Assignment 9 - use pictures too! Flashcards

1
Q

where does a primary immune response take place?

A

secondary lymphoid tissue

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2
Q

what is the main function of effector CD4+ T cells?

A

secretion of cytokines

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3
Q

when are T cells considered naive (Thp)?

A

when they survive the screening process in the thymus

*note they are unable to perform their biological function without a differentiation stage

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4
Q

where does the antigen-induced differentiation stage occur for naive T cells?

A

outside of the thymus

Blood –> spleen
Mucosaltissue –>MALT–>laminapropria
Lymph–>lymphnode–>whitepulp

induced by high avidity interaction with foreign peptide/class II MHC in the presence of costimulatory signals

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5
Q

what 2 things can T cells differentiate into?

A

memory cells

apoptosis

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6
Q

what does the subset of Thp cell activation depend on

A

the cytokines in the local environment

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7
Q

what does the activation of T cells require?

A

the antigen to be displayed on the surface of APC in association with class II MHC

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8
Q

what is the most efficient APC

A

dendritic cell

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9
Q

why is the dendritic cells the most efficient APC

A

because it expresses both class II MHC and various costimulatory molecules (whose counter products are present on the T cell)

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10
Q

what happens when a T cells interacts with a peptide/class II MHC complex in the absence of costimulatory interactions

A

the T cell becomes unresponsive = anergic

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11
Q

what are the interactions that take place between a T cell and APC

A
  • class II MHC peptide ——– TCR
  • class II MHC ——————-CD4
  • ICAM(1,2,3)———————LFA-1 (CD11a/CD18)
  • CD40—————————-CD40L (CD154)
  • LFA-3—————————-CD2
  • CD80—————————–CD28
  • CD86—————————–CD28

*all enhance the avidity of peptide/MHC interactions with TCR

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12
Q

what occurs when class II MHC peptide and TCR interact?

A

Thp express IL-2 receptors and secrete cytokine, IL-2

functions in autocrine + paracrine

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13
Q

what does the interaction of IL-2 with IL-2 receptor induce?

A

clonal expansion of antigen stimulated T cells = increasing the number of T cells with specificity uniquely recognizing the class II MHC peptide complex that induced the initial differentiation

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14
Q

what is hte role of the CD28 and CD80/86 interaction

A

to stabilize mRNA for IL-2

if this doesn’t occur = anergic T cell

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15
Q

where are the two forms of B7 (CD80 = CD86/B7-1 and B7-2) expressed and induced

A

expressed - dendritic cells + peritoneal macrophages

induced - activated B cells, monocytes, Langerhans cells

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16
Q

antigen induced differentiation of Thp proceeds via a _____ intermediate to either a ___ or ___ subset

A

Th0
Th1
Th2

*defined by the cytokines they secrete

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17
Q

what cytokines do Th0 cells secrete?

A

IL-4
IL-2
IFNgamma

common to both subsets

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18
Q

if IFNgamma is high, what subset predominates?

A

Th1

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19
Q

if IL-4 is high, what subset predominates

A

Th2

20
Q

what is hte source of IL-4 before differentiation of Thp to Th2

A

Mast cells
basophils
other non T cells
transiently—Th0

provide in early phase of response
mast cell stimulation –> Th2 development

21
Q

what produces IFNgamma?

A

Th0 cells

IL-12 activated NK cells

22
Q

what cytokines have been shown to enhance the role of IL-12 on NK cell production IFNgamma production

A

IL-15

IL-18

23
Q

what cells secrete IL-12

A

activated dendritic cells
macrophages

influence of IL-12 on development may be indirect

24
Q

what are type 1 cytokines

A

IL-2
TNF
IFNg

25
Q

what are type 2 cytokines

A
IL-4
IL-5
IL-6
IL-10
TGFbeta
IL-13
26
Q

what is the role of type 1 cytokines

A

support immune responses in which macrophages, NK cells and CD8+ T cells are effectors

resposnbile for delayed type hypersensitivity responses that are manifestations of activated memory CD4+ Th1 cells

27
Q

what is the role of type 2 cytokiens

A

support B cell induced activation
support antigen induced B cell differentiation to plasma cells
support isotype switching to IgG1 and IgE
humoral immunity

28
Q

what is required for isotype switching to IgE?

A

IL-4

29
Q

in general, isotype swithcing requires the contribution of both _____ and ___ cytokines

A

type 1 and type 2

30
Q

what is hte role of IL-10

A

key role in down regulation of Th1 (cells/cytokines) – this occurs via inhibition of IL-12 secretion by APC

31
Q

what are hte mechanisms that control T cell activation

A
  1. loss of T cell stimulation because the infectious agent has been eliminated so class II MHC peptide are no longer being presented to T cells
  2. reciprocal regulation of cytokine secretion by Th1 and Th2 cells
  3. CTLA-2/CD152 interaction
  4. CD200-CD200R interaction
  5. apoptosis
  6. regulatory T cells (Tregs)
32
Q

what are the T cells that leave the thymus?

A
  • CD4+ naïve cell (Thp)

- Precytotoxic CD8+ T cells (pCTL)

33
Q

what does an active Thp express? What does it secrete and what does the secretion lead to? what does it stimulate the dendritic cell to secrete? what does this do?

A

IL-2R
secretion IL-2 - induces expansion of Th0 clones form antigen stimulated T-cells

secretion of IL-12 from dendritic cell - activates NK cell to secrete IFN gamma

34
Q

what cytokines are secreted by Th0 clones?

A

IFNy –> Th1 cells (type 1 cytokines)
IL-2 –> makes more Th0 clones
IL-4 -> Th2 cells (type 2 cytokines)

35
Q

what triggers the secretion of IL-4?

A

mast cell

36
Q

how does T cell regulation occur in Th1?

A

CD80/CD86 —CD152(CTLA-4) = T cell downreg

CD80/CD86 —CD28 = T cell activation

37
Q

what is the role of IFNy?

A

its a Th1 cytokine that shuts off Th2

38
Q

what cytokines turn off Th1?

A

IL-10
IL-4
both are Th2 cytokines

39
Q

what is the role of IL-10

A

inhibits secretion of IL-12 by APC

downstream inhibits Th1 and prevents NK cells from producing IFNy

40
Q

how is pCTL (precytotoxic CD8+ T cell) activated

A

interaction with:

  • CD4+ T cell derived IL-2 cytokine
  • Target cell expressing antigen + class I MHC
  • CD2—LFA3
  • LFA1—ICAM (1,2,3)
  • CD8 binds to class I MHC at separate site from where it binds to TCR
41
Q

what is the difference between the differentiation stage environments between CD4+ and CD8+ T cells

A

CD4+ need secondary lymphoid tissue

CD8+ it can do it anywhere, site of infection etc.

42
Q

what occurs in the progression from pCTL to CTL

A
  • IL-2 expression
  • preCTL detaches from target cell expressing antigen
  • differentiation takes about 1 week
43
Q

what occurs when there is a delivery of lethal hit

A

-mature CTL (CD8+) conjugates with target cell
-conjugate formation triggers locatization of lytic granules to membrane where two cells are attached o granules are released outward toward target cell
-polarized release of granules ensures specificity of killing target cell and not self
-death caused by osmotic lysis or apoptosis
-CTL detaches and continues its function of immunological surveillance
-as elimination of virally infected cells occurs the antigenic stimulus for specific CD8+Tcells decrease.
-CTL clones that are generated with TCRs specific for the antigen will die others will become dormant
(memory cells)
-Memory cells will become activated immediately in the event that the antigen reappears
-These cells require less costimulation than for the primary response

44
Q

how long does it take for pCTL–> CTL

A

1 week

45
Q

what does the interaction between CD200 and CD200R lead to?

A

suppression of T cell mediated immune response - immunosupressent

46
Q

CD200 is expressed on what cells?

A

T cells
B cells
Dendritic cells

47
Q

CD200R is expressed on what

A

myeloid lineage cells

and some T cells