •Fine balance b/n host under and over
responsiveness of immune system
•Under responsiveness uncontrolled
infection
•Over responsiveness hypersensitivity
rxn

3. •Our genetic diversity variations in our
ability to mount inflammatory response
•Adaptive immune response to infectious
agent defense
•Adaptive immune response to non
infectious Ag disease

4. Three types of non infectious Ags
1.Innocuous (harmless) Ag
hypersensitivity disease
2.Self Ag autoimmune disease
3.Transplanted Ag graft rejection

5. Allergy and hypersensitivity
diseases
•4 types
1.Type I
2.Type II
3.Type III
4.Type IV

6. Allergy (Type I hypersensitivity
disease)
•Immediate type HSR rapidly developing
rxn
•Mediated by IgE Ab
•Atopic individuals prone to allergy

7. •The Ag Allergen
-small highly soluble proteins
-carried by dry particles e.g. pollen grain,
house dust etc.
-most are inhaled
-most enter trans mucosal at low dose
•The immune response allergic rxn

8. Genetic factors in allergy
•High familial incidence
•Exaggerated tendency to form IgE Ab to
allergens (atopy)

9. •Atopic individuals
-higher IgE levels in circulation
-higher level of eosinophils
-higher affinity IgE receptors on mast cells
-MHC class II type

10. Mechanism
•1
st
exposure to allergen
•Inhaled Ag
•Contact with mucosa
•Allergen diffuse into mucosa
•Dendritic cells take up allergen and
migrate to regional lymph nodes
•Present Ag to lymphocytes (Th2)

11. •Activate B lymphocytes
•IgE produced
•IgE bound to mast cells

12. •2nd exposure
•Ag+ mast cells armed with IgE
•Release of chemical mediators
degranulation (within seconds)
synthesis and release

14. Degranulation
•Histamine, tryptase etc.
•Act on blood vessels
•Tissue destruction
•Influx of inflammatory cells amplify
inflammation
•Smooth muscle contraction etc.

15. Synthesis and release
•Lipid mediators PG, cytokines
•Smooth muscle contraction
•Acts on vessels
•Mucus production
•Recruit cells TH2, eosinophils etc.

16. Allergic reaction
•Immediate phase histamine, cytokines
•Late phase PG sustained
inflammation

17. Clinical presentation
•Depends on
1.Amount of IgE present
2.Route of allergen entry
3.Dose of allergen

18. 1.Allergen via blood vessels or rapidly
absorbed from gut
mast cells associated with all blood
vessels activated
systemic anaphylaxis (wide spread
vasodilatation
can be fatal

19. Anaphylactic shock
•Decreased blood pressure widespread
vessel permeability
•Difficulty in breathing airway constriction
•Suffocation swelling of epiglottis
•Causes drugs e.g. penicillin, insect bite
(venom), foods e.g. nuts
•Prognosis :rapidly fatal

20. 2. Allergen via inhalation
•most common route
rhinitis –mast cells under nasal mucosa
-increased secretion, sneezing
asthma –mast cells in lower airway
-bronchial constriction
-increased secretion
-breathing difficulty

21. 3. Oral administration
•Mast cells in GIT
•Vomiting, diarrhea

22. 4. Subcutaneous (skin)
•Skin mast cells
•Large red skin swelling (urticaria or hives)

23. Type II HSD
•Immunological response involving IgG Ab
•Normally protective against infections
•React with non infectious Ag acute or
chronic HS rxn.
•Binding of Ab to surface of cell or matrix
associated Ag
•Commonly involves circulating blood cells-
RBC, platelet

24. •E.g. drugs (penicillin, quinidine,
methyldopa)
•Bind to cell surface e.g. platelet
•Acts as target for anti drug Ab
complement activation cell death
phagocytosis cell death
•Thrombocytopenia

25. •Other examples
-blood ABO incompatibility
-RH
-autoimmune hemolytic anemia

27. Type III HSD
•Synonym immune complex disease
•Deposition of Ag-Ab aggregates (immune
complex) inflammation
•Administration of large quantities of Ag (Ag
excess)
•Ag is poorly catabolized, soluble Ag in
circulation

28. •Immune complex formed in all Ab
response
•When do they cause disease?
•Large complexes
•C fixation
•Cleared from circulation by macrophages

29. •Ag excess
•Small complexes
•Deposited in blood vessel wall
•Activate leukocytes
•Tissue injury

30. Types of Ag excess
•Failure to clear infectious agents
e.g. hepatitis B virus
•Auto Ag e.g. SLE (self DNA)
•Drugs e.g. horse antititanus serum

31. Small immune complexes
•Circulate longer in circulation
•Bind less avidly to phagocytic cells

32. e.g. Serum sickness
•Injection of horse antiserum to people with
snake bite (horse immunized with snake
venom)
•7-10days later (time for adaptive immunity)
•Ag-Ab complex deposition in tissue
•Inflammation
•Tissue injury

33. Favored site if immune complex
deposition
•Blood vessels
•Glomeruli
•Joints
•Skin
•Heart etc.

34. Consequences
•Blood vessel acute necrotizing vasculitis
•Glomeruli glomerulonephritis
•Joint arthritis

37. Type IV HSD
•Synonym Delayed type reaction
•Mediated by T lymphocytes (TH1,
cytotoxic T cells)
•Mechanism similar to response to
infectious pathogens e.g. TB
•Reaction to non infectious substance
Hypersensitivity

38. •E.g.
proteins- PPD, insect venom
contact hypersensitivity- nickel earrings
celiac disease- Gliadin (wheat protein)

39. Tuberculin skin test
•Non infectious protein derived from M. Tb
•Subcutaneous injection
•Ag taken up by APC
•Presented to memory T cells (TH1)
•Activated T cells inflammatory cytokines
chemotaxis
tissue destruction
swelling

40. •Response takes 24-72 hrs.  DTH
•Clinical examples
-virus infection e.g. herpes
-bacteria infection e.g. M. TB
-graft tissue rxn
-tumor surveillance