Chapter 8: T Cell Activation and T Cell Functions

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How does a T cell antigen go from an infection site to a lymph node?

It gets bound by a dendritic cell, at an infection site, then travels through the lymphatic system to a secondary lymphoid tissue

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How do immature dendritic cells become activated?

when a PAMP or DAMP activates a PRR on its surface

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What do PAMP and DAMP stand for?

Pathogen associated molecular pattern

Damage/danger associated molecular pattern

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What three molecules become upregulated on a dendritic cell surface following activation of the dendritic cell?

The co-stimulatory molecule, B7

Peptide:MHC complexes

Chemokine receptor 7 (CCR7)

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What will the co stimulatory molecule, B7 bind to?

It will eventually bind to CD28 for T cell activation

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What does the CCR7 molecule do?

It directs the dendritic cell toward a chemokine produced in secondary tissues

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What molecule is downregulated on the dendritic cell surface following activation?

PRRs

once a dendritic cell becomes activated, it has no business trying to bind PAMPs.

Its new function is to present antigens to T cells

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How are dendritic cells prevented from being activated by self antigens that are taken up via macropinocytosis?

The self antigen will not activate PRRs on the un activated dendritic cell surface.

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What is macropinocytosis?

non specific engulfing of extracellular material

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Where in the lymph node do T cells sample T cell antigens that are brought to them by dendritic cells?

in the T cell areas of lymphnodes

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What is the first signal needed for T cell activation and proliferation?

T cell receptor binding to a peptide:MHC complex presented to it by a mature dendritic cell

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When does the T cell begin to produce its own supply of IL-2 for proliferation?

after receiving the first 2 activation signals

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What is anergy?

When a T cell or B cell becomes permanently unresponsive/inactive

14
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What happens to a T cell if a T cell receptor binds to a peptide:MHC complex without receiving a co stimulatory signal?

The T cell will become anergic

This is a form of protection to minimize the chances of a T cell becoming activated by self antigen

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What is a naive T cell?

a T cell that has not yet become activated

16
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What is an effector T cell?

a T cell that has been activated and now has an effector function.

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What type of effector T cell does a CD8 T cell turn into following activation?

A cytotoxic T cell

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What is the function of a cytotoxic T cell?

to destroy host cells that are infected with an intracellular pathogen

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How do cytotoxic T cells identify a target cell to destroy?

The target cell will display pathogen peptides on MHC class l molecules. The cytotoxic T cell will look for the MHC complex that activated it and bind to it and destroy the cell.

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What are the 2 classes of cytotoxins stores in granules of cytotoxic T cells?

Perforin and granzymes

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What does perforin do?

it disrupts the membrane of the target cell the cytotoxic T cell wants to kill

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What do granzymes do?

activate caspase proteins inside the target cell which will induce apoptosis of the cell.

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What are the 5 subsets of CD4 T cells?

TH1 cells, TH2 cells, TFH cells, TH17 cells, and Tregs

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How are CD4 T cell subsets determined?

Based on the cytokines present during activation of the naive CD4 T cell

(The cytokines present during activation are dependent on the type of infection present)

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What is the function of TH1 (T Helper 1) cells?

upregulation of macrophages for more effectiveness of phagocytosis.

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What type of pathogens/infection do TH1 cells predominate?

intracellular pathogens.

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Why are macrophages not constantly upregulated?

Macrophages produce potent antimicrobial substances used to perform phagocytosis and if they are always releasing those substances, they can damage healthy host cells. Macrophages being activated also takes a lot of energy.

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What is 1 of 2 signals macrophages need to become activated?

The cytokine, IFN-gamma:delta

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What is a granuloma?

A collection of macrophages and T cells that trap a pathogen to keep it from spreading because they can’t kill it.

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What is a disease that causes granulomas in the lungs?

Tuberculosis.

The TB bacteria get trapped inside and potentially go into a dormant/inactive state, but they never go away completely.

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What is the function of TFH (T follicular helper) cells?

provide an activating signal needed to activate B2 cells

provide signals required for somatic hypermutation and class switching of B2 cells.

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What is the function of TH2 (T Helper 2) cells?

defense against helminth parasites by releasing cytokines.

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What is result 1 of the cytokines released by TH2 cells?

Promotion of immune responses by mast cells, eosinophils, and basophils

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What is the function of TH17 (T helper 17) cells?

To enhance the response to infections with extracellular pathogens like extracellular bacteria and fungi

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What is the first thing cytokines released by TH17 cells results in?

Increased neutrophil production and also recruitment of neutrophils to the infection site

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What innate lymphoid cell performs a parallel function with a TH17 cell during an innate immune response?

ILC 3

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What innate lymphoid cell performs a parallel function with a TH1 cell during an innate immune response?

ILC1

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What innate lymphoid cell performs a parallel function with a TH2 cell during an innate immune response?

ILC2

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What innate lymphoid cell performs a parallel function with a CD8 T cell during an innate immune response?

Natural killer cell

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What are the functions of Treg (T regulatory) cells?

to suppress the activity of other T cell subsets to prevent immune responses to self antigens/environmental antigens

Involved in repairing and restoring damaged tissues after immune responses.

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What are natural Tregs?

cells that are produced in the thymus and are programmed to suppress the immune system to prevent autoimmunity. They arise from T cells that strongly bind to self-peptides during negative selection

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What are induced Tregs?

Cells that begin as regular CD4 T cells but transform into Tregs outside the thymus when exposed to anti-inflammatory signals. They are primarily found in the gut, where they help the body tolerate harmless bacteria and prevent immune attacks on them.

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What is the function of gamma:delta T cells?

To detect and destroy stressed/damaged cells

To promote tissue repair.

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What type of antigen do gamma:delta T cells recognize?

they recognize and bind to antigens produced when a cell is under stress, instead of pathogen antigens because they can’t regonize them.

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Why are gamma:delta T cells described as innate like immune cells?

Because they bind to conserved stress antigens and they act immediately after binding to an antigen during an immune response.

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What does SCID stand for?

Severe combined immunodeficiency disorder

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What does AIDs stand for?

Acquired immunodeficiency disorder

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What is SCIDs?

a rare genetic disorder with many different causes where the immune system is severely weakened, making it difficult for the body to fight infections. AKA, a severe T cell deficiency

It’s often called "bubble boy disease" because affected individuals are highly vulnerable to infections.

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What is AIDs?

a disease caused by the HIV virus, which infects CD4 T cells, leading to a deficiency in these cells over time. This severely weakens the immune system, making the body more vulnerable to infections and certain cancers.

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What symptoms are experienced by patients with severe T cell deficiency?

Patients lack functional T cells, which are essential for adaptive immunity. This makes them highly vulnerable to infections, including those that usually don't cause symptoms in healthy individuals, and these infections can be life-threatening.

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What is the second signal needed for T cell activation and proliferation?

CD28 on the T cell binding to the B7 co stimulatory molecule on the mature dendritic cell

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What is the third signal needed for T cell activation and proliferation?

Cytokine signals

(the cytokines are major determinates of what effector subset the naive CD4 T cell will turn in to)

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What is 2 of 2 signals macrophages need to become activated?

The CD40 Lignad (CD40L)

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What is result 2 of the cytokines released by TH2 cells?

Promotion of class switching to the IgE antibody class

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What is result 3 of the cytokines released by TH2 cells?

Promotion of body responses intended to flush out the parasites (increased epithelial turnover, increased mucus production, muscle contractions)

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What is the second thing cytokines released by TH17 cells results in?

increased turnover rate of mucosal epithelial cells

increased production of antimicrobial molecules to limit colonization of the surface