GI Immunology

Question 1

Types of T cells

Answer 1

• Type 1 Helper T cells: Th1
• Th17 Helper T cells: Th17
• Type 2 Helper T cells: Th2
• Follicular Helper T cells: Tfh
• Regulatory T cells: Treg
• Cytotoxic/killer T cells: CTL

Question 2

Characteristics/fxn of Th1 cells

Answer 2

• helper T cells
• recognize antigen ==> lymphokine (“cytokine”) production ==> attraction of macrophages
  
  • cytokine = IFNgamma & IL-2
  • IFNgamma ==> macrophages = M1 = inflammatory, destructive, “angry”
  • IL-2 ==> activates CTLs

Question 3

Characteristics/fxn of Th17 cells

Answer 3

• helper T cells
• cause focused inflammation
• more powerful than Th1
• cytokine produced = IL-17

Question 4

Characteristics/fxn of Th2 cells

Answer 4

• helper T cells
• stimulate macrophages to become M2 = alternatively activated ==> walled-off pathogens and healing (after M2 response)
• also attract eosinophils
• cytokines = IL-5, IL-4

Question 5

Characteristics/fxn of Tfh cells

Answer 5

• helper T cells
• recognize antigen @ T cell areas of lymph nodes ==> B cell follicles ==> activate B cells

Question 6

Characteristics/fxn of Treg cells

Answer 6

• helper T cell
• cytokines = IL-10 & TGFbeta
• suppress fxn of other helper T cells

Question 7

Molecular marker/antigen prestation of helper T cells

Answer 7

• marker = CD4
• search for antigen on MHC class II

Question 8

Molecular marker/antigen prestation of killer T cells

Answer 8

• marker = CD8
• search for antigent on MHC Class I (on all nucleated cells)

Question 9

Mechanism of T Cell Development @ thymus

Answer 9

• Pre-T cells @ thymus proliferate and express a randomly assembled T cell receptor (TCR).
• T cells/TCR receptors examine the surfaces of stromal cells ==>
  
  • non-selection = no affinity
  • negative selection = high affinity for self-peptide in MHC (autoimmunity) ==> death of cell via apoptosis
  • positive selection = low affinity ==> survival and maturation

Question 10

Further development of T cell

Answer 10

• helpers start @ Th0 (undecided precursor)
• Th0 @ paracortex of lymph nodes/other lymphoid tissues
• dendritic cells (DC) present antigen ==> Th0s divide and differentiate into various helper Ts
• most antigens produce some of each type of helper T

Question 11

Normal cytokines/activated T cells @ Peyer’s Patches

Answer 11

• cytokines: TGFbeta, IL-10
• T cells:
  
  • Tregs = prevent overactivity in response to numerous foreign materials (food) entering through gut
    
    • “iTreg” = prevent chronic inflammation @ gut
  • Tfh = drive B cells toward making IgA

Question 12

Consequence of knocking out Treg vs. iTreg

Answer 12

• Treg knockout ==> systemic autoimmunity & no IBD
• iTreg knockout ==> IBD & no systemic autoimmunity

Question 13

Cytokines/T cells during infections

Answer 13

• Stress/damaged epithelia ==> IL-6 production
• Cytokines: TGFbeta & IL-6 ==>
  
  • downregulation of Treg
  • upregulation of Th1 & Th17

Question 14

Pathways w/risk loci for IBD

Answer 14

• Apoptosis
• Endoplasmic reticulum stress
• Oxidative stress
• Cell migration
• Epithelial barrier
• Immune cell recruitment
• Th17
• Antigen presentation
• Innate immune defense

Question 15

Possible roles of genetic defects @ apoptosis, ER stress, and oxidative stress pathways

Answer 15

• Apoptosis
  
  • Macrophages eating apoptotic cells make insufficient TGFβ
• Endoplasmic reticulum stress
  
  • Could release damage-associated molecular patterns (DAMPs)
• Oxidative stress
  
  • Could release DAMPs

Question 16

Possible roles of genetic defects @ cell migration, epithelial barrier, immune cell recruitment

Answer 16

• Cell migration
  
  • Affects how T and inflammatory cells move through gut
• Epithelial barrier
  
  • Leaky, allows gut enzymes and defensins back through, causing inflammation
• Immune cell recruitment
  
  • Abnormal differentiation, attraction of inflammatory cells

Question 17

Possible roles of genetic defects @ Th17, antigen presentation, innate immune defense

Answer 17

• Th17
  
  • Too easily activated
• Antigen presentation
  
  • Excessive presentation of commensal antigens
• Innate immune defense
  
  • Does not adequately direct Th0 to Treg differentiation

Question 18

Possible mechanism of IBD development

Answer 18

• Infection ==> strong Th1 response to infectious antigens
• during infection: commensal bacteria readily penetrate the gut and are seen between and beyond epithelial ==> Th1 response to commensals
• normally: recover from infection and the memory cells never re-exposed
• pathophys: Th1 cells are reactivated ==> IBD

Question 19

Genetic risks for celiac disease

Answer 19

• seen almost exclusively in people who have the HLA-DQ2 or -DQ8 allele
• This Class II MHC is uniquely able to present immunodominant peptides derived from gliadin (the gluten protein) to Th1/Th17 cells
  
  • this protein is too awkward to fit into most MHC antigen-presenting grooves