Lecture 13-14 - Tcell Mediated Immunity Flashcards
What do dendritic cells do after taking up bacterial antigens in the skin?
Travel via lymph, enter node and settle in T cell areas to present antigens to Tcells
Dendritic cells increase ________ before presentation to lymphocytes
expression of MHC
Dendritic cells present antigens from extracellular bacteria on _____, and viruses on _______
Bacterial antigens = MHC2
VIral = MHC1
Wher aer viral antigens processed (during antigen uptake/presentation)
ER
Naive T cells can enter a draining lymph node via two routes:
- In the blood (HEV)
- afferent lymphatics coming from an upstream node
How do Naive T cells get themselves into a HEV
They express L selectin and other adhesion molecules
Adhesion molecules expression is ____ specific
tissue-specific
L selectin binds to
GlyCAM-1 + CD34
SLC and ELC (T cell chemokines) bind to ___
(on endothelial cells)
CCR7
Activated LFA-1 binds to
ICAM-1
Which adhesion molecule allows for the T cell to rol along surface?
L-selectin
rolLing
CD2 (on T cell) binds to
LFA-3
CD28 binds to
B7.1 and B7.2
Function of LFA-3/CD2 and ICAM1/LFA1
adhesion of Tcell to APC
MHC binds to
TCR and CD4/8
____ is needed for Co-activation of T cell (with TCR)
CD28 binding to B7.1/B7.2
All T cell surface molecules that interact with APC (list them)
- LFA1
- CD2
- CD4
- TCR/CD3
- CD28
- CTLA4
Function of integrins (During interaction between T cells and APC)
They help prolong the activation signal from TCR and CD28 receptors on T cells
ICAM1/LFA1 interaction is ____ when MHC isn’t bound to TCR/CD4
low affinity
For full activation, T cells require signals from…
TCR + CD28 signals
____ is expressed in all T cells
CD28
B7 binds to both ___ and ____
Where are they found and whats the difference?
CD28 + CTLA4
CD28 is costimulatory for T cell activation
CTLA4 on activated T cells, and is an inhibitor of T cell activation
B7 is expressed highly by ________ cells
Activated dendritic cells
What happens when there is no CD28/B7 interaction?
T cell anergy
Professional APC’s: 3 facts
- DCs, BCs, MQs
- Express lots of MHC1 and MHC2
- Express costimulatory receptors like B7
Professional APC’s are each good at specializing in presenting a particular type of antigen. Which ones are they?
DCs = bact/viral in lymphoid tissues
MQ = Extracellular bacteria (at site)
B cells = soluble antigens
____ and ____ can induce dendritic cell maturation
Bacterial products (LPS) and inflammatory cytokines (TNFa)
Mature DC’s express ___, ___, and ____
CCR7
MHC1/2
B7
Immature DC’s are good at ________, but lack _________
Mature DC’s have ____and_____ but lack ___________
Phagocytosis, co-stimulatory/presenting ability
MHC and B7, but lack phagocytic ability
T cell activation signal transduction pathway (5 steps
- Antigen binds MHC
- ITAMs of T cell receptor complex are phosphorylated
- Coreceptor binds MHC
- ZAP-70 binds to phosphorylated ς-chain ITAMs
- Lck phoshphorylates ZAP-70 and activates it
CD3 ITAMS are phosphorylated by ___ or ____.
What effect does this have
Fyn or Lck
Allows zap-70 to bind
What does activated zap-70 do?
activates PLC-gamma
which causes…
PIP2-> DAG + IP3
DAG activates ___ and ____. Downstream effects of those?
PKC and RasGRP
PKC >> NFkB
RasGRP >> MAPK >> AP-1 (Fos)
IP3 function?
increases intracellular Ca++
>> calcineurin activated
>> NFAT activated
NFkB, AP-1, and NFAT all have what effect on the T cell
change the pattern of gene expression to favor
- division
- proliferation
- differentiation
Effects of cyclosporin A and FK506
block NFAT activation, thus blocking IL-2 production
A consequence of T cell activation is enhanced production of _______, and induction of ________ expression
enhanced IL-2
induction of IL-2Ra
Pathway of IL-2 production by activated T cells
Nuclear-ly controlled by Phosphorylated STAT
JAK binds cytokines –> JAKs dimerize –> phosphorylation of intracellular part –> phosphorylation of STAT –> goes to nucleus
What is the “#1 cytokine” according to Dr. Kim?
What are it’s three major effects?
IL-2
- T cell proliferation (++IL4, IFNg)
- B cell proliferation (++Antibodies)
- NK cell proliferation, with increased cytolytic activity
B cells and NK cells need _____ for cellular expansion
IL-2
Naive and effector (activated) T cells express different cell surface molecules. 2 Examples?
- L-selectin (LFA-1…Naive) vs VLA-4 (active)
- CD45RA** (naive) vs CD45RO** (Active)
Both TH1 and TH2 can promote…
humoral immune response
Major Cytokines form active TH1 cell
functions?
IL-2, IFNg
MQ and B cell activation, opsonizing antibodies
Major cytokines from Th2
Function?
IL-4, IL-5
General activation of B cells to make antibodies
Cell mediated response is promoted by ____ T cells,
Humoral / Ig response is largely promoted by ________ cells
TH1
TH2
TH2 cells are functinoally _____ because they stimulate a ____ response
antiparasitic
IgE response
Major cytokine that induce differentiation into Th1 cells
IL-12
Major cytokine that promotes differentiation into TH2 cells
IL4
TH1 pathway major players
- T bet
- IL12
- IFNgamma
- STAT4
TH2 major players
GATA-3
IL4
STAT6
Cytokines secreted by Th1 cell
- IFN gamma
- GM-CSF
- TNFa
- LT
- IL-3
Cytokines secreted by TH2 cell
IL’s 4, 5, 10, 13
Tregs are controlled by ___ transcription factor
FoxP3
Main functions of Th1, Th2, Tfh, Th17, and Treg cells
TH1 = helps MQ with intracellular infections
TH2 = helps granulocytes and Bcells with Parasites
Tfh = Help activate Bcells & switch/mature its antibodies
TH17 = Help neutrophils deal with fungal and extracellular infections
Treg = suppress all the other ones
Tfh cytokines
IL21
IL4
IFNgamma
TH17 cells cytokines
IL- 17, 21, 22, 26
____ induces class switching in antibodies
IL-4
According to Dr. Kim, what is the unique cytokine for Th1 cells?
IFN gamma
Treg cytokines
TGFbeta
IL-10
IL-35
(CORE)
CMI response functions (5)
- Control intracellular pathogens and tumors
- Transplant rejectinon
- Type 4 hypersensitivity
- Granuloma formation
- Chronic inflammation
Three “connections” made by TH1 and MQ to activate the latter
TCR > MHC
CD40L > CD40
IFNg > IFNg receptor
Four cells involved in CMI
- TH1 cells
- CD8+ TC1 & TC2
- NK cells
- MQ
TH1 secretes CXCL2, which is a ..
chemokine
for MQ to travel to site of infection
CD8 T cells kill virus/tumor cells by these four things:
TNFb, perforin, granzymes, FAS ligand
Cytolytic activity of CD8’s are promoted by…
IL-2, IL-12, IFNgamma
CD8+ cells need ___________ from APCs to become effector CD8s
CD28 activation signal
At the effector stage of CD8+ cells, _____ is NOT needed
CD28
Only need to bind to the MHC
CD8 cells secrete ____ which induces apoptosis on target cell
FAS ligand
Role of the endothelium in CMI
expresses P and E selectins
CD8+ mediated killing of cells can be detected by…
51Cr release assay
51Cr enters cells, wash away any extracellular, and cells that get killed by CD8 will release Cr into the medium.
Granulomas are made of _________
aggregated infected epithelioid MQ
Surrounded by T cell
Common in TB infection, where pathogen can persist in MQ for a long time!
IFNg promotes what 4 things?
- Antigen presentation
- Isotype switching
- TH1 development
- MQ activation
TH2 cells suppress…
Macrophage activation
Via IL-10
Functions of TH2 cells
Production of IgG, IgE
Eosinophil activation
MQ suppression
____ activates eosinophils
IL-5
*from TH2
TH2 cells activate B cells via _____and ______
cytokines and CD40L
Tuberculoid vs lepromatous leprosy
TL = Th1 cells produce IFNgamma and activate MQ
LL = TH2 cant activate MQ
TH17 are induced by what cytokines
What cytokines do they produce?
IL- 1, 6, 23
Make IL-17 and IL-22
Cytokines that inhibit the production of TH17 cells
IL-2, IL-4, IFNg
TH17 function
antibacterial and antifungal
role in chronic AI inflammation in skin, joints, CNS
Major subset of Tregs are positive for…
FOXP3+
CD4+
CD25+
Tregs express
CD25 and CTLA4
Tregs produce
TGFb and IL-10
Purpose of Treg cells
prevent AI diseases
Disease from FOXP3 mutation
IPEX (XLAAD)
unchecked TH1 and TH2
Cortisol/Catecholamines suppress…
CD8/TH1 cells
