Download - 10 hypersensitivity appu
HYPERSENSITIVITY AND EVALUATION
METHODS
APARNA.SM.PHARMACYG.PULLA REDDY COLLEGE OF PHARMACY
2
HYPERSENSITIVITY Hypersensitivity reaction resulting from
specific interactions between antigens (allergens) and either antibodies or sensitized lymphocytes.
Hypersensitivity reaction resulting from specific interactions between antigens (allergens) and either antibodies or sensitized lymphocytes
Diffuse urticaria Anaphylactic response to bee sting
TYPE –IMast cell degranulation mediated by antigen cross-linking of IgE bound to IgE Fc receptors (FcRI).
Mediators released during activation of mast cells.
MECHANISM IN TYPE-I
(A)Electron micrograph of normal mast cell illustrating large monocyte-like nucleus and electron-dense granules.
(B) (B) Mast cell that has been triggered and is beginning to release contents of granules, as seen by their decrease in opacity and formation of vacuoles connecting with exterior.
ELECTRON MICROSCOPIC VIEW
Clinical Examples
Hay fever and Asthma----To pollen, house dust, pets etc.
Urticaria(Hives)---Drugs,food. Reddening and itching of skin.
Systemic anaphylaxis---Inj. of Penicillin,Insect bites.
Type II IgE-mediated
THREE TYPES OF MECHANISMS IN TYPE- II HYP
Drug-Induced Reactions:Adherence to Blood
Components
complementcomplement
blood cell adsorbed drug blood cell adsorbed drug or antigen drug metaboliteor antigen drug metabolite
antibody to drugantibody to drug
lysis
DISEASES OF TYPE-II
Autoimmune hemolytic anemia Thrombocytopenia Erythroblastosis fetalis Goodpasture's syndrome
Hemolytic Disease of the New Born
RhD-ve mother
RhD +ve fetus
Anti-RhD Abs
RhD +ve fetus
‘A’ blood group mother
‘B’ blood group fetus
Anti-B Abs
If mother and fetus have different blood groups, hemolytic disease does not occur.
Prophylaxis (RhoGAM)
RhD-ve mother
RhD +ve fetus
Anti-RhD Abs
RhD +ve fetusMid-term injection of RhoGAM and a second injection within a few days of delivery
Immune Complex Mediated Hypersensitivity-III
Type III hypersensitivity mechanism
Type III hypersensitivity mechanism
Examples of Type-III
Serum sickness Arthus reaction Systemic lupus erythematosus (SLE) Glomerulonephrites
Serum sickness
Systemic lupus erythematosus
DELAYED TYPE -IV
TYPE IV OR DTH– REACTION TO POISON IVY
Examples of Type IV
Contact dermatitis Tuberculin skin test Chronic transplant rejection Multiple sclerosis
Contact Dermatitis
ECZEMA
ALLERGIC SKIN REACTIONS
Leprosy
Hyporesponse
Normal response
Hyper response
Fluid filled blebs with bacteria
small skin lesion
Severetissue damage
Type V Hypersensitivity / Auto immune
This is an additional type that is sometimes used as a distinction from Type 2
Instead of binding to cell surface components, the
antibodies recognize and bind to the cell surface receptors , which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling
Examples of Type V Grave's disease Myasthenia Gravis Hashimoto's thyroiditis Systemic lupus erythematosus
OECD TEST GUIDE LINESOECD TEST GUIDE LINES
EVALUATION OF HYP :QUALITATIVE
LYMPH NODE:QUANTITATIVE ASSAY
* The basic principle is to induce proliferation of lymphocytes in the lymph nodes draining the site of test substance application.
* This proliferation is proportional to the dose and to the potency of the applied allergen and provides a simple means of obtaining a quantitative measurement of sensitization.
* Proliferation is measured by comparing the mean proliferation in
each test group to the vehicle treated control (VC) group.
* The ratio of the mean proliferation in each treated group to that in the VC group, termed the SI, is determined, and should be ≥1.8.
* The methods described here are based on the use of measuring ATP content by bioluminescence to indicate an increased number of proliferating cells in the draining auricular lymph nodes
* The bioluminescent method utilises the luciferase enzyme to catalyse the formation of light from ATP and luciferin according to the following reaction:
ATP+LUCIFERIN+OXYGEN luciferase
OXYLUCIFERIN+AMP+Ppi+CO2+LIGHT
* The emitted light intensity is linearly related to the ATP concentration and is measured using a luminometer* The luciferin-luciferase assay is a sensitive method for ATP quantitation used in a wide variety of applications.
IN-VITRO SCREENING METHODS
REFERENCES Willey drug safety evaluation (2002)by shayne c.Gad OECD (2010), Skin Sensitization: Local Lymph Node Assay,
Test Guideline No. 429, Guidelines for the Testing of Chemicals, OECD, Paris. Available at: [http://www.oecd.org/env/testguidelines]
http://iccvam.niehs.nih.gov/docs/immunotox_docs/llna/llnarep.pdf]
OECD (1992), Skin Sensitisation, Test Guideline No. 406, Guidelines for Testing of Chemicals, OECD, Paris. Available at: [http://www.oecd.org/env/testguidelines]
OECD (2002), Acute Dermal Irritation/Corrosion, Test Guideline No. 404, Guidelines for Testing of Chemicals, OECD, Paris. Available at: [http://www.oecd.org/env/testguidelines]