T cell development and Effector function

Question 1

TCR

Answer 1

Very similar to BCR

undergo VDJ recombination
Use RAG proteins
V contains 3 hypervariable regions

no class switching
no affinity maturation 

membrane bound!

Question 2

why dont we want TCR to undergo affinity maturation

Answer 2

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

which would cause autoimmune diseases

Question 3

TCR-MHC interaction

Answer 3

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

Question 4

TCR’s must recognize both…

Answer 4

Peptide

AND

MHC molecule

Question 5

what is missing in the alpha chain of the TCR

Answer 5

Diversity region

Question 6

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

Answer 6

preserve the expression of CD8

which become cytotoxic cells

Question 7

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

Answer 7

preserve the expression of CD4

which become T helper cells

Question 8

Cell-mediated immunity

Answer 8

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

Question 9

where can T lymphocytes be activated?

Answer 9

Spleen

Lymph node

Question 10

CD4 or CD8

Answer 10

interacts with MHC II and MHC I

Question 11

CD3

Answer 11

on all T cells

Question 12

TCR complex

Answer 12

CD3, TCR and zeta chain

Question 13

CD28

Answer 13

interacts with B7 molecules

Question 14

LFA1 and sometimes VLA4

Answer 14

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)

Question 15

signal 1 for T -cells

Answer 15

Antigen
MHC class I or II
CD4 or CD8

Question 16

signal 2

Answer 16

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

Question 17

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

Answer 17

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

Question 18

how are CD8 T cells activated differently

Answer 18

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

Question 19

what is cross presentation

Answer 19

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.

Question 20

what is CD40 and when is it produced?

Answer 20

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

Question 21

What happens after T cell activation

Answer 21

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

Question 22

IL-2

Answer 22

survival, proliferation

produced by CD4 and CD8

Question 23

IL-4

Answer 23

B cell switching to IgE

produced by CD4, mast cells

Question 24

IL-5

Answer 24

activation of eosinophils

produced by CD4 and mast cells

Question 25

IFN-gamma

Answer 25

activation of macrophages Produced by CD4, CD8, NK cells

Question 26

TGF-beta

Answer 26

inhibition of T cell activation differentiation of T reg cells produced by CD4 and many other cell types

Question 27

effects of blocking CTLA-4?

Answer 27

good to shut off T-cell production cancer treatment

Question 28

what does the TCR recognize?

Answer 28

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

Question 29

Once the pre-TCR complex is made what happens...

Answer 29

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)

Question 30

what do class II molecules express

Answer 30

protein antigens that are ingested by APCs from the extracellular milieu into vesicles thus CD4 + T cells recognize antigens ingested from extracellular microbes

Question 31

what do class I molecules express

Answer 31

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

Question 32

what stimulates the expression of B7 on APC's

Answer 32

microbes this leads to fully active T lymphocytes

Question 33

Activation of CD4 TH1 cells

Answer 33

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)

Question 34

DTH

Answer 34

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.

Question 35

Activation of macrophages by CD4 TH1 subset

Answer 35

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

Question 36

Mechanism of action for CD8 cells

Answer 36

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

Question 37

Cooperation b/w CD4+ and CD8+ t cells

Answer 37

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

Question 38

balance between TH1 and TH2

Answer 38

determines the outcome of intracellular infections TH1 activates macrophages TH2 produces IL10, IL-4 and IL-13 which inhibits microbial activity of macrophages

Question 39

Defect in TH1 leads to...

Answer 39

high TH2 cytokines allows bacterium that live in phagosomes to escape and divide