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

T cell differentiation, subsets, receptors Flashcards

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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
What is absolutely required activation?
costimulation
25
CTLA4 interacts with
B7
26
when is IL 2 produced?
after antigen presentation but before proliferation promotes T cell proliferation positive feedback to the cell producing it
27
Naive CD4 T cell secretes IFN-y and IL-12 to induce
Th1 cells
28
Naive CD4 T cells release IL-4 to induce
Th2 cells
29
Naive CD4 T cells secrete TGF-b, IL-6 and IL-23 to induce
Th17 cells
30
IgE
attach to mast cells and Basophils and cross link to induce degranulation also attracts Eosinophils
31
Th17 secretes IL-17 to influence
fibroblasts and endothelial cells to release cytokines to travel to Bone marrow upregulate neutrophils and chemokines to bring neutrophils to the area
32
During the activation of CD8 cells,what processes are happening?
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
What is the danger of T cell activation by Superantigens?
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
Upon activation by antigen presentation in MHC, what signal transduction activities occur?
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
what is Buxton's favorite transcription factor?
Nf-kB
36
how long does it take effector and memory T cells to leave the secondary lymph tissue?
days
37
Where does activation of effector T cells occur?
in the peripheral tissues
38
when a traveling T cell encounters an endothelial cell stop sign, what events then occur?
Tethering/rolling -> activation -> adhesion -> Transmigration
39
In general, cell mediated immunity events involve
release of cytokines Macrophage activation - killing of those ingested microbes inflammation Killing of infected cells
40
Functions of Th1 cells
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
FcR
on professional phagocytes that recognize c3b and IgG on microbes
42
Activation of macrophages happens where?
in tissue
43
what events are occuring during the activation of macrophages by Th1 cells ?
Cd40L interacts with Cd40 on the macrophage | The T cell secretes y-IFN which influences the macrophage
44
What is the macrophages response to Th1 cell stimulation ?
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
what is the role of Th1 cells in inflammation?
through activating macrophages | cytokines are released from the macrophage that induce inflammation
46
What does IL-5 accomplish?
increases Eosinophils in the bone marrow | chemotactic for Eosinophils
47
what happens when IgE encounters a mast cell?
binds the mast cells, when enough are bound, they crosslink and cause degranulation and release of IL-5
48
What leukocyte cannot kill parasites?
Neutrophils
49
What cells do Th2 cells activate?
B cells Eosinophils Macrophages
50
What do Th2 cells indirectly activate?
Mast cells
51
The release of IL-4 from activated CD4 cells
induce the activated CD4 cells to proliferate and differentiate into Th2 cells Th2 cells then secrete IL4, IL13, and IL5
52
What functions do Th2 cells carry out?
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
what molecules are important for effector CD4 T cell interactions?
CD40 ligand on the T cell | and CD40 on the Macs or B cell
54
What is the function of a Th17 cell?
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
What attracts neutrophils?
CXCL8
56
Th17 cells secrete IL-17 and IL-22, what happens?
Epithelial cells are induced to secrete anti-microbial peptides and increase barrier function
57
What do CD8 cells accomplish?
CTLs (CD8 T cell) find infected target cell and is activated CTL granules exocytose and kill the target cells
58
What is the mechanism of the killing done by CTLs?
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
What enters through the perforin holes created by CTLs?
Serine esterases
60
What increases the expression of MHC I on infected cells? what happens when this occurs?
y-IFN allows more expression of MHC I on infected cells, enhancing CTL detection and killing
61
what do regulatory T cells do?
secrete cytokines to Down regulate T cells and B cells
62
During activation, CD8 cells require
co-stimulation | and IL-2 from CD4 cells
63
what cells assists in the generation of acute inflammation by secreting cytokines to promote, recruit and activate neutrophils?
Th17
64
What cells activate macrophages to eradicate intracellular microbes?
Th1
65
What cells assist in the activation and differentiation of B cells ?
Th1 and Th2
66
y-IFN secretion from Th1 cells is essential for
production of IgG
67
IL-4 from Th2 cells is essential for
production of IgE
68
CD8 cells kill by using
granzymes, perforins, Fas-FasL interactions and lymphotoxins
69
How does mycobacteria evade the cell mediated immunity?
inhibiting the fusion of the phagosome and lysosome
70
How does Herpes evade the immune system?
inhibits antigen presentation by blocking TAP
71
How does EBV and Human CMV evade the immune system ?
inhibits proteosomal activity CMV also removes MHC I molecules from the ER
72
what can EBV induce?
production of IL-10 | cause inhibition of macrophages and dendritic cell activation
73
How does Pox virus manipulate the immune system?
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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