1. Hypersensitivity Dr. Sudheer Kher
A damage to the host, mediated by pre-existing immunity to self or foreign antigen.
Dr. Sudheer Kher
Kher

2. Musts for Hypersensitivity
Contact with allergen
Sensitizing/priming dose
Induction of AMI/CMI
Shocking dose
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3. Classification : Hypersensitivity reactions
Immediate hypersensitivity
Anaphylaxis
Atopy
Antibody mediated cell damage
Arthus phenomenon/reaction
Serum sickness
Delayed hypersensitivity
Infection (Tuberculin) type
Contact dermatitis type
Type I
Type II
Type III
Type IV
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4. Classification: Gell & Coombs(1963)
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5. Type II Reactions : Cytolytic, Cytotoxic & Cell Stimulatory
Involve reaction between IgG (rarely IgM) & Ag determinant on the surface of cells.
Leads to cytolytic or cytotoxic effect.
Autoimmune anemias
Hemolytic disease of the new born
Drug induced hemolytic anemias
Drug induced thrombocytopenic purpura
Drug induced agranulocytosis
Rarely normal cell function may be disrupted
Agonist effect -Cell stimulatory effect seen (LATS in Graves’ disease).
Antagonist effect – Myasthenia gravis
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6. Type II (Cytotoxic) Reactions
Involve activation of complement by IgG or IgM binding to an antigenic cell.
Antigenic cell is lysed.
Transfusion reactions:
ABO Blood group system: Type O is universal donor. Incompatible donor cells are lysed as they enter bloodstream.
Rh Blood Group System: 85% of population is Rh positive. Those who are Rh negative can be sensitized to destroy Rh positive blood cells.
Hemolytic disease of newborn: Fetal cells are destroyed by maternal anti-Rh antibodies that cross the placenta.

7. Diagnostic tests for type II
Detection of circulating/fixed antibody against tissues involved. Coombs’ test.
Presence of antibody and complement in the lesion (biopsy) by immunofluorescence.
The staining pattern is normally smooth and linear, such as that seen in Goodpasture’s nephritis (renal and lung basement membrane) and pemphigus (skin intercellular protein, desmosome).
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8. Coombs (Antiglobulin)Tests
Incomplete Ab
Direct Coombs Test
Detects antibodies on erythrocytes + ↔ Y
Patient’s RBCs
Coombs Reagent
(Antiglobulin)

9. Coombs (Antiglobulin)Tests
Indirect Coombs Test
Detects anti-erythrocyte antibodies in serum Y
Patient’s
Serum
Target
RBCs + ↔
Step 1 + ↔ Y
Coombs Reagent
(Antiglobulin)
Step 2

10. Type III (Immune Complex) Reactions
Involve reactions against soluble antigens circulating in serum.
Usually involve IgG, IgM antibodies.
Antibody-Antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage.
Glomerulonephritis: Inflammatory kidney damage.
Occurs when slightly high antigen-antibody ratio is present.

11. Immune Complex Mediated Hypersensitivity
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12. Type III Reaction: Immune Complex Disease
Arthus Reaction – Localized manifestation of generalized hypersensitivity
Ag+Ab precipitates cause C activation and release of inflammatory molecules. Leads to ↑ vascular permeability & neutrophil infiltrate. Leucocyte-platelet thrombi formed which reduce blood supply leading to necrosis.
Clinical example – Farmer’s lung & other hypersensitivity pneumonitis following inhaled Ag like Actinomycetes.
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13. Arthus reaction Arthus reaction Wheal & flare reaction Type-III Type-I
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14. Type III Reaction: Immune Complex Disease
Serum Sickness – Systemic form of Type III reaction.
Takes place following serum therapy
e.g. ADS, ATS, AGGS, Hyperimmune globulin, Anti Snake venum.
Clinically Fever, lymphadenopathy, splenomegaly, arthritis, glomerulonephritis, endocarditis, vasculitis, urticarial rashes, abdominal pain, nausea, vomiting.
Pathogenesis – Formation of immune complexes, its deposition on the endothelial lining of BVs all over the body, leads to inflammation.
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15. Serum Sickness (contd)
Plasma concentration of C falls due to massive activation and fixation to Ag+Ab complexes.
Disease self limited.
Single dose of Antiserum can serve both as sensitizing & shocking dose.
Can also be seen after administration of penicillin or other antibiotics.
Immune complexes occur in many bacterial, viral, parasitic infections e.g. poststreptococcal glomerulonephritis, Hepatitis B & Malaria. Also seen in disseminated malignancies & autoimmunity.
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16. Serum sickness
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17. Type IV Reactions: Delayed Hypersensitivity
Two types –
Tuberculin (Infection) type
Contact dermatitis type
Tuberculin type –
ID inoculation of PPD in sensitized indivisual leads to induration & inflammation in hrs. This is not same as skin test done for Type I hypersensitivity.
Used for diagnosis / exclusion of diagnosis of many bacterial / fungal / parasitic / viral and autoimmune diseases.
Kher

18. Type IV (Cell-Mediated) Reactions
Involve reactions by TD memory cells.
First contact sensitizes person.
Subsequent contacts elicit a reaction.
Reactions are delayed by one or more days (delayed type hypersensitivity).
Delay is due to migration of macrophages and T cells to site of foreign antigens.
Reactions are frequently displayed on the skin: itching, redness, swelling, pain.
Tuberculosis skin test
Poison ivy
Metals
Latex in gloves and condoms (3% of health care workers)

19. Type IV Reactions: Delayed Hypersensitivity
One aspect of CMI
Provoked by specific Ag, involves lymphocytes & Macrophages.
Not induced by circulating Ab but by sensitized lymphocytes.
Sensitized lymphocytes release lymphokines which have biological effects on leucocytes, macrophages & tissue cells.
Transfer possible thru’ lymphocytes / transfer factor.
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20. Granuloma in a leprosy patient
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21. Contact dermatitis Ag possibly enters thru’ sebaceous glands
Lesions vary from macules & papules to vesicles which subsequently breakdown leaving weeping surface typical of acute eczematous dermatitis.
Detected by patch test
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22. Contact dermatitis reaction
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23. Allergic Contact Dermatitis Response to Poison Ivy Hapten
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24. Diagnostic tests Type IV
Diagnostic tests in vivo include delayed cutaneous reaction (e.g. Montoux test) and patch test (for contact dermatitis).
In vitro tests for delayed hypersensitivity include mitogenic response, lympho-cytotoxicity and IL-2 production.
Kher

25. Treatment of type II, III, IV
Antiinflammatory drugs
Corticosteroids & other immunosuppressives
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