This document defines and describes the four main types of hypersensitivity reactions: Type I (immediate), Type II (cytotoxic), Type III (immune complex), and Type IV (cell-mediated). Type I is mediated by IgE and mast cells/basophils and causes rapid allergic reactions. Type II involves IgG/IgM binding to cell surfaces and complement activation, resulting in conditions like hemolytic anemia. Type III occurs when immune complexes deposit in tissues, activating complement and attracting phagocytes and causing inflammation. Type IV is a delayed reaction mediated by sensitized T cells activating macrophages.

1. HYPERSENSITIVITY
DR IRIAGBONSE OSAIGBOVO
DEPT OF MEDICAL MICROBIOLOGY,
UNIBEN

2. OUTLINE
DEFINITION
IMMEDIATE HYPERSENSITIVITY
ANTIBODY MEDIATED HYPERSENSITIVITY
IMMUNE COMPLEX HYPERSENSITIVITY
CELL MEDIATED HYPERSENSITIVITY

3. Introduction
This topic requires background knowledge of:
● Properties of immunoglobulins-IgE, IgG, IgM
● Physiology of blood cells- Mast cells and Basophils
● The complement system

4. Definition
Exaggerated or inappropriate immune reaction to antigenic
stimulus
Results in tissue damage harmful to the host
4 types
Types I,II and III are antibody mediated; Type IV cell mediated

5. TypeI: Immediate hypersensitivity
● Also known as allergy
● Type I is mediated by IgE
● The antigen that triggers this type of hypersensitivity is called
allergen
● On first exposure, allergens induce formation of IgE in large
quantities
● IgE binds via Fc portion to receptors on mast cells, basophils

6. ● On subsequent exposure, allergen binds to cell bound IgE
● Crosslinking of IgE molecules results in influx of calcium which
induces degranulation of cells
● Pharmacologically active preformed mediators are released
● Release is within seconds to minutes i.e immediate
● Histamine is the principal agent. Also heparin, tryptase,
chymase, eosin chemotactic factor, serotonin

7. Approximately 6 hours later, late phase occurs
Lasts several days
De novo synthesis of leukotrienes (SRS-A), prostaglandins
Late phase reactants cause an influx of inflammatory cells like
neutrophils and eosinophils

8. ● Some individuals possess an inherited tendency for
overproduction of IgE antibodies to common environmental
allergens
● This genetic predisposition is called atopy
● Common allergens- pollen, animal dander, nuts, shellfish,
insect venom, some drugs like penicillin
● Type I reactions may be localized-hay fever, urticaria, allergic
conjuctivitis
● Systemic- anaphylaxis

9. Treatment/clinical correlates
● Avoidance of the allergen
● Desensitisationby repeated subcutaneous injection of small
amounts of allergen can lead to improvement
● Blocking action of IgE using monoclonal anti-IgE antibody such
as Omalizumab
● Stabilization of trigger cells- isoprenaline, sodium cromoglycate
render mast cells resistant to triggering
● Mediator antagonism- Histamine receptor antagonists e.g
loratidine. Leukotriene receptor antagonists e.g Pranlukast

10. Type II: Antibody dependent cytotoxic
hypersensitivity
● Caused by IgG or IgM binding to antigens on cell surface or
extracellular matrix molecules
● Subtypes- complement mediated, antibody dependent cellular
cytotoxicity, antibody mediated cellular dysfunction

11. ● Binding of antibody to cell surface antigen whether normal or
altered by exogenous molecule leads to complement activation
● Subsequent formation of the membrane attack complex
damages cell membrane
● In situations where antibody binds to antigen on fixed tissue,
complement activation results in generation of chemotactic
factors (C5a),
● Inflammation is induced with resultant tissue destruction

12. ● Haemolytic anaemias
● ABO transfusion reactions, Rhesus haemolytic disease of the
newborn
● Drug induced haemolytic anaemias, thrombocytopaenic
purpura- penicillin, phenacetin, chlorpromazine, amidopyridine,
quinidine
● Autoimmune haemolytic anaemias due to cross reacting
antibodies induced by Mycoplasma pneumonia against red cell
antigens

13. Rheumatic fever
Goodpasture syndrome

14. Antibody dependent cellular
cytotoxicity
● Target cells coated with antibody are killed by extracellular
non-phagocytic process involving leucocytes that bind by
specific Fc receptors
● Cells involved include NK cells, monocytes, neutrophils,
eosinophils

15. Antibody mediated cellular dysfunction
● Auto-antibody to a cell surface receptor acts as an agonist
leading to stimulation of the cell
● E.g autoantibody against TSH receptor causes continuous
stimulation of the thyroid leads to hyperthyroidism in Graves
disease
● Myaesthenia gravis
● This type does not involve complement

16. Type III- Immune complex
hypersensitivity
● Occurs when there are defects in phagocytic and complement
system that removes immune complexes
● Occurs when the system is overloaded in antigen excess due
to chronic or persistent microbial infection, repeated contact
with environmental antigen, autoimmune conditions
● Immune complexes are deposited in organs and tissues where
they activate complement
● Phagocytes are attracted by chemotactic factors
● Resultant inflammation and tissue damage

17. Arthus reaction
● Localized acute type III rxn elicited in the skin following
experimental intracutaneous injection of antigen in previously
immunised animal.
● Large immune complexes form locally precipitating in vessel
walls
● Subsequent complement activation, chemotaxis , influx of
neutrophils, inflammation
● Intrapulmonary Arthus-type reactions to inhaled exogenous
antigens cause disorders like Farmers lung, bird fanciers lungs

18. Serum sickness
● Systemic prototype of type III reaction
● 3 stages
● Formation of antigen antibody complexes in the circulation
● Deposition of complexes in various tissues
● Initiation of inflammatory reaction in the sites of immune
complex deposition
● Fever, urticaria, arthralgia, usually a few days to 2 weeks after
injection of foreign serum e.g horse serum or drugs like
penicillin or sulphonamides

19. ● Other diseases with serum sickness like pattern
● Acute post streptococcal glomerulonephritis
● Systemic lupus erythematosus (SLE)
● Rheumatoid arthritis

20. Type IV-Cell mediated hypersensitivity
● Mediated by specifically sensitized T-lymphocytes
● The T lymphocytes activate macrophages to cause an
inflammatory response
● Seen in some bacterial, fungal and viral infections-
tuberculosis, coccidioidomycosis
● Contact dermatitis to oil of poison oak, topical sulphonamides,
neomycin, soaps, heavy metal like nickel in jewelry
● Graft rejection