Biology of T Cells Part 2

What is the function of CD8+ cytotoxic T cells?

Defend against intracellular pathogens, such as viruses, bacteria, and protozoa, by killing infected cells to prevent replication and spread

What are cytotoxic T cells also known as?

Cytotoxic T lymphocytes (CTLs)

What are the two types of cytotoxic T cells?

Tc1 and Tc2

What to Tc1 cells secrete?

IFN-gamma, NO IL-4

What can Tc1 cells used to induce death?

Perforin and Fas/FasL

What do Tc2 cells secrete?

IL-4 and IL-5

What cytokine causes Tc2 differentiation?

IL-4

What can Tc2 cells use to induce death?

Perforin

What do naive CD8 cells need when antigen presenting cells have a weak costimulation?

CD4; helper T cells

What do CD4 T cells do to help CD8 cell activation?

Provide cytokines for proliferation and to increase MHC I expression and co-stimulation

What is the key for generation of effector cytotoxic T lymphocytes?

Licensing dendritic cells

What are the two ways for a dendritic cell to become licensed?

Sequential or simultaneous

What is sequential licensing?

The dendritic cell interacts with a helper T cell to increase MHC I and CD80/86 expression before engaging with a naive CD8 cell

What is simultaneous licensing?

The dendritic cell interacts with both the helper T cell and naive CD8 cell

How do CTLs kill the target cells?

Cytotoxins, Fas/FasL, and cytokines

What cytotoxins do CTLs use to kill target cells?

Perforins, granzymes, and granulysin

What do perforins do?

Produce pores

What do granzymes do?

Induce apoptosis

What are granulysins?

Antimicrobial peptides that can induce apoptosis

What are cytotoxins?

Specialized products contained within lytic granules of cytotoxic cells

What cytokine do CTLs produce to kill target cells?

TNF-alpha

What does TNF-alpha do to CTL target cells?

Induce apoptosis

What are the steps of CTL-mediated killing of a target cell?

Golgi and granules are oriented toward the target cell

Cytoplasmic granules migrate to the center of the synapse

They fuse with the T cell membrane and are inserted into the target cell

How do CTLs kill target cells?

Through directional release of granule contents (perforin/granzyme)

What do CTL cells need to kill a cell?

Recognition of peptide-MHC 1 complex on an infected cell

Can CTLs kill infected cells in succession?

Yes. They synthesize a new set of lytic granules before seeking out a new target

What are perforins?

Pore-forming glycoproteins created by CTLs and NK cells

How do perforins work?

They insert themselves into target membrances and oligomerize to form tubular transmembrane channels

What are granzymes?

Serine proteases that trigger apoptosis

How do granzymes enter target cells?

Through perforin pores

How are CTLs not damaged during the perforin/granzyme pathway?

They contain granzyme inhibitors

What is the perforin/granzyme pathway?

A way for CTLs to kill infected cells through synergistic use of perforin and granzyme

How do granzymes induce apoptosis?

By causing target cell mitochondria to release cytochrome C and activating caspase-3

What is the Fas/FasL pathway?

A way for CTLs to kill target cells through surface molecule binding

How does the Fas/FasL pathway work?

T cell sruface molecule FasL binds to cell death receptor Fas on the target cell

Fas activates Caspase 8 which activates Caspase 3

Caspase 3 causes DNA fragmentation and apoptosis

What is the death-inducing signaling complex?

Three Fas receptors drawn together by engagement with FasL, from a CTL, that initiated apoptosis

What are the death receptors?

Fas from the target cell

FasL from the CTL

How is apoptosis different from necrosis?

Apoptosis is tightly regulated and clean

Necrosis is messy and a pathological process

What is apoptosis?

An active, energy-dependent, tightly regulated cell death that is characterized by nuclear dissolution without complete loss of membrane integrity

What is necrosis?

Cell death seen in many commonly encountered injuries. If damage is severe, enzymes leak out of the lysosomes, enter the cytoplasm, and digest the cell

Which type of cell death causes inflammation?

Necrosis

What type of cell death is a normal function and tightly regulated?

Apoptosis

What do CTLs target?

Any cell that presents foreign peptides by MHC I

Cytosolic infections

Tumors

Natural killer cells are required to kill cells missing what?

MHC I

Cells that lack MHC I expression are killed by what cells?

NK cells

Do CTLs kill cells without MHC I expression?

No, MHC I is necessary to activate CTLs

What two cells have synergy and eradicate intracellular infections?

CD4+ and CD8+ T cells

What is immunological memory?

A key feature of adaptive immunity that is long-term and ensures a host will generate a more potent immune response upon re-encounter with the same antigen

What is immunological memory induced in?

B and T cells

Where is immunological memory generated?

Secondary lymphoid organs

What generates immunological memory?

Natural infections or immunizations

What sustains immunological memory?

Long-lived B and T cells

What are memory B cells?

B cells that have undergone affinity maturation and isotype switching that respond quickly to familiar antigens

What are memory CD4+ and CD8+ T cells?

T cells that have undergone differentiation and are more sensitive to activation requiring less co-stimulation

What accumulates throughout life and can become the most abundant T cell population in the body?

Memory T cells

How are memory T cells created?

By asymmetric division of a T cell after activation

What are characteristics of memory T cells?

Apoptosis-resistant

Long-lived

Need less co-stimulation

Quicker activation

What activates memory T cells?

Macrophages, dendritic cells, and B cells

What are the types of memory T cells?

Central memory cells

Effector memory cells

Tissue memory cells

What are central memory cells?

T cells with high CCR7 expression that circulate through secondary lymphoid tissues

What do central memory cells do?

Lack effector functions but have rapid recall responses

Rapidly express CD40L to interact with CD40 on B cells

What are effector memory cells?

T cells that express integrins and receptors for inflammatory cytokines that enable them to home to inflamed tissue

What do effector memory cells do?

Secrete high levels of cytokines

Has nearly immediate effector function upon re encounter with antigens

What are tissue memory cells?

T cells that occupy tissues and provide first response to pathogens

Where do tissue memory cells tend to reside?

Under body surfaces (CD8) or throughout the body in small clusters (CD4)

What do tissue memory cells do?

Rapidly produce cytokines after infections

What do tissue memory cells NOT do?

Circulate in peripheral blood

What is another name for tissue memory cells?

Tissue resident memory cells