hypersensitivity reactions
TRANSCRIPT
Lakhan.M.S
Hypersensitivity Reactions
Hypersensitivity
Undesirable injurious consequences in the
sensitised host,following contact with specific
antigen.
Generally the immune system is protective
Protective mechanisms may result in severe
damages to tissues and may lead to death
Severe damages may occur when the
immune system respond in exaggerated or
inappropriate form.
Sensitising dose or Priming dose.
Initial contact with antigen-
sensitises Immune system-B & T
lymphocytes.
Shocking dose
Subsequent contact with same
antigen-
HYPERSENSITIVITY REACTIONS.
Type of reaction Clinical Syndrome Mediators
Type I (IgE type) 1.Anaphylaxis
2.Atopy
IgE,histamine
Type 2 (Cytolytic &
Cytotoxic)
1.Thrombocytopeni
a
2.Agranulocytosis
3.Haemolytic
Anaemia
IgG IgM
Type 3 (Immune
Complex)
1.Arthus reaction
2.Serum Sickness
IgG IgM
Type 4 (Delayed type) 1.Tuberculin.
2.Contact
Dermatitis.
T cells
Type I Reactions
SENSITISED INDIVIDUALS- antibodies are fixed
on surface of tissue cells-Mast cells & Basophils.
On subsequent exposure
Antigen combines with cell fixed
antibody- release of Pharmacologically Active
Substances.
HYPERSENSITIVITY REACTIONS
Two forms
ANAPHYLAXIS –acute,fatal & systemic
ATOPY – recurrent,non-fatal & localised
Exposure to allergen
Production of IgE Ab+
fix to mast cell
On Re-Exposure
Antigen-Antibody complex
on mast cell surface
Release Mediators Clinical manifestations of
anaphylaxis
Mediators Vasodilation and increased permeability
Histamine
Leukotriene
Prostaglandin
Neutral proteases
Smooth muscle spasm
Histamine
Leukotriene
Prostaglandin
Leukocyte extravasation
Cytokines (e.g. chemokines and TNF)
Leukotriene
Chemotactic factors for neutrophils and eosinophils
Type I – Examples
Allergic asthma
Allergic conjunctivitis
Allergic rhinitis
Angioedema
Urticaria
ATOPY
Familial,occurs spontaneously.
Common antigens- Pollens,House dust & Food.
Atopic individuals have higher levels of IgE and
eosinophils
Mechanism of action- Similar to anaphylaxis but
reaction occurs at the site of entry and sensitising
dose not required.
Type I Hypersensitivity
Prevention of type I hypersensitivity
Identify and avoid allergens
Identify food allergens by eliminating
suspected foods from diet
Immunotherapy can help prevent allergic
reactions
Administer a series of injections of dilute
allergen
Must be repeated every two to three
years
Treatment of type I
hypersensitivity
Administer drugs that counteract inflammatory mediators
Antihistamines neutralize histamine
Treat asthma with a corticosteroid and a bronchodilator
Epinephrine neutralizes many mechanisms of anaphylaxis
Relaxes smooth muscle
Reduces vascular permeability
Severe asthma and anaphylactic shock require emergency treatment
Treatment of Anaphylactic
Shock
1.Inj .Adrenaline (1:1000) 0.3-0.5 ml im.
2.Inj.Hydrocortisone 100-200 mg iv.
3.Inj.Pheniramine 45 mg im/iv.
4.IV fluids.
Type II Reactions
Cytotoxic & Cytolitic
Antibodies produced by the immune response
bind to antigens on the patient's own cell
surfaces.
Causes
1.Phagocytosis of cell through opsonic
adherence.
2.Cytotoxicity by Natural Killer cells.
3.Lysis through activation of complement
system.
Antigens can be
-Intrinsic ("self" antigen, innately part of patient's cells)
-Extrinsic (adsorbed onto the cells during exposure to foreign
antigen).
These cells are recognized by macrophages or dendritic cells,
which act as antigen-presenting cells.
This cause B cell response, where antibodies are produced
against foreign antigen
Examples
Autoimmune Anaemia & Haemolytic disease of the
newborn.- Antierythrocyte antibody causes lysis of
red cells.
Goodpasture's syndrome
Basement membrane(containing collagen type IV) in
the lung and kidney is attacked by our own antibodies
Drug reactions-
Sedormid purpura
Other drugs Sulphonamides,Thiazide
diuretics,Quinidine also causes similar type of
purpura.
Other examples of Type II Pernicious anemia
Immune thrombocytopenia
Transfusion reactions
Hashimoto's thyroiditis
Type III- Immune Complex Reactions
Characterised by
1.Deposition of Antigen-Antibody complex in tissue.
2. Activation of Complement
3.Infiltration of Polymorphonuclear leucocytes.
TISSUE DAMAGE
Antigen combines with Antibody
Producing Free floating Complex
Deposited in tissues
Immune-Complex Reactions
Type III
Two types
-Arthus Reaction (Localised)
-Serum Sickness (Generalised)
Serum sickness- A single dose serves both as the
sensitising and shocking dose. –
Fever,Urticaria,Arthralgia,Lymphadenopathy,Sple
nomegaly.
Type III (Immune Complex–
Mediated) Hypersensitivity
Caused by formation of immune complexes
Can cause localized reactions
Hypersensitivity pneumonitis
Glomerulonephritis
Hypersensitivity pneumonitis
Inhalation of antigens into lungs stimulates antibody production
Subsequent inhalation of the same antigen results in formation of immune complexes
Activates complement
Type III (Immune Complex–
Mediated) Hypersensitivity
Can cause systemic reactions
Systemic lupus erythematosus
Rheumatoid arthritis
Type IV Delayed or cell mediated
Reactions
Mediated by sensitised T Lymphocytes
Contact with specific Antigen
Release Lymphokines
Effect on Macrophage,Leucocytes &
Tissue Cells.
Occurs within 48-72 hours of antigen exposure.
Type IV Delayed or cell mediated
Reactions
Two types
Tuberculin Type
Contact Dermatitis
Type IV
The tuberculin response
An injection of tuberculin beneath the skin
causes reaction in individual exposed to
tuberculosis or tuberculosis vaccine
Used to diagnose contact with antigens of
M. tuberculosis
No response when individual not
infected or vaccinated
Red, hard swelling develops in
individuals previously infected or
immunized
Type V Stimulatory type
Modification of Type II hypersensitivity reactions.
Antigen-Antibody reaction enhances the activity
of affected cells- cell proliferation &
differentiation,instead of inhibition or killing.
Example
-Graves disease
presence of Long Acting Thyroid Stimulating
Antibody
-Mysthaenia Gravis
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