Week 2: T cells and coordinating the immune response Flashcards
How do different types of T cells differ?
Phenotype
MHC restriction
Function
Cytokine Production
How do T cells differ with phenotype?
Different T cells have different molecules expressed on surface or inside the cell
This can be used to distinguish origin, differentiation, activation or exhaustion states and/or function
Many molecules used for phenotyping are called cluster of differentiation (CD) antigens
T cell subsets develop under control of different transcription factors
How is MHC restriction used to distinguish T cells?
Used to denote whether the TCR recognizes peptides presented by MHCI or MHCII molecules
CD4+ T cells - MHCII and see antigens on specialized APC cells
CD8+ T cells - MHCI and see antigens on any nucleated cell
Why are b cells less efficient compared to macrophages when it comes to MHC presenting antigen cells?
Macrophages can phagocytose anything whereas B cells can only bind to a specific antigen/pathogen
How does function help distinguish between T cells?
CD4+ Tfh (T follicular helper) cells help formation of germinal centers and with B cell affinity maturation
CD4+ Th1 (T helper 1) cells and CD8+ T cells activate phagocytes for enhanced killing of intracellular pathogens
CD4+ Th2 responsible for activation of responses targeting extracellular pathogens (worms)
CD4+Th17 responsible for activation of neutrophils/anti-fungal responses/ autoimmunity
CD8+ CTL responsible for Direct killing of infected “target” cells or cancer cells
CD4+ Treg (T regulatory cells) inhibit function of other T cells
Cytokine Production
IL-2: cd4+
IFNy: Th1 and CD8+
IL-4: Th2
IL-17: Th17
IL-21: Tfh
What are the 3 signals required to support T cell activation and differentiation?
signal 1) TCR engagement
signal 2) Costimulation - is the antigen meaningful
signal 3) cytokine - What type of T cell should the T cell become
What is the key role of IL-2 in T cell survival and clonal expansion?
IL-2 is a survival factor and keeps the T cells alive and also is a differentiation factor. It is also a growth factor that facilitate the expansion of other T-cells that recognize antigens during an immune response.
What are the stages of Clonal expansion of T cells?
Naive T cells sees antigen > T cell becomes activated memory cell or effector cell which differentiate,secrete cytokines and express cytokine receptors (Lymph nodes enlargen) > memory cells remain in lymphoid tissue, some memory cells become effects, some effectors become memory cells and most effectors dies
What happens to clonal memory T cells after immunisation?
Higher frequency of memory t cells remain after immunization and react quicker
How do T follicle helper cells function?
Naive CD4+ T cells attach to antigen displayed by dendritic cell in interfollicular area/ T cell zone. T cell becomes activated and becomes pre Tfh cell and moves into the germinal centre along with the B cell with chemokines telling the T cell where to move. B cells undergo affinity maturation in germinal centre and will migrate out as plasma cells or memory cells.
What are the opposing effects of Th1 and Th2 cytokines on macrophage function?
Classical activation - Th1 cells produce IL1 TNF IFNy and result in a type 1 immunity which is responsible for microbial killing, tissue damage and DTH
Alternate Activation - Th2 cells produce IL-4, IL-13, IL-10, GM-CSF and results in a type 2 immunity which is responsible for allergy, helminth responses, fibrosis and repair
What are the ways in which T reg cells can inhibit immune responses?
IL2 consumption by T reg cells can suppress the effector T cells and can lead to apoptosis of T cells
Can supress cytokines that help effector t cells function
T reg cells can be turned on by APCs but can also switch off APCs
What are Senescent T cells?
Cells that enter a terminal differentiation state due to excessive cell replication. This state is associated with irreversible cell cycle arrest and telomere shortening.
What are Anergic T cells?
An unresponsive state by the cell due to suboptimal signals so receiving only 1 signal when binding to antigen
