Flashcards in adaptive immune system (T cells) Deck (34)
describe the lymphoid progenitor cell
→gives rise to lymphocytes.
→ 20-30% peripheral white blood cells
→6-10 microns in diameter with large nucleus and small halo of cytoplasm
→ Upon activation by antigens, they become effector cells or memory cells.
what is the role of the thymus in T-cell development?
→T-cells mature in the thymus.
→Immature T-cells develop in the bone marrow then migrate to the thymus to encounter self-antigens.
→During this process, many T-cells die by apoptosis, leaving just those that can generate a useful response to infection.
→The thymus enlarges during childhood, then atrophies at puberty.
what is the function of helper T cells (alpha beta T cells ) and what do they express?
→Helper T cells (express CD4 and CD3)
→ activated to secrete cytokines to help immune responses or to become memory cells
→2 main sub-groups: TH1 & TH2 ( also Th17)
what is the function of Cytotoxic T cells (alpha beta T cells) and what do they express?
→Cytotoxic T cells (express CD8 and CD3)
→activated to kill infected targets or to become memory cells usually cytotoxic in nature
→kill via the release of the toxic contents of granules or through induction of apoptosis
what is the function of Regulatory T-cells and what do they express?
→mainly CD4+ (some CD8+)
→T cells able to affect immune responses by either suppressing them or activating them through direct cell contact or by the secretion of soluble factors (cytokines)
→2 main types: natural or inducible
what is the function of Gamma/delta T cells and what are they made of?
→TCR formed of g/d chain
→recognize lipid antigens
what is a T cell receptor made from and what is its structure?
→Dimeric molecule; αβ or γδ chains covalently linked by S-S
→Each chain has a variable and constant Ig like domain
→The variable region has hypervariable regions which are the antigen binding sites
→Associated with the signalling complex CD3
→CD3 is the identifier of the T cell
what are properties of αβ T cells?
→ makes up 90% of peripheral blood MNC
→ express CD4 or CD8
→ α consists of germline variable, diversity, joining and constant regions
→ 1x10^17 possible αβ T cell receptors
what are properties of γδ T cells?
→ makes up 10% of peripheral blood MNC
→ 70% of mucosal T cells
→ some express CD8 and a few CD4
→ some γδ T cells are restricted through CD1C
→ some use the NK receptor family
→some recognize cell stress indicators (butyrophilin)
→ can recognize a number of bacterial antigens
→ can recognize small aliphatic molecules
→extensive junctional diversity increases γδ repertoire to 1x10^19 receptors
what is MHC?
→ surface expressed molecule which bind peptides derived from antigens and present to T cells
→ MHC encodes for the human leukocyte antigens
what are the two types of MHC?
→ MHC Class I (HLA-A, B and C) expressed on all nucleated cells
→ MHC Class II (HLA-D) expressed on professional antigen presenting cells
what are MHC I and MHC II made of?
→MHC I is made of an α chain and β2-microglobulin
→ recognised by CD8+ T cells.
→MHC II is made of an α chain and β chain
→ recognised by CD4+ T cells .
what is the process of antigen presenting to CD4 cells?
→Uptake of extracellular proteins into vesicular compartments of APC
→Processing of internalized proteins in endosomal/lysosomal vesicles
→Biosynthesis + transport of class II MHC molecules to endosomes
→Association of processed peptides w/class II MHC molecules in vesicles
→Expression of peptide-MHC complexes on cell surface
what is the process of antigen processing and presentation to CD8 cells?
→Production of proteins in cytosol
→Proteolytic degradation of proteins
→Transport of peptides from cytosol to ER
→Assembly of peptide-class I complexes in ER
→Surface expression of peptide-class I complexes
describe dendritic cells
→Irregularly-shaped cells in most tissues
→DC usually myeloid derived (can be myeloid/lymphoid) →Only APC that can present to naïve T cells
what happens when dendritic cells are immature?
→DCs capture Ag (foreign material) and migrate to
→LYMPHOID TISSUES where they mature and effectively ‘present’ or ‘show’ antigen to T cells (T lymphocytes)
what are the subtypes of dendritic cells?
→Langerhans cells (skin),
→‘follicular DCs’ (actually fibroblasts)
what are other APC?
Tissue specific DC:
→Langerhans cells in skin
→Interstitial DC in dermis
→Blood myeloid DC
→Blood monocyte derived DC
Endothelial cells under some conditions
what are the 3 signals to get correct T cell activation?
1: Peptide bound in MHC (I or II) ligates cognate T cell receptor
2: Costimulation by ligation of CD80/86 to CD28
3: Modulation of signal by cytokine production
how does +ve and –ve selection in the thymus occur?
→T-cells in the thymus enter as thymocytes not expressing either CD4 or CD8 (double negative)
→ go through a stage of expressing both (double positive)
→followed by a decision be either CD4+ or CD8+
→Are positively selected to bind to molecules called MHC
→negatively selected if bind self peptides (‘education’)
what do CD4 T cells do?
→Recognise a peptide in the binding groove of MHCII
→T-helper cells: produce a cytokine profile which directs the immune response to a particular outcome.
→T-regulatory cells: responsible for ending an immune response.
what do CD4+ Th1 cells do?
→Express the co-receptor CD4
→Help to activate the cellular immune response
→Activates Macrophages and cytotoxic T cells
what is the Th1 response effective against?
→ intracellular infections, bacterial, protozoal and viral
what do CD4+ Th2 cells do?
→Express the co-receptor CD4
→Help to activate the humoral immune response →Produce interleukin 4, 5 & 13
→ Activates B cells to produce antibodies
what is the Th2 response effective against?
→extracellular cellular infections, bacterial, protozoal and viral.
→Effective in production of IgE against helminth infection.
what do CD4+ Th17 cells do?
→Express the co-receptor CD4
→Help to protect the gut mucosa
→Produce interleukin 17, 22.
→Recruits neutrophils to sites of infection
what is Th17 response effective against?
→extracellular bacteria and fungi.
→Effective in promoting neutrophil mediated inflammation and helping Th1 cells to induce phagocytosis and subsequent killing of pathogens.
what do CD4+ Treg cells do?
→Express the co-receptor CD4, CD25 and FoxP3
→Maintain immune tolerance and suppress immune responses
→Produce anti-inflammatory cytokines IL10 and TGFb. →Also has contact-dependent immunosuppressive effect
what do Tregs inhibit the effector functions of?
CD4+ and CD8+ T cells.
→Also inhibit antigen presentation function of B cells and other APC.
what do CD8+ cytotoxic T-cells (CTL) do?
→Express the co-receptor CD8.
→Eliminate intracellular infections
→Produce IL2, TNFa and gIFN.
→Also has role in anti-tumour immunity and rejection of transplants.
→Kill infected cells in an antigen-specific and cell-contact dependent manner.
what are CD8+ cytotoxic T-cells killing mechanisms?
→Contact delivers a lethal hit!
→CTL can then detach and target another cell.
→Releases cytolytic molecules from intracellular stores.
→Triggers apoptosis in target cell HLA class + viral peptide + TCR + CD8 = bound together
what are CTL cytolytic proteins?
→Perforin: forms pores in target cell membrane allowing the entry of :
→Granzymes (A,B & C), which are serine-esterase proteases and induce apoptosis.
→This acts at a specific synapse between the CTL and target thus limiting any ‘collateral’ damage.
→Involves cytoskeletal reorganization and granule release
CTL killing mechanisms 2
→Granzymes activate caspases => apoptosis
→Granzyme B: can trigger mitochondrial apoptotic pathway
→ FasL (on CTL) ligates Fas receptor (on target cells) => activation of caspases => apoptosis
→Killing of infected cells by CTL => eliminates reservoirs of infection