Lymphocyte Activation and Differentiation Into Effector Cells Flashcards
Activation of naïve CD8+ T cells:
- CD8+ T cell encounters activated APC
- APC present antigen on its surface within MHC-I
- Antigens can be bound to MHC-I either when they are synthesised within the cell or transferred from phagosomes to cytosolic compratment
- CD8 T cell produces IL-2 to drive its own proliferation
Successful generation of effector CD8+ CTLs requires ‘help’ from CD4 + T cells:
- CD4+ T cells secrete interleukin 2 (IL-2)
2. CD4+ T cells ‘license’ DCs for CD8+ T cell proliferation and differentiation
The Dendritic Cell is activated by CD4+ T cells: licence to kill
TRUE OR FALSE
TRUE
Activated CD8+ T cells differentiate into effector T helper cells or memory CD8+ T cells
FALSE
Activated CD8+ T cells differentiate into effector Cytotoxic T lymphocytes (CTLs) or memory CD8+ T cells
Some activated effector T cells exit lymphoid tissues → re-enter the circulation and traffic into inflammed/infected tissues
- Exit lymph nodes:
Upregulate S1P receptors to exit lymph nodes
- S1P receptor modulators used in the treatment of Multiple Sclerosis
Ability to re-enter lymphoid tissues is reduced
- Decrease in CCR7 and L-selectin expression
- Increased ability to enter inflamed tissues:
- Increased expression of ligand for P- and E- selectins
- Increased expression of receptors for inflammatory chemokines (e.g. CXCR3)
- Increased expression of certain adhesion molecules (e.g. VLA-4)
Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumour cells.
TRUE OR FALSE
TRUE
Cytolytic granules
Secretion of cytotoxic granules at the immunological synapse (IS) involves two successive transport steps:
- A dynein-dependent transport step mediates the minus-end-mediated movement of cytotoxic granules to the MTOC (i.e. the centrosome).
- A plus-end kinesin-dependent transport step enables the polarized cytotoxic granules to reach the membrane and release their contents at the IS.
In this second step, granule-associated Rab27a recruits effector Slp3, which interacts with the kinesin-1 light chain (KLC1).
Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion
The cytokine milieu determines CD4+ T cell differentiation effector fate:
TRUE OR FALSE
TRUE
Macrophage activation by armed CD4+ TH1 cells:
- Effector TH1 cells migrate from secondary lymphoid tissues into infected tissue sites.
- TH1 cells are re-activated by tissue-resident macrophages in an antigen-specific manner
- TH1 cells express co-stimulatory molecules (CD40 ligand) and secrete IFNg) to hyper-activate macrophages, enhancing their killing activities and pro-inflammatory cytokine production.
TH2 cells promote IgG production
TRUE OR FALSE
FALSE
TH2 cells promote IgE production – Defense against parasites (but also allergic reactions/asthma)
Effector functions of TH17 cells:
Clearance of certain classes of extracellular pathogens
e.g. bacteria and fungi
Tissue inflammation, immune-mediated pathology and autoimmunity
Th1 vs Th2 vs Th17 vs Tfh vs Treg
Th1:
- Production of pro-inflammatory cytokines
- Cell-mediated immunity (intracellular pathogens)
Th2:
- Humoral Immunity (promote strong antibody responses; class switching to IgE)
- Cell-mediated immunity (extracellular parasites)
- Allergy/Asthma
Th17:
- Respond to bacteria, fungi, and viruses
- Auto-immune diseases
- Highly pro-inflammatory
Tfh:
- Humoral Immunity
- Migrate into B cell follicles
Treg:
- Maintain immune homeostasis
- Limit the excessive immune response
- Maintain tolerance to self
Tfh cells help B cells respond to protein antigens:
TRUE OR FALSE
TRUE
Some antigen-activated, extra-follicular B cells immediately move into medullary cords and differentiate directly into short-lived Ig secreting Plasma Cells
Others activated B cells migrate into primary follicles, which change morphology to become a secondary follicle known as the “Germinal Centre”
TRUE OR FALSE
TRUE
Somatic Hypermutation:
B cells that make high affinity antibodies are selected for by the process of affinity maturation (or SHM) in the Germinal Centre
The aim is to enhance production of antibodies that can strongly bind to an antigen
Process is mediated by Activation Induced Deaminase (AID) which introduces random single nucleotide mutations into Ig heavy and light chain gene hypervariable regions
Some mutations will increase the affinity of membrane-bound and secreted Ig’s for the target antigen
