Effector Functions of T Cells Flashcards
List the 6 effector T cell variants.
1 - CD4+ Th1.
2 - CD4+ Th2.
3 - CD4+ Th17.
4 - CD4+ TFH (follicular helper).
5 - CD4+ Treg (regulatory).
6 - CD8+ T.
List 3 immune defences against infection in interstitial spaces, blood and lymph.
Repeat the areas in which these immune defences act (as stated in this question).
1 - Complement.
2 - Phagocytosis.
3 - Antibodies.
- Interstitial spaces, blood and lymph.
List 2 immune defences against infection on epithelial surfaces.
1 - Antimicrobial peptides.
2 - Antibodies, especially IgA.
List 2 immune defences against infective agents in the cytoplasm.
1 - NK cells.
2 - Cytotoxic T cells.
Give an example of an immune defence against infective agents in vesicles.
T-cell and NK-cell dependent macrophage activation.
Describe the process of T cell activation.
1 - Binding of the T cell receptor to a class 2 MHC on antigen presenting cells creates an activation signal.
2 - Binding of the CD28 receptor (on the T cell) to B7 proteins CD80 and CD86 (on antigen presenting cells) creates a survival signal if the affinity of co-stimulation is sufficient.
3 - Binding of various different cytokines to receptors on the T cell will produce a differentiation signal, determining the T cell type.
What is the primary function of CD8+ T cells?
To kill intracellular pathogens, especially viruses by destroying the infected host cell.
List the 2 major killing mechanisms of CD8+ T cells.
1 - Granules containing perforin and granzymes.
2 - Fas ligand, which binds to Fas on the target cell, triggering apoptosis.
How does perforin contribute to CD8+ T cell function?
It creates pores in the cell membrane of the pathogen, leading to cell death.
What type of enzyme are granzymes?
Proteases.
List the functions of CD4+ Th1 cells.
1 - To activate infected macrophages that are infected with vacuole-restricted bacteria.
2 - To provide help to B cells for antibody production.
List 4 consequences of infected macrophage activation by CD4+ Th1 cells.
1 - Increased macrophage MHC expression.
2 - Increased macrophage nitric oxide production.
3 - Increased macrophage phagolysosome maturation.
4 - Increased macrophage TNF alpha production.
Which protein stimulates CD4+ Th1 cells to activate macrophages?
Which protein is released by CD4+ Th1 cells that causes macrophage activation?
- The CD4+T cell responds to cognate antigen.
- The CD4+T cell secretes IFN-gamma to cause macrophage activation.
What causes granuloma formation?
Partial removal of live pathogens (vacuole-restricted bacteria) from infected macrophages after activation by CD4+ T cells, which causes infected macrophages to form a fused cluster surrounded by T cells.
What determines the path of CD4+ T cell differentiation?
Give an example of selective T cell differentiation.
- The molecular environment of the dendritic cell - T cell interaction, which is determined by the nature of the pathogen involved.
- E.g. a naive CD4+ T cell will differentiate into a CD4+ Th1 cell if it binds to Th1-polarising factor, which is released by the dendritic cell in response to type 1 PAMPs (other molecules are also implicated).
How are specific lineages of CD4+ T cells upregulated?
Which cells are implicated in this process?
- Cytokines that initiate differentiation of CD4+ T cells of a particular lineage drives downstream pathways that upregulate that particular lineage.
- The cytokines can be derived from the dendritic cell, the T cell itself, macrophages, fibroblasts and epithelial cells.
Describe the process of CD4+ Th1 differentiation.
1 - Differentiation is initiated by a differentiation signal that is generated in response to Th1-polarising factor.
2 - Further differentiation requires IL-12.
3 - Differentiation is amplified by IFN-gamma in a positive feedback loop.
4 - The transcription factor T-bet is expressed to control the transcriptional programme required for CD4+ Th1 cell differentiation.
List 2 risks of CD4+ Th1 deficiency and 2 risks of CD4+ Th1 overabundance.
Deficiency:
1 - Reactivation of latent infections.
2 - Inadequate control of de novo infection.
Overabundance:
1 - Autoimmunity.
2 - Inflammatory diseases.
List 2 functions of CD4+ Th2 cells.
1 - To provide help to B cells for antibody production, especially by switching to IgE.
2 - Drives alternative macrophage activation.
Which pathogens are targeted by CD4+ Th2 cells?
Helminth parasites.
Describe the process of CD4+ Th2 differentiation.
1 - Differentiation is initiated by a differentiation signal that is generated in response to Th2-polarising factor.
2 - Further differentiation requires IL-4, which can be present in the environment and is also secreted by the CD4+ Th2 cell itself.
4 - The transcription factor GATA3 is expressed to control the transcriptional programme required for CD4+ Th2 cell differentiation.
List 3 secretions of CD4+ Th2 cells.
1 - IL-4.
2 - IL-5.
3 - IL-13.
List 2 functions of CD4+ Th17 cells.
1 - To enhance the neutrophil response by increasing neutrophil recruitment.
2 - To promote barrier integrity.
Which pathogens are targeted by CD4+ Th17 cells?
Fungi and some bacteria.
Describe the process of CD4+ Th17 differentiation.
1 - Differentiation is initiated by IL-1 beta, IL-6 and IL-21 (TGF beta).
2 - Differentiation is maintained by IL-23.
3 - The transcription factors ROR alpha and ROR gamma-t are expressed to control the transcriptional programme required for CD4+ Th17 cell differentiation.
Which interleukin do CD4+ Th17 cells secrete?
IL-17.
List 2 functions of CD4+ TFH (follicular helper) cells.
1 - Express the chemokine receptor CXCR5 to allow migration towards B cell areas.
2 - Co-express a wide range of Th phenotypes to allow appropriate B cell help.
Where in the body do CD4+ TFH (follicular helper) cells act?
In secondary lymphoid compartments.
Which interleukin promotes CD4+ TFH (follicular helper) cell differentiation?
IL-21.
Which transcription factor is unique to CD4+ TFH (follicular helper) cells?
Bcl-6.
What is the primary function of CD4+ Treg (regulatory) cells?
How do they carry out their function?
- To restrict other immune responses by suppressing T cell proliferation.
They do this by:
1 - Blocking the priming of effector T cells by reducing co-stimulatory molecule availability.
2 - Preventing dendritic cell maturation.
3 - Killing mature dendritic cells.
4 - Secreting IL-10, an anti-inflammatory cytokine which inhibits the activity of various immune cells.
List the molecules that are necessary for CD4+ Treg (regulatory) differentiation.
1 - IL-21 (TGF beta).
2 - Retinoic acid.
Which transcription factor is required for CD4+ Treg (regulatory) cell differentiation?
FoxP3.
List the 2 major sources from which CD4+ Treg (regulatory) cells are derived.
How do cells from each of these sources differ functionally?
1 - Some cells derived from the thymus.
2 - Some cells derived from the periphery as part of any peripheral immune response.
- The cells derived from the thymus are able to carry out regulatory function as soon as they leave the thymus, whereas those derived from the periphery must undergo further maturation.
