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Immunology > T Lymphocyte Mediated Immunity > Flashcards

T Lymphocyte Mediated Immunity Flashcards

1
Q

general principle of T-cell activation and differentiation

A

antigen recognition - activation - clonal expansion - differentiation - effector functions

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2
Q

what are high endothelial venules

A

specialized blood vessels that bring naive B and T cells to the lymph nodes
- found in T cell zones (paracortical area)

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3
Q

formation and organization of secondary lymphoid organs are controlled by…

A

TNF family members

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4
Q

characteristics of the marginal sinus

A
  • the marginal sinus separates white and red pulp
  • T cells migrate from the marginal sinus to T-cell zones (PALS)
  • B cells migrate from marginal sinus to B-cell follicles
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5
Q

what is the marginal sinus

A

area in SLO’s where circulating B and T cells are first delivered to - it is enriched in marginal zone B cells

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6
Q

difference between marginal zone and follicular B cells

A

marginal zone B cells do not recirculate, follicular do

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7
Q

what are Fibroblast reticular cells

A

stromal cells of the spleen which produce chemokines to attract T cells from the marginal sinus

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8
Q

what are follicular dendritic cells

A

lineage of dendritic cells concentrated mainly in the follicles of SLO’s - produce the chemokine CXCL13 to attract B cells

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9
Q

path of the antigen from delivery to SLO to when it is recognized

A

antigen is delivered to SLO via arterioles - antigen is taken up by dendritic cells - dendritic cell transports antigen into T-cell zones

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10
Q

what are MALT

A

mucosa-associated lymphoid tissue
- lymph node-like structures
- the epithelium overlying them contains M cells which adapt to channel antigens and pathogens directly from the gut lumen into the underlying lymphoid tissue
- e.g. peyer’s patches

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11
Q

what guides naive T-cell migration into the lymph node

A

cell adhesion molecules

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12
Q

what are the chemokines which attract T cells to secondary lymphoid organs

A

CCL19 and CCL21

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13
Q

how do naive T cells migrate into secondary lymphoid organs

A
  • circulating lymphocyte enters an HEV in the lymph node
  • L-selectin on T cell binds to glyCAM-1 and CD34 on endothelial cell to allow rolling
  • CCR7 responds to chemokine CCL21 or 19 on endothelial surface which activates LFA-1
  • LFA-1 binds yo iCAM-1
  • lymphocyte moves into lymph node via diapedesis
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14
Q

which molecules facilitate the movement of T cells from blood vessels into lymph nodes

A

selectins and integrins

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15
Q

which selectins and integrins are used to enter HEV’s

A

selectins: L-selectin + CD34 and GlyCAM-1
integrins: LFA-1 + iCAM-1

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16
Q

which selectins and integrins are used to enter the endothelium of mucosal lymphoid tissue or marginal sinus of spleen

A

selectins: L-selectin + MAdCAM-1
integrins: LPAM-1 + MAdCAM-1

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17
Q

what happens if T cells are activated vs not activated by APC in the secondary lymphoid organs

A

activated T cell: lose ability to exit the T-cell zone and begin to proliferate there over the next several days
non-activated T cell: exits from the lymph node via the cortical sinuses within hours

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18
Q

why can a T-cell not leave the lymph node for a few days after they recognize a pathogen?

A

the T cells need a few days to differentiate from naive to an effector in the SLO’s before they exit via the cortical sinus

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19
Q

T cells encountering properly presented antigens in circulation is very low because of their specificity. how is this resolved?

A

Traffic through SLO’s takes T cells past APC which are likely presenting foreign antigen since both antigen and leukocytes collect in SLO’s

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20
Q

trapping and activation of antigen-specific naive T cells in lymphoid tissue

A
  • within 48 hours of antigen delivery most antigen-specific T cells can be trapped in the lymph fluid
  • local inflammation stimulates an increase in influx/decrease in efflux of lymphocytes in and out of lymph node
  • this is the basis for local lymph node swelling
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21
Q

Egress of lymphocytes from lymphoid tissue is mediated by…

A

Sphingosine 1-phosphate gradient

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22
Q

expression of the S1P receptor

A

antigen not encountered = increased expression
antigen encountered = decreased expression
* controlled by CD69 levels

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23
Q

important proteins involved int eh S1P gradient

A

S1P lyase: degrades S1P
CD69: internalizes S1PR1 when T cells are activated
FTY720: an immunomodulatory molecule that inhibits T-cell aggression by down-modulating expression of S1PR1 by ligand-induced internalization in the lymph node

24
Q

basis of the S1P gradient

A
  • S1P levels in lymphoid tissues are low compared to blood and lymph
    -S1PR1 is present at low levels on the surface of naive T cells as high levels of S1P in blood down-regulate it
  • no antigen recognition = S1PR1 expression increases
  • activated T cells up-regulate CD69 which down-regulates S1PR1 expression
  • activated T cells eventually reexpress S1PR1 as CD69 expression decreases
25
Q

why are S1P levels in lymphoid tissues low compared to blood and lymph

A

S1P lyase is lymphoid tissue degrades S1P

26
Q

very basic explanation of the S1P gradient mechanism

A

the S1P gradient is needed to direct T-cell movement in the body. S1P receptors on T cells detect the gradient which pulls them towards the blood (where gradient is higher) to guide them out of the lymph node

27
Q

dendritic cells in antigen presentation to T cells in SLO’s

A
  • located throughout the body
  • results in activation of naive T cells
28
Q

macrophages in antigen presentation to T cells in SLO’s

A
  • located in lymphoid tissue, connective tissue and body cavities
  • results in activation of macrophages by effector and memory T cells
29
Q

B cells in antigen presentation to T cells in SLO’s

A
  • located in lymphoid tissue and peripheral blood
  • results in delivery of help to B cell by T-helper cell
30
Q

antigen uptake by dendritic cells in non-lymphoid tissues and delivery to T cells in lymphoid tissues

A
  • immature conventional dendritic cells reside in tissues and are activated by MAMP’s
  • TLR signalling induces expression of CCR7 and enhances processing of antigens
  • CCR7 directs migration of DC to lymph node
  • activated dendritic cell in T-cell zone primes naive T cells
31
Q

what is T cell priming?

A

the first contact that antigen-specific naive T cells have with an antigen

32
Q

what are the 2 major classes of dendritic cells

A

conventional DCs
Plasmacytoid DCs

33
Q

characteristics of conventional dendritic cells

A
  • concerned with activation of naive T cells
  • subsets cDC1 and cDC2
  • most abundant in non-lymphoid tissues, but some are also lymphoid tissue resident
34
Q

characteristics of plasmacytoid dendritic cells

A
  • sentinels of viral infection
  • secrete large amounts of type 1 IFNs
35
Q

what are the different routes which DCs can take up, process and present protein antigens

A

receptor mediated phagocytosis (CD4)
macropinocytosis (CD4)
viral infection (CD8)
cross-presentation after phagocytic or macropinocytic uptake (CD8)
transfer from incoming DC to resident DC (CD4 and CD8)

36
Q

cell adhesion molecule pairs in T-cell:DC interactions

A

LFA:1 + iCAM-1
CD2 + CD58
LFA-1 + iCAM-2

37
Q

how specific antigen recognitions stabilizes T-cell:DC interactions

A
  • T-cells initially bind APC through low affinity LFA:iCAM-1 interactions
  • binding of TCRs signals LFA-1 to undergo conformational change
  • this increases affinity and avidity that results in prolonged cell-cell contact
38
Q

3 kinds of signals involved in activation of naive T cells by APCs

A
  1. TCR recognition of antigen peptide:MHC on surface of activated cDC’s
  2. co-recognition of costimulatory molecules (CD28-B7)
  3. cytokines delivered to activated naive T cell by APC
39
Q

initial T-cell response to antigen results in…

A

rapid clonal expansion that is followed by clonal contraction as the immune response wanes

40
Q

what is clonal contraction

A

activated T-cells undergo apoptosis so the immune response does not go out of control

41
Q

clonal expansion of T cells is driven by…

A

IL-2

42
Q

high-affinity IL-2 receptors are three-chain structures present on…

A

only activated T-cells

43
Q

after a naive T-cell moves to an SLO, they are activated and express a high-affinity IL-2 receptor. what are the paracrine and autocrine functions of this?

A

paracrine: binding of IL-2 to its receptor promotes enhanced proliferation and can modulate T-cell differentiation
autocrine: activated T cell makes IL-2 which binds to its own high-affinity receptor and causes clonal expansion

44
Q

what are the effects of additional co-stimulatory and inhibitory receptors (CTLA-4) which help control clonal expansion after T-cell activation

A
  • CTLA-4 binds two B7, has higher affinity and outcompetes CD28 binding
  • CTLA-4 can be internalized with bound B7, removing B7 from the APC surface
  • CTLA-4 may transmit a negative signal that inhibits T-cell receptor signalling
45
Q

what are the 3 subsets that naive T cells differentiate into

A

cytotoxic T cells: kill infected cells
helper T cells
regulatory T cells: stop the adaptive immune response

46
Q

expression of cell-surface molecules in naive T cells

A

L-selectin = YES
CCR7 = YES
LFA-1 = moderate
S1PR1 = moderate
VLA-4 = NO

47
Q

expression of cell-surface molecules in effector T cells

A

L-selectin = NO
CCR7 = NO
LFA-1 = YES
S1PR1 = NO
CLA-4 = moderate

48
Q

what are the 4 subsets of helper T cells

A

TH1
TH2
TH17
T-FH

49
Q

what are the sources of antigens targeted for the different subsets of T cells

A

TH1 = extracellular bacteria, microbes that resist macrophage killing
TH2 = helminth parasites
TH17 = extracellular bacteria, fungi
T-FH = nearly all microbes

50
Q

what proteins are found in granules of cytotoxic T cells

A

perforin: delivers contents of granules into the cytoplasm of target cell
granzymes: serine proteases which activate apoptosis
granulysin: antimicrobial actions which can induce apoptosis

51
Q

what does MHC I present in healthy vs infected cells

A

healthy = presents self-peptides
infected = presents antigens (foreign)

52
Q

how T-cell mediated cytotoxicity directly kills the cell

A
  • CTL recognizes and binds virus-infected cell
  • CTL programs target for death, inducing DNA fragmentation
  • CTL migrates to new target
  • target cells die by apoptosis, neighbouring uninfected cell is not killed
53
Q

how the extrinsic pathway for apoptosis of target cells by T cells starts

A
  • triggered when FasL binds to Fas
  • clustering of death domains in Fas recruits FADD
  • FADD activate pro-caspase 8 which activates pro-caspase 3
54
Q

how the intrinsic pathway for apoptosis of target cells by T cells starts

A
  • when a cell is infected the mitochondria releases cytochrome c
  • cytochrome c binds to Apaf-1
    this complex assembles into an apoptosome which activates pro-caspase 9, which activates pro-caspase 3
55
Q

where the intrinsic and extrinsic pathways of apoptosis by T cells converge

A

the activation of procaspase 3

56
Q

what is the role of pro-caspase 3

A

enters the nucleus and cleaves DNA = cell death

Immunology (20 decks)

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