HYPERSENSITIVITY

Rahmawati Minhajat
Medical Faculty Hasanuddin University
Adaptive immunity serves the important function of
host defense against microbial infections, but
immune responses are also capable of causing
tissue injury and disease.

Disorders caused by immune responses are called

hypersensitivity diseases.
 T & B cell
lymphocytes
Normally function
Host defense againts Microbial infection
without serious injury of host tissue

Adaptive Immunity

Tissue injury/
Hypersensitivity
If respons are inadequatelly controlled or
disease
inapropriatetely targeted to host tissue

Autoimmunity

Reaction against microba

Reaction against enviromental antigens

Autoimmunity :
Failure of the normal mechanisms of self-tolerance results in
reactions against one’s own cells and tissues that are called
autoimmunity

The diseases caused by autoimmunity are referred to as

autoimmune diseases
Reactions against microbes.

Immune responses against microbial antigens may cause

disease if the reactions are excessive or the microbes are
unusually persistent.

T cell responses against persistent microbes may give rise to

severe inflammation, sometimes with the formation of
granulomas; this is the cause of tissue injury in tuberculosis
and some other chronic infections.
The problem in hypersensitivity diseases is that the response is
triggered and maintained inappropriately. Because the stimuli for
these abnormal immune responses are difficult or impossible to
eliminate (e.g., self antigens, commensal microbes, and
environmental antigens) and the immune system has many built-
in positive feedback loops (amplification mechanisms)

 Once a pathologic immune response starts, it is difficult to

control or to terminate it. Therefore, these hypersensitivity
diseases tend to be chronic and progressive.
Hypersensitivity disease

Type of immune response

Effector mechanism responsible for cell/tissue injury

Immediate Hypresensitivity
(Type I Hypresensitivity)

Caused by IgE and mast cells, the most

prevalent type of hypersensitivity disease

the prototypes of diseases caused by activation of the Th2 subset of helper

T cells, in which the T cells stimulate the production of IgE antibodies and
inflammation.
Figure 19-1 Sequence
of events in
immediate
hypersensitivity
reactions. Immediate
hypersensitivity
diseases are initiated
by the introduction of
an allergen, which
stimulates TH2
reactions and IgE
production. IgE
sensitizes mast cells
by binding to
FcεRI, and
subsequent exposure
to the allergen
activates the mast
cells to secrete the
mediators that are
responsible for the
pathologic reactions
of immediate
hypersensitivity.

Downloaded from: StudentConsult (on 20

November 2007 07:29 AM)

There is strong genetic predisposition for the development of immediate hypersensitiivity

 Antibody mediated Hypresensitivity
(Type II Hypresensitivity)

Other then IgE (IgG, IgM) can cause

tissue injury by:
 Activating complement system
 Recruiting inflammatory cells
 Interfering with normal cellular function
These Antibody are spesific for antigens of particular cells or extracellular matrix
and are found either attached to these cells or tissue or as unbound antibody
in circulation

The diseases are often not systemic

 Antibody specifically affect the cell or tissues where the antigens are present
 Antibodies opsonize cells and may activate complement,
generating complement products that also opsonize
cells, leading to phagocytosis of the cells through
phagocyte Fc receptors or C3 receptors
 principal mechanism of cell destruction
in AHA, ITP & hemolysis in transfusion
reactions

Antibodies recruit leukocytes by binding to Fc

receptors or by activating complement and
thereby releasing byproducts that are chemotactic
for leukocytes.

The mechanism of injury in glomerulonephritis

hormones or neurotransmitters may stimulate the

activity of the receptors even in the absence of the
hormone (left panel) or may inhibit binding of the
neurotransmitter to its receptor (right panel)

Antibody-mediated functional abnormalities are

the cause of Graves’ disease and myasthenia gravis.
 Immune Complex mediated
(Type III Hypresensitivity)

Other Antibody may form immune complexes circulation

Deposite of immune complexes in tissuees, particularly in blood vessels

Tissue Injury

Immune Complex mediated diseases tend to be systemic (multiple tissues/organs), although

some are particularly susceptible, such as kidneys and joints

 The patologic feature of diseases cause by immune complexes the site of

immune complex deposition and are not determined by the cellular source of the antigen
T-Cell mediated
(Type IV Hypresensitivity)
T lymphocytes injure tissues either by triggering inflammation
or by directly killing target cells

Tissue injury may be due to T lymphocytes that induce inflammation or

directly kill target cells; such conditions are called type IV
hypersensitivity disorders.

Many hypersensitivity diseases are caused by the activation of TH1 or

TH17 subsets of helper T cells, which secrete cytokines that promote
inflammation, and the tissue injury is caused by the recruited
leukocytes, mainly neutrophils and macrophages.

Helper T cells also stimulate the production of

antibodies that damage tissues and induce inflammation.
CTLs may also contribute to tissue injury in some
diseases.
DISEASES CAUSED BY ANTIBODIES
Antibody-mediated diseases are produced either :

 by antibody that bind to antigens on particular cells or in

extracellular tissues

 by antigen-antibody complexes that form in the

circulation and are deposited in vessel walls
FIGURE 18–1 Types of antibody-mediated diseases. Antibodies may bind specifically to tissue antigens (A), or they may be deposited as immune
complexes that are formed in the circulation (B). In both cases, the deposited antibodies induce inflammation, leading to tissue injury.