Transcript Hypersensitivity

Hypersensitivity
Department of Microbiology
Important terms
• Hypersensitivity reactions are exaggerated antigen-specific immune
responses which is harmful to the host.
• 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: As per Coomb and Gel Classification
hypersensitivity is of four types (Type I, Type II, Type III and Type
IV)
Type I Hypersensitivity
– Mediated by IgE antibodies.
– Also known as “immediate
hypersensitivity
"or
“Allergic response”.
– Antigens that induce type I
hypersensitivity are also
termed as “Allergens”.
Type I Hypersensitivity
– The IgE antibodies produced
against Allergens remain bound
to Mast cells.
– Upon exposure to specific
Allergens IgE antibodies induce
degranulation of Mast cells.
– This leads to release of
inflammatory mediators like
Histamine,
Serotonin,
Prostaglandins etc.
– Some common Allergens are
Pollen, Dust etc.
– Example: P-K reaction
Type I Hypersensitivity
Type I Hypersensitivity
Histamine:
Dilate blood vessel
Increase vascular
permeability
2. Leukotrienes:
Bronchial smooth muscles
contract
Asthmas
3. Prostaglandin:
High concentration of PGE
Inhibit the secretion of
histamine
low concentration of PGE
promote the release of
histamine
4. Platelet activating factor
(PAF) :
Agglutinate and activate
platelets to release
histamine
5. Eosinophil chemotactic
factor（ECF-A）:
6. Bradykinin :
Vasodilator function
Type II Hypersensitivity
• Type II Hypersensitivity is mediated by antibodies that are produced
against the antigenic determinants present on cell surface.
• As the antigenic determinants are present on cell surface, thus type II
reaction is manifested in the form of massive cell destruction.
• The target cells are lysed by:
• activation of Complement cascade by the antibody molecules
bound on the cell surface.
• antibody dependent cell mediated cytotoxicity (ADCC).
• Transfusion reactions and Hemolytic Disease of the Newborn are
examples of type II reaction.
2. Mechanism of Type II hypersentivity
1. Surface antigen on target cells
Target cells: Normal tissue cell, changed or modified self tissue cells
Antigen : Blood group antigen, Common antigen, Drug antigen,
Self-antigen modified by physical factors or infection
Antigen-antibody complex
2. Antibody, complement and modified self-cell
Activate complement
Opsonic phogacytosis
Mf、NK、 T
Lyse target cells
Destroy target cells
ADCC
Stimulating or blocking effect
Promote /surpress the target cell funcion
Antigen or hapten on cell
Antibody (IgG, IgM)
Activate complement
Lyse target cell
Opsonic phagocytosis
Destroy target cell
Target cell injury
NK , phagocyte
Stimulate / block
ADCC
Change the function ofTarget cell
Mechanism of Type II hypersensitivity
3. Common disease of type II hypersensitivity
1)Transfusion reaction
hemolysis : mismatch of ABO blood group, severely destroy RBC
nonhemolysis : repeat transfusion of allogenic HLA
drug anaphylactic shock：penicillin
2) Hemolytic disease of newborn
Mother Rh- : first baby Rh+(Ab), second baby Rh+,
fetal
RBC destroyed
3) Autoimmune hemolytic anemia and type II drug reaction
i. Foreign antigen or hapten
Penicillin
Quinin
Pyramidone
RBC
Platlet
hemolytic anemia
thrombocytopenic purpura
Granulocyte
agranulocytosis
ii. Self-antigen
Drug
conversion from a hapten to a full antigen
induce self antibody
autoimmune hemolytic anemia
Auto-Immune Hemolytic Anaemia
Type II Hypersensitivity
Antibody Dependent Cell Mediated Cytotoxicity
Animation: Antibodies react with epitopes on the host cell membrane and NK cells
bind to the Fc of the antibodies. The NK cells then lyse the cell with pore-forming
perforins and cytotoxic granzymes
Type II Hypersensitivity
Antibody-Mediated Cell Disfunction
Example: Myasthenia Gravis
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Type III Hypersensitivity
– Mediated by immune complexes (Antigen-Antibody
complex).
– During normal immune response only moderate quantity of
immune complexes are formed and they are removed
efficiently from circulation by phagocytosis.
– In case of production of large quantities of immune
complexes, phagocytes fail to remove all the immune
complexes from circulation.
– Thus, Ag-Ab complexes are deposited in various tissues.
They lead to activation of complement components.
Activation of complement may leads to destruction of
bystander cells.
Type III Hypersensitivity
– Moreover, under the influence of chemotactic complement
components polymorphonuclear cells are recruited at the
site.
– These cells, in their attempt to engulf immune complexes,
releases lysozymal enzymes in the tissue and thus cause
tissue destruction.
– Arthus reaction is an example of localized type III
hypersensitivity.
– Serum Sickness is an example of Systemic type III
hypersensitivity.
– Blue Eye: Dogs infected or vaccinated with live canine
adenovirus I develops anterior uveitis. This lead to corneal
oedema and opacity. The blue eye is considered to be an
immune complexes mediated condition.
Type III Hypersensitivity
• “Immune complex
disease”
• Soluble Ag / IgG or IgM
– high titers of each required
• Immune processes involved:
– classical complement pathway
– phagocytic cells
Immunreaktionen der Haut
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Soluble antigen
Body
Antibody
Immune complex
Small molecular soluble
Immune complex
intermediate molecular soluble
Immune complex
Large molecular insoluble
Immune complex
Deposit on the basement of capillaries
Eliminate by phogacytosis
Combine and activate complement system
Basophils and mast cells
C3a,C5a,C3b
Platelets
Infiltration of neutrophils
Blood Clotting Mechanisms
Release of vasoactive amine
Phagocytose complex
Release of vasoactive amine
Aggregation of platlets
Increase vascular permeability
Edema
Release the enzymes in lysosome
Thrombus
Tissue injury
Bleeding
Local or systemic immune complex diseases
Increase vascular permeability
Edema
3. common disease of type III hypersensitivity
1. Local immune complex disease
Arthus reaction ：Experimental local reaction,
Necrotic vasculitis vasculitis, Ulcer
Human local reaction: insulin-dependent diabetes mellitus (IDDM)
2. Acute systemic immune complex disease
serum sickness
Anti-serum
Ab+Ag
systemic tissue injury ,fever, arthritis, skin rash
Pinicillin、Sulfanilamide
Acute immune complex glomerulonephritis :
Streptococcus infection
3. Chronic immune complex disease
SLE
Rheumatoid arthritis ：RF+IgG
Deposit on synovial membrane
Type IV hypersensitivity reaction
– Because of delay in onset of response, type IV
hypersensitive reaction is also known as Delayed Type
Hypersensitivity (DTH).
– It approx takes 24 to 48 hours from the time of antigenic
stimulation.
– Unlike Type I, II, and III response (antibody mediated), Type
IV reaction is mediated by Cellular immune components.
Type IV hypersensitivity reaction
– The effector cells of Type IV hypersensitivity response are
CD4+ (Th), CD8+ cells and activated macrophages.
Some common examples of type IV hypersensitivity reaction:
– Tuberculin test (used for diagnosis of Tuberculosis),
– Johnin test (used for diagnosis of Johnes disease),
– Mallein test (used for diagnosis of Glanders),
– Brucellin test (used for diagnosis of Brucellosis).
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