1. The document summarizes the different types of hypersensitivity reactions: immediate (types I-III) and delayed (type IV). Immediate reactions occur within seconds to minutes after antigen exposure and involve antibody-mediated responses. Delayed reactions occur 24-48 hours after exposure and involve T cell-mediated responses. 2. Type I reactions are anaphylactic and mediated by IgE antibodies binding to mast cells and basophils. Type II reactions are antibody-mediated and cytotoxic, targeting cell surface antigens. Type III reactions involve immune complex deposition and complement activation, causing tissue injury. Type IV reactions are delayed hypersensitivity responses mediated by T cells without antibody formation.

1. ADITYA BANGALORE INSTITUTE OF
PHARMACY.
DEPARTMENT OF PHARMACOLOGY
Advanced Pharmacology-II
Seminar on: Hypersensitivity Reactions
Submitted to: Dr. N VENKATESAN
Presented by: RAJESH YADAV
M. Pharm (2019-2021)

2. Introduction
Hypersensitivity is defined as an exaggerated or inappropriate state of normal immune response with
onset of adverse effects on the body.
The lesions of hypersensitivity are a form of antigen-antibody reaction. These lesions are termed as
hypersensitivity reactions or immunologic tissue injury.
These are grouped into:
Immediate type:
Reaction occurs immediately (within seconds to minutes) on administration of antigen. Immune
response is mediated by humoral antibodies (B cell mediated). It includes type I, II & III.
Delayed type:
The reaction is slower in onset & develops within 24-48 hours & the effect is prolonged. It is
mediated by cellular response ( T cell mediated) & includes type IV reaction.

3. Type I: Anaphylactic (Atopic) Reaction
State of rapidly developing or anaphylactic type of immune response to an antigen to which the
individual is previously sensitized, within 15-30 minutes of exposure to Ag.
Etiology: mediated by humoral Abs of IgE type
1) Genetic Basis
2) Environmental pollutants
3) Concomitant factors
Pathogenesis
It includes participation by B lymphocytes, plasma cells, mast cells & basophils, neutrophils &
eosinophils
Mechanism
i) sensitization during 1st contact with antigen,
B lymphocytes activation & differentiation to form IgE secreting plasma cells
IgE antibodies bind to Fc receptors present on surface of mast cells & basophils
ii) during 2nd contact, IgE antibodies are so firmly bound that it sets in cell damage-membrane lysis,
influx of Na & water and degranulation of mast cells-basophils

4. The released chemicals & enzymes have proinflammatory properties- histamine, serotonin,
vasoactive intestinal peptide, chemotactic factors of anaphylaxis for neutrophils & eosinophils,
leukotrienes B4 & D4, prostaglandins & platelet activating factor
The effects include:
i) increased vascular permeability
ii) smooth muscle contraction
iii) early vasoconstriction followed by vasodilatation
iv) shock
v) increased gastric secretion
vi) increased nasal & lachrymal secretions
vii) increased migration of eosinophils & neutrophils at the site of local injury as well as their rise in
blood

5. Examples
Systemic anaphylaxis
i) Administration of antisera e.g. anti-tetanus serum
ii) Administration of drugs e.g. penicillin
iii) Sting by wasp or bee
Clinical features include itching, erythema, contration of respiratory bronchioles, diarrhoea,
pulmonary oedema, pulmonary haemorrhage, shock & death
Local anaphylaxis
i) Hay fever due to pollen sensitization of conjunctiva & nasal passages
ii) Bronchial asthma due to allergy to inhaled allergens like house dust
iii) Food allergy to ingested allergens like fish, cows milk, eggs.etc
iv) Cutaneous anaphylaxis due to contact of antigen with skin characterized by urticaria, wheal &
flare
v) Angioedema characterized by laryngeal oedema, oedema of eyelids, lips, tongue & trunk

6. Type II: Antibody-mediated (cytotoxic) reaction
Reaction by humoral antibodies that attack cell surface antigens on specific cells & tissues & cause
lysis of target cells. It appears within 15-30 minutes after exposure to antigen.
Etiology & Pathogenesis
Type II reactions have participation by complement system, tissue macrophages, platelets, natural
killer cells, neutrophils & eosinophils while main antibodies are IgG & IgM. It is tissue-specific and
reaction occurs after antibodies bind to tissue specific antigens.
Mechanism
i) Antigen on surface of target cell (foreign cell) attracts & binds Fab portion of the antibody (IgG or
IgM) forming Ag-Ab complex
ii) Unattached Fc fragment of antibodies forms a link between antigen & complement
iii) Ag-Ab binding with Fc forming a link causes activation of classical pathway of serum
complement which generates activated complement component, C3b, by splitting C4 & C2 by C1
iv) Activated C3b bound to the target cell acts as an opsonin and attracts phagocytes to the site of
cell injury and initiates phagocytosis
v) Ag-Ab complex also activates complement system and exposes membrane attack complex(MAC)
(C5b-C9) that attacks and destroys the target cell

7. Examples:
Cytotoxic antibodies to blood cells
i) Autoimmune haemolytic anaemia, red cell injury brought by autoantibodies (direct Coombs’ test)
ii) Transfusion reactions due to incompatible blood transfusion
iii) Erythroblastosis foetalis in which foetal red cells destroyed by maternal isoantibodies
iv) Immune thrombocytopenic purpura (ITP), destruction of platelets by autoantibodies
v) Leucopenia with agranulocytosis, leucocyte destruction by autoantibodies
vi) Drug-induced cytotoxic antibodies, formed in response to administration of certain drugs like
penicillin, methyl dopa, rifampicin, etc. The drugs or metabolites act as haptens binding to surface of
blood cells, which are destructed by antibodies.
Cytotoxic antibodies to tissue components
i) In Grave’s disease (primary hyperthyroidism), thyroid autoantibody is formed which reacts with
TSH receptor to cause hyperfunction and proliferation.
ii) Myasthenia gravis, antibody to Ach receptors of skeletal muscle is formed which blocks the
neuromuscular transmission at the motor-end plate, causing muscle weaknes
iii) In male sterility, antisperm antibody is formed which reacts with spermatozoa
iv) Type I DM, islet cell autoantibodies are formed which react against islet cell tissue
v) Hyperacute rejection reaction

8. Type III: Immune Complex Mediated (Arthus) Reaction
It occurs from deposition of antigen-antibody complexes on tissues, followed by activation of
complement system & inflammatory reaction, resulting in cell injury
6 hours after exposure to antigen
Etiology & Pathogenesis
It is not tissue specific and occurs when antigen-antibody complexes fail to get removed by the
body’s immune system.
1) Persistence of low-grade microbial infection
2) Extrinsic environmental antigen
3) Autoimmune process
Type III has participation by IgG & IgM Abs, neutrophils, mast cells & complement
Mechanism:
i) Immune complexes formed by interaction of soluble Ab and soluble or insoluble Ag
ii) Immune complexes which fail to get removed from body fluid get deposited into tissues
iii) Fc component of Ab links with complement & activates classical pathway of complement
resulting in formation of C3a, C5a, and membrane attack complex
iv) C3a stimulates release of histamine from mast cells and its resultant effects of increased vascular
permeability and oedema

9. v) C5a releases proinflammatory mediators & chemotactic agents for neutrophils
vi) Accumulated neutrophils and macrophages in the tissue release cytokines and result in tissue
destruction
Examples:
i) Immune complex glomerulonephritis in which Ag may be glomerular basement membrane
ii) SLE in which there is nuclear Ag
iii) Rheumatoid arthritis in which there is nuclear Ag
iv) Farmer’s lung in which actinomycetes-contaminated hay acts as Ag
v) Polyarteritis nodosa & Wegner’s granulomatosis with antineutrophil cytoplasmic Ag
vi) Henoch-Schonlein purpura in which respiratory viruses acts as Ag
vii) Drug-induced vasculitis in which drug acts as antigen.
Type IV: Delayed Hypersensitivity (T cell mediated) reaction
It is a tissue injury by T cell mediated immune response without formation of Abs but it’s a slow &
prolonged response. Reaction occurs about 24 hrs. after exposure to Ag, may last upto 14 days

10. Etiology & Pathogenesis
It involves role of mast cells & basophils, macrophages and CD8+ T cells
Mechanism
i) Ag is recognized by CD8+ T cells and is processed by Ag presenting cells
ii) Ag presenting cells migrate to lymph node where Ag is presented to helper T cells (CD4+ T cells)
iii) Helper T cells release cytokines that stimulate T cell proliferation & activate macrophages
iv) Activated T cells and macrophages release proinflammatory mediators and cause cell destruction
Examples
1) Reaction against mycobacterial infection e.g. Tuberculin reaction in tuberculosis
2) Reaction against virally infected cells
3) Reaction against malignant cells in the body
4) Reaction against organ transplantation e.g. Transplant rejection

12. THANK YOU!!!