Hypersensitivity

Question 1

describe type I hypersensitivity

Answer 1

• sensitization
  
  • antigen contact, typically low-dose via mucous membranes (respiratory, GI), IgE production
• elicitation (re-exposure)
  
  • pre-formed IgE (allergen-specific) triggers mast cell activation mediator release
• reactions
  
  • can occur within seconds-minutes of exposure
• severity ranges from irritating to fatal

Question 2

describe the sensitization response

Answer 2

• IgE produced by plasma cells is rapidly taken up by FcER1 on tissue mast cells and circulating basophils (serum 2 days; compare to IgG, which is 21 days)

Question 3

describe the early phase of the sensitization response

Answer 3

• IgE crosslinking by antigen release of preformed mediators
  
  • immedate release of histamine
    
    • smooth muscle constriction, vasodilation, vascular leak, GI motility (increased), mucous secretion, sensory nerve activation
• followed by rapid production of arachidonic acid products
  
  • within minutes: leukotrienes, prostaglandins

Question 4

describe the late phase of the sensitization response

Answer 4

• gene activation leads to new cytokine production ~6 hours after antigen triggering
  
  • TNFa
    
    • recruit inflammatory cells
  • IL-3, IL-5, GM-CSF
    
    • eosinophil production
  • IL-4, IL-13
    
    • propogate Th2 response

Question 5

the innate responder cell in type I hypersensitivtiy is ____

describe this

Answer 5

the innate responder cell in type I hypersensitivtiy is eosinophils

• production of eosinophils in bone marrow driven by: IL-5 (Th2 cytokine); also IL-3 and GM-CSF
• chemotaxis from blood to tissue sites utilizes:
  
  • IL-5
  • eotaxins (CCL11, CCL24, CCL26)
• primed for activation by IL-5, eotaxins C3a/C5a
• expression of FcR for IgG, IgA, IgE

Question 6

the most potent trigger for eosinophils is ____

what does it release?

Answer 6

the most potent trigger for eosinophils is FcR-crosslinking

• results in exocytosis of preformed toxic proteins
  
  • major basic protein
  • eosinophil cationic protein
  • eosinophil-derived neurotoxin
• propagate the response:
  
  • secrete IL-3, IL-5, GM-CSF
  • secrete IL-8 (PMN attractant)

Question 7

describe the manifestations of Type I Hypersensitivity

Answer 7

• respiratory mucosa
  
  • allergic
  • rhinitis
  • asthma
• GI mucosa
  
  • food allergy
• skin
  
  • contact urticaria
• circulation
  
  • anaphylaxis

Question 8

describe the process of anaphylaxis

Answer 8

• response to systemic circulation of allergen
• IgE cross-linking on mast cells in perivascular tissue
• circulating histamine, PGs/LTs –> vasodilation, vascular leak
• high-output shock: decreased BP despite increased CO

Question 9

in Type II (cytotoxic) Hypersensitivity, the damaged is mediated by _____

Answer 9

in type II hypersensitivity, the damage is mediated by tissue-specific IgG or IgM

Question 10

describe the hapten response

Answer 10

• mechanism of sensitization
  
  • a foreign agent (typically drug) acts as a hapten
  • conjugates self protein modified self
  • T cell/B cell response high affinity
  • anti-self IgG or IgM
• on re-exposure
  
  • hapten conjugation to self modified
  • binding of IgG or IgM to modified self tissue (platelet, RBC)
  • activation of normal immunoglobulin effector

Question 11

summarize the antibody function and then the resulting syndrome

Answer 11

Question 12

describe type III (immune complex) hypersensitivity

Answer 12

Question 13

describe type IV (delayed) hypersensitivity

Answer 13

• group of T cell mediated responses to antigen
  
  • direct killing of target cells (by CD8 T cells)
  • indirect via activation of macrophages (CD4 T cells)
  • sensitization is required
  • on re-exposure: reactions occur over 1-3 days
  • T cells are necessary and sufficient

Question 14

____ do not have type IV reactions

Answer 14

athymic subjects do not have type IV reactions

Question 15

describe the pathogenesis of type IV hypersensitivity

Answer 15

Question 16

summarize hypersensitivity type I

Answer 16

Question 17

summarize type II hypersensitivity

Answer 17

Question 18

summarize type III hypersensitivities

Answer 18

Question 19

summarize type IV hypersensitivities

Answer 19