Effector Function of T Cells Flashcards
Give brief summary of development of T cells and what they do once they reach the secondary lymphoid tissues.
- they first differentiate in the thymus
- leave in peripheral circulation and then enter secondary lymphoid organs (spleen and lymph nodes)
- here they search for cognate antigen being presented by APC’s
- dendritic cells and macrophages express antigen in form of MHC and a peptide
- if T cell binds to antigen with high affinity then the T cell with undergo proliferation
- being to differentiate towards a cells with specific effector function
Why is it necessary that T cell effects are diverse?
- each specialised to be able to control certain groups of pathogens
- the diversity of pathogens can explain the diversity of T cell effects
- viruses, bacteria, fungi, helminths and parasites are very diverse
- range in size, routes of infection, location and transmission
- many pathogens also hide inside our own cells, allowing them shielding from some components of the immune system
What are the effector types and subsets that we need to know?
cytotoxic CD8+ T cells
cytotoxic CD4+ T cells - subsets termed Th1, Th2, Th17
Tfh (follicular helper)
Treg (regulatory T cell)
What does the process of creating a differentiated T effector cell start with?
- the initial encounter with the dendritic cell and the antigen it is presenting
What are the 3 signals need to direct a T cell to proliferate and then differentitate?
- primary signal is for the TCR to bind to the peptide/MHC complex with good affinity, if suffiecnt co-stimluation then t cell with being to proliferate; signals termed 1 and 2
- 3rd type of signal, surface molecules on DC and cytokines in microenvironment
How are cytotoxic T cells differentaited from naive T cells?
- acquire cytotoxic granules that contain perforin and granzymes to mediate death of the target cell presenting peptide/MHC complexes
- they can also express Fas ligand to kill susceptible Fas expressing target ells
- the Fas / Fas ligand pathway is one of the apoptotic pathways
The large diversity of CD4+ effector cell types arise in different environments that provide a variety of ……… …….. in addition to ………. molecules expressed by the ………. cells as well
cytokine stimuli
co-stimulatoryy molecules
dendritic
Th1 cells:
- Their differentiation requires …….., and is amplified by ….. …… including the production of this cytokine from the first differentiated T-cells.
- The TF ….. is expressed to control the transcriptional programme required for these cells. They have a particularly important role in the control of ……. that reside in …….
- When encountering …….. antigen presented by the infected macrophage they produce …….. which activates the macrophage.
- Activated macrophages increase their production of ….., up regulate ….. and co-stimluatory molecules and enhance maturation of their ……………… to increase killing of intracellular bacteria
- As well as providing protective immunity, Th1 cells are associated with …………. and ………… conditions, where inappropriate activation, or lack of appropriate control, can lead to pathology
- IL-12, IFN gamma
- T-bet, bacteria, vacuoles
- cognate, IFN
- NO, MHC, phagolysosomes
- autoimmune, inflammatory
Th2 cells:
- The Th2 subset is driven by …… resulting in a T cell that express …….. and secrete the cytokine ……, as well as two additional Th2-associated cytokines ….. and …..
- The main function of these cells is to provide immunity to ………
- Part of this protective function results from the ability of Th2 cells to promote class switching of ……… to the …. isotope
- The …. isotope then acts as the direct protective factor rather than the Th2 cell itself
- Th2 cytokines can also drive an alternative ………… differentiation programme that is very different from the
Th1-activated macrophages
- ………… disease is driven by Th2 cells and cytokines and an imbalance between Th1:Th2 disease is the basis of the ………… hypothesis
- IL-4, GATA-3, IL-4, IL-5, IL-13
- helminths
- B cells, IgE
- IgE
- macrophage
- Allergic
- hygiene
Th17 cells:
- they are associated with a number of ……………/………….. diseases including including ……….. and ………. ………..
- differentiation requires a combination of cytokines including …., …. and …..
- the TF associated with these cells is …….. and they secrete …….
- Th17 cells play an important protective role against ……. and some ……, increasing ………. recruitment and controlling barrier function of the ………
- autoimmune/inflammatory, psoriasis, multiple sclerosis
- IL-6, IL-1beta, TGFbeta.
- RORyt, IL-17
- fungi, bacteria, neutrophil, epithelium
Tfh (follicular helper):
- The Th subsets described above frequently act in the ……….., but many of them may also be required to influence ……….. responses in the ………….. ………….. compartment.
Tfh, expressing ……, perform this task by providing ……… …… for antigen-specific B-cells and directing ……… ……….. .
The final effector function of the Tfh cell overlaps with many of the other Th subsets to proved a range of helper phenotypes for the …. cells. One key signature molecule expressed by these cells is ……., allowing the Tfh to ….. towards the B cell zone
periphery, Bcell, secondary lymphoid
Bcl-6, survival signals, class switching
B, CXCR5, migrate
Treg (regulatory):
- It is important that all immune responses are appropriately regulated.
- These cells are derived from both the ….., where they leave already able to carry out ………. function, as well as in the ……. where they can be induced from …….. cells by cytokines that include ……..
- Both of these Treg subsets express the TF …… . They function in a number of ways including restricting the …………….. …………… availability for other T cells and secreting regulatory ………
A defect in Treg can cause …………… …………….
- thymus, regulatory, periphery, naïve, TGFbeta
- FOXP3, costimularoy molecule, cytokines
- autoimmune disease
Describe briefly the development of the effector functions of Tcells.
Dendritic cells interact with the CD4 Tcell via MHC class II
There are 5 possible effector functions which are determined by a transcription factor
1. Tbet –> Th1
2. GATA3 –> Th2
3. RORgammaT –> Th17
4. Bcl6 –> Tfh
5. FOXP3 –> Treg
What are the functions of the 5 effector T cells and what do they secrete?
- Th1 –> intracellular e.g. macrophages infected with salmonella and mycobacterium tuberculosis
- makes IFNgamma - Th2 –> helminths
- IL-4 produced (needed to make IgE - allergy) - Th17 –> extracellular bacteria and fungi
- IL-17 (autoimmunity) - Tfh –> antibody production from B cells
- expresses CXCR5 –> migration of cell towards Bcell zone - Treg –> shuts things down
- IL-10 aand TGFbeta
