Download Type III Hypersensitivity - Dow University of Health Sciences

Allergy and Hypersensitivity
Zahaib Quadri MD
Department of physiology
Dow medical college , DUHS
Important definitions
Hypersensitivity reactions
Are harmful antigen-specific immune responses ,
occur when an individual who has been primed by an
innocuous antigen subsequently encounters the same
antigen , produce tissue injury and dysfuntion.
Allergen:
The antigens that give rise to immediate
hypersensitivity
Atopy：
The genetic predisposition to synthesize inappropriate
levels of IgE specific for external allergens
Types of Hypersensitivity
1.
2.
3.
4.
5.
Type I
Type II
Type III
Type IV
Type V
Hypersensitivity
Hypersensitivity
Hypersensitivity
Hypersensitivity
Hypersensitivity
Type I Hypersensitivity
(Anaphylactic)
Reactions/Allergy
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Occur within minutes of exposure to antigen
Antigens combine with IgE antibodies
IgE binds to mast cells and basophils, causing
them to undergo degranulation and release
several mediators:
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Histamine:
Prostaglandins:
Leukotrienes:
Anaphylactic shock: Massive drop in blood pressure.
Can be fatal in minutes.
Type I Hypersensitivity
(Anaphylactic)
Reactions/Allergy
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Exposure to an allergen activates B cells to
form IgE secreting plasma cells
Secreted IgE molecules bind to Fce
receptors on mast cells
A subsequent exposure to the allergen
results in crosslinking of the bound IgE
which triggers
the release of various
compounds
Mast Cells and the Allergic Response
Mast Cells and the Allergic Response
Examples of type 1
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Atopy
Anaphylaxis
Asthma
Type II Hypersensitivity (Cytotoxic)
Reactions/antibody-dependent
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Involve activation of complement by IgG or IgM binding
to an antigenic cell.
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Antigenic cell is lysed
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Transfusion reactions:
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ABO Blood group system: Type O is universal donor.
Incompatible donor cells are lysed as they enter
bloodstream.
Rh Blood Group System: 85% of population is Rh positive.
Those who are Rh negative can be sensitized to destroy Rh
positive blood cells.
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Hemolytic disease of newborn: Fetal cells are destroyed by
maternal anti-Rh antibodies that cross the placenta.
Hemolytic disease of the newborn is caused by type
II hypersensitivity reactions
When an Rh- mother carries an Rh+ fetus
Examples of type II
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Autoimmune hemolytic anemia
Thrombocytopenia
Erythroblastosis fetalis
Goodpasture's syndrome
Type III Hypersensitivity
(Immune Complex) Reactions
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Involve reactions against soluble antigens
circulating in serum.
Usually involve IgA antibodies.
Antibody-Antigen immune complexes are
deposited in organs, activate complement, and
cause inflammatory damage.
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Glomerulonephritis: Inflammatory kidney damage.
Occurs with slightly high antigen-antibody
ratio is present.
Immune Complex Mediated
Hypersensitivity
Type III Hypersensitivity
Insect bites—if an individual has been previously
sensitized and has circulating antibodies, the initial
reaction will be type I at the site of the bite and 48 hours later a type III reaction might develop
Arthus reaction: deposits of immune complexes
draw neutrophils, leading to an accumulation of
fluid (edema) and RBC’s (erythema)
Severity of the reaction varies from mild swelling
and redness to tissue necrosis
Type III reactions can also be generalized (as
opposed to localized to a specific tissue)
Large amounts of circulating antigen can form
immune complexes which are not easily cleared by
phagocytic cells
Example: “serum sickness” following the injection
of an anti-toxin
Examples of type III
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Serum sickness
Arthus reaction
Systemic lupus erythematosus (SLE)
Type IV (Cell-Mediated)
Reactions/Delayed-type
hypersensitivity/antibody-independent
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Involve reactions by TD memory cells.
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Reactions are delayed by one or more days (delayed type
hypersensitivity).
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First contact sensitizes person.
Subsequent contacts elicit a reaction.
Delay is due to migration of macrophages and T cells to site
of foreign antigens.
Reactions are frequently displayed on the skin: itching,
redness, swelling, pain.
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Tuberculosis skin test
Poison ivy
Metals
Latex in gloves and condoms (3% of health care workers)
Anaphylactic shock may occur.
Type IV Mechanism
APC resident in the skin
process antigen and
migrate to regional lymph
nodes where they
activate T cells
Sensitised T cells migrate
back to the the skin
where they produce
cytokines which attract
macrophages which
cause tissue damage
Type IV or delayed type hypersensitivity – cell
mediated
Many contact dermatitis reactions are
mediated by TH1 cells
The molecules (such as pentadecacatechol)
complex with skin proteins and this complex
is then internalized by antigen presenting
cells, processed and presented with Class II
MHC molecules which are recognized by
appropriate TH1 cells and which are now
“sensitized” to pentadecacatechol
Subsequent exposure to
pentadecacatechol will
activate these TH1 cells and
induce cytokine production;
approximately 48 to 72
hours after this second
exposure macrophages
accumulate at the site and
release lytic enzymes that
cause the redness and
pustule formation of poison
oak exposure
Examples of Type IV
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Contact dermatitis
Mantoux test
Chronic transplant rejection
Multiple sclerosis
Type V Hypersensitivity / Auto
immune
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This is an additional type that is sometimes
(often in Britain) used as a distinction from Type
2
Instead of binding to cell surface components,
the antibodies recognize and bind to the cell
surface receptors , which either prevents the
intended ligand binding with the receptor or
mimics the effects of the ligand, thus impairing
cell signaling
Examples of Type V
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Grave's disease
Myasthenia Gravis
Hashimoto's thyroiditis
Systemic lupus erythematosus
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