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61 Cards in this Set

  • Front
  • Back
activation of T cells requires what kind of cell?
APC- antigen presenting cells ( express MHC)
T cell response are directed towards what kind of invader
intracellular pathogens
2 types of T cells
cytotoxic
Th1
cytotoxic

effector T cell
antigen recognition
action
Cytotoxic CD8 T cell
peptide-MHC Class I complex on infected cell
kill infected cells
Th1
effector T cell
antigen recognition
action
Th1 cell
peptide-MHC Class II complex on macrophages
activate infected macrophages
humoral immnity

effector T cell
antigen recognition
action
TH1 and Th2
peptide-MHC Class II complex on antigen specific B cell
activation of specific B cell to make antibody
What cytokine drives T cell production?
IL-2
2 interactions that stimulate decline of T cells
Fas- FasL
TNFalpha- TNF receptor
What downregulates the decline of T cells?
FLIP
purpose of dendritic cells
transport antigens from periphery to lymphoid organs where T cells become activated following antigen presentation
APC in lymph nodes
dendritic cells
macrophages
B cells
where dendritic cells are found in lymph node
cortex
here macrophages are found in the lymph node
marginal sinus
meduallary cords
where B cells are found in the lymph nodes
follicles
purpose of immature dendritic cells
facilitates phagocytosis of antigens in peripheral tissues
purpose of mature dendritic cells
stimulate T cells

DC-SIGN
how do pathogens induce expression of important APC molecules?
most APCs express little MHC and costim molec

after phagocytosis, they are degraded and relase molec that lead to an innate reponse.

innate response is necessary for an adaptive response

binding of microbrial degradatin productions leads to an increase in MHC and costim molec
two fates for T cells in lymph nodes
1. don't encounter antigen. They are returned to the blood stream

2. if encounter antigen, are retained in the lymph node. proliferate and differentiate into effector cells
purpose of leukocyte adhesion molecules
act to direct migration of leukocytes to specific areas of the body

act as costimulatory molecules that are directly involved in the activation of specific leukocyte cell types
L-selectin
a leukocyte adhesion molecule in naive T cells that binds to either GlyCam-1 or CD34 expressed on the HEV that allows them to leave blood and enter peripheral lymphoid tissues

--non specific, non activated situation
HEV
HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system.
diapedesis
leaving the vessel
MadCam-1
on mucosal endothelium

can bind to L selectin that is bound to T cell and allows them to leave blood and enter mucosal lymphoid tissue of gut
process to cross HEV
1. L-selectin binds to Glycam-1 and CD34 which enables rolling interaction

2. LFA-1 is activated by chemokines

3. activated LFA-1 binds tightly to ICAM-1

4. diapedesis

ICAM and LFA-1 stabilize
LFA-1 is an
integrin that is expressed on all leukocytes and binds to ICAM-1 on APC
LPAM-1 is an adhesion
that is on a subset of naive cells and minds to MAdCAM-1 on the mucosal endothelium
VLA-4 is an
integrin that is on activated effector T cells that binds to VCAM-1 on endothelium

VCAM is upregulated at the site of inflammation. VLA4 on the T cells will bind to it and let it know where the T cell can be found
steps in antigen presentation
1. T cell binds APC through LFA1-ICAM-1 (slows down T cell rolling so it can pay attention to what is going on with dendritic cells- sampling peptide bound to MHC)

2. this allows for other T cell receptors to be bound

3. conformational change in LFA-1 increases affinity and prolongs cell-cell contact
T cell activation
2 signals needed

1. MHC ClassII w/ antigen -- TCR along with CD4/ CD8

2. CD28 (T)- CD80(APC)
How does the T cell signal get transduced?
release of Ca after receptor engagement
ex of how the innate immune response potentiates the later adaptive immune respons
the phagocytosis and breakdown of bacteria by macrophage induces expression of MHC ClassII and CD80
adjuvants
microbial products known to increase T cell responses

if on APC next to bacteria, will co-stim T cells
Is costim signal (Cd28-CD80) needed for both naive and effector T cells?
No, only for naive
B cells as APCs
antigen derived presented on surface of B cell

need 2 signals

CD40-CD40L
CD28-CD80
CTLA-4
on T cell, binds to CD80 to shut down proliferation of t cell
VLA-4
controls migration of effector T cells

expressed on activated T cells

interacts with VCAM-1 which is expressed on endothelium of blood vessels in inflamed tissue
naive vs activated T cells and IL-2
naive have low affinity IL-2 R
activated have high affinity IL-2R and they also secrete IL-2 which stimulates proliferation of T cells
function of Th1 cells
macropahge activation
B cell activation
production opsonizing antibodies such as Ig1
function of Th2 cells
general activation of B cells to make antibodies
where do Th1 and Th2 cells come from?
CD 4 T cells
pathway of Th1 and Th2 cell production
maive CD4 T cell + APC--> proliferating T cell

cytokine IFN gamma induces TF Tbet which activates transcription of TF STAT4. STAT4 is activated by IL-12 --> Th1

cytokine IL4 induces GATA-3 which turns into STAT6 which with IL-4 --> Th2
if equal amt of IL12 and 4 in production of T helper cells, which cell will result?
Th2
What cytokines does Th1 produce?
IFN gamma, IL3
What cytokines do Th2 produce?
IL 3, 4, 5, 10, 13

no IFN gamma
cytotoxic effecotr molec
perforin
granzymes
granulysin
main function of CD8 T cell
cytotoxic T cell
main function of CD4 T cell, Th1
activate macrophage
main fxn of CD4 T cell Th2
produce antibodies
effector function of Th1 cell
produce IFN gamma which acts on:

activate macrophage to kill intracellular pathogens

B cells to stimulate IgG that oposonize microbes for phagocytosis

produce LT and TNF to activate nuetrophils and stimulate inflammation
how is the activation of macrophages controlled?
by inhibiting activated macrophages

Th2 cells relase cytokines GF, IL4, IL10, IL13

these cytokines also reduce Th1 production of IFN gamma which reduces Th1 direct effects on macrophages
granuloma
bunch of bacteria surrounded by T cells in order for containment
effector functions of Th2 cells
produce IL4 that stimulate B cells to produce neutralizing IgG and IgE

produce IL5 that activates eosinophils

produce IL10 and IL4 to suppress activated macrophages
what chenokines are importnat in regulation of T regulatory cells?
IL10

TGF-beta (lead to development of T regulatory and effector cells)
do effector T cells require costim?- consequence
nope

can kill any cell that expresses target antigen on MHC molec
2 mechanisms of CTL killing
1. granzymes enter through perforin holes on T cell --> activation of capsases --> apoptosis

2. Fas- FasL
specificity of CTL response vs macrophage response
CTL response is targeted, activated macrophages are not specific- there will bebystander damage
perforin
pore spans entire membrane to allow entry of granzymes
cytokines that CTL cells make
IFN gamma, TNF gamma, TNF beta
purposes of IFN gamma
increase MHC expression and make targets more visible
inhibits viral replication directly
activates macrophages
function of TNF
activates macrophages
kills through TNFR-1
cognate interaction
B and T cell recognize same antigen.

helps with vaccines