Lecture 13-14 - Tcell Mediated Immunity Flashcards by Chris Rodarte

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

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Dendritic cells increase ________ before presentation to lymphocytes

expression of MHC

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Dendritic cells present antigens from extracellular bacteria on _____, and viruses on _______

Bacterial antigens = MHC2

VIral = MHC1

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Wher aer viral antigens processed (during antigen uptake/presentation)

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Naive T cells can enter a draining lymph node via two routes:

In the blood (HEV)
afferent lymphatics coming from an upstream node

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How do Naive T cells get themselves into a HEV

They express L selectin and other adhesion molecules

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Adhesion molecules expression is ____ specific

tissue-specific

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L selectin binds to

GlyCAM-1 + CD34

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SLC and ELC (T cell chemokines) bind to ___

(on endothelial cells)

CCR7

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Activated LFA-1 binds to

ICAM-1

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Which adhesion molecule allows for the T cell to rol along surface?

L-selectin

rolLing

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CD2 (on T cell) binds to

LFA-3

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CD28 binds to

B7.1 and B7.2

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Function of LFA-3/CD2 and ICAM1/LFA1

adhesion of Tcell to APC

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MHC binds to

TCR and CD4/8

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____ is needed for Co-activation of T cell (with TCR)

CD28 binding to B7.1/B7.2

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All T cell surface molecules that interact with APC (list them)

LFA1
CD2
CD4
TCR/CD3
CD28
CTLA4

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Function of integrins (During interaction between T cells and APC)

They help prolong the activation signal from TCR and CD28 receptors on T cells

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ICAM1/LFA1 interaction is ____ when MHC isn’t bound to TCR/CD4

low affinity

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For full activation, T cells require signals from…

TCR + CD28 signals

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____ is expressed in all T cells

CD28

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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

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B7 is expressed highly by ________ cells

Activated dendritic cells

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What happens when there is no CD28/B7 interaction?

T cell anergy

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Professional APC's: 3 facts

1. **DC**s, **BC**s, **MQ**s 2. Express lots of **MHC1** and **MHC2** 3. Express costimulatory receptors like **B7**

Professional APC's are each good at specializing in presenting a particular type of antigen. Which ones are they?

**_DC_**s = 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

1. Antigen binds MHC 2. ITAMs of T cell receptor complex are _phosphorylated_ 3. Coreceptor binds MHC 4. ZAP-70 binds to phosphorylated ς-chain ITAMs 5. **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 1. **T cell proliferation** (++IL4, IFNg) 2. **B cell proliferation** (++Antibodies) 3. **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?

1. **L-selectin** (LFA-1...Naive) vs **VLA-4** (active) 2. **CD45R**_A_**** (naive) vs **CD45R**_O_**** (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

1. T bet 2. IL12 3. IFNgamma 4. 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)

1. Control intracellular pathogens and tumors 2. Transplant rejectinon 3. Type 4 hypersensitivity 4. Granuloma formation 5. 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

1. TH1 cells 2. CD8+ TC1 & TC2 3. NK cells 4. 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?

1. Antigen presentation 2. Isotype switching 3. TH1 development 4. 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