T cell subsets and functions Flashcards
How are naive CD8+ cells activated?
Recognise antigen or infected APC
Costimulators B7 and CD28 provide survival signal
APC release cytokines IFN-A, IFN-G and IL-12
Clonal expansion and differentiation of effector CTLs
What do CD8+ cells cause?
Lysis of target cells by either:
- releasing cytotoxic granules at site of contact with target cell
- engage Fas/FasL interaction
Describe perforin-granzyme-mediated cell killing
CD8+ cell binds target cell and releases granule contents into immune synapse
Perforin induces uptake of granzymes into target cell endosome and release into the cytosol
Caspases become activated and target cell undergoes apoptosis
Describe Fas/FasL mediated cell killing
FasL on CTL interacts with Fas on target cell
Apoptosis of target cell
What cell types can up regulate MHC II during infection and be lysed by cytolytic CD4+ cells?
WNDV-infected MHC II positive epithelial cells
EBV-infected B cells
HIV-infected CD4+ cells
How do CD4+ cells act as Th cells?
Activate and help other cell types to coordinate immune response
Achieved through expression of cell surface proteins and soluble cytokines
What causes acquired immune deficiency syndrome (AIDS)?
Results from loss of helper T cells following HIV infection
What are the types of Th cells?
Th1
Th2
Th17
Tfh
What cytokine is released by Th1 cells?
IFN-G
What are the functions of Th1 cells in the adaptive immune response?
Activate infected macrophages
Provide help to B cells for Ab production
What pathogens are targeted by Th1 cells?
Microbes that persist in macrophage vesicles
e.g. mycobacteria, Listeria, Leishmania donovani, Pneumocystis carinii
Extracellular bacteria
What cytokines are released by Th2 cells?
IL-4
IL-5
IL-13
What are the functions of Th2 in the adaptive immune response?
Provide help to B cells for Ab production, especially switching to IgE
What pathogens are targeted by Th2 cells?
Helminth parasites
What cytokines are released by Th17 cells?
IL-17
IL-22
What are the functions of Th17 cells in the adaptive immune response?
Enhance neutrophil response
Promote barrier integrity (skin, intestine)
What pathogens are targeted by Th17 cells?
Klebsiella pneumoniae
Fungi (Candida albicans)
What cytokine is released by Tfh cells?
IL-21
What are the functions of Tfh cells in the adaptive immune response?
B cell help
Isotype switching
Ab production
What pathogens do Tfh cells target?
All types
What determines the outcome of naive CD4+ Th cell differentiation?
Signals generated by DCs
What DC signals cause differentiation of Th1 cells?
IL-12
IL-18
IFN
What DC signals cause differentiation of Th2 cells?
IL-4
IL-5
What DC signals cause differentiation of Th17 cells?
IL-6
TGF-B
What DC signals cause differentiation of Tfh cells?
IL-6
What DC signal causes differentiation of Treg cells?
TGF-B
What do Th1 cells do?
Activate macrophages to kill bacteria within them
How do Th1 cells activate macrophages?
Some infections hide in phagosomes e.g. mycobacteria - this protects them from MHC-I antigen presentation
Peptides from these bacteria will be presented by MHC-II as macrophages are professional APCs
Recognition of peptide/MHC-II on an infected macrophage causes Th1 cell to produce IFN-G
IFN-G activates the macrophage
What happens once macrophages are activated?
Macrophage fuses phagosome containing bacteria with lysosomes
ROS and nitrogen species kill the bacteria
Why can macrophages not be activated all the time to prevent infection?
Requires too much energy
Results in localised tissue destruction due to release of reactive species
How can activation of CD8+ cells be CD4+ dependent?
Recruited CD4+ cells can induce secretion of chemokines from DC, leading to attraction of CD8+ cells
How do Th1 cells help B cells in Ab production?
B cells process and present antigens that bind to their surface Ig
Binding of antigen by surface Ig causes receptor mediated endocytosis
Antigen is delivered to MHC-II for presentation
This stimulates helper T cells that recognise the same antigen as the B cells
What does IFN-G production from Th1 cells stimulate?
Stimulated B cells to upregulate Ab production
Mainly IgG2a
What do Tfh cells do?
Stimulate B cell proliferation and differentiation
Stimulate Ig class switching
What are Tfh cells critically needed for?
Germinal centre formation and function
What do Th2 cells do?
Help to control parasitic infection by promoting IgE production and by promoting function of eosinophils and mast cells
How do eosinophils clear parasitic infections?
IgE connects eosinophils to outer surface of a parasitic worm
IgE-bound pathogens bind to high affinity FceRI and FceRII receptors found on surface of eosinophils and mast cells
Large cytoplasmic granules of eosinophils contain variety of proteases and toxic proteins that aggregate and kill larval intestinal parasites that the eosinophils are attached to
How do mast cells clear parasitic infections?
Activated by IL-5 and coated by IgE
Mast cells degranulate and release histamine, serotonin and leukotriene at the site of infection
These can cause contractions of the smooth muscle cells of the intestinal walls as a physical mechanism for expelling the worms from the digestive tract
What does IL-4 promote?
Promotes Ig gene class switching leading to IgE transcription
How does IL-4 promote Ig class switching to IgE?
IL-4 binds to IL-4 receptor
Leads to recruitment and activation of tyrosine kinases JAK1, JAK3 and TYK1
These activate STAT6
Interaction of CD40L with CD40 allows for recruitment and activation of tumour necrosis factor receptor associated factors (TRAFs) and nuclear translocation of TFs NG-kB and AP1
Stimulation of IL-4R and CD40 promote enhancement of both Ce germ line transcripts
How does Th1/Th2 balance determine the outcome of infection in leprosy?
If Th1 cells predominate (tuberculoid leprosy) then bacterial growth is controlled and minor damage occurs
If Th2 cells predominate (lepromatous leprosy) the bacteria grow abundantly and gross tissue damage occurs
What do Th17 cells do?
Secrete IL-17
Help protect against extracellular bacteria and fungi by stimulating neutrophils
Over-represented in autoimmune diseases
What happens when infection is cleared?
Majority of effector B and T cells die by neglect and enter apoptosis
Some remain as memory cells but this is not well understood
Both CD8+ and CD4+ populations can establish memory
Describe memory T cells
They are relatively short-lived and therefore need to divide fairly frequently
Memory T cells are maintained by IL-7 and IL-15 with stimulation from self-antigens
Why are CD8+ T memory cells longer lived than CD4+ memory?
CD4+ are inherently less proliferative than B cells and CD8+ T cells
The CD4+ memory population appears to decline following antigen clearance, while CD8+ memory population if established are typically stable
What are the typed of memory T cells?
Tscm
Tcm
Tem
Teff
Trm
Describe Tscm memory cells
Stem cells
2 populations
Commonly short lived
Half life 7 months
Rarer, long lived have a half life of 9 years
Describe Tcm memory cells
Central memory
Circulate between the blood and secondary lymphoid organs
Describe Trm cells
Tissue resident
Mainly CD8+ cells
Often quite long lived
Describe Tem cells
Effector memory
Migrate from blood into non-lymphoid tissues
Describe Teff cells
Effector cells