Hypersensitivity

Question 1

Type I (Immediate) Hypersensitivity

Answer 1

occurs immediately • Mediated by binding of allergen crosslinking IgE bound to the
FcεRI on mast cells, basophils, & eosinophils

1. Production of IgE in response to antigen exposure
2. Binding of IgE to FcΕRI on mast cells (sensitization)
3. Cross-linking of bound IgE by antigen (activation)
4. Mast cell degranulation Release of mediators (effector)

Question 2

Type II Hypersensitivity

Answer 2

Mediated by binding of IgG or IgM antibodies to cell surface & recruiting of inflammatory cells

(toxicity)

Caused by IgG or IgM antibodies binding to antigens on cell surfaces which can trigger inflammation of interfere with normal function
• Cell bound antibody can cause damage to cell by
• Complement mediated lysis (Mac)
• Opsonization (C3b–phagocytosis)
• Antibody dependent cell cytotoxicity
• Antibody mediated cellular dysfunction

Question 3

Type III Hypersensitivity

Answer 3

Mediated by immune complex deposition

Arises when soluble antigen forms immune complexes with circulating antibody and deposits in tissue or vessels walls and activates complement
• Reaction develops over 2 - 8 hours
• Reaction is localized when complexes are deposited at
site of antigen entry (Arthus Reaction)
• Reaction is systemic when complexes are formed in the blood and get deposited in various tissues (Serum sickness)
• First observed with passive immunization
• Diptheria infection treated with horse serum from horses immunized with diptheria toxin

Question 4

Type IV (Delayed) Hypersensitivity (occurs 24-72 hours later)

Answer 4

Mediated by effector T-cells (TH1 and CD8)

Not mediated by antibody
• Mediated by CD4 TH1& TH17 and CD8 T cells
• Basis for the tuberculin or Mantoux test (PPD= purified protein derivative) for exposure to M tuberculosis.
• Positive skin reaction occurs when person exposed to the tubercle bacillus or BCG vaccine is injected with mixture of peptide from M tuberculosis
• DTH develops 24-48 hours after antigen challenge
• Basis for allograft response and graft vs. host disease
• Response characterized by erythema (redness) and induration (raised thickening) due to deposition of fibrin

• Characterized by early infiltration of macrophages, NK cells and T cells
• Can be elicited by reactive metals such as nickel, gold and chromium that can come in contact with skin (contact sensitivity). These molecules form haptens with skin proteins.
• Can also be elicited by intracellular bacteria, viruses, allograft and chemicals capable of coupling to the skin: contact dermatitis
• Poison ivy can elicit a rash due to chemical in its leaves (urushiols; pentadecacatechol). Couples covalently with skin protein (modifies it) and can be presented by Langerhan cells (skin APCs) to TH1 cells.

Question 5

Produced before degranulation and stored in granules

(mast cells) type 1 hypersensitivity

Answer 5

• Histamine
• Binds H receptors (H1, H2) and causes immediate increase in blood flow(vasodilation), endothelial cell contraction & increase in vessel permeability
• Heparin
  acidic glycoprotein to which histamine is bound
  Involved in reconstitution of mast cell
• Eosinophil Chemotactic Factor (ECF)
  Attracts eosinophils to inflammatory site
• Neutrophil Chemotactic Factor (NCF) Attracts neutrophils to inflammatory site

Question 6

Newly Generated, secondary Mediators – type 1 hypersensitivity

Answer 6

Synthesis of lipid mediators controlled by phospholipase A1 (PLA2)
• PLA2 is activated by increase in Ca2+ & MAP kinases and hydrolyzes phospholipids to release arachidonic acid
• Arachidonic acid converted to cyclooygenase & lipoxygenase

Leukotrienes: LTC4, LTD4, LTE4 (SRS-A)
• Major arachidonic acid derived mediator produced by the lipoxygenase pathway
• Causes smooth muscle contraction
• Induces prolonged bronchoconstriction
• Stimulates increase in vascular permeability
• Increases mucus production
• 1000x more potent than histamine, slower in onset, longer lasting
• Not responsive to antihistamines
• Inhibited by inhibitors of arachidonic acid metabolism

Prostaglandin D2 (binds smooth muscle cells)
• Induces vasodilation and bronchochonstriction
• chemotactic for neutrophils, basophils, eosinophils and monocytes
• Major arachidonic acid derived mediator produced by the cyclooxygenase pathway (synthesis can be prevented by aspirin)

Platelet Activating Factor (PAF)
• Induces broncoconstriction
• Dilation of vascular smooth muscle
• Activates and attracts neutrophils, eosinophils and platelets

CYTOKINE RECRUITMENT

Question 7

Manifestations of Type I Hypersensitivity

Answer 7

• Wheal & Flair Response • Atopic Derma55s
• Rhinitis
• Food Allergies
• Asthma
• Anaphylaxis