Hypersensitivity

• What does hypersensitivity refer to?

  Undesirable immune reactions produced by the immune system to an antigen (ALLERGEN)

  
• How many types of hypersensitivity are there?

  Five types (I, II, III, IV, and V)

  
• On what basis is the classification of hypersensitivity types made?

  Based on the mechanisms involved and time taken for the reaction

  
• What types of responses can hypersensitive reactions develop in?

  Humoral or cell-mediated responses

  
• How many types of hypersensitivity occur within the humoral branch?

  Four types (I, II, III, and V)
• What is the fourth type of hypersensitivity called?

  Delayed-type hypersensitivity (DTH) or type IV

  
• What do different antibody isotypes induce?

  Different immune effector molecules
• Which antibody isotype induces mast-cell degranulation?

  IgE

  
• What do IgG and IgM antibodies activate?

  Complement

  
• What is atopy?

  The genetic predisposition to allergic reactions

  
• What are the most common manifestations of atopy?

  Allergic rhinitis, allergic asthma, atopic dermatitis

  
• Which chromosomes have been identified to affect IgE production in atopic families?

  Chromosome 11q and 5q

  
• What genes are located on chromosome 5 related to atopy?

  IL-4, IL-5, and granulocyte-macrophage colony-stimulating factor

  
• What does chromosome 11 encode related to atopy?

  The beta subunit of the high-affinity IgE receptor

  
• What does increased expression of the high-affinity IgE receptor lead to?

  A more sensitive response to small numbers of antigens

  
• When do immediate (type I) hypersensitivity reactions occur?

  Within minutes of exposure to an antigen

  
• What is required for immediate (type I) hypersensitivity reactions?

  Pre-sensitization
• What mediates immediate (type I) hypersensitivity reactions?

  Mostly IgE
• What does the allergen induce in immediate (type I) hypersensitivity?

  Cross-linking of IgE bound to mast cells and basophils with release of vasoactive mediators

  
• Where are high concentrations of mast cells found?

  Skin, mucous membranes of the respiratory and gastrointestinal tracts

  
• What is the proliferation potential of mature mast cells?

  Mature mast cells retain an extensive proliferation potential

  
• Where do immature progenitor mast cells mature?

  Within vascularized tissues

  
• Where are higher numbers of mast cells observed?

  At the interfaces of host and environment, such as skin and mucosal surfaces

  
• What regulates the local differentiation and maturation of mast cells?

  Tissue environmental factors

  
• What is the most important factor for human mast cells?

  Stem cell factor (SCF)

  
• What cytokines help in the maturation of mast cells?

  IL-4, IL-6, and IL-10

  
• What initiates mast-cell degranulation?

  Allergen cross-linkage of bound IgE, anaphylatoxins, and drugs

  
• What does it mean when mast cells and basophils are coated by IgE?

  They are said to be sensitized

  
• What happens during a later exposure to the same allergen?

  It cross-links the membrane-bound IgE on sensitized mast cells and basophils, causing degranulation

  
• What occurs within 15 seconds after cross-linkage of FcERI?

  Methylation of various membrane phospholipids occurs, increasing membrane fluidity and forming Ca$^{2+}$ channels

  
• When does the peak of Ca$^{2+}$ increase occur?


  Within 2 minutes
• What leads to the formation of arachidonic acid?

  The increase of Ca$^{2+}$
• What is arachidonic acid converted into?

  Prostaglandins and leukotrienes
• What does the increase of Ca$^{2+}$ promote?


  The assembly of microtubules and contraction of microfilaments
• How can mediators be classified?

  As either primary or secondary

  
• What are primary mediators?

  Produced before degranulation and stored in granules
• What are secondary mediators?

  Synthesized after target-cell activation or released by the breakdown of membrane phospholipids during degranulation
• What is the major component of mast-cell granules?

  Histamine

  
• When are the biological effects of histamine observed?

  Within minutes of mast-cell activation

  
• How many types of histamine receptors are there?

  Four types (H1, H2, H3, H4)