Hypersensitivity, also known as allergy, refers to excessive or inappropriate immune responses that damage tissues. There are four main types of hypersensitivity reactions: 1. Type I are immediate hypersensitivity reactions mediated by IgE antibodies, as seen in allergic reactions like anaphylaxis. 2. Type II involve IgG and IgM antibodies binding to cells, leading to cell damage through phagocytosis or complement activation as seen in hemolytic disease of newborns. 3. Type III are immune complex-mediated reactions where antigen-antibody complexes deposit in tissues, activating complement and attracting inflammatory cells, seen in conditions like serum sickness. 4. Type IV are delayed hypersensitivity reactions mediated

1. HYPERSENSITIVITY
By Dr. Rakesh Prasad Sah
Assistant Professor, Microbiology

2. History
The term allergy (most commonly used as synonym for
hypersensitivity) means an altered state of reactivity to
an antigen, it may include both protective as well as
injurious immune response) was originally coined by Von
Pirquet (1905).

3. Definition
Hypersensitivity refers to a condition in which immune
response results in excessive reactions leading to tissue
damage, disease or even death in the sensitized host.
Adverse clinical reaction to the antigen or,“when the
immune system does something bad to the host, i.e.
tissue damage”
Contcat  Ag (allergen)  T & B –cells (sensitization)
same Ag (allergen)  Shocking dose  Allergy

5. Classification
Traditional classification
Feature Immediate type Delayed type
1. Onset and
duration
Appears and recedes
rapidly
Appears slowly in 24-72
hours and lasts longer
2. Immune response Antibody mediated Cell mediated
(T - lymphocytes)
3. Passive transfer Possible with serum Possible with lymphocyte
or transfer factor
3. Desensitisation Easy but short lived Difficult but long lasting
4. Induction Antigen or haptens,
by any route
By antigen injected
intradermally or by skin
contact

6. Coombs and Gell’s Classification of
Hypersensitivity

8. Type I Hypersensitivity
 The term anaphylaxis (ana-wihout, phylaxis-
protection) was described by Richet (1902)
 It is mediated by IgE antibodies.
 Type I reaction occurs in two forms
i) The acute, potentially fatal, systemic
form called anaphylaxis.
ii) The recurrent non-fatal localised
form called atopy.

9. Mechanism of action

10. Mechanism of action

12. Chemical mediators
Two types :
1) Primary mediators : which are performed content of
mast cells and basophils granules.
a) Histamin
b) Serotonin (5HT)
c) Proteolytic enzyme
d) Eosinophil chemotactic factor of anaphylaxis (ECF-A)

13. Chemical mediators
2) Secondry mediators : which are newly
formed upon stimulation of mast cells, basophils
and other leucocytes.
a) Slow reacting substance of anaphylaxis
b) Prostaglandins and thromboxane
c) Platelet activating factor (PAF)
d) Other mediators

14. Features of Anaphylaxis
1. Anaphylaxis occurs within a few seconds to few
minutes following shocking dose of antigen.
2. IgE antibody is responsible.
3. It can be induced artificially by serum of sensitised
individual.
4. It is not release to heredity.
5. Tissue or organ which are affected in anaphylaxis
are called ‘target tissue’ or ‘shock organ’.

16. Types of anaphylaxis
1. Anaphylaxis in vitro (schultz – Dale phenomenon).
2. Cutaneous anaphylaxis
3. Passive cutaneous anaphylaxis

17. Atopy
Atopy :
The term atopy (literally meaning out of place or
strangeness) was first introduced by Coca (1923).
To refer to naturally occuring familial hypersensitivities
of human being, typified by hay fever and asthma.

18. 1. Atopy runs in families. These individuals have tendency to
produce IgE Abs. In usually large amounts.
2. Reaction occur at the site of entry of the antigen,
inhalation of pollens affects lungs (bronchial asthma),
ingestion of fish, milk, eggs, drugs etc. (GI disorders)
and contact leads to local allergy (conjunctivitis).
3. It is IgE mediated hypersensitivity reaction.
4. Induction of atopy is difficult artificially because
atopens are poor antigen
Features of atopy

19. Mechanism of action of atopy
The atopens combine with the cell bound IgE Abs. fixed on the
surface of mast cells and the basophils and this antigen-antibody
complex stimulates these cells to release the mediators resulting
in clinical features of atopy.
Examples :
1. Food allergy : e.g. – eg, mushroom, shelfish.
2. Dust allergy : e.g. – pollens of ragweeds, grasses or trees, house
dust.
3. Drug allergy : e.g. – penicillin, sulphonamides.

21. Prausnitz – kustner (PK) reaction :
Prausnitz – kustner (1921)
This was the original method for detecting atopic antibody.
Anaphylactoid reaction :
The reaction resembles anaphylactic shock clinically and is
provoked by intravenous injection of peptone, trypsin and some
others substances.
- It has no immunological basis.
.

22. Vasculature
Skin
Lower
respiratory
Upper
respiratory
GI Tract

24. Type II Hypersensitivity
Cytotoxic reaction
 - Mediated by IgG (or rarely IgM) antibodies
directed against antigens on the surface of
the cells resulting in cell damage.
 Antibodies bind to an antigen on the cell
surface and cause
1. Phagocytosis of the cell through opsonic or
immune adherent.
2. Cytotoxicity by natural killer (NK) cells.
3. Lysis through activation of complement
system.

25. Mechanism of action

26. Examples
1. Haemolytic Disease Newborn (HDN) or
Erythroblastosis. :
2. Drug reactions :
- Sedormid purpura is a classical example. It is not used
now a days.
- Other drugs : sulphonamid, quinidine.

27. Haemolytic Disease Newborn
(HDN) or Erythroblastosis

28. Demonstration of type II reaction
 Coombs test ( indirect antiglobulin test) is
usually positive.

31. Type III Hypersensitivity
Immune complex reaction
It is characterised by deposition of antigen –
antibody complexes in tissues, activation of
compliment and infiltration of
polymorphonuclear leucocytes leading to
tissue damage.
“Immune complex each required
Immune processes disease”
Soluble Ag/IgG or IgM
high titers of involved:
classical complement pathway
phagocytic cells

32.  Type III is two typical type reaction :
i) Arthus reaction (localised) due to antibody
excess.
ii) Serum sickness (generalised) because of antigen
excess.

33. Arthus Reaction
- Arthus (1903)
- The arthus reaction can be passively transferred with sera
containing high titre of antibodies (IgG, IgM).

34. Arthus Reaction
Ag-Ab complex  deposited on wall of blood vessels 
complement activation  attract leucocyte  leucocytes-
platelets thrombi formation  reduced blood supply 
tissue necrosis

35. Serum sickness
- It is systemic form of type III hypersensitivity reaction.
- It appears following a single injection of high concentration of foreign
serum.
- Serum sickness is differs from other hypersensitivity in that a single
injection serves both as the sensitising and socking dose.
- Ag-Ab complex  deposited on the endothelial lining of the
blood vessels various parts of the body complement
activation  attract leucocyte  leucocytes-platelets thrombi
formation  reduced blood supply  tissue necrosis
- Some important immune complex diseases are :
Post streptococcal glomerulonephritis, Endocarditis, Hepatitis B,
Dengue haemorrhagic fever and Malaria.

36. Sites of Complex Deposition
Site Outcome
Glomeruli Glomerulonephritis
Blood vessel wall Arteritis
Synovial membrane Arthritis
Skin Rash
Note: Ab responsible for immune complexes may be
generate at a site distant from the point of deposition.

39. Type IV Hypersensitivity
Delayed or cell mediated reaction
- It is mediated by sensitised T lymphocytes
- Two types Deayed hypersensitivity reaction.
1. Tuberculin (infection) type
2. Contact dermatitis type.

41. Tuberculin (infection) type
 Positive skin test does not indicate present infection but implies
that the person has been infected or immunised by the
microorganism in the past.
 Some of these skin test include :
i. Lepromin test : It is positive in tuberculoid leprosy but negative
in lepromatous type of leprosy.
ii. Frei test : This test is positive in lymphogranuloma venereum
(LGV).
iii. Histplasmin test : It ispositive in histoplasmosis.

42. Positive Tuberculin Reaction

43. Contact dermatitis type
 Delayed hypersensitivity sometime results from skin contact
with a variety of
1. chemicals – metals such as nickel and chromium.
2. Drugs such as penicillin or other antibiotics in ointments.
3. Simple chemicals like hair dyes, picryl chloride,
dinitrochlorobenzine.
4. Cosmetics.
5. Soaps

44. CONTACT DERMATITIS

45. Allergic Contact Dermatitis Response to
Poison Ivy Hapten

46. Patch test
This test is used to diagnose delayed
allergic reactions such as Contact
Dermatitis.
It involves taping traces of various
known contact allergens on the
skin and keeping them there for
48 hours.

47. Examples of Type IV Hypersensitivity

49. Type V hypersensitivity
 Type V - Cell surface receptors
 Instead of killing or inhibition (not whole cell like
type II)
 Leads to proliferation & differentiation
 Ag-Ab complex enhances activity of affected cell.
 Graves' disease  excess production of thyroid
hormone
