Lecture 6: T Cell-Mediated Immunity

Flashcards covering the activation, signaling, costimulation, and migration of T cells in cell-mediated immunity based on Chapter 5 lecture notes.

What is the title of Chapter 5?

T Cell-Mediated Immunity – Activation of T Cells by Cell-Associated Antigens

What provides the first activating signal for T cell recognition?

Antigen recognition of the peptide/MHC complex by the $TCR$ and $CD4$ or $CD8$

Which figure describes the induction and effector phases of cell-mediated immunity?

Figure 5-2

What cell type is responsible for the induction of a T cell response in lymphoid organs?

Dendritic Cell (DC)

Where does antigen recognition by naive T cells typically occur?

In lymphoid organs

What happens to T cells after antigen recognition in lymphoid organs?

T cell expansion and differentiation

Through what system do differentiated effector T cells enter the circulation?

The blood vessel or circulation

Where do effector T cells encounter antigens after leaving the circulation?

In peripheral tissues

What is the principal effector function of $CD4^+$ effector T cells at the site of infection?

Leukocyte activation (inflammation), phagocytosis, and killing of microbes

What is the principal effector function of $CD8^+$ cytotoxic T lymphocytes (CTLs)?

CTL killing of infected cells

According to Figure 5-3, what occurs immediately after antigen recognition by a naive T cell?

Cytokine secretion and cytokine receptor expression

What cytokine is specifically mentioned in Figure 5-3 as an example of proliferation signaling?

$$IL-2$$

What are the two potential fates of a T cell after proliferation?

Differentiation into an Effector T cell or a Memory T cell

What is the function of $CD4^+$ helper T cells in peripheral tissues?

Activation of macrophages, B cells, and other cells

What is the function of $CD8^+$ CTLs in peripheral tissues?

Killing of infected "target cells" and macrophage activation

Which molecule on the T cell recognizes the Class II MHC molecule on an APC?

$$CD4$$

Which complex is responsible for signal transduction by the TCR?

The $CD3$ and $\zeta$ (zeta) chain complex

What motif is found within the $CD3$ and $\zeta$ chains for signal transduction?

$ITAM$ (Immunoreceptor Tyrosine-based Activation Motif)

What is the ligand for the T cell receptor $CD28$?

$B7-1$ or $B7-2$

What is the function of the $CD28$:$B7-1/B7-2$ interaction?

Signal transduction (costimulation)

Identify the inhibitory receptor on T cells that also binds to $B7-1$ and $B7-2$.

$$CTLA-4$$

What signaling motif is associated with $CTLA-4$ and $PD-1$?

$$ITIM$$

What are the ligands for the inhibitory receptor $PD-1$?

$PD-L1$ and $PD-L2$

Which adhesion molecule on T cells binds to $ICAM-1$ on APCs?

$$LFA-1$$

Which T cell surface molecule recognizes Class I MHC?

$$CD8$$

On which cells are Class I MHC molecules expressed?

All nucleated cells

On which cells are Class II MHC molecules expressed?

Antigen presenting cells

What is the function of the $LFA-1$:$ICAM-1$ interaction?

Adhesion and signal transduction

Where are $PD-L1$ and $PD-L2$ ligands expressed?

Antigen presenting cells, tissue cells, and tumor cells

Which kinase is associated with the $CD4$ tail during antigen recognition?

$$Lck$$

What constitutes the "first activating signal" in Figure 5-5?

Antigen recognition (TCR binding to MHC-peptide complex)

What type of protein is $LFA-1$?

An integrin protein

What happens when a "resting" (costimulator-deficient) APC presents antigen to a naive T cell?

No response or tolerance occurs

What induces the expression of costimulators and cytokines on an APC?

Activation of APCs by microbes or the innate immune response

What molecule, secreted by an activated APC, contributes to T cell differentiation?

$$IL-12$$

Which receptor-ligand pair is considered the major costimulatory pathway?

$CD28$ on the T cell and $B7$ on the APC

What is the synonym provided for the ligand $B7-1$?

$$CD80$$

What is the synonym provided for the ligand $B7-2$?

$$CD86$$

What is the receptor for the ligand $ICOS-L$ ($CD275$)?

$$ICOS$$

What is the primary function of the $ICOS$ receptor?

Activation (specifically for follicular helper T cells in antibody responses)

What is the numeric designation for $PD-L1$?

$$CD274$$

What is the numeric designation for $PD-L2$?

$$CD273$$

In Figure 5-8, how are APCs described when they activate both $CD4^+$ and $CD8^+$ T cells?

They engulf virus-infected cells (Class II source) and are infected themselves (Class I source)

How does a $CD4^+$ helper T cell assist in $CD8^+$ T cell activation according to Figure 5-8?

The $CD4^+$ cell helps activate the $CD8^+$ cell when the APC engages both

What three outcomes result from the expression of proteins following T cell recognition of antigens and costimulators?

Cell division, differentiation, and effector functions

What is the location of the "immunological synapse" mentioned in Figure 5-10?

The interface between the T lymphocyte and the APC

Name two drugs mentioned in Figure 5-10 that inhibit signal transduction pathways in T lymphocytes.

Cyclosporine and Rapamycin

What is the principal function of $IL-2$ in T cell biology?

Survival and proliferation of antigen-specific T cells

Explain the "autocrine cytokine action" of $IL-2$.

$IL-2$ stimulates the same $CD4^+$ T cell that produced it

What happens to the $IL-2R$ (receptor) when a T cell is activated?

The T cell expresses a high-affinity $IL-2R$ complex

According to Figure 5-12, what is the relative peak number of $CD8^+$ T cells compared to $CD4^+$ cells during infection?

$CD8^+$ T cells reach a higher number ($10^6$) than $CD4^+$ T cells ($10^4$ - $10^5$)

How many days after infection does the T cell response typically peak before contraction?

$7$ to $14$ days

What refers to the return to baseline levels of T cells after an infection is cleared?

Contraction (homeostasis)

How many days post-infection is the memory phase represented in Figure 5-12?

$200$ days

Identify the three subsets of effector $CD4^+$ T cells distinguished by cytokine profiles.

$Th1$, $Th2$, and $Th17$

What ligand is expressed on $CD4^+$ helper T cells to activate macrophages?

$CD40$ ligand ($CD40L$)

What receptor on macrophages and B lymphocytes binds to $CD40L$?

$$CD40$$

How does a $CD4^+$ T lymphocyte contribute to humoral immunity?

By activating B lymphocytes through $CD40L$ and cytokines to secrete antibodies

What is the result of macrophage activation by a $CD4^+$ T cell?

Killing of phagocytosed microbes

Which adhesion molecule on a naive T cell is responsible for initial weak adhesion to HEVs?

$$L-selectin$$

What is the ligand for $L-selectin$?

$L-selectin$ ligand

Which chemokine receptor is expressed on naive T cells for homing to lymph nodes?

$$CCR7$$

What chemokines are produced in the lymph node to attract naive T cells?

$CCL19$ and $CCL21$

What does "HEV" stand for in the context of T cell migration?

High Endothelial Venule

Which receptor on activated T cells is involved in stable arrest on cytokine-activated endothelium?

Integrins $LFA-1$ or $VLA-4$

What ligands on the endothelium bind to $LFA-1$ and $VLA-4$ in peripheral tissues?

$ICAM-1$ (for $LFA-1$) or $VCAM-1$ (for $VLA-4$)

Which chemokines are involved in the chemotaxis of activated effector and memory T cells?

$CXCL10$ and others

Which chemokine receptor is expressed on activated (effector and memory) T cells?

$CXCR3$ and others

What molecule is involved in T cell exit from the lymph node into the blood?

$S1P$ and its receptor $S1PR1$

What is the ligand for $E-selectin$ and $P-selectin$ on effector T cells?

$E-$ or $P-selectin$ ligand

Which integrin is also known as $\beta 2$-integrin?

$$LFA-1$$

Which integrin is also known as $\beta 1$ integrin?

$$VLA-4$$

What is the function of the $CCR7$:$CCL19/21$ interaction?

Activation of integrins and chemotaxis in the lymph node

What is the function of the $CXCR3$:$CXCL10$ interaction?

Activation of integrins and chemotaxis in peripheral tissues

What allows for the initial weak adhesion of effector and memory T cells to peripheral sites?

$E-$ and $P-selectin$:$selectin ligand$ interaction

Which type of bacteria/microbe is typically combated by cell-mediated immunity?

Intracellular microbes

In Figure 5-4, what is the function of $CTLA-4$?

Inhibition

What is the specific numeric ID of the receptor $ICOS$?

$CD278$ (though the text highlights the ligand as $CD275$)

Which receptor-ligand pair is responsible for stable arrest on HEVs in the lymph node?

$LFA-1$ and $ICAM-1$

What is the effect of antigen recognition on T cell cytokine secretion?

It induces the secretion of cytokines like $IL-2$

What is the main role of memory T cells?

Long-term protection and rapid response to re-exposure

What signaling unit is specifically found on the $CD3$ and $\zeta$ chains?

$$ITAM$$

What is the structural ligand for effector T cell adhesion to endothelium during inflammation?

$VCAM-1$ or $ICAM-1$

How does the T cell return to the circulation from the lymph node?

Via the efferent lymphatic vessel

What induces the expression of E- and P-selectins on the peripheral endothelium?

Activation by cytokines at the site of infection

What is the source of Class II MHC peptides in an APC?

Engulfed extracellular microbes/infected cells

What is the source of Class I MHC peptides in an APC?

Intracellularly synthesized proteins (e.g., from virus-infected cytoplasm)

Which molecules are involved in the "stable arrest" phase of T cell migration?

Integrins ($LFA-1$, $VLA-4$) and their ligands ($ICAM-1$, $VCAM-1$)

Is $IL-2$ production considered an autocrine or paracrine function in this text?

Autocrine cytokine action

What is the function of the $CD28$ family?

Costimulation and inhibition of T cell responses

What are the primary cells targeted by $CD4^+$ helper T cells for activation?

Macrophages and B lymphocytes

What is the effect of T cell activation on cytokine receptor expression?

It increases the expression of receptors, such as the $IL-2R$

Identify the receptor that mediates the suppressive function of regulatory T cells.

$$CTLA-4$$

What is the numeric name for the ligand of $PD-1$ known as $B7-H1$?

$$CD274$$

What is the numeric name for the ligand of $PD-1$ known as $B7-DC$?

$$CD273$$

Which molecule is responsible for the signal transduction through the TCR complex when antigen is recognized?

The $CD3$ and $\zeta$ proteins

According to the transcript, how do effector T cells find the site of infection?

By migrating through the blood and adhering to cytokine-activated endothelium

What is the effect of inflammatory cytokines on the peripheral endothelium?

They increase the expression of selectins and integrin ligands

What happens to the T cell population during the 'Contraction' phase?

Most cells die, and the population returns to homeostasis

What is the specific ligand for the receptor $L-selectin$ on naive T cells?

$L-selectin$ ligand on HEV