Hypersensitivity types

1. P:2 U:2
VEDANTI GHARAT
M.SC. PART-1
ROLL NO. - 09
HYPERSENSITIVITY:
TYPE 1 & 2

2.  Hypersensitivity reactions are immune responses that are
exaggerated or inappropriate against an antigen or allergen.
 They are usually referred to as an over-reaction of the immune
system and these reactions may be damaging and uncomfortable.
 May develop in the course of either humoral or cell-mediated
responses.
 Anaphylactic reactions within the humoral branch initiated by
antibody or antigen-antibody complexes as immediate
hypersensitivity, because the symptoms are manifest within minutes
or hours after a sensitized recipient encounters antigen.
 Delayed-type hypersensitivity (DTH) is so named in recognition of
the delay of symptoms until days after exposure.

3. Gell and Coombs Classification
 Gell and Coombs proposed a classification scheme in
which hypersensitive reactions are divided into four
types.
1. IgE-mediated (type I)
2. Antibody-mediated/ IgG mediated cytotoxic (type II)
3. Immune complex–mediated (type III)
4. Cell mediated or DTH (type IV)

5. IgE-Mediated (Type I) Hypersensitivity
 A type I hypersensitive reaction is induced by certain types of
antigens referred to as allergens.
 In type I hypersensitive response, the plasma cells secrete IgE.
 This class of antibody binds with high affinity to Fc receptors on
the surface of tissue mast cells and blood basophils.
 A later exposure to the same allergen cross-links the membrane-
bound IgE on sensitized mast cells and basophils, causing
degranulation of these cells. (release of primary mediators,
vasoactive amines, smooth muscle contraction, etc.)

7. There Are Several Components
of Type I Reactions
 ALLERGENS
- Allergen refers specifically to non
parasitic antigens capable of
stimulating type I hypersensitive
responses in allergic individuals.
-Some persons, may have an abnormality
called atopy.
 REAGINIC ANTIBODY (IgE) and
MAST CELLS AND BASOPHILS
-Serum IgE levels in normal individuals
=0.1–0.4 g/ml.
-the half-life of IgE in the serum is 2–3
days, once IgE has been bound to its
receptor on mast cells and basophils, it
is stable in that state for a number of
weeks.
 IgE-BINDING Fc RECEPTORS
-The reaginic activity of IgE depends on
its ability to bind to a receptor specific
for the Fc region of the heavy chain.
-two classes of FcR, designated FcRI and
FcRII.
 IgE CROSSLINKAGE INITIATES
DEGRANULATION
-the binding of IgE to FcRI apparently has
no effect on a target cell. It is only after
allergen crosslinks the fixed IgE-receptor
complex that degranulation proceeds.
 INTRACELLULAR EVENTS ALSO
REGULATE MAST-CELL
DEGRANULATION
-Within 15s after crosslinkage of FcRI,
methylation of various membrane
phospholipids is observed.

9.  Systemic anaphylaxis is a very rapid, life- threatening, severe whole
body allergic reaction. It is caused by re-exposure to a previously
encountered antigen. (Epinephrine is the drug of choice)
 Localized response (or Atopy) is limited to a specific target tissue or
organ, often involving epithelial surfaces at the site of allergen entry.
 The antigen dose, mode of antigen presentation, and genetic
constitution of an animal influence the level of the IgE response induced
by an antigen.
 Type I hypersensitivity is commonly identified and assessed by skin
testing, radioimmunosorbent test (RIST) and radioallergosorbent test
(RAST).
 Immunotherapy with repeated injections of increasing doses of allergens
(hyposensitization) has been known.
 Another form of immunotherapy is the use of humanized monoclonal
anti-IgE.
 Drug therapy for allergies E.g. Antihistamines, Cromolyn sodium,
Epinephrine, etc.

10. Antibody-mediated cytotoxic (type II)
Hypersensitivity
 Type II hypersensitive reactions involve antibody-mediated
destruction of cells.
 Antibody can activate the complement system, creating pores in
the membrane of a foreign cell, or it can mediate cell destruction
by antibody dependent cell-mediated cytotoxicity (ADCC).
 In this process, cytotoxic cells with Fc receptors bind to the Fc
region of antibodies on target cells and promote killing of the
cells.
 Antibody bound to a foreign cell also can serve as an opsonin,
enabling phagocytic cells with Fc or C3b receptors to bind and
phagocytose the antibody-coated cell.

11. Transfusion Reactions Are Type II
Reactions
 An individual possessing one allelic form of a blood-group antigen can recognize other allelic
forms on transfused blood as foreign.
 In some cases, the antibodies have already been induced by natural exposure to similar
antigenic determinants. This is the case with the ABO blood-group antigens.
 Antibodies to the A, B, and O antigens, called isohemagglutinins, are usually of the IgM
class.
 If a type A individual is transfused with blood containing type B cells, isohemagglutinins
bind to the B blood cells and mediate their destruction by means of complement-mediated
lysis.
 Typical symptoms include fever, chills, nausea, clotting within blood vessels, pain in the lower
back, and hemoglobin in the urine.
 Treatment involves prompt termination of the transfusion and maintenance of urine flow with
a diuretic.

13. Hemolytic Disease of the Newborn
Is Caused by Type II Reactions
 Hemolytic disease of the newborn develops when maternal IgG antibodies specific
for fetal blood-group antigens cross the placenta and destroy fetal red blood cells.
 Severe hemolytic disease of the newborn, called erythroblastosis fetalis, most
commonly develops when an Rh+ fetus expresses an Rh antigen on its blood cells
that the Rh– mother does not express.
 The presence of maternal IgG on the surface of fetal red blood cells can be detected
by a Coombs test.
 The mother can also be treated during the pregnancy by plasmapheresis.
 The majority of cases (65%) of hemolytic disease of the newborn have minor
consequences and are caused by ABO blood-group incompatibility between the
mother and fetus.
 Type A or B fetuses carried by type O mothers most commonly develop these
reactions.

15. BIBLIOGRAPHY
 Immunology by Kuby 6th edition.