Transcript Hypersensitivity Reactions

Diseases of
Immunity (1)
Hypersensitivity
Reactions
Normally, a balanced system optimizes
the eradication of infecting organisms
without serious injury to host tissues.
 However, immune responses may be
inadequately controlled or inappropriately
targeted to host tissues, and in these
situations, the normally beneficial
response will cause of disease.
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Hypersensitivity
Reactions
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The term hypersensitivity is used to describe immune
responses which are damaging rather than helpful to the
host.
WHY?
This term originated from the idea that individuals who
mount immune responses against an antigen are said to
be "sensitized" to that antigen, and therefore, pathologic
or excessive reactions are manifestations of
"hypersensitivity."
CAUSES OF HYPERSENSITIVITY
REACTIONS
Autoimmunity.
 Reactions against microbes.
 Reactions against environmental antigens.
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Hypersensitivity Reactions
Classification:
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Type I “Allergy & anaphylaxis”
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Type II “Antibody dependant”
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Type III “Immune complex - mediated”
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Type IV “Cell-mediated (delayed type)”
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N.B: First 3 types are antibody-mediated injury &
the last type is cell-mediated injury
Type
I
Hypersensitivity
Reaction
ALLERGIC REACTION
 ANAPHYLACTIC REACTION
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Type I Hypersensitivity
Definition :
 It is rapidly developing immunologic reaction
occurring within minutes after the interaction
of an antigen (allergen) with IgE antibodies
bound to surface of mast cells or basophils in
individuals previously sensitized to the antigen
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Type I Hypersensitivity
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Antigen is usually exogenous , environmental
and is called allergen
Allergens may be introduced by inhalation,
ingestion, touch, or by intravenous injection.
The reaction is mediated by IgE produced by
previously sensitized B lymphocytes..
IgE binds to the main effector cells ; the mast
cell (in tissues) or basophils (in blood).
The initiated reaction passes through 2 phases
an early one and a late one.
Type I Hypersensitivity:
Phases
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As Seen in the localized reactions
Initial response:
 Characterized
by;
 Vasodilatation,
 Vascular leakage, and
 Smooth muscle spasm
 Increased glandular secretions
 These changes become evident within 5 to 30 minutes
after exposure to an allergen and subside in 60 minute.
 It is mainly mediated by histamine released by MAST
CELLS.
Type I Hypersensitivity:
Phases
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Late-phase reaction:
 Develop
in 2 to 8 hours later without additional
exposure to antigen and lasts for several days.
 Characterized by intense infiltration of tissues with
eosinophils, neutrophils, basophils, monocytes, and
CD4+ T cells, and tissue destruction.
 Occurs under effect of esinophils and neutrophils
chemotactic factors released by mast cells.
Type I Hypersensitivity:
Clinical Manifestations
 The
resultant reaction can occur as
a systemic disorder or as a local
reaction depending on the route of
entry of allergen
Type I Hypersensitivity
clinical presentation
Local reactions:
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Antigen is confined to a particular site
Skin contact  Localized cutaneous swellings (urticaria,
hives) and eczema,
Ingestion  Allergic gastroenteritis (food allergy) 
diarrhoea
Inhalation  bronchospasm  allergic rhinitis, and
bronchial asthma .
Type I Hypersensitivity:
Clinical Manifestations
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Systemic Anaphylaxis:
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This usually follows an intravenous injection of an antigen to which the host
has already became sensitized for.
 systemic vasodilatation  “anaphylactic shock” is produced and even death
within minutes
Example: IV administration of Penicillin, Bee venom.
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NOTE: The immune response in the late-phase inflammatory reaction, plays
an important protective role in parasitic infections.
Type
II
Hypersensitivity
reaction
Type II Hypersensitivity
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Antibody-mediated diseases;
Target antigens are present on the surface of cells or other
tissue components
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The antigens may be intrinsic to the cell membrane, or they
may take the form of an exogenous antigen, such as a drug
metabolite, adsorbed on the cell surface
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The antibodies unite with the antigens MAINLY in the
bloodstream,
This union sets off the complement system, and destruction of
the local tissue cells ensues.
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Type II Hypersensitivity
Mechanism
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A, Opsonization
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B, Inflammation
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C, Antireceptor antibodies
Type II Hypersensitivity
Mechanism
 Clinical
examples;
Incompatible transfusion reactions (mismatched blood
transfusion reaction)
 Erythroblastosis fetalis “Rhesus antigen
incompatibility”
 Autoimmune haemolytic anemia, or thrombocytopenia
 Certain drug reactions “penicillin  hemolysis”
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Type
III
Hypersensitivity
reaction
Type III Hypersensitivity
Immune Complex - Mediated
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Type III hypersensitivity is mediated by the deposition of
antigen-antibody complexes formed in blood vessels.
The antigens may be
 Exogenous antigens, such as bacteria, or viruses
 Endogenous antigens, such as DNA.
Immune complexes deposit in blood vessels in various tissue
beds ,they have the ability to fix complement and trigger the
subsequent injurious inflammatory reaction (either systemic or
Localized )
Systemic Immune Complex Disease
Mechanism
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Favoured sites of immune complex deposition are;
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Renal glomeruli,
Joints,
Skin,
Heart,
Serosal surfaces,
Small blood vessels
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Type III Hypersensitivity
Examples
Autoimmune diseases as:
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Systemic lupus erythematosis
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Scleroderma
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Sjogren syndrome
Type
IV
Hypersensitivity
reaction
Type IV Hypersensitivity
(Cell Mediated)
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Two types of T-cell reactions are capable of
causing tissue injury and disease:
(1) delayed-type hypersensitivity (DTH), initiated
by TH1-type CD4+ T cells
(2) direct cell cytotoxicity, mediated by cytotoxic
CD8+ T cells that are responsible for tissue
damage.
1-Delayed-Type
Hypersensitivity
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It is responsible for mediating immune reaction in case
of;
 Defence against variety of intracellular persistent or
non-degradable antigens, such as tubercle bacilli.
 pathogens, including mycobacteria, fungi, and certain
parasites,
 It may also be involved in transplant rejection.
 Tumour immunity
NOTE:
In AIDS  loss of CD4+ T lymphocytes  increased
susceptibility for developing TB & fungal infection.
Delayed-Type Hypersensitivity
Sequence of Cellular Events
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On subsequent exposure of an individual previously sensitised, the memory
TH1 cells interact with the antigen on the surface of APC .
APC become activated, they produce IL-12 that activate CD+4 cells.
In turn CD+4 cells will secrete:
 IFN-γ that activates macrophages to produce substances that
cause tissue damage and promote fibrosis,
 TNF promotes inflammation.
When macrophages become activated they transform into epithelioid cells
And they occasionally fuse  multinucleated giant cells.
Delayed-Type Hypersensitivity
Morphology
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DTH is characterized histologically by the
formation of Granuloma (a specific form
of chronic inflammation)
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It refers to microscopic aggregate of
epithelioid cells, usually surrounded by a
collar of lymphocytes with or without the
formation of multinucleated giant cells.
Example for DTH
Tuberculin reaction
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A classic example of DTH elicited by antigen challenge in an individual
already sensitized to the tubercle bacillus by a previous infection.
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Between 8 and 12 hours after intracutaneous injection of tuberculin
(a protein extract of the tubercle bacillus), a local area of erythema and
induration appears, reaching a peak (typically 1-2 cm in diameter) in 24 to 72
hours (hence the adjective, delayed) and thereafter slowly subsiding.
2- Direct cell cytotoxicity
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In this variant of type IV hypersensitivity, sensitized CD8+
T cells kill antigen-bearing target cells
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These effector cells are called cytotoxic T lymphocytes
(CTLs)
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They mediate their action through class I MHC molecule,
where they directly lyse infected cells or stimulates their
apoptosis.
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It plays an important role in graft rejection, resistance to
virus infections, and possibly tumor immunity