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DEMS: Unit 1 > GI Immunology > Flashcards

Flashcards in GI Immunology Deck (19):
1

Types of T cells

  • 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

2

Characteristics/fxn of Th1 cells

  • 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

3

Characteristics/fxn of Th17 cells

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

4

Characteristics/fxn of Th2 cells

  • 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

5

Characteristics/fxn of Tfh cells

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

6

Characteristics/fxn of Treg cells

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

7

Molecular marker/antigen prestation of helper T cells

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

8

Molecular marker/antigen prestation of killer T cells

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

9

Mechanism of T Cell Development @ thymus

  • 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

10

Further development of T cell

  • 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

11

Normal cytokines/activated T cells @ Peyer's Patches

  • 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

12

Consequence of knocking out Treg vs. iTreg

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

13

Cytokines/T cells during infections

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

14

Pathways w/risk loci for IBD

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

15

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

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

16

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

  • 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 

17

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

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

18

Possible mechanism of IBD development

  • 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

19

Genetic risks for celiac disease

  • 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