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MEDICAL VETERINARY PROGRAME

UB
DR. SRI MURWANI, DRH, MP
HYPERSENSITIVITY DISEASE

 Disorder caused by immune responses

 Immune responses may be pathologic because of
several different abnormalities
1. Autoimmunity. Failure of the normal mechanisms of
self tolerance, results in reactions against one’s own
cell or tissue autoimmune diseases
2. Reactions against microbes.
Excessive immune responses Ags & Abs bind
immune complexes deposit in tissue
inflammation
T cell responses against persistent microbes
severe inflammation, sometimes formation of
granulomas
3. Reaction against environmental Ags
Most healthy individual do not react common
environmental substances
20% of the population is abnormally responsive
caused immediate or delayed-type hypersensitivity
(DTH)
In all these conditions, the mechanisms of tissue
injury are the same as those that normally function
to eliminate infectious pathogens: antibodies, T
lymphocytes, & various other effectors cells

Hypersensitive triggered & maintained by

inappropriate RI

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TYPE OF
HYPERSENSITIVITY

 Immediate hypersensitivity: Hypersensitivity type I

 Antibody mediated hypersensitivity:
Hypersensitivity type II
 Immune complex mediated hypersensitivity:
Hypersensitivity type III
 T cell mediated hypersensitivity: Hypersensitivity
type IV

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IMMEDIATE
HYPERSENSITIVITY
IMMEDIATE
HYPERSENSITIVITY
Environmental Ags differentiation & proliferation of
CD4+ TH2 IgM switching antibody IgE
bind Fc receptors on mast cell & basophils (sensitized)

Second exposure:
Cross linked between mast cell/basophile-IgE-Ags mast
cell/basophile are activated degranulation release
rapidly variety mediators (eg. histamine by mast cell,
cytokines by CD4+TH2) collectively cause
vascular permeability, vasodilatation, bronchial & visceral
smooth muscle contraction (within minutes)

Allergy or atopy
GENERAL FEATURES OF IMMEDIATE
HYPERSENSITIVITY REACTIONS
 Common environmental Ags (potentially
allergenic substances=allergen) atopic
individuals (susceptible genes) develop
strong TH2 responses & production of IgE
 Binding of IgE to receptors of mast cell
Re-exposure Ags degranulation of mast cell
releasing mediators from the mast cell
pathologic reaction
Binding of IgE to receptors of mast cell is also
called sensitization because IgE-coated mast
cell are ready to be activated on Ags encounter
Figure 19.1a The mechanism of anaphylaxis.

Mast cell or
basophil
Granule

Histamine and
other mediators
IgE
Antigen

IgE antibodies, produced in response to an antigen,

coat mast cells and basophils. When an antigen bridges
the gap between two adjacent antibody molecules of the
same specificity, the cell undergoes degranulation and
releases histamine and other mediators.
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 · Histamine
· PAF (platelet activating factor)
Vasodilation and increased · Leukotriene C4, D4 and E4
permeability · Prostaglandin D2
· Neutral proteases

· Histamine
· PAF
Smooth muscle spasm · Leukotriene C4, D4 and E4
· Prostaglandin

· Cytokines (e.g. chemokines and TNF)

· Leukotriene B4
Leukocyte extravasation · Chemotactic factors for neutrophils and
eosinophils

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 Mast cell are present in all connective tissue
Under all epithelia

Site of Immediate Hypersensitivity/IH reaction

 Some IH reactions triggered by nonimmunologic
stimuli (exercise, cold exposure) --- repeat
exposure

Mast degranulation
Release of mediators
Without Ags exposure or IgE production

Nonatopic reactions
 Immediate Hypersensitivity reactions are
manifested as:
 Skin and mucosal allergies
 Food allergies
 Asthma
 Systemic anaphylaxis
 The most extreme systemic form anaphylaxis
Mast cell-derived mediators restrict airways
asphyxiation & cardiovascular collapse
death
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ANTIBODY MEDIATED
HYPERSENSITIVITY
 Antibody (other than IgE) C activation (C3a,
C5a) & Fc receptor recruiting inflammatory
cells interfering normal cellular functions
 Ags present in particular cell or extracellular
matrix
 Foreign ags:
 mimicry process
 Ags present or bound to cell or tissue
Opzonization & phagocytosis
of cells (ADCC)

Antigen
Antibodies directly Antibodies

Opsonize C activation
opsonize
cells/tissue (matrix) lysis of cells
Where the antigens are present

phagocytosis

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Complement- and Fc receptor-mediated
inflammation
Antigen (absorbed onto the cells)

Antibodies

Recognized by phagocytes

Complement activation lysis of cells

Recruitment inflammation cells (neutrophil, macrophage)

Activated leucocytes

Acute inflammation & tissue injury

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Abnormal physiologic responses
without cell/tissue injury
Antigen (self / foreign)

Antibodies

Bind to normal cellular receptors or other protein

Interfere these function

Alternation organ/ tissue function

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IMMUNE COMPLEX MEDIATED

HYPERSENSITIVITY
 Immune complexes in circulation deposit in
tissue (particularly: blood vessel) C activation
inflammation (bind to the Fc) product of
activated inflammatory cell tissue injury

 Ags-Abs complexes are produce during normal

immune responses, but they cause disease only
when produced in excessive amounts (not
efficiently cleared)
Ags

Abs

Complex Ags-Abs/immune complexes

Deposit in C3a, C5a

tissue

MAC Inflammation

Enzymes,
Tissue injury Reactive Oxygen
Species
Figure 19.6 Immune complex–mediated hypersensitivity.

Basement
membrane of
blood vessel
Immune complexes
are deposited in wall
Ag of blood vessel.
Neutrophils

Presence of immune
complexes activates Enzymes released
complement and from neutrophils
attracts inflammatory cause damage to
cells such as endothelial cells
neutrophils. of basement
Endothelial membrane.
cell
Immune –Complex
Glomerulonephritis
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MECHANISM
Step 1
Large quantities of
soluble antigen-
antibody complexes
form in the blood and
are not completely
removed by
macrophages.
Step 2

These antigen-
antibody complexes
lodge in the
capillaries between
the endothelial cells
and the basement
membrane.
Step 3

These antigen-
antibody complexes
activate the classical
complement
pathway leading to
vasodilatation.
Step 4

The complement proteins and antigen-antibody complexes

attract leukocytes to the area.
Step 5

The leukocytes
discharge their
killing agents and
promote massive
inflammation. This
can lead to tissue
death and
hemorrhage.
size of the immune complex, time, and
place determine if this reaction will
occur or not
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T CELL MEDIATED
HYPERSENSITIVITY
 T cell injury tissue triggering by
- Delayed Type Hypersensitivity (DTH)
- T cell mediated cytolysis
 Inflammatory reaction associated T cell-mediated
is typically chronic inflammation
A). DTH

DTH reactions are elicited by CD4+ cell-TH1

CD4+ IFN- macrophage activation
lysosomal enzymes, reactive oxygen intermediate
(ROI), reactive oxygen species (ROS), nitric oxide
(NO), proinflammatory cytokins (TNF-, IL-1β)
tissue injury
Production of growth factor tissue fibrosis
B). T cell Mediated Cytolysis

TMC reactions are elicited by CD8+ cell (CTL)

CTL responses to intracellular m.o. infection can
lead to tissue injury by killing infected cell (CPE
viruses & Non CPE viruses) harmfull to the
host
A
Self Ags or Foreign Ags

CD4+ TH1 CD8+

IFN-

Macrophage
activation

TNF-α

Enzymes, Free
Radical: ROI, Tissue injury
ROS, NO, etc
B
Intracellular m.o

MHC-I

CD8+/ CTL

Killed target
cells

Tissue injury

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Type of Reaction Time After Exposure for
Clinical Symptoms
Type I (anaphylactic) <30 min
Type II (cytotoxic) 5–12 hours
Type III (immune complex) 3–8 hours
Type IV (delayed cell-
≥1 day
mediated)

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