Pod 9 T Cell Mediated Immunity Lopez

Front 1

Describe the main T cell types
1-1-1

Back 1

2 forms of CD4 T cells (Th1 and Th2)
+ CD 8 T cells

Front 2

Explain the fate of activated T cells
1-1-1

Back 2

3 forms of activated T cells
1) Effector CD4 Th2 cells that stay in the secondary lymph tissue
2) Effector CD4 Th1 - go to site of infection
3) Effector CD8 T cell- goes to infection

Front 3

Describe the process of clonal selection of T cells in the secondary lymphoid
1-1-1

Back 3

the antigen, a peptide from the pathogen associated with a MHC molecule, selects the clones of T cells ( only a few out of a million)
the basis for this selection is the interaction of the TCRs with the peptide/MHC molecules
called clonal selection

Front 4

Describe the steps of DC differentiation and locations from antigen uptake to antigen presentation to T cells
1-1-2

Back 4

Morphology of DC cells:
1) in peripheral tissues DCs show prolongation and pseudopodia typical of phagocytic cells
2) in lymph circulation the cells looks as having sails (makes it more efficient to move in the system)- also shows a high level of lysosomal activity at this time b/c they are degrading the molecules from the pathogen (in the phagolysosome)
3) in the secondary lymphoid tissue, they are EXTENDED, allowing for the interaction with many T eclls. A this time the cells show high level expression of MHC II because they are presenting antigens to naive CD4 T cells

Front 5

Describe the mechanism by which HEVs become activated
pg 343

Back 5

antigen loaded dendritic cells secrete cytokines that activate the endothelial cells
these also attract T cells, to migrate to the area where the DC has settled)
Cytokines --> activate the expression of addressins on the cells of the HEVs
addressins= CD34 and GlyCAM-1
adressins are on the HEVs
bind to L-selectins that are found on T-cells (and also on B cells..)

Front 6

Describe the mechanisms involved in the entry of T cells in the secondary lymph nodes
pg 342

Back 6

DCs must come to the lymph node, secrete cytokines. T cells follow the cytokines & T cells bind addressins (CD34 GlyCAM-1) which are displayed on the endothelial cells --> diapedesis

Front 7

Name the molecules involved in binding of the T cell to the endothelium
pg 343

Back 7

addressins: CD34 & GlyCAM-1 which are present on endothelial cells of HEVs
T-cells have L-selectins that bind to these addressins

Front 8

Explain the mechanism leading to diapedesis of the naive T cells towards the interior of the lymph node
1-1-3

Back 8

cytokines secreted by dendritic cells, addressins on endothelial cells, selectins on T-cells, diapedesis

Front 9

Describe the mechanisms involved in chemotaxis of the naive T cell to the antigen- loaded dendritic cell
pg 344

Back 9

chemokines are made by endothelial cells --> induce T cells to express IFA-1, an integrin
LFA-1 binds with high affinity to an intercellular adhesion molecule, ICAM-1, expressed on the dendritic cells
thus chemotaxis allows the FIRST cell-cell membrane interaction btw DCs and T-cells
ICAM-1 is an ADHESIN, along with CD2 and ICAM-3

Front 10

Name the molecules involved in the first contact between dendritic cells and naive T cells
pg 344

Back 10

this contact is direct result of chemotaxis
on T cells: ADHESINs: LFA-1,CD2, ICAM-3
on DCs: ICAM-1
I think the LFA-1 to ICAM-1 is the most important interaction

Front 11

Describe the signals needed to activate a naive T cell
pg 345

Back 11

1) specific binding of the TCR with the MHC/ peptide
2) activation molecules - B7 (CD80) with CD28
Dendritic cells express B7 when encounter antigen. They are the ONLY APCs that express this, thus they are the ONLY cells that can activate naive T cells

Front 12

Describe the fate of a naive T cell that does not receive the second signal (co-stimulation)
pg 345

Back 12

anergy
the second signal comes from the expression of B7 (CD80) on dendritic cells

Front 13

Name 3 antigen presenting cells involved in the activation of T cells in the lymph nodes
pg 346

Back 13

dendritic cells- these migrate to lymph nodes, are confined to T-cell areas
macrophages- located thru out lymph nodes- present PAMPS (express CD80, CD86, MHC II)
b cells- only in germinal centers where they interact with CD4 Th2 cells= Cognate Recognition

Front 14

Describe how macrophages and B cells express activation molecules for the T cell on their membranes
pg 222. summary on 230 Parham

Back 14

macs- they phagocytose bacteria and breakdown in phagolysosomes whcih leads to the release of substances that induce the expression of co-stimulatory B7 molecules,-- activation of naitve T cells is accomplished by combination of B7 binding to CD28 and peptide MHC complexes binding to the TCR receptor
B cells: bind soluble and particulate protein fromt eh extracellular environment by means of its surface immunoglobulin. antigen is internalized (endocytosis); then they are presented via MHC II molecules

Front 15

Explain the concept of cognate recognition
pg 347(notes)
pg 255 Parham

Back 15

cognate= refers to having the same origin, or be similar
hence, the process by which B cells act as an APC and present antigens to the T helper cells is referred to as Cognate Recognition, or interaction
in our notes it is mentioned that this occurs in the B-CELL areas

Front 16

Define adjuvants
pg 347 (notes)
pg 226 (Parham)

Back 16

microbial PAMPs that activate macrophages & dendritic cells so they express activation molecules and become more effective in the activation of Tcells
B cells do NOT need adjuvants
think of adjuvants as "jumper cables"

Front 17

Describe the role of PAMPs in the activation of macrophages and dendritic cells
Why don't PAMPS have this same role for B cells?
pg 347 notes
pg 226 Parham

Back 17

PAMPS act as adjuvants, acting as "jump start cables" that induce the initial signal needed by the APC to activate naive T cells
B cells do not need adjuvant jumper cables because during the process of endocytosis of the pathogen, they get the same kick start by the BCR receptor

Front 18

Describe the cytoplasmic events leading to activation of a T cell after engagement of the TCR with the MHC molecule
pg 348 (notes)
pg 222-224 in Parham, (section 8-7)

Back 18

Once the BIG 3- TCR-MHC-Peptide complex is together, it's said to be the "IMMUNE SYNAPSE"
leads to Phosphorylation of proteins, first ITAMS (immunoreceptor Tyrosine activation motifs) and then the all important ZAP-70
ZAP30 "zaps" in 3 different directions- NFAT, NFkB, AP-1
they all have the end effect in increasing gene transcription- IL2 & IL2R
which leads to proliferation and differentiation of the T cell

Front 19

Describe the events leading to T cell proliferation and differentiation after Zap70 is phosphorylated
pg 348 (notes)
pg 223 Parham

Back 19

ZAP30 "zaps" in 3 different directions- NFAT, NFkB, AP-1
they all have the end effect in increasing gene transcription- IL2 & IL2R
which leads to proliferation and differentiation of the T cell

Front 20

Describe the mechanism leading to proliferation due to transcription of the IL2Ralpha
pg 348 (notes)
pg 223 Parham

Back 20

Once the BIG 3- TCR-MHC-Peptide complex is together, it's said to be the "IMMUNE SYNAPSE"
leads to Phosphorylation of proteins, first ITAMS (immunoreceptor Tyrosine activation motifs) and then the all important ZAP-70
ZAP30 "zaps" in 3 different directions- NFAT, NFkB, AP-1
they all have the end effect in increasing gene transcription- IL2 and IL2R
which leads to proliferation and differentiation of the T cell

Front 21

Name 2 populations of CD4 T cells based on the secretion of cytokines
pg 351 (notes)
pg 227 Parham- see fig 8.19

Back 21

b/c there aren't diff markers on the two types of Th cells, they are distinguished by the cytokines they secrete
Th1: IL-2, INF gamma, TNF-beta --> MAcrophage activation, B cell activation, and production of opsonizing antibodies such as Ig1
Th2: IL-4, IL-5 ...il 10, IL13, TFG-B--> general activation of B cells to make antibodies

Front 22

Describe the main cytokines secreted by Th1 and Th2 cells
pg 350 (notes)

Back 22

Th1: IL-2, INF gamma, TNF-beta --> MAcrophage activation, B cell activation, and production of opsonizing antibodies such as Ig1
Th2: IL-4, IL-5 ...il 10, IL13, TFG-B--> general activation of B cells to make antibodies

Front 23

Explain the Th1-Th2 paradigm in the context of protection against infection
pg 351 (notes)
pg 228 Parham

Back 23

in leprosy, the immune response becomes strongly biased toward either a Th1 or Th2 response, a choice that profoundly influences disease progression
TH1= Tuberculoid Leprosy (TL): red lesions in face, extremities and trunk- good prognosis
Th2= lepromatous Leprosy (LL)= extensive skin involvement , poor prognosis
The outcome of leprosy is based MAINLY on the host response

Front 24

Define cytokines and its receptors
pg 352 (notes)
pg 233 Parham (fig 8.26)

Back 24

Cyto= cell, kines= to move.... cytokines= small proteins secreted by CELLS that cause effects, like moving
Cytokine receptors are connected with Jak and STAT... STATs go to the nucleus and induce transcription of genes
just think.... JACK and STAT follow cytokines

Front 25

Describe the attributes of cytokines
pg 351, 352 (notes)

Back 25

1) pleitropy - same cytokine, acts on diff populations, inducing diff effects
2) redundancy- 2+ cytokines act on same cell, same effect
3) synergy- one cytokine can add to the the effect of another (ie IL 6 and IL1 are needed before B cell will differentiate into plasma cells)
4) antagonism: one cytokine can block another (e gamma IFN is a TH1 cytokine, which can block Th2 cytokines and vice versa)

Front 26

Describe the general mechanism of signal transduction between cytokines and their receptor leading to gene transcription
pg 352

Back 26

cytokines bind to their receptor, excite the "cytokine fans" JACK and STAT
STAT goes to the nucleus and induces gene transcription

Front 27

Explain the 3 types of activation for CD8 T cells
pg 353

Back 27

1) Spatial- where the same DC cell activated a TH1 cell (thru MHC II)- produces IL2 and a CD8 T cell (thru MHC-1) to produce IL-2R
2) Temporal - first interacts with CD4 Tcell -- which expresses activation molecules (like B7), later the DC cell kisses a CD8 Tcell, which produces IL-2R and IL2
3) Infected dendritic Cell- a virus causes DC cell to express B7, induces CD8 to produce IL2R and IL2

Front 28

Describe the main features of effector T cells
pg 356

Back 28

no longer naive! Tcells know travel to the site of infection or germinal centers, and express moelcules that attract them to these sites (when they were naive, they expressed molecules like L-selectin for diapedesis)

Front 29

Compare the molecule pattern expressed on cell membranes of effector T cells
pg 357

Back 29

no longer naive! Tcells know travel to the site of infection or germinal centers, and express moelcules that attract them to these sites (when they were naive, they expressed molecules like L-selectin for diapedesis)

Front 30

Describe the function of each of these molecules in effector T cells
pg 357

Back 30

VLA-4 (CD49d) binds to VCAM (CD106) which is present in inflamed endothelial cells
LFA-1, CD2, CD44, - to bindly tightly to other cells
diff isoform of CD45 associated with the TCR complex- decreased the threshold for activation

Front 31

Compare the activation of a naive T cell with effector CD8 T cells
pg 358

Back 31

EFFECTOR CD8 t cells are "preactivated" - do NOT need a second signal
how are they preactivated? they have a different isoform of CD45 (RO instead of RA) which decreases the threshold for activation= "preactivated"
R/O= doesn't take much to get them excited

Front 32

Describe the events leading to induction of apoptosis by a CD8 T cells to a target cell
pg 359- 361

Back 32

once activated, CD8 T cells need to:
1) adhere to the target cell LFA-1, CD2, CD44
2) Specific recognition - needs to be strongly attracted- MTOC, Golgi, and granules align toward target
3) induce apoptosis- release the granules! perforins, granulysins, granzymes

Front 33

Describe the mechanisms involved in the induction of apoptosis to target cells
og 361

Back 33

activates the Caspase cascade by Granzymes
also thru FasL/Fas interaction
Fas is found on lymphos, macs, and neutrophils
FasL is on CD8 T cells

Front 34

Describe the events leading to apoptosis by Fas/FasL interaction
pg 237 of Parham

Back 34

Fas is on lymphos, macs and neutrophils
FasL on CD8Tcells
when they come together, apoptosis happens

Front 35

Describe the role of cytokine IFNgamma in the activation of macrophages
pg 362

Back 35

a 3rd role of CD8 t cells is to secrete gamma IFN, which activates macs so they can go eat apoptotic cells

Front 36

Explain the role of IFNgamma, CD40, (LT) TNFbeta, Fas, and IL-2 against intracellular pathogens
These are all coming from which Effector T-cell?
pg 363

Back 36

This is the CD4 Th1 effector response
IFN gamma and CD40= activate macs to eat more
IL-2= induces TH1 cells to proliferate
LT/ Fas/FASL = cause macs that are heavily infected to apoptose

Front 37

Explain the physiological role of granulomas
Granulomas are a result of which effector cell?
pg 363 (notes)
pg 241 (Parham)

Back 37

granulomas are a result of CD4 Th1
granulomas help to wall off intracellular pathogens so they cannot spread

Front 38

Explain why B-T cell interactions are cognate though the BCR and TCR recognize different antigens
pg 365
*8pg 241 Parham

Back 38

" the principle governing T-cell help to B cells is that cooperation occurs ONLY between B and T cells that are specific for the same antigen, altho they usually recognize DIFFERENT EPITOPES. Such interactions are called COGNATE interactions"

Front 39

Describe the mechanisms involved in the activation of a B-Cell
pg 366 (notes)
pg 241 Parham

Back 39

CD40
IL4, 5, 10
IL 10, TFG B

Front 40

Describe the main characteristics of the Treg (TR) population of T cells<BR>pg 367

Back 40

TR s secrete IL4, IL10, and TGF-B= ANTI-inflammatory cytokines
they down-play the immune response after an infection

Front 41

Explain why lack of a functional fox3p gene induces generalized autoimmunity
pg 367

Back 41

connect this "foxy-3P" to TR
gotta think "when JR's foxy gene is transcribed, he can downplay the immune response after infection"

Front 42

What cytokine is causes the formation of TH17 cells?
What do TH17 largely function to do?
pg 368

Back 42

IL-23 induces differentiation of naive T cells into TH17 T cells
TH17 cells function to induce ACUTE inflammation upon detection of a pathogen at the site of infection

Front 43

Explain the role played by cytokines and chemokines secreted by TH17
pg 368

Back 43

TH17 secretes IL 17, IL6 and TNF
IL17 binds to endothelial & stromal cells to induce more chemokines and cytokines
mainly CSF- which has effects on the bone marrow to release neutrophils and macs
CXCL 1,6,8 are chemoattractants for macs and neutrophils
therefore, TH17 induces acute INFLAMMATION at the site of infection

Front 44

Describe the main features of toxic shock syndrome
pg 370

Back 44

its a MASSIVE activation of T cells
produced by a "SUPER antigen" (can be caused by SUPER absorbent tampons......)
superantigens bind to the VH portion (NOT the CDRs) of the beta chain- this is the "conserved" region
therefore, 1 superantigen can activate MANY tcells regardless of their specificity
so many cytokines are released that they cause shock

Front 45

Compare septic shock with toxic shock
pg 372

Back 45

macrophages vs T cells
TNF vs IL-1, IL2, TNF