Grant Govt. Medical College, Mumbai.

1. DR. SHUBHANGI V. AGALE
ASSOCIATE PROFESSOR
GRANT GOVT MEDICAL
COOLEGE
MUMBAI
HYPERSENSITIVITY

2. HYPERSENSITIVITY
 All forms of immune-mediated
injuries are collectively denoted as
hypersensitivity reactions.
 Subdivided into four types:

3. TYPE 1
 Allergy and Anaphylaxis.
 Allergen cross-links Ig-E ab---
release of vaso-active amines and
other mediators from mast cells and
basophils—recruitment of
inflammatory cells
 eg Anaphylaxis, Br.asthama.

4. TYPE 2
 Ab to fixed Ag:IgG or IgM binds to
Ag on cell surface --- phagocytosis
of target cell by complement or
ADCC.AIHA. Erythroblastisis
foetalis,GP synrome.

5. TYPE 3
 Immune –complex disease: Ag-Ab
complex –activate complement---
attracts neutrophils---release of
lysosomal enzymes, oxygen free
radicals. Serum
sickness,SLE,Arthus.

6. TYPE 4
 Cell mediated (delayed)
hypersensitivity: Sensitised T
lymphocytes---release of cytokines
& T cell mediated cytotoxicity.
Tuberculosis, contact dermatitis,
transplant rejection.

7. Type 1 hypersensitivity
reaction
 Rapidly developing immunologic
reaction occurring within minutes
after the combination of an Antigen
with Antibody bound to mast cells in
an individual previously sensitized
to the antigen.
 Reaction ---- Allergy
 Antigen ----- Allergen
 Two reactions---- 1.systemic 2.
local

8. Type 1 hypersensitivity
reaction
• Initial response---primary
mediators
• Late phase reaction—sec
mediators

9. 1. Systemic reaction
 Follows injection of an antigen to which
host has become sensitized
 Within minutes , state of fatal shock
develop.
 Ig G mediated antibody reaction
 Mast cells
 Primary mediators- histamine, enzymes
(chymase, tryptase), proteoglycans
 Secondary mediators- leukotriens
C4,D4,B4, PG D2 , PAF, Interlukins

10. 2. Local reaction
Skin allergy
Allergic rhinitis
Allergic conjunctivitis
Bronchial asthma
Food allergy
Hay fever

11. Immediate response
 Evident within 5 to 30 minutes
 Vasodilatation
 Vascular leakage
 Smooth muscle contraction
 Glandular secretion
 Subside within 60 minutes

12. Late phase reaction
 Sets in 2 to 24 hrs after exposure
 Without additional exposure to antigen
 May last for several days
 Infiltration of tissues by eosinophils
/neutrophils /monocytes/ lympocytes.
 Tissue destruction, mucosal damage
 E.g.- Bronchial asthma, allergic rhinitis

13. Type 1 hypersensitivity reaction

14. ATOPY
 Genetically predisposed - local type
- I reaction to inhaled or ingested
allergens
 E.g. pollen, house dust, food.
 High Ig E levels
 Family history - positive

15. PATHOGENESIS
 Ig E mediated antibody reaction
 Mast cells
 Primary mediators- histamine,
enzymes (chymase, tryptase),
proteoglycans
 Secondary mediators- leukotriens
C4,D4,B4, PG D2 , PAF,
Interleukins

16. Type 1 hypersensitivity reaction

18. PATHOLOGIC LESIONS
 Vasodilatation
 Smooth muscle spasm
 Cellular infiltration
 Inflammation
 Mucus production
 Oedema

19. Type-1

20. TYPE II - ANTIBODY MEDIATED
 Mediated by Ab directed against Ag present on
cell surface / extra-cellular matrix.
 Secreted antibodies participate directly in injury
to cells.
phagocytosis
lysis
injury to tissue by inducing inflammation.
 Antibodies may also interfere with cellular
functions & cause disease without tissue injury.

21. Type 2 hypersensitivity
reaction
 Three different mechanisms
 Complement---direct lysis or
opsonisation.Transfusion reactions,
erythroblastosis foetalis,AIHA,drug
reactions,pemphigus vulgaris.
 ADCC—leukocytes—neutrophils,
eosinophils, macrophages & mast cells.
 Ab mediated cellular dysfunction.e.g:
myasthenia graves,greaves disease.

22. PATHOGENESIS
 Production of Ig G / Ig M antibodies
 Antibodies bind to antigen on target cell
or tissue
 Phagocytosis or lysis of target cell by
complement activation
 Leukocyte recruitment & inflammation

23. Type 2 hypersensitivity reaction

24. 1. Opsonisation & complement
mediated cell destruction and
phagocytosis
 Mismatched (Incompatible) blood
transfusion- lysis of RBC (ABO
incompatibility)
 ERYTHROBLASTOSIS FETALIS -
there is antigenic difference
between mother and fetus. Ig G
isoantibodies from mother cross
placenta and cause destruction of
fetal red cells (Rh incompatibility)

25. 2. COMPLEMENT – AND FC
RECEPTOR MEDIATED
INFLAMMATION
 Antibody deposition in extracellular matrix
 Complement activation
 Recruitment of neutrophils and monocytes
 Release of injurious substances by activated
leukocytes
 Damage to tissue. e.g.-vascular rejection in organ
graft.
 No phagocytosis or lyses of cells.

26. 3. ANTIBODY MEDIATED
CELLULAR DYSFUNCTION
 Antibodies directed against cell-surface
receptors impair or dysregulate function.
Both cells & antibodies take part In
diseases. (ADCC)
 Examples –Myasthenia Gravis
Pemphigus vulgaris
Graves disease
Pernicious Anemia
Rheumatic fever

28. GRAVE’S DISEASE

30. Type III – IMMUNE COMPLEX
MEDIATED REACTION
 Antigen – antibody complexes produce tissue
damage mainly by eliciting inflammation at the site of
deposition.
 Antigen combines with antibody - circulate and are
deposited in vessel walls, kidney & other sites.
 Ag-Ab complexes are formed at extra-vascular sites
where antigen may have been previously deposited.
 Two types of antigens = exogenous (streptococci) and
endogenous (DNA)

31. 1. GENERALIZED (SYSTEMIC) ICD
 Immune complexes are formed in circulation &
are deposited in many organs.
 Acute serum sickness Early 1900
Clemens von Pirquet
 Pts with Diphtheria infection were being treated
with serum from horses immunized with
diphtheria toxin.
 Pts developed fever ,skin rash & arthritis.
 Symptoms appeared more rapidly with repeated
injections of serum.
 Conclusion : Treated pts made antibodies to
horse serum proteins, & formed complexes with
injected proteins.

32. PATHOGENESIS
 Formation of ag-ab complexes in
circulation
Deposited in various tissues.
- An inflammatory reaction at the sites of
immune complex deposition. Neutrophilic
lysosomal enzyme degradation
-Complement activation
-Platelet aggregation- Micro thrombi-
ischemia- fibrinoid necrosis- vasculitis

33. Type 3 hypersensitivity

34. EXAMPLES
 Systemic lupus erythematous
 Acute post-streptococcal GM
 Poly arteritis nodosa (PAN)
 Arthus reaction
 Rheumatoid arthritis
 Farmer’s Lung
 Henoch schonlein purpura.

35. SLE

36. Type IV –T CELL MEDIATED
(DELAYED HYPERSENSITIVITY)
 Initiated by antigen-activated (sensitized)
T – lymphocytes
 Delayed type reaction – CD 4 +
 Direct cell cytotoxicity - CD 8 + (CTL)
 Principle pattern of immunologic response
to intracellular microbiologic agents
 Mycobacterium tuberculosis, viruses, fungi,
parasites & protozoa.
 Tuberculosis & Leprosy

39. TUBERCULIN REACTION
 Intracutaneous injection of tuberculin, a protein
lipopolysacharide component of the tubercle
bacillus.
 In previously sensitized individual reddening
and induration of site appear in 8 to 12
hours, & reach a peak in 24 to 72 hours.

40. PROCEDURE
POSITIVE REACTION

41. Transplant rejection
 Rejection is a complex process in
which both cell mediated immunity
and circulating antibodies have a
role to play.

42. Transplant rejection
 T cell mediated rejection: in direct recognition
(activates DTH) & direct recognition. –dendritic
cells express high levels of MHC1 & MHC2 mole.
 Antibody mediated rejection:Anti-HLA humoral
abs develop concurrently with T cell mediated
rejection.
 Hyperacute rejection –where preformed anti-
donor abs are present.
 Acute rejection: within days to weeks.combined
process of cellular & humoral mech contribute.
 Acute cellular rejection: c/f of renal
failure.Extensive CD4+ & CD8+T cells with
oedema & interstitial haemorrhage.
 Acute rejection vasculitis: necrotising vasculitis
with endothelial cell necrosis.
 Chronic rejection ---renal ischemia.

43. Rejection
Rejection
ACUTE REJECTION
CHRONIC REJECTION

45. SUMMARY
 WHAT IS HYPERSENSITIVITY?
 TYPES OF HYPERSENSITIVITY?
 TYPE 1
 TYPE 2
 TYPE 3
 TYPE 4
 TUBERCULIN TEST
 TRANSPLANT REJECTION

46. THANK
YOU