TYPE

MEDIATOR

REACTION

IgE

Immediate

IgG, IgM
(Cell-Ag)

Cytotoxic

Ag-Ab
Complex

Immune complex

T cell

Cell-mediated

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
Divided into 4 types:
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.
Initial Exposure
Initial exposure to antigen
Antigen phagocytosed by Antigen Presenting Cell (APC)
T cell differentiates into Th-2
Stimulation of Th2
Th2 secreted cytokines (IL-4 and IL-13) causes plasma cells
to make antibody
Antibody Production
IgE antibodies is produced to fight against allergen
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

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 (6-24 hours)
Cytokines (IL-4 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 nonself) on surface of a cell or tissues
IgG or IgM mediated which activated the complement system
2 types : antibody-dependent cytotoxicity and antibodydependent cell cytotoxicity (ADCC)
Causing either 3 plausible outcome, which is:
1. Inflammation,
2. Opsonization and phagocytosis, or
3. Functional derangements

Antibody(IgG or IgM) bounds to cell or tissue activated

complement
Products of complement activates macrophage
Once macrophage is activated, pro-inflammatory mediators,
lysosomal enzymes and reactive oxygen species are released
Neutrophils are activated in the same time
This causes inflammatory reaction
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)

Opsonization and Phagocytosis

Cell-Ag
Antibodies directed against a protein antigen on the
surface of cell
Recognition
Fc receptor on macrophage bind to antibody that is bound
to antigen of the cell

 Phagocytosis
Macrophage engulf the cell marked by the antibody

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
But for 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
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
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

1.
2.
3.
4.

Induced inflammatory response:

Ag-Ab Complex activates the complement system
Chemical mediators released
Increased vascular permeability
Chemotaxis of neutrophils and monocytes

5. Macrophage proceed to phagocytosis and releasing proinflammatory mediators which degrade basement membrane
and extracellular matrix of vascular wall
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
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.
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.