Allergic Responses

Presented by: Kiran Hanif

Allergic Responses

Also called Hypersensitive responses

Hypersensitive immune reaction to a substance harmless for

healthy individuals.

A type of abnormal immune reaction

Substances induces abnormal immune responses are called

Allergen.

Atopy

A genetic trait to have a predisposition for localized

anaphylaxis.

Atopic individuals have higher levels of IgE and

eosinophils.

Genetic Predisposition

Candidate polymorphic genes include:

IL-4 Receptor

IL-4 cytokine (promoter region)

FceRI

Class II MHC (present peptides promoting Th2 response)

Types of Allergic Reactions

1. Type I or IgE-mediated Hypersensitivity

2. Type II or IgG or IgM-mediated cytotoxic

Hypersensitivity

3. Type III or Complex-mediated Hypersensitivity

4. Type IV or Cell-Mediated Hypersensitivity

Type I or IgE-mediated Hypersensitivity

Commonly called Allergy

Allergen presented by antigen presenting cells

TH2 cells activate the B cells

B cells give clonal cells

Plasma cells

Memory cells

Cont……

Plasma cells secreted IgE antibody

Secreted IgE bind to the Fc Receptors

Receptors present on Mast cells & Basophills

Degranulation is induced

Mediators (Histamine) releases

Results in clinical manifestations

General mechanism showing type I hypersensitivity reaction

Allergens

Nonparasitic antigens responses capable of

stimulating type I hypersensitivity

Stimulate inappropriate IgE production

Binds to IgE and induces degranulation of cells

Proteins

• Foreign serum

• Vaccines

Plant pollens

• Rye grass

• Ragweed

• Timothy grass

• Birch trees

Drugs

• Penicillin

• Sulfonamides

• Local anesthetics

• Salicylates

Foods

• Milk

• Sea Food

• Nuts

Insect products

• Bee venome

• Wasp venom

• Drugs Ant venom

• Cockroach calyx

• Dust mites

Animal hair and dander

Fc Receptors

Receptors present on the surface of the Mast cells

and Basophills

Two types of Fc receptors are found

High affinity receptor (FcɛRI)

Low-affinity receptor (FcɛRII)

Binding of IgE to receptors induces degranulation

Structure of high affinity receptor FcɛRI

Structure of low affinity receptor FcɛRII

Biochemical events in mast-cell activation and degranulation

Mediators releases after Degranulation of Mast cells

Mediators are the molecules mediate clinical

menifestations

Pharmacologically active agents act on local tissues

Mediators release induced by allergens results in:

Increase in Vascular permeability

Inflamation

Classification of Mediators

Classified as:

Primary mediators

Secondary mediators

Primary Mediators

Histamine

Constriction of smooth muscles.

Bronchiole constriction = wheezing.

Constriction of intestine = cramps-diarrhea.

Vasodilation with increased fluid into tissues causing

increased swelling or fluid in mucosa.

Activates enzymes for tissue breakdown

Secondary Mediators

Leukotrienes

Prostaglandins

Cytokines

Effect of mediators

Phases of type I Hypersensivity reactions

Immediate phase

Involves LTC4 and PGD2

Late phase

Involves IL-4, IL-5, ECF, PAF

Type I reactions

Type I reactions may be systemic or localized

Systemic anaphylaxis

Localized hypersensitivity reactions

Allergic rhinitis

Food allergies

Asthma

Asthma

Triggering of disease involve exposure to airborne

& blood-borne allergens such as pollens, dust,

fumes, insects products etc.

Asthematic response can also be divided into:

Early response

Late response

Early and late responses in asthema

Effect of degranulation of mast cells in asthema

Regulation of Type I response

Many factors are responsible for regulating the type

I response which include:

IL-4

IL-5

IL-9

IL-13

Medical control of Hypersensitivity

Antihistamines

Cromolyn sodium

Theophylline

Epinephrine

Type II or IgG or IgM-mediated cytotoxic Hypersensitivity

Also called Antibody-mediated cytotoxic

hypersensitivity

Involve antibody-mediated destruction of cells

Antibody bound to a cell surface antigen can

activate complement system

Cell destruction by ADCC

Type II Reactions

Transfusion reactions

Drug-induced Hemolytic Anemia

Hemolytic disease of Newborn

Hemolytic disease of the newborn

Also called Erythroblastosis fetalis

Develops when maternal IgG antibodies specific for

fetal blood- group antigens cross the placenta

Destroy fetal red blood cells

Commonly develops when an Rh+ fetus expresses

an Rh antigen on its blood cells

Type III or Complex-mediated Hypersensitivity

Reaction of antibody with antigen generates

immune complexes

Complexing facilitates the clearance of antigen by

phagocytic cells.

Effector mechanism

Immune complexes activate the complement system

Anaphylatoxins C3a, C4a, and C5a cause localized

mast-cell degranulation.

C3a, C5a, and C5b67 are also chemotactic factors

for neutrophils

Release of lytic enzymes by neutrophils

Development of localized type III hypersensitivity

Type III reactions

Poststreptococcal glomerulonephritis

Rheumatoid arthritis

Type IV or T Cell-Mediated

Hypersensitivity

TH cells encounter certain types of antigens

Secrete cytokines induces localized inflammatory

reaction

Reactions are delayed by one or more days

Phases of DTH response

Sensitization phase

begins with an initial contact with an antigen.

Effector phase

subsequent exposure to the antigen

TH1 cells secrete a variety of cytokines

Activate the macrophages

Phases of type IV hypersensitivity

Contact dermatitis is type of DTH response

Molecules complex with skin proteins

Complex internalized by skin cells

Processed & presented with MHC II

Results in activation of sensitized TH1 cells

Development of DTH response after second exposure to

poison oak

Four types of Allergic responses