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Cmbm 2 Gopi > T cell differentiation, subsets, receptors > Flashcards

T cell differentiation, subsets, receptors Flashcards

0
Q

if mature t cell expresses 10 million TCR molecules on its plasma membrane, how many antigen specificities would the cell express?

A

1

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1
Q

T and B cell lymphocytes begin to express antigen receptors …

A

as precursor cells in the primary lymphoid tissue following random recombination of genes

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2
Q

where are gamma-delta T cells found?

A

found as intraepithelial lymphocytes

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3
Q

What cytokines do Th1 cell produce?

A

Y-IFN

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4
Q

what cytokines do Th2 cells produce?

A

IL4, IL5, IL13

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5
Q

what cytokines do Th17 cells produce?

A

IL 17

IL 22

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6
Q

Where do Naive T cells encounter antigen?

A

In the paracortex of lymph nodes or the PALS of the spleen

when APCs and T cell travel to the lymph nodes this optimizes the interaction of antigen presentation

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7
Q

What happens upon Naive CD4 T cell activation?

A

after antigen presentation, there is clonal expansion and differentiation to either Th1, Th2 or Th17 cells

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8
Q

What type of infection do Th1 cells aid in?

A

intracellular

and aid in inflammtion

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9
Q

what type of infection doe Th2 cells aid in?

A

Parasitic - Helmiths

Allergic reactions

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10
Q

what type of infections do Th17 cells aid in?

A

Some bacteria and fungi
inflammatory disorders
extracellular pathogens
bring in additional neutrophils

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11
Q

what is the main leukocyte that Th1 cells recruit?

A

monocytes

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12
Q

what is the main leukocyte recruited by Th2 cells?

A

Eosinophils

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13
Q

what is the main leukocyte recruited by Th17 cells?

A

Neutrophils

monocytes

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14
Q

what kind of antibody isotypes are stimulated by Th1 cells?

A

complement

Fc receptor binding IgG subclasses

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15
Q

What types of antibody isotypes does Th2 stimulate?

A

IgE

IgG4

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16
Q

Naive CD4 T cells interact with antigen

A

presented on MHC II molecules by APCs in the secondary lymphoid tissue

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17
Q

List the steps of T cell activation

A 
Antigen recognition 
Activation 
Clonal expansion 
Differentiation - during differentiation get effector and memory 
Effector functions
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18
Q

Effector CD4 T cells

A

activate macrophages and B cells

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19
Q

Effector CD8 T cell

A

Kill infected target cells

activate macrophages

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20
Q

where are T cells activated?

A

paracortex of lymph nodes

or PALS of spleen

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21
Q

what molecules are required for T cell activation?

A

APC - MHC2, CD80/86 (B7)

T cell - CD3, CD4, CD28, TCR

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22
Q

what are the three signals required for T cell activation? CD4 or CD8

A

signal 1 - interaction with MHC - adhesion molecules stabilize interaction.

signal 2 - co stimulation

signal 3 - cytokines from APC

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23
Q

In cell to cell interactions of activation of Cd4 cells, what molecules play a role in adhesion?

A

LFA-1 on CD4 T cells

ICAM-1 on the APC

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24
Q

What is absolutely required activation?

A

costimulation

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25
Q

CTLA4 interacts with

A

B7

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26
Q

when is IL 2 produced?

A

after antigen presentation but before proliferation
promotes T cell proliferation
positive feedback to the cell producing it

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27
Q

Naive CD4 T cell secretes IFN-y and IL-12 to induce

A

Th1 cells

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28
Q

Naive CD4 T cells release IL-4 to induce

A

Th2 cells

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29
Q

Naive CD4 T cells secrete TGF-b, IL-6 and IL-23 to induce

A

Th17 cells

30
Q

IgE

A

attach to mast cells and Basophils and cross link to induce degranulation
also attracts Eosinophils

31
Q

Th17 secretes IL-17 to influence

A

fibroblasts and endothelial cells to release cytokines to travel to Bone marrow upregulate neutrophils and chemokines to bring neutrophils to the area

32
Q

During the activation of CD8 cells,what processes are happening?

A

The T cell is interacting with an APC presenting an ingested antigen (but remember that Dendritic cells can cross present)
this interaction induces it to proliferate. It is also being stimulated by CD4 helper cell cytokines such as IL2 and y-IFN to upregulate expression of granules and induce differentiation to mature effectors
Remember during clonal expansion that memory T cells are also being made

33
Q

What is the danger of T cell activation by Superantigens?

A

superantigens can bind about 30% of Tcells. The induction of so many T cells can lead to a cytokine storm which can lead to septic shock

34
Q

Upon activation by antigen presentation in MHC, what signal transduction activities occur?

A

CD3 on the cytosolic side is Phosphorylated (at ITAM?) leads to interactions with adaptor proteins which activates biochemical intermediates. Through PLC and GTP/GDP exchange, these increase Ca+2, DAG and Ras-GTP. These activate enzymes PKC, ERK, JNK which induce transcription factors - NFAT, NF-kB and AP-1 leading to transciption of cytokine genes

35
Q

what is Buxton’s favorite transcription factor?

A

Nf-kB

36
Q

how long does it take effector and memory T cells to leave the secondary lymph tissue?

A

days

37
Q

Where does activation of effector T cells occur?

A

in the peripheral tissues

38
Q

when a traveling T cell encounters an endothelial cell stop sign, what events then occur?

A

Tethering/rolling -> activation -> adhesion -> Transmigration

39
Q

In general, cell mediated immunity events involve

A

release of cytokines
Macrophage activation - killing of those ingested microbes
inflammation
Killing of infected cells

40
Q

Functions of Th1 cells

A

releases y-IFN to induce macrophage activation to enhance microbial killing and to induce B cells to IgG for opsonization to further enhance recognition and phagocytosis.

41
Q

FcR

A

on professional phagocytes that recognize c3b and IgG on microbes

42
Q

Activation of macrophages happens where?

A

in tissue

43
Q

what events are occuring during the activation of macrophages by Th1 cells ?

A

Cd40L interacts with Cd40 on the macrophage

The T cell secretes y-IFN which influences the macrophage

44
Q

What is the macrophages response to Th1 cell stimulation ?

A

enhanced killing of microbes by increasing expression of ROS and iNOS
increases expression of MHC molecules and costimulators (B7)
the macrophage secretes TNF, IL-1, chemokines, IL-12

45
Q

what is the role of Th1 cells in inflammation?

A

through activating macrophages

cytokines are released from the macrophage that induce inflammation

46
Q

What does IL-5 accomplish?

A

increases Eosinophils in the bone marrow

chemotactic for Eosinophils

47
Q

what happens when IgE encounters a mast cell?

A

binds the mast cells, when enough are bound, they crosslink and cause degranulation and release of IL-5

48
Q

What leukocyte cannot kill parasites?

A

Neutrophils

49
Q

What cells do Th2 cells activate?

A

B cells
Eosinophils
Macrophages

50
Q

What do Th2 cells indirectly activate?

A

Mast cells

51
Q

The release of IL-4 from activated CD4 cells

A

induce the activated CD4 cells to proliferate and differentiate into Th2 cells
Th2 cells then secrete IL4, IL13, and IL5

52
Q

What functions do Th2 cells carry out?

A

IL-4 release stimulates B cells to release neutralizing IgG antibodies and IgE, which activates Mast cell degranulation
IL-5 release causes Eosinophil activation allowing it to kill helminths
IL-4 and IL-13 together induce alternative macrophage activation leading to tissue repair and fibrosis

53
Q

what molecules are important for effector CD4 T cell interactions?

A

CD40 ligand on the T cell

and CD40 on the Macs or B cell

54
Q

What is the function of a Th17 cell?

A

secretes IL-17 which induces Leukocytes and tissue cells to secrete G-CSF, GM-CSF, CXCL1, CXCL8, TNF, IL-1 to induce a neutrophil response

55
Q

What attracts neutrophils?

A

CXCL8

56
Q

Th17 cells secrete IL-17 and IL-22, what happens?

A

Epithelial cells are induced to secrete anti-microbial peptides and increase barrier function

57
Q

What do CD8 cells accomplish?

A

CTLs (CD8 T cell) find infected target cell and is activated
CTL granules exocytose and kill the target cells

58
Q

What is the mechanism of the killing done by CTLs?

A

release granzymes which enter the target cells via receptor mediated endocytosis and enter via perforin dependent mechanisms
inside the target cell, these activate apoptotic pathways

59
Q

What enters through the perforin holes created by CTLs?

A

Serine esterases

60
Q

What increases the expression of MHC I on infected cells? what happens when this occurs?

A

y-IFN allows more expression of MHC I on infected cells, enhancing CTL detection and killing

61
Q

what do regulatory T cells do?

A

secrete cytokines to Down regulate T cells and B cells

62
Q

During activation, CD8 cells require

A

co-stimulation

and IL-2 from CD4 cells

63
Q

what cells assists in the generation of acute inflammation by secreting cytokines to promote, recruit and activate neutrophils?

A

Th17

64
Q

What cells activate macrophages to eradicate intracellular microbes?

A

Th1

65
Q

What cells assist in the activation and differentiation of B cells ?

A

Th1 and Th2

66
Q

y-IFN secretion from Th1 cells is essential for

A

production of IgG

67
Q

IL-4 from Th2 cells is essential for

A

production of IgE

68
Q

CD8 cells kill by using

A

granzymes, perforins, Fas-FasL interactions and lymphotoxins

69
Q

How does mycobacteria evade the cell mediated immunity?

A

inhibiting the fusion of the phagosome and lysosome

70
Q

How does Herpes evade the immune system?

A

inhibits antigen presentation by blocking TAP

71
Q

How does EBV and Human CMV evade the immune system ?

A

inhibits proteosomal activity

CMV also removes MHC I molecules from the ER

72
Q

what can EBV induce?

A

production of IL-10

cause inhibition of macrophages and dendritic cell activation

73
Q

How does Pox virus manipulate the immune system?

A

inhibits effector cell activation

causes production of soluble cytokine receptors which binds of cytokines preventing them from activating effector cells

Cmbm 2 Gopi (16 decks)

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