T-Lymphocytes Flashcards

0
Q

TCR variable region genes form by…

A

chromosomal rearrangements.

a chains are 2 gene segments and b chains are 3 gene segments.

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1
Q

T-cell receptor complex

A

TCR, and 2 CD3 molecules

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2
Q

alpha chain TCR variable region is made of…

A

one V and one J genes are paired together.

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3
Q

beta chain variable region of TCR contain…

A

one V, one D, and one J gene.

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4
Q

TCR variability

A

there are 10^18 possible TCR variable regions

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5
Q

TCR part of TCR complex

A

recognizes antigenic peptides bound to MHC molecules

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6
Q

CD3 part of TCR complex

A

transmits the recognition signal to the cytoplasm & nucleus

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7
Q

Types of TCR

A

TCRalpha-beta

TCRgamma-delta

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8
Q

Severe Combined Immunodeficiency (SCID)

A

inherited immunodeficiency in Arabian foals due to inability to splice chromosomes together after strand breaks like the ones needed to create functional variable region genes.
Foals can’t make Ag receptors & lack T & B cells

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9
Q

How can you diagnose a large lymph node as a lymphoma or leukemia?

A
  • PCR-amplification of lots of lymphocytes’ genes which are varied in size.
  • PCR-amplification of lymphoma or leukemia give ONE PCR product from every cell.
  • Running PCR through gel electrophoresis can let you determine which one it is.
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10
Q

Lymphocyte precursors commit to become NK, T or B cells in..

A

bone marrow

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11
Q

T & B cell precursors do….

A
  1. Migrate to their unique primary lymphatic tissue
  2. Rearrange their TCR or Ig genes
  3. Express the Ag receptor on their plasma membrane.
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12
Q

When are T & B cell precursors considered “immature” lymphocytes

A

Once they express their rearranged Ag receptor on their plasma membrane

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13
Q

In primary lymphoid tissues, T cells

A

Precursor T cells differentiate into Tgamma-delta and Talpha-beta cells.
AND
Talpha-beta cells differentiate into Th and Tc cells

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14
Q

T-cells mature and becoming “immature” T-cells

A

BEFORE seeing antigen

in bone marrow and thymus

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15
Q

In secondary lymphoid tissues, Th cells..

A

differentiate into Th1, Th2, Th17, Tfh, and Treg cells

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16
Q

Differentiation of Th cells occurs

A

AFTER seeing Ag

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17
Q

T Cell maturation in Thymus

A
  1. Rearrange TCR genes
  2. Positive Selection
  3. Negative Selection
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18
Q

Rearrangement of TCR genes involves…

A

rearranging gamma chain and delta chains Tgamma-delta cells OR rearranging of alpha and beta genes and become Talpha-beta cells

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19
Q

Positive Selection

A

recognition = survival

Tab cells selected for ability to recognize self-antigens + MHC

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20
Q

Rules of Positive Selection

A
  1. Tab doesn’t recognize self MHC molecules at all = DEATH
  2. Tab recognizes self MHC I => mature CD8 T cell
  3. Tab recognizes self MHC II => mature CD4 T cell
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21
Q

Negative Selection

A

T cells DELETED if affinity for self antigens + MHC is too high

CHECKS AFFINITY

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22
Q

Rule for immature lymphocytes in primary lymphatic tissue

A

T cell recognizes antigen in primary lymphatic tissue it is probably a self-antigen, and T cell dies cause it MIGHT be dangerous.

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23
Q

Possible effect of having high affinity for self antigens

A
  1. CD4 and CD8 cells die

2. CD4 become natural Treg cells

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24
Q

Moderate affinity means

A

T cell binding affinity for self antigens presented by MHC is too weak for activation

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25
Q

General features of Lymphocytes responses to Ags

A
  1. Recognition
  2. Activation
  3. Proliferation
  4. Differentiation (effector or memory cells)
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26
Q

Recognition

A

done via Ag receptors in cell membranes

SIGNAL 1

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27
Q

Signal 1 in T-cell Responses to Ags

A

Ag Recognition

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28
Q

location of Signal 1

A

diffuse lymphoid tissues

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29
Q

Important cells for Signal 1

A

Dendritic cells for presenting Ag to naive T-cells

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30
Q

Signal 1 Mechanism

A

T cell enters lymph nodes via high endothelial venules & scan dendritic cells. When it recognizes its Ag, it stops scanning and forms longer term interaction with DC

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31
Q

Signal 2 is what step in T cell response to Ags

A

Activation

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32
Q

Activation of T cell occurs

A

via costimulatory signals received from another cell

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33
Q

Signal 2 involves…

A

activation of DCs by PAMPs, DAMPs & inflammatory cytokines

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34
Q

Signal 2’s activated DCs

A

express new cell-surface molecules (B7 family) required for T-cell activation

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35
Q

What occurs if Signal 2 is absent?

A

T cell recognizes Ag but isn’t activated.

T cell becomes anergic

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36
Q

anergic

A

refractory to activation even under optimal conditions

37
Q

IL-2

A

required for T-cell proliferation

produced by activated T cells

38
Q

Signal 3

A

Differentiation of T cells into effector or memory cells

39
Q

Signal 3 caused by…

A

various combinations of cytokines

40
Q

Signal 3 induces…

A

CD4 T cells to differentiate into different subclass (TH1, TH2, etc)
CD8 T cells to acquire cytotoxic (effector) function

41
Q

IL-12

A

promotes TH1 differentiation

42
Q

Thymic Antigen Presenting Cells (Thymic APCs)

A

located only in thymus and present MHC I and II molecules + self-Ags to Tab cells.

43
Q

No T cell affinity for MHC + Self Ag =>

A

DIE

44
Q

Low/Moderate affinity of T cell for MHC + self-Ag =>

A

T cell survives & prospers

45
Q

High affinity of T cell for MHC + self-Ag =>

A

Death

46
Q

mature, naive T cells…

A

interact with animal’s MHC molecules and DO NOT react to self-Ags

47
Q

Th1 Lymphocytes Function

A

do macrophage recruitment and activation in cell-mediated immunity
(activate infected macrophages & provide help for B cell Ab production)

48
Q

Th1 lymphocyte structure

A

CD4 & have TCR’s that recognize Ags presented by MHC II

49
Q

Th1 cells work by…

A

recognizing Ags presented by Macrophages & secreting interferon-gamma

50
Q

interferon-gamma

A

activates macrophages to produce NO, increasing macrophages’ capacity to killl

51
Q

Th1 activation site

A

secondary lymphatic tissue

52
Q

Th1 cell mechanisms

A
  1. Ags taken from infection site to secondary lymphatic tissues
  2. Th1 cells activated there
  3. Th1 cells migrate to infection site and are presented Ags by MHC II on infected macrophages
  4. Th1 cells release interferon-gamma
  5. IFN-gamma activates all macrophages in vicinity & increases killing efficiency
53
Q

Th2 cells Function

A

esosinophil recruitment & activation

help B cells in Ab production, esp switching to IgE

54
Q

Th2 cell structure

A

CD4 & TCR that recognize Ags presented by MHC II

55
Q

Th2 cells secrete

A

IL-4 & IL-5

56
Q

IL-4

A

promotes IgE synthesis by B cells

57
Q

IL-5

A

promotes production of eosinophils from bone marrow & activation of mature eosinophils

58
Q

Why is eosinophil recruitment & activation important?

A

Eosinophils contribute to resistance to migrating helminth larvae & certain protozoan pathogens.

59
Q

Th2 Cell Pathway

A
  1. Ag carried to 2ndary lymphatic tissues
  2. Th2 cells activated in 2ndary lymphatic tissues
  3. Th2 cells go to infection site
  4. Th2 cells recruit and activate eosinophils
60
Q

Th17 Cells Fuction

A

neutrophil recruitment and activation
&
promote barrier integrity

61
Q

Th17 cell help in

A

certain autoimmune diseases

62
Q

Th17 cells secrete

A

cytokines that are important for defense agains certain extracellular bacteria

63
Q

Th17 cytokines

A

activate tissue cells (fibroblasts & epithelial cells) to release cytokines that recruit neutrophils to tissues.
THEN fibroblasts also release G-CSF & GM-CSF that increase bone marrow production of neutrophils

64
Q

Tfh Cells Function

A

B lymphocyte activation
Isotope switching
Ab production

65
Q

Tfh cells are also called

A

Follicular helper T cells

66
Q

Tfh cells activated by..

A

myeloid DC in diffuse cortex

67
Q

Tfh cell mechanism

A
  1. Activation by myeloid DCs in diffuse tissue
  2. Tfh cells migrate to border of B-cell follicles
  3. Activated B-cells migrate to follicle’s border
  4. B cells and Tfh cells contact & interact with each other
68
Q

Tfh cell structure..

A

express membrane molecules & cytokines needed for B-cell activation

69
Q

Treg Cells job

A

Suppress T-cell responses

70
Q

Effect of Tfh activation of B cells

A

isotope switching & affinity maturation

71
Q

CD8 Tc Cells (Killer T-cells) Function

A

kill virus-infected cells

72
Q

CD8 Tc Cells recognize…

A

Ags presented by MHC I

73
Q

Tc Cells specialty

A

combatting intracellular parasites

74
Q

Tc Cell mechanism

A

kill infected cell by depriving intracellular parasite of its “home” & exposing parasites to host defense components (Abs, complement, etc) & limit intracellular parasite replication

release granules

75
Q

Tc Cell granules contain

A

protein that form pores in membrane & proteins that activate apoptosis from inside the cell

76
Q

Tc Cells Activated by…

A

Ag in secondary lymphatic tissues

77
Q

Th1 Cells target

A

microbes that persist in macrophage vesicles, extracellular bacteria

78
Q

Th2 Cells target

A

helminth parasites

79
Q

Th17 cells target

A

fungi, Klebsiella pneumoniae

80
Q

Tfh cells target

A

all types of pathogens

81
Q

CD8 Cytotoxic T cells target

A

viruses, some intracellular bacteria

82
Q

What drives differentiation of CD4 T cells into Th1 cells?

A

IL-12

83
Q

Natural Killer Cells

A

large granular lymphocytes

innate lymphocytes

84
Q

NK cells recognize

A

“stressed” cells & IgG (FcR for ADCC) but not SPECIFIC antigens

85
Q

NK Cell functions

A

kill infected cells & secrete IFN-gamma

86
Q

NK cell receptors

A

2 types: an inhibitor and an activator

87
Q

NK cell activation

A

when NK cell recognizes DAMPs on its activator receptor, the balance shifts & induces cell to kill

88
Q

NK cells are part of

A

the innate immune system

89
Q

importance of NK cells being part of innate immune system

A

they arrive at site of infection earlier and secrete IFN-gamma earlier (almost immediately) than the TH cells