CD4+ and CD8+ T cells Flashcards
Which cytokine(s) are made by Th1 cells?
IFN-y, TNF, IL-10
Which homing molecules are present on Th1 cells?
CXCR3 and CCR5, which bind to chemokines produced in tissues during innate immune responses
Ligands for E-selectin and P-selectin, which are expressed on endothelium at sites of strong inflammation
Which JAK kinases are activated by IFN-y?
JAK1 and JAK2
Which transcription factor is activated by IFN-y?
STAT1
What are 5 functions of IFN-y?
1) Activation of macrophages to kill phagocytosed microbes
2) Differentiation of CD4+ T cells to Th1 subset
3) Inhibition of Th2 and Th17 differentiation
4) Expression of proteins that contribute to enhanced antigen presentation and T cell activation (MHC molecules, B7 costimulators)
5) Activation of macrophages, DCs and other cells to produce cytokines that amplify the host response
Name some defects that can result in Mendelian susceptibility to mycobacterial disease.
Defects in IFN-y, IL-12, IL-12R, and STAT1
What is the cause of X-linked hyperIgM syndrome?
Mutations in the gene encoding CD40L
Which signals from Th1 cells activate macrophages?
IFN-y
CD40 (macrophage) - CD40L (T cell) interactions
Name three effects of macrophage activation by Th1 cells.
- Production of reactive oxygen species, nitric oxide, increased lysosomal enzymes
- Secretion of cytokines (TNF, IL-1, IL-12)
- Increased expression of B7 costimulators, MHC molecules
Name 4 functions of IL-4.
- B cell Ig heavy chain class switching to the IgE isotype
- Development of Th2 effector cells from naive CD4 T cells
- Alternative macrophage activation pathway
- Peristalsis in the gastrointestinal tract
Name 4 functions of IL-13.
- B cell Ig heavy chain class switching to the IgE isotype
- Alternative macrophage activation
- Peristalsis in the gastrointestinal tract
- Increased mucus secretion from airway and gut epithelial cells
Note that it is not involved in Th2 differentiation.
Name 2 functions of IL-5.
- Activation of mature eosinophils.
- Growth and differentiation of eosinophils.
Which cytokine(s) induces Th2 differentiation?
IL-4
Which homing molecules are present on Th2 cells?
CCR3, CCR4, and CCR8, which recognize chemokines highly expressed a sites of helminthic infection or allergic reactions, especially in mucosa
Which transcription factors are associated with Th2 cells?
STAT6, which induces GATA3
Which transcription factors are associated with Th1 cells?
STAT4 and STAT1, which induces T-BET
Which cytokine(s) inhibit Th2 responses?
IFN-y
Which cytokine(s) inhibit Th17 responses?
IFN-y, IL-4
Which homing molecules are expressed by Th17 cells?
CCR6, which binds CL20 produces by tissue cells and macrophages in some bacterial and fungal infections
Name 2 functions of IL-17.
1) Induces neutrophil-rich inflammation
2) Stimulates the production of antimicrobial substances, including defensins from numerous cell types
Name 3 Th17 cytokines.
1) IL-17
2) IL-22
3) IL-21
What is the function of IL-22?
Maintenance of epithelial barrier integrity
What are some functions of IL-21?
Generation of Tfh cells, activation of B cells in follicular centers
Proliferation, differentiation and effector function of CD8+ T cells
What is the principal function of Th17 cells?
Destruction of extracellular bacteria and fungi, mainly by inducing neutrophilic inflammation
What is the cause of Job syndrome?
Job syndrome (hyper-IgE syndrome) is causes by mutations in the gene encoding STAT3, resulting in defective Th17 development
Chronic mucocutaneous candidiasis is associated with defects in the function of which CD4 helper T cell subset?
Th17
What is the mechanism of candidiasis in patients with autoimmune polyendocrine syndrome?
Antibodies against IL-17
Which transcription factor(s) are associated with Th3 cells?
RORyt and STAT3
Which cytokine(s) activate RORyt in Th3 cells?
TGF-B
Which cytokine(s) activate STAT3 in Th17 cells?
IL-1, IL-6
Which cytokines contribute to activation of CTLs?
IL-2, IL-12, type 1 interferons
Which adhesion molecules stabilize CTLs on target cells?
LFA-1 on CTLs and ICAM-1 on target cells
What are the two methods of killing used by CTLs?
1) Perforin and granzymes
2) FAS-L on CTL binds FAS on target cell
What is the pathophysiology of hemophagocytic lymphohistiocytosis (HLH)?
Mutations in genes encoding perforin and other proteins involved in granule exocytosis
CTLs secrete IFN-y but cannot kill target cells
IFN-y leads to activation of macrophages
What is “signal 3” for CD4 Th1 activation by APCs?
IL-12 from macrophages, IFNy from NKs
What is “signal 3” for CD4 Th2 activation by APCs?
IL-4 from mast cells, eosinophils, or other Th2 cells
What is “signal 3” for CD4 Th17 activation by APCs?
IL-1, IL-6 and TGF-B from APCs
What is “signal 3” for CD8 activation by DCs?
IL-2, IL-12, type 1 interferons
What is “signal 3” for B cell activation by Th2 cells?
IL-4 from Th2
What is “signal 2” for B cell activation by Th2 cells?
CD40L (Th2 cell) - CD40 (B cell)
What is “signal 3” for macrophage activation by T cells?
IFN-y
Which cytokines simulate alternative macrophage activation?
IL-4, IL-13
Describe classical macrophage activation.
When Th1 cells are stimulated by antigen, they express CD40L on their surface and secrete IFN-y. CD40 signals actviate transcription factors NF-kB and AP1. IFN-y signals activate STAT1. Transcription factors result in expression of genes encoding enzymes present in phagolysosomes.
In macrophages, which transcription factor(s) are activated by CD40 signals?
NF-kB and AP1
In macrophages, which transcription factor(s) are activated by IFN-y?
STAT1
