Hypersensitivity refers to excessive or harmful immune reactions. There are four main types: I. Type I is an immediate reaction mediated by IgE antibodies binding to mast cells. Common examples include allergic reactions. II. Type II involves IgG or IgM binding to cells, activating complement and causing cell lysis. Examples include hemolytic anemia. III. Type III occurs when antigen-antibody complexes are deposited in tissues, activating complement and attracting inflammatory cells. Examples include serum sickness. IV. Type IV is delayed hypersensitivity mediated by T cells. The tuberculin skin test detects exposure to tuberculosis bacteria.

1. HYPERSENSITIVITY

2. Hypersensitivity
• Hypersensitivity (also called hypersensitivity
reaction or intolerance) refers to excessive, undesirable
(damaging, discomfort-producing and sometimes fatal) reactions
produced by the normal immune system.
• Hypersensitivity reactions require a pre-sensitized (immune) state of
the host.
Hypersensitivity Types
• On the basis of mechanisms involved and time taken for the reaction,
hypersensitivity reactions can be divided into four types:
I. type I
II. type II
III. type III
IV. type IV

3. Type I hypersensitivity
• Type I hypersensitivity is also known as immediate or anaphylactic
hypersensitivity.It develops within few minutes of exposure to an allergen.
• Anaphylactic reactions are mediated by IgE and other factors involved in
inflammation (inflammation means the protective response of the tissues to
the damage or destruction of cells). When the body is exposed to an allergen,
the IgE immunoglobulins are produced.
• These immunoglobulins bind with the surface receptors of mast cells and
circulating basophils.
• Mast cells are the granulated wandering cells found in connective tissue and
beneath the mucous membrane in the throat, lungs and eyes.
• During subsequent exposure of the body to the same allergen, the allergen
IgE antibody reaction takes place.
• This leads to degranulation of mast cells and basophils, with the release of
some chemical mediators such histamine. The chemical mediators produce
the hypersensitivity reactions.
• Most serious reactions are fall in blood pressure (due to
vasodilatation),obstruction of air passage and difficulty in breathing (due to
bronchoconstriction) and shock

4. Anaphylactic and anaphylactoid reaction
• The reaction is systemic, which involves multiple organ systems, and
is a direct result of the release of chemical mediators from mast cells
and basophils.
• Specifically, the condition anaphylaxis requires the patient to be
sensitized, and their reaction mediated through IgE antibodies. An
anaphylactoid reaction doesn’t need the presence of IgE antibodies
for a hypersensitivity reaction to occur.
• Substances initiating the anaphylactoid reaction, such as radiopaque
contrast media, nonsteroidal anti-inflammatory drugs (NSAIDs) and
aspirin cause a direct breakdown of the mast cell and basophil
membranes.
• Thus, an anaphylactic reaction occurs only after the patient has been
previously exposed at least once to the antigen and is sensitized; an
anaphylactoid reaction can occur following a single, first-time
exposure to certain agents in nonsensitized patients.

6. Diagnosis and Treatment
• Diagnostic tests for immediate hypersensitivity include skin (prick
and intradermal) tests,
• measurement of total IgE and specific IgE antibodies against the
suspected allergens. Increased IgE levels are indicative of an atopic
condition,
• Symptomatic treatment is achieved with antihistamines which block
histamine receptors. Chromolyn sodium inhibits mast cell
degranulation,
• Hyposensitization (immunotherapy or desensitization) is another
treatment which is successful in a number of allergies, particularly
to insect venoms
• The primary treatment of anaphylaxis is injection
of epinephrine, the administration of intravenous fluids, and
positioning the person flat

7. Type II hypersensitivity
• Type II hypersensitivity is also known as cytotoxic hypersensitivity and
may affect a variety of organs and tissues.
• The antigens are normally endogenous, although exogenous chemicals
(haptens) that can attach to cell membranes can also lead to type II
hypersensitivity.
• Drug-induced hemolytic anemia, granulocytopenia and
thrombocytopenia are such examples.
• The reaction time is minutes to hours.
• Type 11 reactions involve the activation of complement by the
combination of IgM or IgG antibodies with an antigenic cell.
• This activation stimulates the complement to lyse the affected
cell,which might be either a host cell or foreign cell that carries a
foreign antigenic determinant (such as a drug)on its surface.

8. • Additional cellular damage may be caused within 5-8
hours by the action of macrophages and other cells that
attack antibody –coated cell.
• Eg. Transfusion reactions, in which red blood cells are
destroyed as a result of reacting with circulating
antibodies.These involve blood group system
Diagnosis and treatment
Diagnostic tests include detection of circulating antibody against
the tissues involved by immunofluorescence
• Staning procedures also used in diagnosis
• Treatment involves anti-inflammatory and immunosuppressive
agents.

9. TYPE III HYPERSENSITIVITY
• Type III hypersensitivity is also known as Arthus or
immune complex hypersensitivity. The reaction may be
general (e.g., serum sickness) or may involve individual
organs including skin (e.g., systemic lupus erythematosus,
reaction), kidneys (e.g., lupus nephritis) joints (e.g.,
rheumatoid arthritis) or other organs.
• The reaction may take 3 - 10 hours after exposure to the
antigen.
• Excess amounts of antibodies like IgG or IgM are
produced in this type. The antigen-antibody complexes
are precipitated and deposited in localized areas like
joints causing arthritis, heart causing myocarditis and
glomeruli of kidney producing glomerulonephritis.

10. Diagnosis and treatment
• Diagnosis involves examination of tissue biopsies for deposits
of Ig and complement by immunofluorescence.
• Treatment includes anti-inflammatory agents.

11. Type IV hypersensitivity
• Type IV hypersensitivity is also known as cell mediated or delayed type
hypersensitivity.
• The classical example of this hypersensitivity is tuberculin (Montoux)
reaction which peaks 48 hours after the injection of antigen (tuberculin)
• Mechanisms of damage in delayed hypersensitivity include T lymphocytes
and monocytes and/or macrophages.
There are two different types of reactions capable of causing
tissue injury in this way.
1.delayed type hypersensitivity is mediated by CD4+ helper T
cells
2. cell mediated cytotoxicity, is mediated by CD8+ T cells.
• Cytotoxic T cells (Tc) cause direct damage whereas helper T (TH1) cells
secrete cytokines which activate cytotoxic T cells and recruit and activate
monocytes and macrophages, which cause the damage.
• The delayed hypersensitivity lesions mainly contain monocytes and a few T
cells.

13. Diagnosis and treatment
• Diagnostic tests include
• Montoux test
• patch test (for contact dermatitis)
• mitogenic response
• IL-2 production.
• Corticosteroids and other immunosuppressive agents are used in
treatment.

14. Table - Comparison of Different Types of hypersensitivity
characteristics
type-I
(anaphylactic)
type-II
(cytotoxic)
type-III
(immune complex)
type-IV
(delayed type)
antibody IgE IgG, IgM IgG, IgM None
antigen exogenous cell surface soluble tissues & organs
response time 15-30 minutes minutes-hours 3-8 hours 48-72 hours
appearance weal & flare lysis and necrosis
erythema and
edema, necrosis
erythema and
induration
transferred with antibody antibody antibody T-cells
examples
allergic asthma,
hay fever
erythroblastosis
fetalis,
SLE,
tuberculin test,
poison ivy,
granuloma

15. •A tuberculin skin test (also called a Mantoux
tuberculin test) is done to diagnose tuberculosis (TB). The
test is done by putting a small amount of TB protein
(antigens) under the top layer of skin on your inner forearm.
If you have ever been exposed to the TB bacteria
(Mycobacterium tuberculosis), your skin will react to the
antigens by developing a firm red bump at the site within 2
days.