Lecture 7: Effector Mechanisms of T Cell-Mediated Immunity

Flashcards covering effector mechanisms of T cell-mediated immunity based on lecture notes, including CD4+ and CD8+ functions, cytokine properties, and macrophage activation pathways.

What type of cells were originally found to transfer immunity from one lab animal to a naïve animal?

T-cells

According to Figure 6-1, which cell type acts on phagocytes with ingested microbes in vesicles via cytokine secretion?

$CD4^+$ effector T cells ($Th1$ cells)

In Figure 6-1, what is the primary effector function of $Th1$ cells after macrophage activation?

Killing of ingested microbes

Which subset of $CD4^+$ effector T cells is responsible for inflammation and killing of microbes?

$Th17$ cells

According to Figure 6-1, which cell type acts on infected cells with microbes in the cytoplasm?

$CD8^+$ T cells ($CTLs$)

What is the outcome of $CD8^+$ $CTL$ action on an infected cell?

Killing of infected cells

In the discovery of cell-mediated immunity, could immunity be transferred to a naïve animal by serum?

No, only by cells ($T-cells$)

In vitro tests showed that while T cells are transferred, which cells actually become activated to kill microbes?

Macrophages

How are subsets of $CD4^+$ helper T lymphocytes primarily distinguished?

By the cytokines they produce

What is the property described when T cell cytokines are produced only when needed in response to an antigen?

Produced transiently

What is the term for a cytokine acting on the same cell that produces it?

Autocrine

What is the term for a cytokine acting on nearby cells?

Paracrine

What does the property of 'pleiotropism' mean in the context of T cell cytokines?

Each cytokine has multiple biological actions

What does 'redundancy' mean regarding cytokine biological activities?

Multiple cytokines may share the same or similar biological activities

According to the lecture notes, what do systemic effects of cytokines usually reflect?

Severe infections or autoimmunity

What is a clinical downside to the pleiotropism of cytokines?

It may limit clinical utility because of unwanted effects

Why might blocking a single cytokine fail to achieve a desired therapeutic effect?

Because of redundancy (multiple cytokines share activities)

What is the cellular source of $IL-2$?

Activated T cells

What are the two principal actions of $IL-2$?

T cell proliferation and regulatory T cell survival

What are the cellular sources of $IFN-\beta$ ($Interferon-\beta$) mentioned in the Table on Page 4?

$CD4^+$ and $CD8^+$ T cells; natural killer ($NK$) cells

What is the principal action of $IFN-\beta$ ($Interferon-\beta$)?

Activation of macrophages

What are the cellular sources of $IL-4$?

$CD4^+$ T cells and mast cells

What is the principal action of $IL-4$?

B cell switching to $IgE$

Which cells are sources of $IL-5$?

$CD4^+$ T cells, mast cells, and innate lymphoid cells

What is the principal action of $IL-5$?

Activation of eosinophils

What is the principal action of $IL-17$?

Stimulation of acute inflammation

Which cells produce $IL-17$?

$CD4^+$ T cells and other cells

What is the principal action of $IL-22$?

Maintenance of epithelial barrier function

What are the cellular sources of $IL-22$?

$CD4^+$ T cells, $NK$ cells, and innate lymphoid cells

What are the principal actions of $TGF-\beta$?

Inhibition of T cell activation and differentiation of regulatory T cells

Which cytokine acts as an inhibitor and is involved in the early activation of T cells?

$$TGF-\beta$$

What is the signature cytokine produced by $Th1$ cells?

$$IFN-\beta$$

In Figure 6-5, what process is triggered by $Th1$ cells acting on a macrophage?

Classical macrophage activation

What is the result of classical macrophage activation mentioned in Figure 6-5?

Enhanced microbial killing

Which surface molecules on the $Th1$ cell and macrophage interact to trigger activation?

$CD40L$ (on T cell) and $CD40$ (on macrophage)

Besides $CD40L$, what cytokine is secreted by $Th1$ cells to activate macrophages?

$$IFN-\beta$$

What does the macrophage produced to kill phagocytosed bacteria after activation?

$ROS$ (Reactive Oxygen Species) and $NO$ (Nitric Oxide)

Activated macrophages secrete which three specific cytokines for leukocyte recruitment?

$TNF$, $IL-1$, and $IL-12$

What is the role of chemokines secreted by activated macrophages?

Leukocyte recruitment (inflammation)

What molecules are increased on the surface of macrophages to amplify the T cell response?

$B7$ costimulators and $MHC$ molecules

What is the specific role of $IL-12$ secreted by macrophages in the context of T cell-mediated immunity?

$Th1$ differentiation and $IFN-\beta$ production

Where does the killing of microbes occur within the macrophage?

Phagolysosomes

Which cytokine, produced by Dendritic cells and $NK$ cells, drives $Th1$ development?

$$IL-12$$

Which transcription factor is the primary regulator for $Th1$ differentiation?

$$T-bet$$

Which two $STAT$ proteins are involved in $Th1$ development?

$STAT4$ and $STAT1$

What stimuli induce the development of $Th2$ cells?

Parasitic worm infections (helminths)

Which transcription factor is essential for $Th2$ cell development?

$$GATA-3$$

Which $STAT$ protein is associated with the $IL-4$ signaling pathway in $Th2$ development?

$$STAT6$$

What are the three signature cytokines of $Th2$ cells?

$IL-4$, $IL-5$, and $IL-13$

In helminth infections, which cytokine is responsible for eosinophil activation?

$$IL-5$$

Which antibody isotype is involved in the killing of helminths alongside eosinophils?

$$IgE$$

What is the name of the high-affinity receptor for $IgE$ found on mast cells and eosinophils?

$$Fc\beta RI$$

What is the outcome of eosinophil activation against a helminth?

Release of eosinophil granule contents leads to helminth death

Which cytokines produced by $Th2$ cells inhibit classical macrophage activation ($M1$)?

$IL-4$ and $IL-13$

What is the 'alternative' macrophage activation associated with $Th2$ responses?

$M2$ activation

Which $Th1$ cytokine inhibits the developmental possibilities of $Th2$ and $Th17$?

$$IFN-\beta$$

What initiates immediate hypersensitivity reactions?

Introduction of an allergen

Allergens stimulate the production of which immunoglobulin?

$$IgE$$

Once $IgE$ is produced, where does it bind?

$Fc\beta RI$ receptors on mast cells

What happens when a mast cell is subsequently exposed to an allergen it is sensitized to?

It secretes mediators responsible for pathologic reactions

What is the outcome for most mouse strains infected with $Leishmania$ major?

Recovery (due to $Th1$ response)

Why do $BALB/c$ mice develop disseminated infection when infected with $Leishmania$ major?

They produce a $Th2$ response instead of $Th1$

What determines the clinical outcome of a $Mycobacterium$ leprae infection?

The balance between $Th1$ and $Th2$ cell activation

A patient with a strong $Th1$ response to $Mycobacterium$ leprae will likely develop which form of the disease?

Tuberculoid leprosy

A patient with a defective $Th1$ or dominant $Th2$ response to $Mycobacterium$ leprae develops which disease form?

Lepromatous leprosy

Which form of leprosy is characterized by a high bacterial count?

Lepromatous leprosy

Which cytokines from Dendritic cells drive $Th17$ development?

$IL-1$, $IL-6$, and $IL-23$

Which member of the $TGF$ family is involved in $Th17$ differentiation?

$$TGF-\beta$$

Which transcription factor is the hallmark of $Th17$ cells?

$$ROR\beta t$$

Which $STAT$ protein is involved in the signaling for $Th17$ development?

$$STAT3$$

What kind of microbes typically induce a $Th17$ response?

Extracellular fungi and bacteria

What are the two signature cytokines of $Th17$ cells?

$IL-17$ and $IL-22$

What is the major function of $IL-17$?

Recruitment of neutrophils resulting in inflammation

$IL-17$ stimulates the production of which factors from leukocytes and tissue cells?

Chemokines, $TNF$, $IL-1$, $IL-6$, and $CSFs$

What is the function of antimicrobial peptides produced in response to $Th17$ cytokines?

Inflammation and neutrophil response

How does $IL-22$ affect epithelial cells?

It increases barrier integrity

In Figure 6-1, what is the primary role of $CD8^+$ $CTLs$?

Development and function in killing infected cells

What do $CD4^+$ T cells provide to help macrophages kill microbes in phagolysosomes?

$$IFN-\beta$$

Which T cell type is specialized in killing microbes that escape into the cytosol?

$CD8^+$ $CTL$

True or False: $CD4^+$ and $CD8^+$ T cells can cooperate to eradicate intracellular infections.

True

How do some microbes evade cell-mediated immunity regarding $MHC$ molecules?

By reducing $MHC$ class I display on the cell surface

What is the host's counter-defense when a microbe reduces $MHC$ class I display?

Activation of natural killer ($NK$) cells

What does $CSFs$ stand for in the context of $Th17$ functions?

Colony-stimulating factors

Where are the microbes located that are targeted by $CD8^+$ $CTLs$?

In the cytosol

What role do lysosomal enzymes play in macrophages?

Killing of microbes in phagolysosomes

Which cytokine is specifically mentioned as promoting $Th1$ differentiation?

$$IL-12$$

Which transcription factor is induced by $STAT1$ and $STAT4$?

$$T-bet$$

Which transcription factor is induced by $STAT6$?

$$GATA-3$$

Which transcription factor is induced by $STAT3$?

$$ROR\beta t$$

What cell types, besides $CD4^+$ T cells, produce $IL-5$?

Mast cells and innate lymphoid cells

What cell types, besides $CD4^+$ T cells, produce $IL-22$?

$NK$ cells and innate lymphoid cells

Is $IL-2$ produced by mast cells?

No, it is produced by activated T cells

Based on Page 4, which cytokine is associated with regulatory T cell survival?

$$IL-2$$

Based on Figure 6-6, what does increased expression of $B7$ costimulators on macrophages lead to?

Increased T cell activation (amplification)

Which helper T cell subset is primarily induced by mycobacteria?

$$Th1$$

In Figure 6-7, which cells provide the initial $IL-4$ to steer a T cell toward the $Th2$ lineage?

Mast cells and eosinophils

In Figure 6-9, which cytokines inhibit the 'classical' pathway?

$IL-4$ and $IL-13$

What is the cellular source of inflammatory mediators in immediate hypersensitivity?

Mast cells

The term 'CMI' in the transcript stands for what?

Cell-mediated immunity

According to the Page 1 diagram, where are the microbes located in the context of a $Th17$ response?

Extracellular (implied by Th17 function against fungi/bacteria)