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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
Allergic responses

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Allergic responses

  • 2. 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.
  • 3. Atopy  A genetic trait to have a predisposition for localized anaphylaxis.  Atopic individuals have higher levels of IgE and eosinophils.
  • 4. Genetic Predisposition  Candidate polymorphic genes include:  IL-4 Receptor  IL-4 cytokine (promoter region)  FceRI  Class II MHC (present peptides promoting Th2 response)
  • 5. 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
  • 6. 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
  • 7. 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
  • 8. General mechanism showing type I hypersensitivity reaction
  • 9. Allergens  Nonparasitic antigens responses capable of stimulating type I hypersensitivity  Stimulate inappropriate IgE production  Binds to IgE and induces degranulation of cells
  • 10. Proteins • Foreign serum • Vaccines Plant pollens • Rye grass • Ragweed • Timothy grass • Birch trees Drugs • Penicillin • Sulfonamides • Local anesthetics • Salicylates
  • 11. Foods • Milk • Sea Food • Nuts Insect products • Bee venome • Wasp venom • Drugs Ant venom • Cockroach calyx • Dust mites Animal hair and dander
  • 12. 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
  • 13. Structure of high affinity receptor FcɛRI
  • 14. Structure of low affinity receptor FcɛRII
  • 15. Biochemical events in mast-cell activation and degranulation
  • 16. 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
  • 17. Classification of Mediators  Classified as:  Primary mediators  Secondary mediators
  • 18. 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
  • 21. Phases of type I Hypersensivity reactions Immediate phase  Involves LTC4 and PGD2 Late phase  Involves IL-4, IL-5, ECF, PAF
  • 22. Type I reactions  Type I reactions may be systemic or localized  Systemic anaphylaxis  Localized hypersensitivity reactions  Allergic rhinitis  Food allergies  Asthma
  • 23. 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
  • 24. Early and late responses in asthema
  • 25. Effect of degranulation of mast cells in asthema
  • 26. 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
  • 27. Medical control of Hypersensitivity  Antihistamines  Cromolyn sodium  Theophylline  Epinephrine
  • 28.
  • 29. 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
  • 30. Type II Reactions Transfusion reactions Drug-induced Hemolytic Anemia Hemolytic disease of Newborn
  • 31. 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
  • 32. Type III or Complex-mediated Hypersensitivity  Reaction of antibody with antigen generates immune complexes  Complexing facilitates the clearance of antigen by phagocytic cells.
  • 33. 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
  • 34. Development of localized type III hypersensitivity
  • 35. Type III reactions Poststreptococcal glomerulonephritis Rheumatoid arthritis
  • 36. 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
  • 37. 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
  • 38. Phases of type IV hypersensitivity
  • 39. 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
  • 40. Development of DTH response after second exposure to poison oak
  • 41. Four types of Allergic responses