Test 1: lecture 7 + 8 T cells cont. Flashcards

1
Q

T cells are generated by ___

A

random recombination

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2
Q

activation of T cells requires ___

A

antigen presenting cell to have the correct:

MHC pepide antigen

costimulatory molecules (CD80, CD86)

cytokines-

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3
Q

CD80 or CD86 binds to ___ on the t cell

A

CD28

(costimulatory molecules)

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4
Q

what types of cells have MHC class 1

A

almost all types of cells

CD8 T cells can see these → cytokines or direct lysis of target cells

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5
Q

CD4 T cells can produce ___

A

help B cells

cytokines

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6
Q

what kind of T cells lead to lysis

A

CD8

can see MHC class 1

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7
Q

what type of cells have class II MHC?

A

antigen presenting cells such as:

B cells

Macrophages

DC

as well as epithelial cells of the thymus

class 2 → CD4 → helper B cells and cytokines

Class II is involved in activation of other cells of the immune system

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8
Q

class I pathways gets pathogens from the ___

A

inside (cytosol)

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9
Q

class II MHC get pathogens from ___

A

outside cell

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10
Q

__ pathway - peptides from the cytoplasm gain access to this pathway (endogenous).

A

Class I MHC

CD8 T cells → cytokines and lysis

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11
Q

___ pathway - peptides are within acidified endosomes. They are derived from proteins or pathogens that have been phagocytosed. Thus, they come from outside of the cell (exogenous).

A

•Class II

CD4 T cells → cytokines and helper B cells

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12
Q

Class I pathway

A

class 1= intracellular pathogen= CD8 = cytokines and lysis

. Class I made in Endoplasmic Reticulum.

  1. intracellular proteins from pathogens are degraded by proteasomes.
  2. Peptides are transported into the ER by TAP (Transporters assoc. w/ Ag processing.
  3. Peptides bind to Class I
  4. Peptide loaded Class I molecule goes to cell surface and is expressed .
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13
Q

Class II pathway

A

Class II = CD4 Tcells = helper B and cytokines

  1. Class II made in ER
  2. Invariant chain protects from peptide loading in ER, and targets endosome.
  3. outside /extracellular Pathogen or Proteins are taken into acidified vesicles and proteases degrade antigen to peptides.
  4. Invariant chain is degraded, and Class II can bind peptide.
  5. Peptide loaded Class II molecule is expressed on surface.
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14
Q

invariant chain prevents the breakdown of ___ when it moves from ER to ___

A

class II

acid vesicle

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15
Q

where do T cells come from?

where do they mature?

A

from bone marrow → thymus to mature (self vs nonself) → secondary lymphoid tissue (lymphnodes, spleen) to wait for pathogen to trigger

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16
Q

3 main events in the thymus

A
  • TCR gene rearrangement
  • Cell selection- positive and negative selection.
  • Acquisition of T cell markers (CD4, CD8).
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17
Q
A

thymus

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18
Q

positive selection in the thymus

A

•ensures that T cells recognize self-MHC.

T cells that are unable to identify self MHC are killed, the left over T cells that CAN see self MHC are positively selected for

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19
Q

Negative selection in thymus

A

eliminates many of the T cells that recognize self antigen

T cell presented with self and non self antigens. Those that react to self antigens are killed. Leaving only those that react to non-self

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20
Q
A

positive selection of T cell

T cell that CAN see self is kept.

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21
Q
A

negative selection

cells that bind to self antigen are killed

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22
Q

explain + and - selection in thymus

A

T cells that can identify self MHC are positively selected for. those that can not see self MHC are killed

T cells that react to self antigen are killed. T cells that do not react to self antigen are kept (negative selection)

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23
Q

T cells undergo tolerance induction outside the thymus by ___

A

peripheral tolerance

anergy

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24
Q

Autoimmune regulator: AIRE- a transcription factor expressed in the thymus that leads to transcription of a wide range of organ-specific genes that are usually only expressed in the ___ tissues

A

peripheral

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25
Q

how to determine CD4 or CD8

A

baby T cells have both

in the thymus, pre-T cell will bind to class I or class II

if it binds to class I → CD8+

if it binds to class II→ CD4+

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26
Q

When T cells leave the thymus they have the following characteristics

A
  • They are MHC restricted. (only respond to class I or class II)
  • They are self-tolerant (do not react to self antigen)
  • They are either CD4 (class 2) or CD8 (class 1)
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27
Q

____ are extensively pleiotropic- having multiple phenotypes, redundant, primarily involved in local effects. They also have a short half-life in vivo, Receptors with several chains, nonantigen-specific.

A

cytokines

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28
Q

•Binding of a ___ to a receptor induces dimerization or polymerization of receptors

A

cytokine

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29
Q

•Juxtaposition of the cytoplasmic tails allows engagement of intracellular ___

A

signaling.

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30
Q

•__ kinases phosphorylate tyrosine residues on receptor and on STATs (signal transducers and activators of transcription)

A

JAK

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31
Q

•STATs dimerize, translocate to ___and bind enhancer regions of genes induced by cytokines

A

nucleus

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32
Q

how do cytokines work?

A

binds to receptor

causes dimerization and activation of JAK

this causes phosphorylation of STATs

these dimerize and enter the nucleus and trigger transcription

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33
Q

Xeljanz

A

Jak3 inhibitor

prevent transcription from cytokine signal

treat RA, alopecia and psoratic arthritis

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34
Q

apoquel is a ___

A

Jak inhibitor

prevent cytokine signalling

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35
Q

M1 macrophages

A

interferon gamma tiggers macrophages into classically activated to kill

IL12 trigger T0 → TH1 → produces INF gamma, IL-2, TNF beta → which trigger “killer” macrophages and NK cells

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36
Q

M2 macrophages

A

macrophages triggered by IL4, 13

wound healing/tissue repair

TH2 cells produce IL13, TH2 mast cells and basophils produce IL4

IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies

B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)

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37
Q

regulatory macrophages

A

macrophages that get IL-10

→ anti inflammatory activity

macro, Treg, and other cells produce TGF beta

TGFbeta → T0 → Treg→ will produce TGF beta and IL10

TGF beta→ increases IgA, inhibits immune response, promotes wound healing

IL10→ inhibits T cell and macrophage function

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38
Q

IFN-gamma triggers ___

A

M1 macrophages to kill

(classically activated)

IFN gamma is made by TH1 and TFH cells, NK and CD8 cells

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39
Q

IL4 and IL13 trigger __

A

M2 macrophages to become wound healing or tissue repair

TH2 cells produce IL13, TH2 mast cells and basophils produce IL4

IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies

B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)

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40
Q

IL 10 triggers

A

regulatory macrophages

→ anti-inflammatory activity

IL10 is made by Treg, TH2, TH1 and TH17 cells

41
Q

How do M1 macrophages kill

A

produce Nitric oxide (NO)

respiratory burst (creates reactive oxygen species) that kill things the macrophage eats

42
Q

macrophages can do what three major things

A

kill pathogen (M1 → Interferon gamma (made by T cells))

wound healing (M2→type 2 IL4, IL13 (made by T cells))

anti-inflammatory (regulatory→ IL10 (made by T cells))

43
Q

how does baby T cell get to dendritic cell?

A

immature DC will sample environment looking for pathogen with TLR

binds to pathogen and eats it

dendritic cell will become active and present MCH class 2, CD80, CD86 and produce IL-12

mature DC will move into lymph node and wait to bind with T cell with the correct receptor

44
Q

spectral diseases will have high antibodies at what level of pathogen load

A

high

45
Q

spectral diseases will have high delayed-type hypersensitivity at what level of pathogen load

A

low

46
Q

____– a reaction dependent upon T cells and IFN-g, but not antibodies. Examples- tuberculin skin test; contact dermatitis

A

DTH- Delayed-type Hypersensitivity

(spectral disease)

47
Q

subsets of CD4 cells

A

Th1 → IL-2, IFN- gamma (kill macrophages)

Th2→ IL-4, IL-5 (tissue repair macrophages)

48
Q

Th1 is a ___

A

type of CD4 T cell

produces IL-2 and IFN gamma to produce killer macrophages

IL12 trigger T0 → TH1 → produces INF gamma, IL-2, TNF beta → which trigger “killer” macrophages and NK cells

49
Q

Th2 is a ___

A

type of CD4 T cell

produced IL-4 and IL-5 → wound healing macrophages (M2)

TH2 cells produce IL13, TH2 mast cells and basophils produce IL4

IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies

B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)

50
Q

IFN- gamma

A

made by Th1 cells, TFH cells, NK cells, CD8 T cells→ killing macrophages

–Activates macrophages(killer), increases Class II and costimulator expression, and enhances IgG2a.

–Acts on macrophages, dendritic cells, B and T cells.

51
Q

IL-4

A

made by Th2 CD4 T cells → wound healing macrophages

–T and B cell growth factor, enhances IgE and IgG1, suppresses macrophage activation.

–Produced by T cells, mast cells, et al.

–Acts on T cells, B cells, macrophages, et al.

TH2 cells produce IL13, TH2 mast cells and basophils produce IL4

IL13 + IL4 → T0 → TH2→ produces IL4,IL5, IL10, IL13 → defense against worms, allergies

B cell growth factor, increase TH2, increase IgE isotype, Eosinophil growth factor, inhibit T cells and macrophages, increase wound healing macrophages (type 2)

52
Q

Th1 cells help phagocyte mediated elimination of pathogens by ___

A

IFN gamma → triggering B cells to produce complement binding and opsonizing antibodies

IFN gamma and IL2→activating CD8 T cells → lysis

IFRN gamma → activating M phi (M2- wound healing macrophages)

53
Q

Th2 cells- mediators of allergy, protection again helminths by ___

A

IL4 → B cells making IgE (mast cell degranulation)

IL5→ eosinophil recruitment and activation

IL4 and IL13 → alternate way to activate M phi (M2) (wound healing macrophages)

54
Q

How does Thyroid cell → TH1

A

IL-12 from macrophage or pathogen tell TH0 to become TH1

TH1 will produce IFN gamma and is important in forming killer macrophages

55
Q

how does a T cell become TH2

A

Mast cell and CD4 Tcell produce IL-4

TH2 cells will produce IL 4,IL 13 to create M2 macrophages (wound healing macrophages)

TH2 cells will also create IL-10 to create regulatory macrophages to help with anti-inflammatory activity

56
Q

___, produced by cells associated with the innate immune response (Macs, DCs), stimulate T cells to develop into Th1 cells.

A

•IL-12

Th1 produce IFN gamma that stimulate M1 (killer macrophages)

57
Q

___ produced by T cells, mast cells, basophils, (and other cells) stimulate T cells to develop into Th2 cells.

A

•IL-4,

Th2 create IL4 IL13→ M2 macrophages (tissue repair)

and IL10 → regulatory macrophages (anti inflammatory)

58
Q

TH2 cells help basophils, mast cells, eosinophils and B cells respond to parasite infection and mediate ___ responses

A

allergic

produce IL 4,5, 10,13

IL 4, 13 → M2 tissue repair

IL 10 → regulatory anti-inflammatory

59
Q

TH1 cells help ___ to suppress intracellular infections

A

macrophages

produce IL-2, IFN gamma and TNF beta

IFN gamma → killer macrophages

60
Q

TFH cells

A

produce IL-21, IL-4, IFN gamma

help B cells become activate, switch isotype and increase antibody affinity

happens in germinal centers

IL-4 → M2 (wound repair)

IFN gamma → killer macrophages

61
Q

TH17 cells

A

produce IL-17, IL21

enhance the neutrophil response to fungal and extracellular bacterial infection

T naive (IL6, IL1 TGF beta)→ Th17 (occurs in the lymph node)

62
Q

____ enhance the neutrophil response to fungal and extracellular bacterial infection

A

TH17

produce IL-17 and IL21

63
Q

___ help B cells become activates, switch isotype and increase antibody affinity

A

TFH cells

produce IL21, IL4 and IFN gamma

64
Q

Treg cells

A

produce TGF beta, IL-10

suppress the activities of other effector T cell populations

IL-10 → regulatory macrophages (anti-inflammatory)

Tnaive (TGF beta)→ T reg

65
Q

___suppress the activities of other effector T cell populations

A

T reg

produce TFG-Beta, IL-10

IL-10 → regulatory macrophages (anti-inflammatory)

66
Q

where does CD4 T cell change into TH cells

A

in the lymph node

67
Q

high levels of IL4 and IL10 inhibits ___

A

TH1

68
Q

high levels of IFN-gamma inhibits ___

A

TH2

69
Q

cytotoxic T

A

CD8 cell

produces cytokines → IFN gamma and TNF

cytotoxins → perforin, granzymes, granulysin

–Perforin- form transmembrane channels

–Enzymes, such as serine esterases and proteoglycans.

–Cytokines- specifically lymphotoxin (TNF)

–Induction of Apoptosis-

kill virus infected cells

70
Q

___- form transmembrane channels

A

–Perforin

made by cytotoxic T cells

71
Q

how to activate cytotoxic T cell

A

naive T cells binds with antigen presenting cell and specializes

proliferates

travels to tissues → seek and destroy the pathogen

72
Q

Three Rs of immune response

A

recognition

response

regulation

73
Q

•Th1 and Th2 cytokines cross regulate each other. For example, ___ inhibits the development of Th2 cells, while ___ inhibits the development or function of Th1 cells

A

IFN-gamma

IL-4

74
Q

•Certain cytokines are particularly important in suppressing immune responses– ___

A

IL-10

→ regulatory macrophage (anti-inflammatory)

75
Q

how to create Treg

A

T naive (TGF beta)

76
Q

what are some functions of Treg

A
  • Inhibitory Cytokines
  • Metabolic disruption
  • Targeting Dendritic cells
  • Cytolysis of cells

Treg produce TGF beta and IL10

77
Q

IL10 can inhibit ___

A

-antigen presentation and IL-12 production

IL-12 → changes naive T to TH1. TH1 cells produce IFN gamma to create killer macrophages

-inhibit the ability of IFN gamma to activate macrophages/ DC

78
Q

Th2, Treg, TH1 and Th17 all create ___ which will turn off immune response

A

IL-10

79
Q

how to create Th2 and what does it do

A
80
Q

how to create TH1 and what does it do

A
81
Q

how to create Th17 and what does it do

A
82
Q

how to create Tfh and what does it do

A
83
Q

how to create Treg and what does it do

A
84
Q

•After the expansion of T cells in response to an infection (or immunization), the majority of cells ___

A

die.

induced cell death

85
Q

IL-1

produces by

major function

A

monocytes, many other cell types

pro- inflammatory fever

Tnaive (IL6, IL1, TGF beta)→ TH17 → IL17, IL21

86
Q

IL2 produced by ___. major function

A

T cells

T cell growth factor

87
Q

IL-4 produced by ___, major function ___

A

Th2 cells, mast cells, basophils

B cell growth factor, promotes Th2 cells, IgE isotype, induces alternatively activated macrophages

(wound healing macrophages)

Th2 also make IL 4,5, 10, 13

naive T (CD40L, IL21, IL4)→ Tfh→ IL21, IL4, IFN gamma

naive T (IL-4) → TH2 → IL 4,5,10,13

88
Q

IL-5 produced, major function

A

Th2 cells

eosinophil growth factor

naive T (IL-4) → TH2 → IL 4,5,10,13

89
Q

IL-6 produced by ___, major function

A

T cells, many other cell types

pro-inflammatory

naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21

90
Q

IL-7 produced by ___ , major function

A

stromal cells

T cell and B cell growth factor

91
Q

IL-10 produced by

major function

A

T cells (regulatory T cells , Th2, Th1, Th17), macrophages

inhibit T cell and macrophage function

(anti-inflammatory)

naive T (TGF beta)→ Treg → TGF beta, IL10

naive T (IL-4) → TH2 → IL 4,5,10,13

92
Q

IL-12 made by, major function

A

dendritic cells, macrophages

stimulate NK cells and TH1 cells to make IFN gamma

93
Q

IL-13 made by, major function

A

TH2 cells

induce alternatively activated macrophages (wound healing macrophages) (IL-4 does similar thing)

naive T (IL-4) → TH2 → IL 4,5,10,13

94
Q

IL15

made by and function

A

T cells and epithelial cells

T cell growth factor

95
Q

IL-17

made by, function

A

Th17 cells

pro-inflammatory, increases neutrophil recruitment (fight against fungal and extracellular bacteria)

Th17 also make IL21

Tnaive (IL6, IL1, TGF beta)→ TH17 → IL17, IL21

96
Q

IFN gamma made by __ and function

A

Th1 cells, NK cells, CD8 T cells

Activates macrophages (killer), Upregulates Class II, Promotes IgG2a isotype Abs

97
Q

TNF

made by ___ function___

A

macrophages, T cells (Th1), other

pro- inflammatory

killer macrophages

98
Q

TGF beta

made by. function.

A

Macrophages, T cells (Treg), many other cell types

Increases IgA, inhibits immune responses, promotes wound healing, promotes Treg cells

naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21

naive T (TGF beta)→ Treg → TGF beta, IL10

99
Q

IL-21

A

T cells (TH17, Tfh)

important for Tfh help for B cells

naive T cell (IL21, IL4, CD40L)→ TFh → IL21, Il4 and IFN gamma

naive T cell (IL6, IL1, TGF beta)→ Th17 → IL17 and IL21