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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