1. HYPERSENSITIVITY

2. I intend to cover in next 30 mins!
 Hypersensitivity overview
 Classification of hypersensitivity
 Type I Hypersensitivity
 Anaphylaxis
 Atopy
 Type II Hypersensitivity
 Blood transfusion reactions
 Hemolytic disease of newborn
 Drug induced hemolysis
 Type III Hypersensitivity
 Localized
 Generalized
 Type IV Hypersensitivity
 Tuberculin reaction
 Contact dermatitis

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

4. Hypersensitivity
Antigen Immunity
• Hypersensitivity is the term used when an
Antigen Antigen
immune response results in exaggerated killed
Host or
inappropriate reaction harmful to the host.
Antigen
?
Hypersensitivity

5. Common terms
• Allergen Antigen ( bland substance
like serum protein or pollen)
• Sensitizing / Priming dose  initial
contact with allergen
• Shocking dose  2nd contact with same
allergen  Manifestations of
Hypersensitivity
• Haptens  Incomplete antigen

6. Classification
Based on time required Based on Pathogenesis
• Immediate
– Anaphylaxis
– Atopy I
– Antibody mediated cell damage
II
– Arthus phenomenon
– Serum sickness III
• Delayed
– Infection
– Contact IV

7. Distinguishing features
Immediate Delayed
• Appears and recedes rapidly • Appears slowly and lasts
longer
• Induced by antigens /
• Antigen /Hapten intradermally
haptens by any route or skin contact
• Circulating antibodies may • Circulating antibodies need
be present not be present
• Passive transfer possible • Transfer not possible with
serum but possible with T cells
with serum or transfer factor
• Desensitization easy but • Desensitization is difficult but
short lived long lasting

8. Classification
Based on Pathogenesis (Coombs
Based on time required & Gell)
• Immediate • Type I  anaphylactic, IgE
– Anaphylaxis or reagin dependent
– Atopy I
• Type II  IgG mediated,
– Antibody mediated cell damage rarely IgM
II
• Type III  immune
– Arthus phenomenon
complex/ toxic complex
– Serum sickness III disease
• Delayed • Type IV  delayed or cell
– Infection mediated immunity
– Contact IV

9. Type 1 Hypersensitivity
• Anaphylaxis
• Atopy
– Richet
– Theobald smith theory

10. Sensitization
• Most effective parentrally but can occur via any route
– Antigens & Haptens can induce anaphylaxis.
– Interval of 2-3 weeks is required between priming &
shocking dose
– Once sensitized person remains so for a long period
– Shocking dose is more effective
• Intravenous
• Intraperitoneally
• Subcutaneous
• Intradermal
– Shocking antigen must be identical or immunologically
identical to sensitizing antigen.

12. Features of Anaphylaxis
• Edema
• Decreased coagulablity of blood
• Fall in Blood Pressure
• Fall in temperature
• Leucopenia
• Thrombocytopenia

13. Susceptibility to Anaphylaxis

14. Anaphylaxis reaction in Humans
• Itching of scalp and tongue
• Flushing of skin all over the body
• Bronchospasm
• Nausea, vomiting, Abdominal pain, Diarrhoea &
Malena
• A/c Hypotension, loss of consciousness  Death
• Cutaneous Anaphylaxis
– Small shocking dose  local wheal & flare reaction
– Used for allergen testing in atopic diseases

15. • Passive Cutaneous Anaphylaxis
in vivo method of detection of antibodies
Intradermal antibody injection to Normal animal
4-24 hours
Antigen + Evan’s Blue
Immediate blueing at the intradermal site
Use
To detect human IgG
Cannot detect IgE

17. Mechanism of Type 1 reaction
B cell to
plasma
cell
Binding
Activation Release

18. What comes out??
Vasoactive amines Histamine Dilatation of blood
vessels
Transient contraction
of smooth muscles
Proteases Local tissue damage
Prostaglandins Vascular dilatation
Leukotrienes Prolonged smooth
muscle contraction
Cytokines IL2, IL3, IL4, IL6, TGF-ß, Local inflammation
GM-CSF, IL1 & TNF-α

19. What comes out?
• Seratonin
• Eosinophil chemotactic factor (ECF-A)
1
• Neutrophil chemotactic factor ( NCF-A)
• Platelet activating factor 2
• Bradykinin

20. ANAPHYLACTOID REACTIONS
 Peptone , Trypsin etc  anaphylaxis like
reactions (anaphylactoid reactions)
 No immunological basis
 Non specific mechanisms involving activation
of complement & release of anaphylotoxins

21. ATOPY
• Naturally occurring familial hypersensitivities
• Inhalants  Pollens, House dust
• Ingestants  Eggs, Milk
• Contact allergens  antigens not effective
parenterally but induce IgE formation
• Predisposition to atopy is genetically determined
• Atopy runs in families
• Bottle fed infants tend to develop atopy in later life

22. IgE
• Intially demonstrated by Radioallergo sorbent test (RAST)
• Now ELISA and Passive agglutination is used
• Prausnitz – kutsner (PK reaction)
Kustner  atopic to cooked fish
serum from Kustner
injected s/c to Prausnitz
24hrs
s/c injection of cooked fish antigen at same site
wheal & flare reactions in few mins

23. IgE
• Heat sensitive
• Do not cross placenta
• IgE overproduction  deficiency of IgA  Atopy
• IgE &IgA lymphocytes reside in submucosa
• Antigens are dealt by IgA so IgE never comes into contact
• When IgA is deficient IgE producing cells are exposed  IgE
overproduction
• Clinically
– Eye  conjunctivitis
– Respiratory system  Rhinitis
– Intestine  G.I Symptoms
– Skin  Dermatitis

24. TYPE II HYPERSENSITIVITY

25. Type II hypersensitivity
BLOOD TRANSFUSION REACTIONS
HEMOLYTIC DISEASE OF NEWBORN
DRUG INDUCED HEMOLYTIC ANAEMIAS

26. Blood transfusion reactions
• RBC has a large number Mismatched
transfusion
of proteins &
glycoproteins Complement
mediated lysis
• Antibodies formed are of
IgM class Free Hb in plasma
(Isohemagglutinins)
• Clinically Filtered through
kidneys
– Immediate
• Fever, Chills, Nausea, DIC,
Low back pain & Hemoglobinuria
Hemoglobin in urine.
– Delayed Hemoglobin Bilirubin

27. Delayed reactions !
• Seen in people with repeated blood transfusions (
Rh, Kidd, Kell & Duffy)
• Predominant isotype involved is IgG 
incomplete lysis  RBC destroyed in
extravascular sites ( Agglutination, Opsonization
& Subsequent phagocytosis by macrophages)
• Clinically
– Fever, Low Hb%, Increased Bilirubin, Mild Jaundice.
Free Hb absent in urine.

28. Hemolytic disease of Newborn
• Minor
• Serious
• Lethal  Erythroblastosis fetalis
Hemoglobin
Accumulate Brain
converted
in brain damage
to Bilirubin

29. Hemolytic disease of Newborn

30. • Prevention
– Rhogam  antibodies against Rh antigen within 24-48
hours of delivery
– Binds to fetal blood cells and clears them before B-cell
activation and memory cell production.
• Diagnosis
– Testing of maternal serum for antibodies to Rh antigen.
Rise in titre is Diagnostic.
– Presence of maternal IgG on surface of fetal RBC detected
by coombs test
• Treatment
– Intrauterine blood exchange transfusion
– Exposure to U-V light
– Plasmapheresis to mother

31. Drug induced Hemolytic anaemia
Antibiotics attach to RBC
Drug protein complex
Formation of antibody
Bind to drug on RBC
Activates complement
Lysis of RBC

32. Type III Hypersensitivity

33. • Antigen + Antibody  Immune complex
Small Large
Clearance of antigen Tissue damage
• Tissue damage Localized
Generalized

34. Formed in blood
Blood vessel wall
Synovial membrane
Glomerular basement membrane
Choroid plexus
Initiates reaction
Increase in Neutrophils
Granular release
Tissue damage

35. • C3a, C4a & C5a  Anaphylotoxins Local mast cell
degranulation Increase in local vascular permeability
• C3a, C5a & C5b67  Chemotactic  Attract
Neutrophils
• Tissue damage is as a result of lytic enzymes by
neutrophils
• C3b  Opsonin
• Large complexes deposited in basement membrane
• Small complexes deposited in subepithelium
• Phagocytosis unsuccessful as complexes are attached
to basement membrane  more lytic enzymes poured
in  membrane attack mechanism of complement 
destruction of tissue
• Microthrombi formed due to complement induced
aggregation of platelets & release of clotting factors.

37. Localized hypersensitivity
Increase in
Formation of local Mediate arthus
Antigen entry circulating
immune complexes reaction
antibody
Neutrophils adhere
Localized tissue & Accumulation of
to vascular Reach target site
vascular damage fluid & RBC
endothelium
Pronounced
edema & erythema Sensitized individual
at a faster rate
Intrapulmonary arthus type reactions induced by bacterial spores, Fungi or
dried fecal proteins  Pneumonitis, Alveolitis
Eg- Farmer’s lung
Pigeon farmer’s disease

38. Generalized hypersensitivity
• Large amount of uncleared complexes cause
reactions at various sites
– Horse anti tetanus
– Anti diptheria serum
• Combination of symptoms in patient who has
received foreign antiserum  Serum sickness
• Clinically  fever, weakness, rash,edema,
erythema, lymphadenopathy, arthritis,
Glomerulonephritis

39. Circulating immune complexes
• Autoimmune
– Systemic Lupus Erythmatosis
– Rheumatoid Arthritis
– Good pastuer’s syndrome
• Drug
– Penicillins
– Sulfonamides
• Infections
– Post streptococcal glomerulonephritis
– Meningitis
– Hepatitis
– Mononucleosis
– Malaria
– Trypanosomiasis

41. Type IV
• Activation of sensitized TDTH Cells  Secretion of
cytokines  Draws macrophages & activate them
 Promote phagocytosis  Lytic enzymes into
surrounding tissue  Localized tissue damage.
• Hallmark of type IV
– Delay in time required for reaction
– Recruitment of macrophages
• Important defense mechanism against
intracellular pathogens

42. Clinical applications
• PPD antigen for detecting previous exposure
to M.TB
• Lepromin test for leprosy
• Coccidiodin test for coccidiomycosis
• Depletion of CD4+ T cells associated with AIDS
 repeated skin test with various antigens or
haptens

43. Contact dermatitis
• Common allergens  Hairdyes, Cosmetics,
Nickel, Turpentine, Formaldehyde,
Trinitriophenol,Poison oak, Poison Ivy.
• These complex with skin proteins and internalized
into APC in skin. These are processed and
presented to class II MHC  activation of TDTH 
Release of lymphokines
• Detected by PATCH TEST sensitivity is indicated
by itching in 4-5hours, Local reactions varying
from erythema to vesicles to blisters in 24-48
hours.

44. CONCLUSION!

45. References
 Kuby immunology
 Basic immunology – Abbas

47. Diagnosis
Type 1 Provocation test
Skin test
IgE RadioAllergo Sorbent Test (RAST)
Leukocyte histamine release assay
Surface markers for basophil activation
Leukotriene release test
Type 2 IgG Serum test
(Anti- GBM, Anti Neutrophil cytoplasmic IgG
Antibody)
Type 3 IgG
Type 4 Skin test
Lymphocyte transformation test
MELISA - Memory Lymphocyte Immuno Stimulation
Assay