A brief description over Hypersensitivity and its types, Introduction, Classification, Examples, Discussion.

1. 1
HYPERSENSITIVITY AND ITS TYPES
Introduction: -
A Quick review to the Hypersensitivity and its types, Hypersensitivity also known as
Hypersensitivity reaction or intolerance. It refers to excessive, undesirable, damaging,
discomfort- producing and sometimes fatal reactions produced by the normal immune
system, including allergies and autoimmunity e.g. fever, skin rash, wheezing, itchy and
watery eyes. Hypersensitivity reactions require pre-sensitized (immune) state of the host.
Based on the duration and mechanism of the reaction Hypersensitivity is classified as-
Type I (Immediate/Atopic/Anaphylactic Hypersensitivity)
Type II (Cytotoxic Hypersensitivity/ Antibody Mediated Hypersensitivity)
Type III (Immune Complex/ Arthus Hypersensitivity)
Type IV (Cell Mediated/ Delayed Type of Hypersensitivity)
Type I Hypersensitivity-
It is also known as immediate or anaphylactic hypersensitivity. It develops within few
minutes of exposure to an allergen. Anaphylactic reactions are mediated by Ig E 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
Ig E immunoglobulins are produced. These immunoglobulin’s bind with the surface
receptors of mast cells and basophiles (Mast cells are the granulated wandering cells found

2. 2
in connective tissue and circulating basophiles), 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 basophiles, with the release of some
chemical mediators such histamine.
Causes-
The allergens are considered to be the cause of hypersensitivity. The allergens are the non-
parasite antigens that stimulate the type I hypersensitivity response. This is some of the list
of allergens commonly associated with type I hypersensitivity.

3. 3
Signs of Type I Hypersensitivity-
The chemical mediators produce the hypersensitivity reactions such as fall in blood
pressure (due to vasodilatation), obstruction of air passage and difficulty in breathing (due
to bronchoconstriction) and shock. The reaction may involve skin (urticaria and eczeema),
eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues
(asthama) and gastroinestinal tract (Gastroenteritis).
The reaction may cause a range of symptoms from minor inconvenience to death.
Diagnosis of Type I Hypersensitivity-
Diagnostic tests for immediate hypersensitivity include skin (prick and intradermal) tests,
Measurement of Total Ig E and specific Ig E antibodies against the suspected allergens.
Total Ig E and specific Ig E antibodies are measured by a modification of enzyme linked
immune sorbent assay (ELISA). Increased Ig E levels are indicative of an atopic condition,
although Ig E may be elevated in some non-atopic diseases (e.g., myelomas, helminthic
infection, etc). The Normal level of IgE is <75kU/L.

4. 4
Treatment of Type I Hypersensitivity-
The treatments include the drugs and certain steroids. Drugs such as Non-steroidal anti-
inflammatory (NSAIDs), Antihistamines block histamine receptors. Steroids such as
Theophylline or epinephrine -prolong or increases CAMP levels in mast cells which inhibit
degranulation. While, Immunotherapy’s such as Desensitization or hypo sensitization, also
known as allergy shots, on repeated injections of allergen to reduce the Ig E on Mast cells.
Type II Hypersensitivity-
It is also known as cytotoxic hypersensitivity and Antibody Mediated Hypersensitivity.
This 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,
thrombocytopenia are such examples. Penicillin allergy also belongs to this class. The
reaction time is minutes to hours. The reaction is mediated by antibodies of
Immunoglobulin M or Immunoglobulin G Class and complements.

5. 5
Hemolytic Disease in New born-
Let us understand with an example, Hemolytic disease in Newborn. If the mother is Rh (-
ve) and the foetus is Rh (+ve). Rh factor incompatibility Ig G antibodies to Rh antigen
innocuous Rbc antigen > Rh (+ve) baby born to Rh- mother first time fine. 2nd
time can
have antibodies to Rh from 1st pregnancy. Antibodies crosses placenta and baby kills its
own Rbcs. Treatment includes treat mother with antibody to Rh antigen right after birth
and mother never makes its own immune response.
Diagnosis of Type II Hypersensitivity-
Diagnostic tests for detection of circulating antibodies against the tissues involved by
immunofluoresence. Staining procedures also used in the diagnosis.
Treatment of Type II Hypersensitivity-
The treatments include the Drugs such as Non-steroidal anti-inflammatories (NSAIDs),
Immunosuppressive Agents.

6. 6
Type III Hypersensitivity-
It is also known as Antigen- Antibody Immune Complex/Arthus Hypersensitivity. Ig G
mediated large amount of antigen and antibodies form complexes in blood. If not
eliminated can deposit in capillaries or joints and trigger inflammation. The reaction may
be general (e.g., serum sickness) or may involve individual organs including skin (e.g.,
systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g.,
aspergillosis), joints (e.g., rheumatoid arthritis) or other organs. This reaction may be the
pathogenic mechanism of diseases caused by many microorganisms. The reaction may take
3 - 10 hours after exposure to the antigen. It is mediated by soluble immune complexes.
They are mostly of the Ig G class, although Ig M may also be involved. The antigen may
be exogenous (chronic bacterial, viral or parasitic infections), or endogenous (non-organ
specific autoimmunity: e.g., systemic lupus erythematosus, SLE).The antigen is soluble
and not attached to the organ involved TYPE III PMNs (Poly morphonuclear Neutrophils)
and macrophages bind to immune complexes via FCR and phagocytize the complexes.
But, If unable to phagocytize the immune complexes can cause inflammation via C'
activation ---> C3a C4a, C5a and "frustrated phagocytes".

7. 7
Signs of Type III Hypersensitivity-
Signs of Type III Hypersensitivity involve SLE (subcutaneous lupus erythematosus),
Various disease asssociated with the fungus aspergillus., Arthus reaction, rheumatoid
arthritis are observed.

8. 8
Diagnosis of Type III Hypersensitivity-
Diagnosis involves examination of tissue biopsies for the deposit of Immunoglobulin’s and
complement by immunofluoresence microscopy. The presence of immune complexes in
the serum and depletion in the level of complement are also diagnostic.
Treatment of Type III Hypersensitivity-
The treatments include the Drugs such as Non-steroidal anti-inflammatories (NSAIDs),
Immunosuppressive Agents.
Type IV Hypersensitivity-
It is also known as Cell Mediated/ Delayed Type of 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 Tcells
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.

9. 9
Signs of Type IV Hypersensitivity-
Signs of Type IV Hypersensitivity involve Contact dermatitis, Poison ivy.
Diagnosis of Type IV Hypersensitivity-
Diagnostic test involves Montoux test, Patch test (for contact dermatitis), Mitogenic
response, Interleukin- 2 production.
Treatment of Type IV Hypersensitivity-
The treatments include the Drugs such as Corticosteroids, other Immunosuppressive
Agents.
Summary of the Hypersensitivity and its types: -
A broad overview of Hypersensitivity and its types, its mechanism and classification based
on the duration of the reaction and its signs, diagnosis, treatment and examples.

10. 10

11. References: -
1. Immunology and Medical Microbiology, R.P. Singh
2. Textbook of Microbiology& Immunology, 2nd
Edition, Subhash chandra Parija