Shanes

Faculty, DOBT, JNC,

Bangalore - 95

Immune reactions offer protection against

infectious agents, their metabolites and other
harmful substances in a healthy individual.
But in some cases, immune response instead
of providing protection, may lead to
deleterious reactions inducing extensive
damage or even death to the host. Such
injurious reactions are commonly termed as
hypersensitivity.

Definition of hypersensitivity
reactions
Hypersensitivity reactions is a state of altered

reactivity in which body reacts with an

exaggerated immune response to what is
perceived as a foreign substance (or antigen).
Hypersensitivity reaction is found in immunologically
sensitized individual after subsequent contact
with same antigen resulting in exaggerated or lethal
process of immunity.
This can be localized to one area or generalized and
may include: rash, itching, hives, swelling, difficulty
breathing, and/or low blood pressure.
Hypersensitivity is also termed as allergic reactions.

 The concept of hypersensitivity was introduced by two

French scientists Paul Portier and Charles Richet.

They found that localized reactions of bathers in
Mediterranean to stings to Portuguese man of war
(jelly fish) was due to toxins.
Antigens causing hypersensitivity reactions are referred
as allergens.
The initial contact with antigen leading to synthesize of B
or T lymphocytes in a sensitized individual is known as
sensitizing or priming dose.
The second contact with the same specific antigen
resulting in hypersensitivity reactions are called as
shocking dose.

Types of hypersensitivity reactions

On the basis of time taken to develop the

effector molecules during the course of reactions.
Immediate hypersensitivity reactions: appears and
recedes rapidly, induced by antigens or haptens
through any route, antibody mediated reactions.
Ex: anaphylaxis, atopy, hemolytic diseases, autoimmune
diseases, Arthus reactions and Serum sickness.

Delayed hypersensitivity reactions: appears slowly

and lasts longer, induced by infections or injection of
antigen or hapten intradermally or by skin contact,
cell mediated reactions etc.
Ex: Contact dermatitis,Tuberculin reactions.

Gell and Coombs classification of

hypersensitivity reactions
P. G. H. Gell and R. R. A. Coombs revised the
classfication of hypersensitivity reactions based on
mechanisms of pathogeneiss into five types:
1. Type I (IgE mediated or anaphylactic
hypersensitivity reactions.
2. Type II (Cytotoxic) hypersensitivity
3. Type III (immune complex mediated )
hypersensitivity reactions.
4. Type IV (Delayed or cell mediated)
hypersensitivity
5. Type V (Stimulatory) hypersensitivity.

This reactions occur when an antigen (allergen)

attaches with IgE on the surface receptors of
mast cells and basophiles.
A subsequent exposure to the same antigen
(allergens) cross link to the cell bound IgE and
initiate the release of various pharmacologically
active mediators leading to clinical
manifestations.
This reactions takes usually within 15 20
minutes, so it is a immediate hypersensitivity
reactions.

Activation of mast cells in

type I hypersensitivity and
release of their mediators.
ECF, eosinophil chemotactic
factor; NCF, neutrophil
chemotactic factor; PAF,
platelet-activating factor.
(From Robbins Basic
Pathology ,2003

Slide 7.9

http://www.youtube.com/watch?v=UfLAwO4
_NTQ&feature=related

http://www.theimmunology.com/animations/IgE%20Mediated%20(Type%2
0I)%20Hypersensitivity.htm

Allergy reactions:
http://www.youtube.com/watch?v=y3bOgdvV-_M

for hypersensitivity reactions 2

http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapter33/animation_quiz_5.html

for hypersensivity reactions 3

http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapter33/animation_quiz_3.html

Histamine: occurs in granules of mast cells and basophils. Release

of histamine results in vasodilation increased capillary
permeability and smooth muscle contraction.
Ex: Allergic rhinitis (hay fever), Urticaria and Angioderma.

Leukotrienes: these are slow reacting substances do not occur in

preformed state, but produced during reaction. Shows increased
vascular permeability and smooth muscle contraction.
Ex: Asthama.

Eosinophil chemotactic factor (ECF): this is tetra peptide that

exists in preformed state in mast cell granulation, it attracts
eosinophils play prominent role in immediate allergic reactions.
Prostaglandins and thromboxanes: these are closely related to
leukotrienes. Helps in aggregation of platelets.
Serotonin: found in mast cells and platelets, released during
anaphylaxis. Increased vascular permeability, capillary dilation
and smooth muscle contraction are caused by serotonin.

a nonspecific exaggerated physiologic

response which involves a vascular response
and a cellular response by phagocytic cells
to infection/injury
Mildest may be only edema. Reaction is
triggered by mast cells, basophils. If
inflammatory cells are present, many are
eosinophils

OPSONIZATION

- coating of Antibody and/or complement to

facilitate phagocytosis
ex. of opsonins - C3b, C4b, C5b, fibronectin,
leukotrienes, immunoglobulins (i.e. IgG)
engulfment - achieved through amoeboid motion. Final structure
vacuole or phagosome.

degranulation and digestion

is called

Animation of Phagocytosis by
Enhanced Attachment (Opsonization)

 Urticaria and angioneurotic edema

Asthma
Hay fever
Insect allergy: serious or fatal
anaphylaxis may follow. Edema of
larynx, with airway obstruction may
occur.

Cytolytic or cytotoxic reactions

(1) Mechanism:

Complement-dependent reactions
Transfusion reactions
Erythroblastosis fetal
Autoimmune hemolytic anemia
Certain drug reactions


Antibody-dependent
cell-mediated
cytotoxicit (ADCC).
May be relevant to:
Graft rejection
The destruction of targets too large to be
phagocytosed, such as parasites or tumor
cells.

Antibody-mediated cellular dysfunction

Myasthenia gravis: muscle weakness

Graves disease: hyperthyroidism

Schematic illustration of three different mechanisms of antibodymediated injury in type hypersensitivity. A, Complement-dependent
reactions that lead to lysis of cells or render them susceptible to
phagocytosis.
Slide 7.10
(From

Robbins Basic Pathology ,2003

Antibody-dependent cell-mediated cytotoxicity (ADCC). IgG-coated target

cells are killed by cells that bear Fc receptors for IgG (e.g., NK cells,
macrophages). . (From Robbins Basic Pathology ,2003
Slide 7.11

Antireceptor antibodies disturb the normal function of receptors. In this

example, acetylcholine receptor antibodies impair neuromuscular
transmission in myasthenia gravis. (From Robbins Basic Pathology ,2003
Slide 7.12

(1) Reaction types

Arthus reaction
serum sickness
Collagen diseases

 Acute glomerulonephritis

Systemic
lupus
erythematosus
Necrotizing angiitides
Rheumatoid arthritis
Progressive systemic sclerosis
Dermatomyositis etc.

Schematic illustration of the three sequential phases in the

induction of systemic type (immune complex) hypersensitivity.
(From Robbins Basic Pathology ,2003
Slide 7.13

Schematic representation of the pathogenesis of immune complexmediated tissue injury. The morphologic consequences are depicted as
boxed areas. . (From Robbins Basic Pathology ,2003
Slide 7.14

Immune complex vasculitis. The necrotic vessel wall is replaced by smudgy, pink
fibrinoid (Dr. Trace Worrell)
(From Robbins Basic Pathology ,2003
Slide 7.15

Delayed hypersensitivity reaction

(1) Tissue reaction: Consist of
parenchymal destruction associated
with perivascular lymphocytic and
macrophage reaction.

 Chronic active hepatitis

Viral exanthem
Contact dermatitis
Graft rejection
Inflammatory bowel disease.

Delayed hypersensitivity in the skin. Immunoperoxidase staining reveals a

predominantly perivascular cellular infiltrate that marks positively with anti-CD4
antibodies. ( Dr. Louis Picker) .
(From Robbins Basic Pathology ,2003
Slide 7.16

A section of a lymph node shows several granulomas, each made up of an

aggregate of epithelioid cells and surrounded by lymphocytes. The granuloma in
the center shows several multinucleate giant cells. ( Dr. Trace Worrell)
(From Robbins Basic Pathology ,2003
Slide 7.17

Schematic illustration of the

events that give rise to the
formation of granuloma in type
hypersensitivity reactions. Note
the role played by T cell-derived
cytokines. . (From Robbins Basic
Pathology ,2003

Slide 7.18

Advise of the Day

To Be Continued