HYPERSENSITIVITY REACTIONS BY MBBSPPT COM INTRODUCTION Inappropriate and

HYPERSENSITIVITY REACTIONS BY MBBSPPT. COM

INTRODUCTION Ø Ø Ø Inappropriate and damaging immune response is termed Hypersensitivity ‘Anaphylaxis’ termed by Richet (1913) Either Humoral or Cell-mediated Initial contact with Ag – priming/sensitizing dose Subsequent contact – Shocking dose Allergy (Priquet-1905) – Altered state of reactivity to antigen

CLASSIFICATION Ø Based on time required by sensitized host to develop clinical reactions upon exposure to the shocking dose of the antigen Ø Immediate type Ø Delayed type

CLASSIFICATION Feature Immediate type Delayed type Onset & duration Appears and recedes rapidly Appears slowly and lasts longer Immune response Ab. -mediated Cell-mediated Desensitisation Easy but short lived Difficult but long lasting Induction Antigen by any route Intradermally or by skin contact

CLASSIFICATION Ø Coomb’s and Gel classification (1963) Ø Ig. E mediated (type I) hypersensitivity Ø Antibody-mediated cytotoxic (type II) Ø Immune complex-mediated (type III) Ø Delayed type-DTH (type IV)

Ig. E-MEDIATED HYPERSENSITIVITY (type I) Exposure to allergen Activates TH 2 cells Stimulates B-cells Ig. E secreting plasma cells Bind to Ig. E specific Fc receptors on mast cells 2 nd exposure to allargen Crosslinking of bound Ig. E Muscle contraction Release of active mediators. Increased vascular permeability Increased vasodilation

Ig. E-MEDIATED HYPERSENSITIVITY (type I)

ALLARGENS ASSOSIATED WITH Ig. E -MEDIATED HYPERSENSITIVITY Ø Proteins – Foreign serum, vaccines Ø Plant pollens – Rye grass, Ragweed Ø Foods– Nuts, Seafoods, Eggs & milk Ø Insect products – Bee, Ant & Wax venom Ø Drugs – Penicillin’s, Sulfonamides Ø Animal hairs, dander, latex etc.

PRINCIPLE MEDIATORS - PRIMARY Histamine Increased vascular permeability, smooth muscle contraction, vasodilatation Serotonin Increased vascular permeability, smooth muscle contraction, vasoconstriction ECF-A Chemotaxis NCF-A Chemotaxis Proteases Mucus secretion, degradation of blood vessel basement membrane

PRINCIPLE MEDIATORS -SECONDARY PAF Platelet aggregation & degranulation, smooth muscle contraction Leukotriens (SRS- Increased vascular permeability, A) sustained smooth muscle contraction Prostagalandins Platelet aggregation, vasodilatation, smooth muscle contraction Bradykinins Increased vascular permeability, smooth muscle contraction Cytokines Systemic anaphylaxis, Increased Ig. E production

TYPES OF ANAPHYLAXIS Ø Systemic anaphylaxis Ø Shock and fatal state Ø Onset within minutes Ø Allergen induced directly into the blood stream Ø Animal model-guinea pig Ø Epinephrine-is drug of choice Ø Clinical manifestations: Ø -labored respiration Ø -decreased BP Ø -contraction muscles of GIT and bladder Ø -bronchial constriction

ANTIGENS RELATED TO SYSTEMIC ANAPHYLAXIS Antigen trigger the reaction in Guinea pig: - Egg albumin Antigen trigger the reaction in humans: -venom from bee -Wasp -hornet and stings Drugs: penicillin insulin antibiotics Foods: sea foods and nuts

Localized hypersensitivity – ATOPY (out of place or strangeness) Ø Tendency to manifest localized hypersensitivity reaction is inherited &multigenic. Ø First introduced by coca(1923) Ø Specific to target tissue or organ Ø Common antigens causing atopy -Pollen -House dust -foods

Localized hypersensitivity - ATOPY Mechanism: atopens+cell bound Ig. E antibodies of mast cell Ag-Ab complex Release mediators Localized hypersensitivity

ALLERGIC RHINITIS Ø Known as hay fever Ø Inhalation due to common air born allergens Ø Localized vasodilations, and increased capillary permeability Ø Watery exudation Ø Sneezing Ø Coughing

FOOD ALLERGY Ø Allergen cross linking of Ig. E on mast cells Ø Smooth muscle contraction and vasodilation-GIT Ø Symptoms: Ø Vomiting or diarrhea Ø Mast cell degranulation along the Gut-allergen enters blood streams Ø Asthmatic attack Ø Atopic urticaria

ATOPIC DERMATITIS (ALLERGIC ECZEMA) Ø Ø Inflammatory disease of skin Observed most frequently in infancy and young children Ø Serum Ig. E level increased Ø Skin eruption Ø Erythematous filled with pus

Detection of Type 1 hypersensitivity Ø Skin testing Ø Advantage Ø inexpensive Ø allow screening for large no. of allergens at one time Ø Disadvantages Ø sensitised in rare cases Ø less commonly induced systemic anaphylactic shock

SKIN TESTING

Detection Of Type 1 Hypersensitivity Ø Serum Ig. E determination Ø Radio immuno sorbent test (RIST) Ø Radio allergo sorbent test (RAST)

Treatment Ø Ø Immunotherapy: With repeated injections of increasing doses of allergens (Hyposensitizations) Ø - DNA vaccine Ø - Adjuvant Ø Humanized monoclonal anti-Ig. E -Omalizumab-first anti Ig antibody approved in US in 2003.

Drug therapy DRUGS ACTION Ø Anti histamins Block H 1 and H 2 receptor Ø Cromolyn sodium Block calcium Influx Ø theophylline Increased cyclic AMP level Ø Epinephrine Stimulate cyclic AMP production Ø Cortisone Reduces histamine levels

ANTIBODY-MEDIATED CYTOTOXIC (type II) HYPERSENSITIVITY Ø Mediated By Ig. G, rarely Ig. M Ø Ab. Binds to Ag. On cell surface Ø Phagocytosis of cell through opsonic or immunoadherence Ø Cytotoxic - NK cells Ø Lysis –Activated complement system Ø Transfusion reactions Ø Hemolytic disease of new born Ø Drug induced hemolytic anemia

Haemolytic disease of newborn

Detection & Treatment Ø Coomb’s test (Direct antiglobulin test) Ø Foetal RBCs + Coomb’s reagent Ø Incubate Ø Maternal Ig. G bound to Foetal RBC Ø Cells agglutinate with Coomb’s reagent Ø Treatment in foetus Ø Intrauterine blood exchange transfusion (every 10 -21 days) Ø Exposed to low levels of UV light Ø Treatment in mother Ø Plasmapheresis Ø Treated with anti-Rh Abs or Rhogam

IMMUNE COMPLEX MEDIATED (type III) HYPERSENSITIVITY

ARTHUS REACTION (localized) Ø Due to relative Ø Antibody excess

SERUM SICKNESS (Generalized) Ø Ø Ø Ø Ø Due to relative antigen excess Anti toxins – Anti-tetanus or Anti-diphtheria serum Antibiotic treatment and certain vaccinations Symptoms Tissue damage at various sites Fever Weakness Generalized vasculitis lymphadenopathy

DELAYED TYPE HYPERSENSTIVITY (type IV) Mechanism: 1. Sensitization phase Initial contact with antigen Cytokine Secreted Proliferate TH cells Differentiate into TH 1 cells

DELAYED TYPE HYPERSENSTIVITY (type IV) 2) Effector Phase Sensitized TH 1 Cells Secrete cytokine and chemokines Activate Macrophage and inflammatory cells Perpetuating DTH response

TUBERCULIN TYPE REACTION

CONTACT DERMATITIS TYPE REACTIONS Simple chemicals/substance act as Absorption through skin haptens Combines with skin proteins and becomes antigenic Fat soluble Portal of entry through sebaceous gland Langerhans cells Regional lymph modes Sensitized T lymphocytes Subsequent exposure to agent senstized lymphocytes release lymphokines Superficial inflammation of skin

CONTACT DERMATITIS TYPE REACTIONS

DETECTION OF TYPE IV HYPERSENSITIVITY Ø Tuberculin test Ø Lepromin tests Ø Frei test Ø Histoplasmin test Ø Patch test

STIMULATORY TYPE REACTION (type V) Ø Ø Modified of Type II hypersensitivity Reactions Cell proliferation and differentiation instead of inhibition or killing Auto antibodies directed to hormone receptor molecules &function in a stimulatory fashion Abs to TSH receptor result over activity of thyroid(Graves disease).

STIMULATORY TYPE REACTION (type V)

SUMMARY Type III Type IV Type V Ig. E Ig. G/Ig. M Immune Cell Ab. mediated complex mediated Ag induces cross linking Ab directed against cell surface Ag-Ab complexes in various tissues Sensitized TH 1 cells release cytokines Cell surface Systemic & Localized anaphylaxis Erythroblasto sis Foetalis, Blood transfusion reactions Arthus reaction, Serum sickness, SLE Tubercular lesions, Contact dermatitis Grave’s disease

THANK YOU