EXAM 3 T Cell-Mediated Immunity Flashcards

1
Q

Describe CD8 T cells

A
  • kills infected or diseased cells
  • direct effector T cell arm
  • targeted
  • repeated activity until inhibited
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2
Q

describe CD4 T cells

A
  • enhance innate and adaptive immunity
  • regulatory T cell arm
  • targeted
  • direct and indirect effector functions; can kill
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3
Q

describe the basic process of T cell activation and differentiation

A

for both CD8 and CD4 T cells:

  • antigen presenting cell interacts with naive T cell (antigen recognition)
  • T cells are activated by IL-2 and IL-2R (same for CD8 and CD4)
  • clonal expansion
  • differentiation
  • effector cell and memory cell
  • CD4 - activation of macrophages, B cells, other cells
  • CD8 - killing of infected target cells; macrophage activation
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4
Q

___ initiates T cell immunity

A

antigen presentation

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5
Q

___ are the most common T cell activator

A

dendritic cells

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6
Q

dendritic cells must be ___, and presentation occurs in ___

A
  • activated
  • secondary lymphoid organs
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7
Q

tissue dendritic cells take up antigen by what 2 mechanisms?

A

macropinocytosis and phagocytosis

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8
Q

MHC expression is ___ on immature DCs and ___ on DCs in lymphoid tissue

A
  • low
  • high
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9
Q

describe the location of DCs in the body

A

ubiquitous throughout the body

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10
Q

what are the 3 antigen presenting cells?

A

dendritic cells, macrophages, and B cells

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11
Q

which antigen presenting cell is primarily responsible for presenting antigen to T cells?

A

dendritic cells

most common and most prevalent T cell activator

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12
Q

dendritic cells mature though ___

A

antigen activation

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13
Q

describe the process of DC maturation via antigen activation

A
  1. immature DCs in peripheral tissues encounter pathogens and are activated by PAMPs
  2. TLR signaling induces CCR7 and enhances processing of pathogen-derived antigens
  3. CCR7 directs migration into lymphoid tissues and augments expression of co-stimulatory molecules and MHC molecules
  4. mature dendritic cell in T-cell zone primes naive T cells
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14
Q

DCs are targeted to lymph nodes by ___ binding ___ and ___

A
  • CCR7
  • CCL19 and CCL21
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15
Q

dendritic cells take up bacterial ___ in the skin and then move to enter a draining lymphatic vessel. DCs bearing ___ enter the draining lymph node, where they settle in the ___ areas

A
  • antigen
  • antigen
  • T-cell
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16
Q

where do the different antigen presenting cells distribute in lymph nodes?

A
  • DCs - T cell areas
  • macrophages - all areas
  • B cells - B cell areas
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17
Q

DCs present antigen by ___ and ___

A

MHC I and II

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18
Q

___ is critical for CD8 T cell activation

A

cross-presentation

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19
Q

what 2 ways do DCs present antigen to CD4 T cells?

A
  • receptor-mediated endocytosis of bacteria
  • macropinocytosis of bacteria or viruses
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20
Q

what 3 ways do DCs present antigen to CD8 T cells?

A
  • viral infection
  • cross-presentation of exogenous viral antigens
  • transfer of viral antigens from infected DC to resident DC
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21
Q

naive T cells can enter a draining lymph node by which two routes?

A
  • in the blood
  • in the afferent lymph coming from an upstream lymph node
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22
Q

___ monitor antigens presented by DCs

A

naive T cells

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23
Q

naive T cell population rotates/circulates through ___, resulting in ___

A
  • lymph nodes
  • systemic antigen exposure (aka systemic ability to target infection)
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24
Q

T cells and DCs form immune ___

A

synapses

the strength of the synapse dictates whether or not the T cell will be activated

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25
Q

T cell activation requires which 3 signals?

A
  • activation
  • survival
  • differentiation
  • *process is the same for both CD4 and CD8 T cells
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26
Q

antigen presenting cells deliver 3 kinds of signals to naive T cells to activate them. describe.

A
  1. T Cell Receptor
  • Peptide recognition
  • MHC I or II
  • CD8 or CD4
  1. Co-stimulatory Molecules
  • Survival signal
  • B7 family (APC)
  • CD28 family (T cell)
  • B7-CD28 required for T cell activation
  1. Cytokines
  • Paracrine and autocrine
  • Propagation (IL-2)
  • Differentiation
  • IL-2: CD8, All TH
  • IL-4: TH2
  • IL-6: TFH
  • IL-12: TH1
  • TGF-β + IL-16 + IL-23: TH17
  • TGFβ: Treg
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27
Q

naive T cell TCR activation in the absence of co-stimulation (from ___ and ___) leads to ___

A
  • B7 and CD28
  • anergy
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28
Q

describe co-stimulation of T cells and antigen presenting cells, which is required for T cell activation

A
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29
Q

activation induces T cell changes in what 5 ways?

A
  • differentiation
  • clonal expansion
  • changes in surface protein expression
  • migration to target tissues
  • effector functions
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30
Q

in what ways does activation induce T cell differentiation?

A
  • CD8 T cells
    • effector cells, memory cells
  • CD4 T cells
    • Th1, Th2, Th17, Tfh, Treg
    • effector cells, memory cells
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31
Q

activated can induces T cells to migrate to which two target tissues?

A
  • lymph nodes
  • sites of infection or damage
32
Q

how does activation induce changes in T cell molecule expression?

A
  • upregulates expression of adhesion, signaling, and protease molecules
33
Q

which IL drives clonal expansion?

A

IL-2

34
Q

IL-2 drives clonal expansion in ___ T cell lineages, and involes what kind of signaling?

A
  • all
  • autocrine
35
Q

how does IL-2 drive clonal expansion?

A

T cells produce their own IL-2, stimulation to more sensitive IL-2 receptor, driving proliferation (clonal expansion)

36
Q

___ inhibits continued T cell activation and proliferation

describe how this works

A

CTLA-4

  • T cells don’t die after effector functions are performed
  • CTLA-4 is expressed on activated T cells
  • binding an antigen presenting cell after activation leads to T cell inhibition
  • B7 binds CTLA-4 20-fold stronger than CD28
37
Q

what is CTLA-4?

A

cytotoxic T lymphocyte-associated protein 4

38
Q

do CD8 T cells dies once their effector function is complete?

A

no; they kill repeatedly

39
Q

CD8 T cells only kill cells expressing targeted peptide via ___

A

MHC I

40
Q

how many ways can naive CD8 T cells be activated?

A

2

41
Q

describe the two ways that naive CD8 T cells can be activated

A
  • DCs infected with some types of virus can activate a naive virus-specific T cell on their own
  • DCs infected with some viruses need help to activate a naive virus-specific CD8 T cell
42
Q

CD8 T cells kill through ___ and ___

A

perforin and granzymes

43
Q

how do CD8 T cells kill through perforin and granzymes?

A
44
Q

what are the 3 proteins in granules of cytotoxic T cells?

A

perforin, granzymes, and granulysin

45
Q

what is the action of perforin on target cells?

A

aids in delivering contents of granules into the cytoplasm of target cell

46
Q

what is the action of granzymes on target cells?

A

serine proteases, which activate apoptosis once in the cytoplasm of the target cell

47
Q

what is the action of granulysin on target cells?

A

has antimicrobial actions and can induce apoptosis

48
Q

DCs have ___ that dictate what ILs they express when they are presenting pathogen

A

PPRs

49
Q

___ drives a cellular mediated response to a pathogen

A

Th1

50
Q

___ drives a humoral response to pathogen

A

Th2

51
Q

CD4 Th1 and Th2 differentiation involves what 3 things?

A
  • cytokine induction
  • transcription factor
  • effector cytokines
52
Q

___ induce CD4 T cell subtype differentiation

A

cytokines

53
Q

what is Th0?

A

naive CD4 T cell

54
Q

which cytokines lead to the production of Th1 cells, and what is the function of Th1 cells?

A
  • IL-12 and IFN-gamma
  • activate macrophages
55
Q

which cytokines lead to the production of Th17 cells, and what is the function of Th17 cells?

A
  • IL-16, TGF-beta, and IL-23
  • enhance neutrophil response
56
Q

which cytokines lead to the production of Th2 cells, and what is the function of Th2 cells?

A
  • IL-4
  • activate cellular and antibody response to parasites
57
Q

which cytokines lead to the production of Tfh cells, and what is the function of Tfh cells?

A
  • IL-6 and IL-21
  • activate B cells, maturation of antibody response
58
Q

which cytokines lead to the production of Treg cells, and what is the function of Treg cells?

A
  • TGF-beta
  • suppress other effector T cells
59
Q

how do Th1 cells activate macrophages?

A
60
Q

describe activated macrophages

A
  • express co-signaling ligands
  • kill intracellular pathogens
  • release cytokines and antimicrobial effectors
  • present antigen
61
Q

Th1 cells form ___ when pathogens cannot be cleared

A

granulomas

62
Q

what is a granuloma that Th1 cells form when pathogens cannot be cleared?

A
  • a compact aggregate of leukocytes that sequester a pathogen
  • occurs during chronic inflammation
  • infectious and non-infectious agents
  • several types
  • pyogenic granulomas are not true granulomas
63
Q

Th1 cytokines enhance the ___ response

A

induced innate

64
Q

what are the cytokines that activated Th1 cells express?

A
  • IFN-gamma and CD40 ligand
  • Fas ligand or LT-beta
  • IL-2
  • IL-3 + GM-CSF
  • TNF-alpha and LT-alpha
  • CXCL2
65
Q

when activated Th1 cells express IFN-gamma and CD40 ligand, what happens?

A

activates macrophage to destroy engulfed bacteria

66
Q

when activated Th1 cells express Fas ligand or LT-beta, what happens?

A

kill chronically infected cells, releasing bacteria to be destroyed by fresh macrophages

67
Q

when activated Th1 cells express IL-2, what happens?

A

induces T cell proliferation, increasing numbers of effector cells

68
Q

when activated Th1 cells express IL-3 + GM-CSF, what happens?

A

induces macrophage differentiation in the bone marrow

69
Q

when activated Th1 cells express TNF-alpha + LT-alpha, what happens?

A

activates endothelium to induce macrophage binding and exit from blood vessel at site of infection

70
Q

when activated Th1 cells express CXCL2, what happens?

A

causes macrophages to accumulate at site of infection

71
Q

___ cells activate B cells and induce class switching

A

Tfh

72
Q

how do Tfh cells activate B cells?

A
73
Q

how do Treg cells suppress other T cells?

A
74
Q

___ and ___ cells regulate mucosal inflammation

A

Th17 and Treg

75
Q

Th17 and Treg cells are enriched in the ___

A

gut

76
Q

how do Th17 and Treg cells regulate mucosal inflammation?

A
  • Treg cells inhibit mucosal inflammation
  • Th17 cells:
    • neutrophil recruitment
    • antimicrobial peptide production
    • tissue repair
77
Q

persistent Th17 can be negatively involved in which autoimmune disorders?

A
  • rheumatoid arthritis
  • multiple sclerosis
  • psoriasis
  • inflammatory bowel disease