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