This document summarizes the four main types of hypersensitivity reactions: Type I (immediate or anaphylactic), Type II (antibody-dependent cytotoxic), Type III (complex-mediated), and Type IV (cell-mediated or delayed). It provides details on the mechanisms, examples, diagnostic tests and treatments for each type of hypersensitivity reaction.

2. WHAT IS HYPERSENSITIVITY
•A condition in which the immune system reacts
abnormally to a foreign substance.
•Unwanted immune responses, termed as allergic or
hypersensitivity reactions, are generally classified
into four types.

3. TYPES OF HYPERSENSITIVITY
Hypersensitivity
Immediate or
anaphylactic
Antibody-
dependent
cytotoxic
Complex-
mediated
Cell-mediated
or delayed

4. TYPE I HYPERSENSITIVITY
•Also called immediate or anaphylactic hypersensitivity.
•Often known simply as ‘allergy’.
•Type I hypersensitivity occurs in individuals who
predominantly exhibit a th2 rather than a th1
response to antigen.

5. •In type I hypersensitivity individuals,
substances that are not inherently
noxious such as:
-Grass pollen
-House dust mites
-Certain foodstuffs or drugs
-animal fur
Provoke the production of IgE
antibodies.
Such individuals are said to be atopic (out of
place).

6. •These fix on mast cells, in the lung, and also to
eosinophils. Subsequent contact with the substance
causes the release of histamine, PAF, eicosanoids and
cytokines.
•The effects may be localised to the nose (hay fever),
the bronchial tree (the initial phase of asthma), the
skin (urticaria) or the gastrointestinal tract.

7. Hay fever:
-pollens
-running nose
-watery eyes
-sneezing

10. Hives or urticaria

11. COMMON TYPES OF ALLERGY
•Drug allergy: an abnormal reaction of the immune system to a medication.
•Food allergies: an unpleasant or dangerous immune system reaction after a
certain food is eaten.
•Contact dermatitis: a skin rash caused by contact with a certain substance.
•Latex allergy: an allergic reaction to certain proteins found in natural rubber
latex.

12. •Allergic asthma: asthma triggered by exposure to the same substances that
trigger allergy symptoms.
•Seasonal allergies: an allergic response causing itchy, watery eyes, sneezing
and other similar symptoms.
•Animal allergy: an abnormal immune reaction to proteins in an animal's skin
cells, saliva or urine.
•Anaphylaxis: a severe, potentially life-threatening allergic reaction.
•Allergy to mold: an abnormal allergic reaction to mould spores.

13. DIAGNOSTIC TEST
•Skin (prick and intradermal) tests
•Measurement of total IgE and specific IgE antibodies against the
suspected allergens by a enzyme immunoassay (ELISA).
•Increased IgE levels are indicative of an atopic condition
•A genetic predisposition for atopic diseases.

14. TREATMENTS
•Antihistamine which block histaminic receptors.
•Chromolyn sodium inhibits mast cell degranulation by inhibiting Ca2+
influx.
•Leukotriene receptors blockers or inhibitors of the cyclooxygenase
pathway.
•Bronchodilators (inhalants) for bronchoconstriction.

15. •Inhibitors for cAMP phosphodiesterase.
•Use of IgG antibodies that binds to mast cells block mast cell
sensitization.
•Hypo-sensitization (immunotherapy or desensitization) to
insect venom and pollens.

16. TYPE II HYPERSENSITIVITY
•Also called antibody-dependent cytotoxic hypersensitivity
•Type II hypersensitivity occurs when the mechanisms outlined
in type I hypersensitivity are directed against cells within the
host that are (or appear to be) foreign.
•For example, host cells altered by drugs are sometimes
mistaken by the immune system for foreign proteins and
evoke antibody formation.

17. •The antigen–antibody reaction triggers complement
activation (and its sequelae) and may promote attack
by NK cells.
•Examples include alteration by drugs of neutrophils,
leading to agranulocytosis or of platelets, leading to
thrombocytopenic purpura.
•These type II reactions are also implicated in some
types of autoimmune thyroiditis (e.g. Hashimoto’s disease)

20. DIAGNOSIS
•Detection of circulating antibody against the tissue that are involved
in hypersensitivity.
•The presence of antibody and complement in the lesion (biopsy) by
immunofluorescence.

21. TREATMENT
•Anti inflammatory agents
•immunosuppressive agents

22. TYPE III HYPERSENSITIVITY
•Also called complex-mediated hypersensitivity, type
III hypersensitivity occurs when antibodies react
with soluble antigens.
•The antigen–antibody complexes can activate
complement or attach to mast cells and
stimulate the release of mediators.

26. •Arthus reaction that occurs if a foreign protein is injected
subcutaneously into a rabbit or guinea pig with high
circulating concentrations of antibody.
•Within 3–8 hours the area becomes red and swollen
because the antigen– antibody complexes precipitate in small
blood vessels and activate complement.
•Type III hypersensitivity is also implicated in lupus
erythematosus (a chronic, autoimmune inflammatory disease).

27. •Neutrophils are attracted and activated (by c5a) to
generate toxic oxygen species and to secrete enzymes.
Mast cells are also stimulated by c3a to release
mediators.
•Damage caused by this process is involved in serum
sickness, caused when antigen persists in the blood
after sensitisation, causing a severe reaction, as in the
response to mouldy hay (known as farmer’s lung), and
in certain types of autoimmune kidney and arterial
disease.

28. DIAGNOSIS
• Tissue biopsies for deposits of Ig and complement by immunofluorescence.
• The presence of immune complexes in serum and depletion in the level of complement.
• Polyethylene glycol mediated turbidity to detect immune complexes.
Treatment
Anti inflammatory agents

29. TYPE IV HYPERSENSITIVITY
•Also known as cell mediated or delayed hypersensitivity
•The prototype of type IV hypersensitivity is the
tuberculin reaction, a local inflammatory response seen
when proteins derived from cultures of the tubercle
bacillus are injected into the skin of a person who
has been sensitised by a previous infection or
immunisation.

30. •An ‘inappropriate’ cell-mediated immune response is
stimulated, accompanied by infiltration of mononuclear
cells and the release of various cytokines.
•Cell-mediated hypersensitivity is also the basis of the
reaction seen in some other infections (e.g. Mumps
and measles), as well as with mosquito and tick
bites.

31. •It is also important in the skin reactions to drugs or
industrial chemicals, where the chemical (termed a hapten)
combines with proteins in the skin to form the ‘foreign’
substance that evokes the cell-mediated immune response.
•In essence, inappropriately deployed t-cell activity underlies all
types of hypersensitivity, initiating types I, II and III, and
being involved in both the initiation and the effector
phase in type IV.
•These reactions are the basis of the clinically important group
of autoimmune diseases.

32. •Immunosuppressive drugs and/or glucocorticoids are routinely
employed to treat such disorders.
•In essence, inappropriately deployed t-cell activity underlies all
types of hypersensitivity, initiating types I, II and III, and
being involved in both the initiation and the effector
phase in type IV.
•These reactions are the basis of the clinically important group
of autoimmune diseases. Immunosuppressive drugs and/or
glucocorticoids are routinely employed to treat such disorders.

33. Classification Of Type IV
Hypersensitivity

34. DIAGNOSTIC AND TREATMENT
•In vivo include:
delayed cutaneous reaction (montoux test) and patch test (for contact
dermatitis)
•In vitro include:
mitogenic response, lympho-cytoxicity, and IL-2 production.
•Treatment:
Corticosteroids and other immunosuppressive agents

36. REFERENCE:
• Rang HP, Ritter JM, flower RJ, Henderson G. Rang & dale's pharmacology. Chapter 6: cellular
mechanism : host defence. Elsevier health sciences; 8th edition 2016 dec 2; pg: 88-89.