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Flashcards in T cells Deck (51):

Name the 2 effector T cell classes and what they do:

-CD4 T cells: help other cells (B cells) to respond to extracellular sources of infx.

-CD8 T cells: kill cells that are infected w virus or other intracellular pathogens (CYTOTOXIC).


What interaction determines whether a T cell and B cell of the same Ag specificity will result in B cell activation (via CD40 expression + cytokines)?

Cognate interaction.


T cells activate infected macrophages to kill intravesicular bacteria/pathogens. What 2 signals are required for this?

-IFN-gamma (produced by TH1)

-CD40 ligand on T cell must bind CD40 receptor on macrophage


What to classes of T cell receptors (TCR) are there?

* a:B (alpha: beta)--> CD4 and CD8, common circulating T cell
-y:d (gamma: delta): funx not understood


Where does TCR rearrangement and selection occur?

Thymus. (precursor T cells travel here from the BM)


Epitopes are presented to TCR in the context of what?

An MHC (self) molecule.

This is a specialized Ag-presenting glycoprotein.


What does MHC restriction mean?

TCRs can only bing to a particular peptide bound to a particular MHC molecule.


What are the two classes of MHC molecules and where are they found?

-MHC class I: HLA A,B,C; found on most NUCLEATED cells

-MHC class II: HLA DP, DQ, DR; found only on APCs.


What MHC do CD8 and CD4 T cells recognize?

CD8: MHC I (intracellular infx ex. viruses)

CD4: MHC II (extracellular infx ex. bacteria)


How are do antigens get processed and presented by MHC I and MHC II?

intracellular antigen--> proteosome--> ER--> peptide binds MHCI--> presented on cell surface (to CD8 cells)

extracellular antigen--> endocytosed in vesicle--> phagolysozome--> peptide binds MHC II--> presented on cell surface ( to CD4 cells)


Where are each of the following found within the thymus:

cortical epithelial cell
dendritic cell
medullary epithelial cell
Hassall's corpuscle

cortical epithelial cell (thymic origin): cortex

thymocyte (BM origin): throughout the thymus as it develops

medullary epithelial cell (thymic origin): cortico-medullary jnx/medullar

dendritic cell (BM origin): medulla

macrophage (BM origin): medullar

Hassall's corpuscle: medullar


Where does gene rearrangement of T cells (thymocytes) occur?

cortex of thymus.


What is:

Positive selection

Negative selection

-positive selection: selecting for T cells that are restricted by 'self' MHC

-negative selection: eliminating T cells that recognize Ags of self tissue (autoreactive)


Where does positive selection take place?

cortex of the thymus (cortical epithelial cells present MHC+peptide to TCR)


During positive selection, what happens to the co-receptor that is not involved in the epithelial APC-TCR interaction?

The co-receptor (either CD8 or CD4) not involved in the interaction ceases being expressed.


Self-restrcited CD4 or CD8 cells are tested for their reactivity to self-peptide in what process?

negative selection


What cells present self-peptide to CD4/CD8 cells during negative selection?

dendritic cells and macrophages


What TF extends negative selection to proteins that are specific to one or a few cell types (self)?

AIRE: autoimmune regulator

ex. transcription of insulin which is usually made only by beta cells in the pancreas


Where is AIRE active?

AIRE is active in a sub-population of epithelial cells in the thymic medulla.


Where does central T cell tolerance happen?

thymic medulla


Where are naive T lymphocytes activated by their specific Ag?

secondary lymphoid tissue


What chemokines do CCR7 receptors expressed by T cells bind to? Where are these secreted?


secreted in the lymph node cortex.


What happens when T cells interact with their specific Ag in the lymph node?

They complete differentiation and proliferate (become effector cells).


What 'professional' APCs are required to provide the necessary 'co-stimulation' to activate T cells?

dendritic cells
B cells


What ligand and receptor form the costimulation signal (signal 2)?

CD80 ligand (APC)
CD28 receptor (T cell)


How do T cells become 'anergic' (unable to be activated)?

When there only a specific signal (MHC-Ag + TCR) with no co-stimulation signal occurring.


the NFAT transcription factor requires what other complex of TF's to transcribe IL-1? What upstream interaction allows for this?

API complex works with NFAT to induce IL-2 transcription

CD28-CD80 interaction (co-stimulation) must take place.


What cytokine do activated T cells produce high-affinity receptors for? What does this cytokine drive?


IL-2 drives proliferation and differentiation of T cells


What T cell type needs a stronger signal to be activated? What cell type aids with this?

CD8 (CTL) - because they can cause damage to host cells (all cell expressing MHC I)

CD4 cells sometimes help to express additional IL-2 in order to activate CD8 cells.


What effector molecules fo activated T cells release?



Do ACTIVATED T cells require co-stimulation in addition to MHC-Ag in order to respond?

No. Only naive T cells require co-stimulation.


What types of CD4 T cells are there and what do they do?

TH1, TH2, TFH, TH17: activate and help other cell types carry out immune defense. Key for eradicating pathogens.

iTreg: maintain self-tolerance in the periphery and modulate the immune response to infx


How do CD8 cells (CTL) kill infected cells?

-Lytic granules
-FasL-Fas interaction


List the following for TH1 effector CD4 cells:
-cytokines inducing diff'ion
-defining TF
-characteristic cytokine

- IL-12, IFN-gamma
-IL-12, IFN-gamma
-activate macrophages


List the following for TFH effector CD4 cells:
-cytokines inducing diff'ion
-defining TF
-characteristic cytokine

-IL-16, TGF-B, IL-23
-IL-21, IL-4
-Activate B cells, maturation of Ab response (germinal centre activity)


List the following for TH2 effector CD4 cells:
-cytokines inducing diff'ion
-defining TF
-characteristic cytokine

-IL-4, IL-5
-Activate cellular and Ab response to parasites


List the following for TH17 effector CD4 cells:
-cytokines inducing diff'ion
-defining TF
-characteristic cytokine

-IL-6, IL-21
-IL-17, IL-6
-Enhance neutrophil response


List the following for Treg effector CD4 cells:
-cytokines inducing diff'ion
-defining TF
-characteristic cytokine

-TGF-beta, IL-10
-Suppress other effector T cells


What do TH1 cells do?

-macrophage activation (cell mediated immunity)
*IFN-gamma (know this)


What two signals do macrophages require in order to become activated and kill intravasicular (in addition to being bound to the TCR via MHC-Ag)?

-CD40 ligand (TC) + CD40 receptor on macrophage


What do TH2 cells do? What are the key cytokines involved?

-help B cells mount Ab response against parasite pathogens
-IL-4, IL-5


What do TFH cells do?

these helper T cells cooperate with naive B cells to initiate Ab response to infx. The interaction bw the two results in CD40L expression on the TFH and IL secretion (stimulates B cell proliferation and Ab secretion).


What do TH17 cells do?

defend against pathogens not covered by TH1 and TH2.

important in autoimmune disease

secrete IL-17


What cytotoxins to CTL release?

-perforin: make pores in target PM
-granulysin: ''
-granzymes- cleave cell proteins--> triggers apoptosis


What does the FasL (CTL) - Fas (target cell) interaction result in?

apoptosis of the target cell


What T cell type is responsible for 1. cell mediated immunity 2. humoral immunity ?

1. TH1
2. TH2


What is polarization of the immune response? What disease polarisation cause differing clinical presentations in?

When cytokines in the environment cause bias towards TH1 or TH2 response.

Leprosy (mycobacterium leprae)


Describe a TH1 (cell-mediated) bias response to leprosy

-infected macrophages can suppress bacterial growth
-slow progression
-damage to skin and peripheral nerves


TH2 (humoral) biased response to leprosy is:

-bacteria inaccessible to Abs inside macrophages
-bacteria grows unchecked
-severe tissue destruction--> death


What TF doe Tregs express?

Foxp3 (suppressive funx)


What are the two types of Tregs?

-nTreg: natural Tregs, made in the thymus

-iTreg: inducible Treg, arise from peripheral naive conventional T cells