Hypersensitivity Reaction

PowerPoint PresentationHypersensitivity Reaction Hypersensitivity or allergy
* It is used to describe a state in which the immune responses frequently take place in such a way that the cell damage occur
and harmful pathological lesions may occur.
It depends on the reaction between antigen & antibody
- Substances that induce hypersensitivity:-
- Feeble antigen (plant pollens)
Types of Hypersensitivity:-
3- Type III Toxic complex syndrom
4- Type IV Delayed reaction
Type I Anaphylactic reaction
leading to release of soluble molecules
An antigen (allergen)
soluble molecules (mediators)
* Systemic life threatening; anaphylactic shock
* Local atopic allergies; bronchial asthma, hay fever
and food allergies
Allergen stimulates formation of antibody (Ig E type)
Ig E fixes, by its Fc portion to mast cells and basophiles
* Second exposure to the same allergen
It bridges between Ig E molecules fixed to mast cellsleading to activation and degranulation of mast cells and release of mediators
Pathogenic mechanisms * Three classes of mediators derived from mast cells:
!) Preformed mediators stored in granules (histamine)
2) Newly sensitized mediators:
3) Cytokines produced by activated mast cells, basophils
e.g. TNF, IL3, IL-4, IL-5 IL-13, chemokines
* These mediators cause: smooth muscle contraction,
mucous secretion and bronchial spasm, vasodilatation,
vascular permeability and edema
Type I hypersensitivity - pathogenesis
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FIGURE 14.6. Overview of induction and effector mechanisms in type I hypersensitivity .
Pathogenesis of atopic dermatitis (1)
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* Exposure to allergen to which a person is previously sensitized
* Allergens:
* Clinical picture:
Shock due to sudden decrease of blood pressure, respiratory distress due to bronhospasm, cyanosis, edema, urticaria
* Treatment: corticosteroids injection, epinephrine, antihistamines
Atopy * Local form of type I hypersensitivity
* Exposure to certain allergens that induce production of specific Ig E
* Allergens :
Ingestants: milk, egg, fish, choclate
Contactants: wool, nylon, animal fur
Drugs: penicillin, salicylates, anesthesia insect venom
* There is a strong familial predisposition to atopic allergy
* The predisposition is genetically determined
Methods of diagnosis
2) Skin tests:
A wheal and flare (erythema) develop at the site of
allergen to which the person is allergic
3) Determination of total serum Ig E level
4) Determination of specific Ig E levels to the different allergens
Management
2) Hyposensitization:
allergen and prevent combination with Ig E
- It may induce T cell tolerance
3) Drug Therapy:
* An antibody (Ig G or Ig M) reacts with
antigen on the cell surface
* This antigen may be part of cell membrane
or circulating antigen (or hapten) that
attaches to cell membrane
1) Complement fixation to antigen antibody complex on cell surface
The activated complement will lead to cell lysis
2) Phagocytosis is enhanced by the antibody (opsinin) bound to cell antigen leading to opsonization of the target cell
Mechanism of cytolysis 3) Antibody depended cellular cytotoxicity (ADCC):
- Antibody coated cells
be killed by cells possess Fc receptors
- The process different from phagocytosis and
independent of complement
NK, macrophages, neutrophils and eosinophils
Figure 15.1 Schematic illustration of three different mechanisms of antibody- mediated injury in type II hypersensitivity
Clinical Conditions
1) Transfusion reaction due to ABO incompatibility
2) Rh-incompatability (Hemolytic disease of the newborn)
3) Autoimmune diseases The mechanism of tissue damage is cytotoxic reactions e.g. autoimmune haemolytic anaemia, myasthenia gravis, nephrotoxic
nephritis, Hashimoto’s thyroiditis
4) A non-cytotoxic Type II hypersensitivity is Graves’s disease It is a form of thyroditits in which antibodies are produced against TSH
surface receptor This lead to mimic the effect of TSH and stimulate cells to over- produce
thyroid hormones
Clinical Conditions 5- Graft rejection cytotoxic reactions:
In hyperacute rejection the recipient already has performed antibody against the graft
6- Drug reaction:
induce antibodies which are cytotoxic for the
cell-drug complex leading to haemolysis
Quinine may attach to platelets and the antibodies
cause platelets destruction and thrombocytopenic
purpura
AB AB A and B none
O OO H anti-A/B
RhD positive
red cells
anti-RhD
lysis
circulating antibodies with the formation of micro-
precipitates in and around small blood vessels
causing inflammation
• Autoimmunity – self antigens
– deposition of immune complexes in kidneys, joints, arteries and skin
• Extrinsic factors – environmental antigens
Diseases associated with immune complexes
Soluble antigen Body Antibody
Deposit on the basement of capillaries
Combine and activate complement system
C3a,C5a,C3b
Tissue injury
Local or systemic immune complex diseases
Figure 15.2 Schematic illustration of the three sequential phases in the induction of systemic type III (immune complex) hypersensitivity
Disease Models
• Serum sickness
• Arthus reaction
Serum Sickness
Arthus Reaction
Figure 15.5 Type III hypersensitivity Arthus reaction. (A) Gross appearance, showing hemorrhagic appearance (purpura); (B) Histologic features of Arthus reaction showing neutrophil infiltrate
Type IV delayed hypersensitivity - The reaction doesn’t occur immediately (several hours or longer) - It involves only cells, antibodies and complement are not concerned - Antigens are infectious agents react with sensitized T cells - Immunity can be transferred by cells not by antibodies
Figure 16.1 The DTH reaction
Pathogenesis of type IV hypersensitivity
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Delayed type hypersensitivity
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1- Tuberculin reaction
It is an immunologically specific reaction mediated by T cells.
- Other skin tests such as:-
- Brucellin test (Brucella abotus)
- Johnin test (Mycobacterium paratuberculosis)
- salts of metals such as nickel
3- Graft rejection
False negatives:
Decreased immune response
blood → IFN-γ
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Contact allergy dermatitis
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