Immunology - Exam 1 (Part 5 - T Cells)

What are the white blood cells (from bone marrow) that are matured/educated in the thymus which circulate in the blood and lymph and can enter the tissue?

T cells

(T for Thymus)

What are the "antibody like receptors" on the surface of T cells that specialize in recognizing protein antigens presented by MHCs?

T cell receptors (TCRs)

NOTE: NOT antibodies, unlike BCR which is just an antibody tethered to B cell

Which type of T cells kill other cells but must get permission to do so? Which type of T cells help other cells but must get permission to do so?

Killer T cells (Tk)

helper T cells (Th)

Which type of T cell is activated by MHC I and abnormal peptide presented on cell, causing it to connect to the target cell and trigger cell the cell to undergo cell death?

Killer T cells

(Cytotoxic T cells -- CTLs; CD8+)

NOTE: kill other cells but must get permission to do so

Which type of T cell is activated by MHC II and abnormal peptide on Antigen Presenting cells to secrete cytokines? What are 3 cytokines that it can secrete?

Helper T cells

(Th cells; CD4+)

Cytokines:

interleukin 2 (IL-2), Interferon gamma (IFN-gamma), or TNF

NOTE: help other cells but must get permission to do so

Which type of T cell keeps the immune system from overreacting and secretes IL-10?

(NOT ON EXAM 1; on Exam 2)

Regulatory T cells

(Tr cells; CD4+)

T/F: Tk requires activation before they can funciton, Th does not.

FALSE

BOTH Tk and Th require activation before they can function (takes 4-10 hours)

In T cell activation, what is the function of the TCR (T cell receptor)?

Must recognize its cognate antigen

In T cell activation, what must recognize the MHC (I or II)?

Co-receptor

(this is the CD4 & CD8 parts)

NOTE: Not on B cells

In T cell activation, what is the process where other receptors must recognize other molecules?

Co-stimulation

What are the 3 T cell responses? (ON EXAM)

1) If T cell sees/recognizes "self" peptides being presented by MHC, it triggers apoptosis on self

2) If the T cell sees "non-self"/cognate antigen but doesn't get co-stimulated, rendered inactive (anergtized -- incapacitated)

3) If T cells sees "non-self"/cognate antigen AND gets co-stimulated, T cell activated

What are the 3 things that T cells need to become activated?

1) Non self/cognate antigen recognition and CD4 or CD8 co-receptors

2) Co-stimulation: B7 on APCs/CD28 on T cells

3) Co-stimulatory signal to nucleus via CD3

T/F: T cell receptors on the surface of the T cell recognize peptides presented by MHC I, MHC II, and soluble molecules.

FALSE

-- recognizes ONLY peptides presented on MHC I or MHC II

--> NOT soluble molecules

T/F: BCRs are more diverse than TCRs

TRUE

T/F: All TCRs on a given mature T cell are identical

TRUE

What are the two types of TCRs? Which makes up 95% of TCRs?

1) alpha-beta (Traditional) --> 95%

2) gamma-delta (Non-traditional)

What is the name given to the group of signaling proteins in traditional TCR anatomy made up of gamma, delta, epsilon, and zeta?

CD3

The non-traditional T cells expressing gamma-delta as receptors is most abundant where? (3)

Intestine, uterus, tongue

T/F: alpha-beta receptors are more diverse than gamma-delta, but gamma-delta is more effective at recognizing protein fragments from pathogens.

FALSE

-- Alpha-beta is both MORE DIVERSE & MORE EFFECTIVE at recognizing

Why are the co-receptors binding T cells to MHCs (type I or II) so important?

Without CD4 or CD8, the T cell would not know if it was interacting with an APC presenting an antigen that needs help, or an infected cell that needs to be killed

Which co-receptor is MHC I restricted (peptides made in the cell)? Which co-receptor implies MHC II (peptides outside cell)?

MHC I = CD8

MHC II = CD4

The TCR-MHC complex interaction signal is strengthened by the addition of what?

CD4 / CD8 (co-receptors)

Which Co-receptor is expressed on killer T cells (CTLs), attach TCR to MHC I, and signal to kill?

CD8

Which Co-receptor is expressed on helper T cells, attaching TCR to MHCII molecules, and signal to help?

CD4

NOTE: the product (x) is ALWAYS 8 (way to remember)...

CD4 x MHC 2 = 8

CD8 x MHC 1 = 8

What is needed for Recognition of T cell? (2)

Recognition

1) TCR (alpha/beta)

2) Co-receptor (CD4 or CD8)

What is needed for Co-stimulation of T cell? (2)

1) B7 on APC

2) CD28 on T cell

What is needed for Signaling of T cell? (2)

1) CD3 (gamma, delta, epsilon, zeta)

2) CD28 on T cell

The connection between the receptor and nucleus of naive T cells is week, so it needs activation with what to create a better connection?

Co-stimulation

What molecule co-stimulates T cells? What does it bind to on the T cell?

B7 proteins (B7-1; B7-2; CD80; CD86)

-- B7 (from APCs) connect with CD28 receptor on T cell

NOTE: one of MANY molecules that can costimulatory, but only one we need to know

How does the APC know it needs to express B7?

Upon initial contact with APC and T cell

- APC CD40 engages CD40L on T cell which signals upregulation of B7

When CD40-CD40L happens on T cell, what happens? When CD40-CD40L happens on B cells, what happens?

T cell = Upregulates B7 (CD80/86; which co-stimulates to ACTIVATE T cell by doing B7-CD26 coupling)

B cell = Activates B cell (because helper T cell is already ACTIVE, so the coupling is costimulatory to activate the B cell)

What is the co-receptor for activating a B cell?

NONE

-- only T cells have co-receptors (CD8 & CD4)

The combination of co-stimulation molecules (T cell) will depend on the ________ & the __________?

The pathogen & the AREA of the body-regional identity

T/F: T cell will activate and scan lipids & carbohydrate antigens.

FALSE

-- scans MHC which ONLY holds protein

-- carbs & lipids scanned by NK cells (PAMPs) & B cells & Macrophages

Helper T cells constantly scan what cells in the lymph nodes? If we arn't in the lymph nodes, what are we scanning for?

Dendritic cells (DCs)

Not lymph nodes = APCs

If the Helper T cell finds its cognate antigen, what is the process that happens? (5)

1) TCR engages antigen/MHC

2) CD4 coreceptor on helper T cell attaches to MHC II molecules on dendritic cells (APCs)

3) CD40L proteins attach to CD40 proteins on dendritic cells

4) Dendritic cell (or APCs) makes more co-receptors and co-stimulatory molecule (B7)

5) Adhesion molecules bind the two cells (immiunological synapse)

What cell travels from the tissue to the lymph nodes to initially activates the T cells? What cell reactivates the T cell once its reached the tissue?

Initial = Dendritic cells

Reactivated = Macrophages

NOTE: macrophages do not leave the tissue once they're in the tissue

Once the Helper T cell and APC separate, what happens to the dendritic (APC) cell? What happens to the Th?

Dendritic (APC) = goes on to activate other Th

Th = proliferate and make more IL-2 (positive feedback for division)

Naive T cells don't have IL-2 receptors on their surface, which means what about replication?

T cells replicating are the specific ones needed to combmat this particular antigen

NOTE: The Th are all being made the same so they are all specific for cognate antigen

Killer T cell activation is the same as helper T cells except what?

MHC I

-- still meets activated dendritic cell that presents cognate antigen (NOW on MHC I); then co-receptors/co-stimulation occurs, and finally follows rest of same concept

When dendritic cells and helper T cells bind (for hours), they emit what molecule which attracts CTLs?

Cytokines

NOTE: remember also supplies IL-2 for CTL proliferation

Helper T cell SUMMARY slide

TCRs

-- alpha and beta recognition proteins

-- CD3 signaling protein complex

Co-receptor

-- CD4

-- Binds to MHC II

Co-stimulation

-- many different molecules

-- Remember B7

Activation

-- recognize cognate antigen on ADCs MHC II

-- co-stimulate from ADC

Experienced cells more easily activated

Emits cytokines

Killer T cells SUMMARY slide

TCRs

-- alpha and beta recognition proteins

-- CD3 signaling protein complex