T cell development and Effector function Flashcards

1
Q

TCR

A

Very similar to BCR

undergo VDJ recombination
Use RAG proteins
V contains 3 hypervariable regions

no class switching
no affinity maturation 

membrane bound!

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2
Q

why dont we want TCR to undergo affinity maturation

A

b/c it increases the liklihood a Tcell would recognize a self peptide

which would cause autoimmune diseases

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3
Q

TCR-MHC interaction

A

TCR’s recognize as few as 1-3 residues of the MHC peptide complex

compared to antibody/antigen interaction, the binding of TCR to MHC molecules is weak

additional cell surface molecules are necessary for TCR activation

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4
Q

TCR’s must recognize both…

A

Peptide

AND

MHC molecule

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5
Q

what is missing in the alpha chain of the TCR

A

Diversity region

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6
Q

T cells whose TCR’s recognize class I MHC peptide complexes …

A

preserve the expression of CD8

which become cytotoxic cells

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7
Q

T cells whose TCR’s recognize class II MHC peptide complexes…

A

preserve the expression of CD4

which become T helper cells

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8
Q

Cell-mediated immunity

A

Combats intracellular microbes

either in:
ingested microbes (phagocytosed and living in vesicles)
viruses (present in cytoplasm)

t cells help the phagocytes kill the microbes they have ingested 
t- cells help by binding to MHC class I presented on the surface of infected cells
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9
Q

where can T lymphocytes be activated?

A

Spleen

Lymph node

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10
Q

CD4 or CD8

A

interacts with MHC II and MHC I

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11
Q

CD3

A

on all T cells

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12
Q

TCR complex

A

CD3, TCR and zeta chain

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13
Q

CD28

A

interacts with B7 molecules

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14
Q

LFA1 and sometimes VLA4

A

adhesion molecules that are slowing down T cell down so all interaction can occur

LFA-1 interacts with ICAM-1 (on endothelium) for activation lymph nodes

VLA-4 interacts with VCAM-1 (on endothelium) important for getting T cells into peripheral tissues (out of blood)

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15
Q

signal 1 for T -cells

A

Antigen
MHC class I or II
CD4 or CD8

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16
Q

signal 2

A

CD28 binding to B7 on APC’s

this induces expression of IL-2 and change in the affinity of the IL-2 receptor–> activation of T cell

17
Q

after period of time of having T cells activated…. CTL4 comes up and does what?

A

it is an inhibitory signal
shuts down IL-2 production
binds B7 molecules so it outcompetes the CD28
T cell shuts down

18
Q

how are CD8 T cells activated differently

A

involves cross presentation

infected cell is phagocytosed by APC
APC presents antigen which is recognized by CD8 and CD4 cells
dendritic cell presents peptide of class I and II
CD4 T helper cell after it is activated by binding then releases cytokines which help activate CD8

CD 8 cell gets costimulation from APC and from CD4 cell, and can then go on to undergo clonal expansion and differentiation

19
Q

what is cross presentation

A

to indicate that one cell type (the dendritic cell) can present antigens from another cell (the virus-infected or tumor cell) and prime, or activate, T cells specific for these antigens.

20
Q

what is CD40 and when is it produced?

A

CD40L increases on CD4 T cells after they are activated and interacts with CD40 on APC’s to strengthen adhesion

prolongs APC-T cell contact

21
Q

What happens after T cell activation

A

Protein production cascade!

CD40 L
IL-2
IL-2 receptor changes to high affinity for IL-2 b/c of expression of IL-2 Ralpha chain leading to proliferation
IL-4
IL-5
IFN-gmma
TGF-beta
22
Q

IL-2

A

survival, proliferation

produced by CD4 and CD8

23
Q

IL-4

A

B cell switching to IgE

produced by CD4, mast cells

24
Q

IL-5

A

activation of eosinophils

produced by CD4 and mast cells

25
Q

IFN-gamma

A

activation of macrophages

Produced by CD4, CD8, NK cells

26
Q

TGF-beta

A

inhibition of T cell activation
differentiation of T reg cells

produced by CD4 and many other cell types

27
Q

effects of blocking CTLA-4?

A

good to shut off T-cell production

cancer treatment

28
Q

what does the TCR recognize?

A

MHC associated peptide antigens and the MHC that is holding the peptide

29
Q

Once the pre-TCR complex is made what happens…

A

Once Pre-TCR complex is made is starts to produce signals which promote survival, proliferation and TCR alpha gene recombination and allelic exclusion (so inhibits VDJ recombinase at the second TCR-beta chain locus)

30
Q

what do class II molecules express

A

protein antigens that are ingested by APCs from the extracellular milieu into vesicles

thus CD4 + T cells recognize antigens ingested from extracellular microbes

31
Q

what do class I molecules express

A

protein antigens present in the cytosol are processed into peptides that are expressed by MHC class I
thus…
CD8 + T cells recognize peptides derived from cytosolic or nuclear antigens

32
Q

what stimulates the expression of B7 on APC’s

A

microbes

this leads to fully active T lymphocytes

33
Q

Activation of CD4 TH1 cells

A

CD4 T cell CD40 Ligand binds CD40 on Macrophage

IFN gamma from NK cells binds to macrophage

TLR on macrophage binds microbe

all this stimulates IL-12 gene transcription/production

IL-12 stimulates differentiation of CD4+ T cell into TH1 subset

TH1 then produces IFN gamma which stimulates macrophages activation to kill microbes (CLASSICAL)

34
Q

DTH

A

Delayed-type hypersensitivity

Macrophages activation by TH1 cells is dependent on antigen -recognition

PPD test looking for DTH response

primary infection
1-2 weeks later elicit challenge with antigen
pt responds 24-48 hours later with raised red area
those T cells and macrophages are influxing into the area, and this leads to the red raised area.

35
Q

Activation of macrophages by CD4 TH1 subset

A

CD40 L on CD4 cell binds to CD40 on macrophage

macrophage with ingested microbes presents MHC class II with peptide of microbe

CD4 TH1 cell secretes IFN-gamma which activates the macrophage to:

  • produce ROS, NO and lysosomal enzymes
  • secrete cytokines (TNF, IL-1, IL-12) (inflammation)
  • increased expression of MHC molecules and costimulators
36
Q

Mechanism of action for CD8 cells

A

antigen recognition and binding of CTL to target cell
(target cell has microbe in cytoplasm- most often virus)

in the bind it has LFA-1-ICAM-1
CD8 binding MHC II
TCR with peptide and MHC II

CD8 cell is now activated and releases perforin (pokes holes) and granzyme (cleave proteins) which poke holes in the target cell

cell then dies by apoptosis

37
Q

Cooperation b/w CD4+ and CD8+ t cells

A

Some APC’s put up both MHC class I and MHC class II so CD4 and CD8 can both bind

IFN -gamma released by CD4 cells can also activate CD8 cells

38
Q

balance between TH1 and TH2

A

determines the outcome of intracellular infections

TH1 activates macrophages

TH2 produces IL10, IL-4 and IL-13 which inhibits microbial activity of macrophages

39
Q

Defect in TH1 leads to…

A

high TH2 cytokines

allows bacterium that live in phagosomes to escape and divide