Hypersensitivity Reactions

Question 1

Are people born with an effector response to allergens? Why or why not?

Answer 1

• No, there must be a first exposure to the allergen in which the primary immune response is generated, but no symptoms of hypersensitivity are experienced
• After this first exposure, subsequent exposures elicit hypersensitivity response and its symptoms

Question 1

Describe the 7 features of inhaled allergens that may promote the priming of TH2 cells that drive IgE responses, and lead to immediate hypersensitivity.

Answer 1

• Molecular type: must be proteins b/c must be T-dependent antigens. T-helper cell response is needed for activation of B cells, and class switching to IgE
• Function: very often proteases (typical mast cell effector function is to expel parasites, and they produce abundant enzymes to allow them to remodel tissue, move around)
• Low dose: low antigen dose favors differentiation of TH0 cells into TH2 effector type
• Low molecular weight: if protein is small, it can diffuse out of dust particle that delivered in into respiratory tract
• High solubility: the more soluble, the more effectively the allergen will elute out of its dust particle
• Highly stable: must be stable to survive when part of desiccated (dehydrated) particle
• Contains peptide that binds MHC II: required for any T-dependent antigen

Question 2

What are Type IV hypersensitivity reactions?

Answer 2

• Delayed type: Mediated by T cells (either CD4+ or CD8+ T cells)
• It takes 24-72 hours for T cells to initiate symptomatic inflammatory responses

INFO FROM CHART:

• Immune reactant: 1) TH1, 2) TH2, 3) CTL
• Antigen:

1 & 2. Soluble antigen

3. Cell-associated antigen
   - Effector mechanisms:
4. Macro activation
5. Eosinophil activation
6. Cytotoxicity
   - Examples:
7. Contact dermatitis, tuberculin rxn
8. Chronic asthma, chronic allergic rhinitis
9. Contact dermatitis

Question 3

What are Type I hypersensitivity reactions?

Answer 3

• Immediate-type hypersensitivity reactions: initiated by mast cell degranulation, mediated by crosslinking of IgE bound to high affinity IgE receptors of mast cells
• Occur within minutes following exposure to antigen

INFO FROM CHART:

• Immune reactant: IgE
• Antigen: soluble
• Effector mechanism: mast-cell activation
• Examples: allergic rhinitis, asthma, systemic anaphylaxis

Question 5

What are Type II hypersensitivity reactions?

Answer 5

• Altered self hypersensitivity reactions: initiated by allergen-specific IgG antibodies, and the inflammatory response is mediated by the complement cascades, phagocytes and NK cells
• Take longer to develop than Type I reactions: 4-12 hours

INFO FROM CHART:

• Immune reactant: IgG
• Antigen:
  1. Cell- or matrix-associated Ag
  2. Cell-surface receptor
• Effector mechanism:
  1. Complement, FcR+ cells (phagocytes, NK)
  2. Ab alters signaling
• Examples:
  1. Some drug allergies, e.g., penicillin
  2. Chronic urticaria (Ab to FalphaRIalpha)

Question 6

What molecular mechanism prompts mast cell degranulation?

Answer 6

• Crosslinking of the IgE Abs bound to high affinity IgE receptors on mast cell surface

Question 7

What are the enzyme, toxic mediator, and chemokine effector molecules of mast cells?

Answer 7

• Enzymes: tryptase, chymase, cathepsin G, and carboxypeptidase -> remodeling of CT matrix
• Toxic mediator: histamine, heparin -> toxic to parasites, increase vascular permeability, cause smooth muscle contraction
• Chemokine: CCL3 -> chemotactic for monocytes, macrophages, and neutrophils

Question 8

What are the cytokine and lipid mediator effector molecules of mast cells?

Answer 8

• Cytokines:
  1. TNF-alpha: promotes inflammation, stimulates cytokine production by many cell types, and activates endothelium
  2. IL-4, IL-13: stimulate/amplify TH2-cell response
  3. IL-3, IL-5, GM-CSF: promote eosinophil production and activation
• Lipid mediators:
  1. Leukotrienes C4, D4, and E4: cause smooth muscle contraction, increase vascular permeability, and cause mucus secretion
  2. Platelet activating factor: chemotactic for leukocytes, amplifies production of lipid mediators, activates neutrophils, eosinophils, and platelets

Question 9

What are Type III hypersensitivity reactions?

Answer 9

• Immune complex hypersensitivies: result of immune complex deposition and ensuing inflammatory responses as phagocytes encounter these immune complexes deposited in the host tissues
• Altered-self hypersensitivities (type II) often become immune complex hypersensitivities.

INFO FROM CHART:

• Immune reactant: IgG
• Antigen: soluble antigen
• Effector mechanisms: complement phagocytes
• Examples: serum sickness, Arthus reaction