HYPERSENSITIVITY
BY YUNDZIR FURQAN
HYPERSENSITIVITY
Undesired/ exaggerated immune reaction
produce by normal immune system due to
repeated exposure to antigen
The cause of this reaction is idiopathic but
some has asserted that it may be a genetic
factor
Antibody plays an integral role in forming a
cascade of reaction into producing an
adverse effect on its surrounding tissues,
forcing an unfavourable inflammation
HYPERSENSITIVITY
Divided into 4 types:
TYPE
MEDIATOR
REACTION
IgE
Immediate
IgG, IgM (Cell-Ag)
Cytotoxic
Ag-Ab Complex
Immune complex
T cell
Cell-mediated
Classification of Immunologic Reaction (Gell And
Coombs)
Type 1 (Immediate)
Hypersensitivity
Rapid IgE and mast cell mediated reaction.
Reaction presented can be systemic (systemic
anaphylaxis) or localized (asthma, allergy,
rhinitis).
Occurs in genetically susceptible individuals
upon exposure to antigen (allergen) through
ingestion, inhalation, injection or direct
contact.
Allergen may be of a vast variety of metals,
drugs, dust, pollen etc which normally would
be harmless to the body.
Type 1 (Immediate)
Hypersensitivity
Initial exposure to antigen
Antigen phagocytosed by Antigen
Presenting Cell (APC)
Initial
Exposure T cell differentiates into Th-2
Th2 secreted cytokines (IL-4 and IL-13)
Stimulatio causes plasma cells to make antibody
n of Th2
IgE antibodies is produced to fight
Antibody against allergen
Production
Type 1 (Immediate) Hypersensitivity
IgE binds to Fc
receptor of mast
cell waiting for a
second exposure
Antigen binds to
IgE on the mast
cell and caused a
cross-linkage.
Thus, activating
the mast cell
Mast cell reacts
by degranulating
and releasing its
mediators
Type 1 (Immediate) Hypersensitivity
Early Phase
(minutes after
exposure)
Histamine:
dilate small
blood vessels,
increase
vascular
permeability,
stimulate
contraction of
smooth
muscles
Protease: direct
damage to local
tissues
Late Phase (624 hours)
Cytokines (IL4 and TNF)
release to
promote
inflammation
Chemotaxis
of neutrophils
and
eosinophils to
site of
inflammation
Type 2 (cytotoxic) Hypersensitivity
Result of antibodies direct reaction towards
antigen (self or non-self) on surface of a cell or
tissues
IgG or IgM mediated which activated the
complement system
2 types : antibody-dependent cytotoxicity and
antibody-dependent cell cytotoxicity (ADCC)
Causing either 3 plausible outcome, which is:
1. Inflammation,
2. Opsonization and phagocytosis, or
3. Functional derangements
Type 2 (cytotoxic) Hypersensitivity
Inflammation
Antibody(IgG or IgM) bounds to cell or tissue
activated complement
Products of complement activates macrophage
Once
macrophage
is
activated,
proinflammatory mediators, lysosomal enzymes
and reactive oxygen species are released
Neutrophils are activated in the same time
This causes inflammatory reaction
Type 2 (cytotoxic) Hypersensitivity
Opsonization and Phagocytosis
Plasma cells start producing antibodies errantly
directed against circulating cells such as blood cells
These circulating cells will be opsonized and targeted
for destruction by macrophage (phagocytosed)
Cell-Ag
Recognition
Antibodies directed
against a protein
antigen on the surface
of cell
Fc receptor on
macrophage bind to
antibody that is bound
to antigen of the cell
Phagocytosis
Macrophage
engulf the cell
marked by the
antibody
Type 2 (cytotoxic) Hypersensitivity
Functional derangement
Antibdy may act as an antagonist or competitive
antagonist for variety of receptor
This could be disastrous, particularly if the receptor is
involved in endocrine or neuromuscular signaling
For example, Pernicous Anaemia:
Normal
In the gut, intrinsic
factor bind to B12 in
order to be absorbed
Pernicious Anaemia
Antibody produce react against
intrinsic factor
Neutralizing its ability to bind to
B12
Thus B12 cannot be absorbed
Type 3 (Immune complex)
Hypersensitivity
Occurs when the immune complexes
form is not completely cleared from
the circulation
Mostly arise from intermidiate to
small sized immune complexed
which are deposited in the vascular
walls
This desposition bring about
inflammatory response which then
affects the vascular walls
Type 3 (Immune complex)
Hypersensitivity
Factors which increase
the risk of complexes
causing disease are:
1. Large excess of
antibody for particular
circulating antigen
2. Persistent complexes
3. Fast deposition of
complexes into tissues
Antigen-Antibody Complex
formed in the blood vessel
Type 3 (Immune complex)
Hypersensitivity
Factors which influenced
Ag-Ab Complex deposition:
1. Size: Small and medium
sized, longer-lived
complexes
2. Ab-Ag affinity: higher
affinity complexes,
dissociates longer, thus
having more time to be
lodged in tissue
3. Haemodynamics: high
pressured vascular bed
favours complex
deposition
Type 3 (Immune complex)
Hypersensitivity
Induced inflammatory
response:
1. Ag-Ab Complex activates
the complement system
2. Chemical mediators
released
3. Increased vascular
permeability
4. Chemotaxis of
neutrophils and
monocytes
5. Macrophage proceed to
phagocytosis and
releasing pro-
Type 4 Hypersensitivity
The only hypersensitivity that is not
antibody mediated but is cell
mediated.
It is an excessive immune reaction by
T- cells.
Starts hours after contact with
antigen and often last for days. Thus
the name delayed hypersensitivity.
Divided into 2 types: Delayed and
Cell- mediated hypersensitivity
Type 4 Hypersensitivity
Delayed type hypersensitivity
Activated Th-1 secretes interferon
gamma which stimulates macrophages.
Macrophage produce pro-inflammatory
mediators and increase growth factor
(GF) production.
GF stimulates proliferation and
differentiation of fibroblast.
Resulting in fibrosis and granulomatous
inflammation.
Type 4 Hypersensitivity
Cell-mediated hyspersensitivity
Begin with the activation of CD8+ cytotoxic
T cells.
Cytotoxic T cell release enzyme responsible
for cell apoptosis signaling.
This T cell also release INF-gamma which
influence the recruitment and activation of
macrophages
Chronic reaction will result in severe fibrosis
This reaction plays a major role in organ
transplant.
