Flashcards in adaptive immune system (T cells) Deck (34)
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1

describe the lymphoid progenitor cell

β†’gives rise to lymphocytes.
β†’ 20-30% peripheral white blood cells
β†’6-10 microns in diameter with large nucleus and small halo of cytoplasm
β†’ Upon activation by antigens, they become effector cells or memory cells.

2

what is the role of the thymus in T-cell development?

β†’T-cells mature in the thymus.
β†’Immature T-cells develop in the bone marrow then migrate to the thymus to encounter self-antigens.
β†’During this process, many T-cells die by apoptosis, leaving just those that can generate a useful response to infection.
β†’The thymus enlarges during childhood, then atrophies at puberty.

3

what is the function of helper T cells (alpha beta T cells ) and what do they express?

β†’Helper T cells (express CD4 and CD3)
β†’ activated to secrete cytokines to help immune responses or to become memory cells

β†’2 main sub-groups: TH1 & TH2 ( also Th17)

4

what is the function of Cytotoxic T cells (alpha beta T cells) and what do they express?

β†’Cytotoxic T cells (express CD8 and CD3)
β†’activated to kill infected targets or to become memory cells usually cytotoxic in nature

β†’kill via the release of the toxic contents of granules or through induction of apoptosis

5

what is the function of Regulatory T-cells and what do they express?

β†’mainly CD4+ (some CD8+)
β†’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)
β†’2 main types: natural or inducible

6

what is the function of Gamma/delta T cells and what are they made of?

β†’TCR formed of g/d chain
β†’recognize lipid antigens

7

what is a T cell receptor made from and what is its structure?

β†’Dimeric molecule; Ξ±Ξ² or Ξ³Ξ΄ chains covalently linked by S-S

β†’Each chain has a variable and constant Ig like domain

β†’The variable region has hypervariable regions which are the antigen binding sites

β†’Associated with the signalling complex CD3

β†’CD3 is the identifier of the T cell

8

what are properties of Ξ±Ξ² T cells?

β†’ makes up 90% of peripheral blood MNC
β†’ express CD4 or CD8
β†’ Ξ± consists of germline variable, diversity, joining and constant regions
β†’ 1x10^17 possible Ξ±Ξ² T cell receptors

9

what are properties of Ξ³Ξ΄ T cells?

β†’ makes up 10% of peripheral blood MNC
β†’ 70% of mucosal T cells
β†’ some express CD8 and a few CD4
β†’ some Ξ³Ξ΄ T cells are restricted through CD1C
β†’ some use the NK receptor family
β†’some recognize cell stress indicators (butyrophilin)
β†’ can recognize a number of bacterial antigens
β†’ can recognize small aliphatic molecules
β†’extensive junctional diversity increases Ξ³Ξ΄ repertoire to 1x10^19 receptors

10

what is MHC?

β†’ surface expressed molecule which bind peptides derived from antigens and present to T cells
β†’ MHC encodes for the human leukocyte antigens

11

what are the two types of MHC?

β†’ MHC Class I (HLA-A, B and C) expressed on all nucleated cells
β†’ MHC Class II (HLA-D) expressed on professional antigen presenting cells

12

what are MHC I and MHC II made of?

β†’MHC I is made of an Ξ± chain and Ξ²2-microglobulin
β†’ recognised by CD8+ T cells.

β†’MHC II is made of an Ξ± chain and Ξ² chain
β†’ recognised by CD4+ T cells .

13

what is the process of antigen presenting to CD4 cells?

β†’Uptake of extracellular proteins into vesicular compartments of APC

β†’Processing of internalized proteins in endosomal/lysosomal vesicles

β†’Biosynthesis + transport of class II MHC molecules to endosomes

β†’Association of processed peptides w/class II MHC molecules in vesicles

β†’Expression of peptide-MHC complexes on cell surface

14

what is the process of antigen processing and presentation to CD8 cells?

β†’Production of proteins in cytosol

β†’Proteolytic degradation of proteins

β†’Transport of peptides from cytosol to ER

β†’Assembly of peptide-class I complexes in ER

β†’Surface expression of peptide-class I complexes

15

describe dendritic cells

β†’Irregularly-shaped cells in most tissues
β†’DC usually myeloid derived (can be myeloid/lymphoid) β†’Only APC that can present to naΓ―ve T cells

16

what happens when dendritic cells are immature?

β†’DCs capture Ag (foreign material) and migrate to

β†’LYMPHOID TISSUES where they mature and effectively β€˜present’ or β€˜show’ antigen to T cells (T lymphocytes)

17

what are the subtypes of dendritic cells?

β†’Langerhans cells (skin),
β†’Interdigitating
β†’plasmacytoid
β†’β€˜follicular DCs’ (actually fibroblasts)

18

what are other APC?

Tissue specific DC:
β†’Langerhans cells in skin
β†’Interstitial DC in dermis
β†’Blood myeloid DC
β†’Plasmacytoid DC
β†’Blood monocyte derived DC

Macrophages
B-cells
Endothelial cells under some conditions

19

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

20

how does +ve and –ve selection in the thymus occur?

β†’T-cells in the thymus enter as thymocytes not expressing either CD4 or CD8 (double negative)

β†’ go through a stage of expressing both (double positive)

β†’followed by a decision be either CD4+ or CD8+

β†’Are positively selected to bind to molecules called MHC

β†’negatively selected if bind self peptides (β€˜education’)

21

what do CD4 T cells do?

β†’Recognise a peptide in the binding groove of MHCII

β†’T-helper cells: produce a cytokine profile which directs the immune response to a particular outcome.

β†’T-regulatory cells: responsible for ending an immune response.

22

what do CD4+ Th1 cells do?

β†’Express the co-receptor CD4
β†’Help to activate the cellular immune response
β†’Produce gamma-interferon
β†’Activates Macrophages and cytotoxic T cells

23

what is the Th1 response effective against?

β†’ intracellular infections, bacterial, protozoal and viral

24

what do CD4+ Th2 cells do?

β†’Express the co-receptor CD4
β†’Help to activate the humoral immune response β†’Produce interleukin 4, 5 & 13
β†’ Activates B cells to produce antibodies

25

what is the Th2 response effective against?

β†’extracellular cellular infections, bacterial, protozoal and viral.
β†’Effective in production of IgE against helminth infection.

26

what do CD4+ Th17 cells do?

β†’Express the co-receptor CD4
β†’Help to protect the gut mucosa
β†’Produce interleukin 17, 22.
β†’Recruits neutrophils to sites of infection

27

what is Th17 response effective against?

β†’extracellular bacteria and fungi.
β†’Effective in promoting neutrophil mediated inflammation and helping Th1 cells to induce phagocytosis and subsequent killing of pathogens.

28

what do CD4+ Treg cells do?

β†’Express the co-receptor CD4, CD25 and FoxP3
β†’Maintain immune tolerance and suppress immune responses
β†’Produce anti-inflammatory cytokines IL10 and TGFb. β†’Also has contact-dependent immunosuppressive effect

29

what do Tregs inhibit the effector functions of?

CD4+ and CD8+ T cells.
β†’Also inhibit antigen presentation function of B cells and other APC.

30

what do CD8+ cytotoxic T-cells (CTL) do?

β†’Express the co-receptor CD8.
β†’Eliminate intracellular infections
β†’Produce IL2, TNFa and gIFN.
β†’Also has role in anti-tumour immunity and rejection of transplants.
β†’Kill infected cells in an antigen-specific and cell-contact dependent manner.

31

what are CD8+ cytotoxic T-cells killing mechanisms?

β†’Contact delivers a lethal hit!

β†’CTL can then detach and target another cell.

β†’Releases cytolytic molecules from intracellular stores.

β†’Triggers apoptosis in target cell HLA class + viral peptide + TCR + CD8 = bound together

32

what are CTL cytolytic proteins?

β†’Perforin: forms pores in target cell membrane allowing the entry of :
β†’Granzymes (A,B & C), which are serine-esterase proteases and induce apoptosis.

β†’This acts at a specific synapse between the CTL and target thus limiting any β€˜collateral’ damage.

β†’Involves cytoskeletal reorganization and granule release

33

CTL killing mechanisms 2

β†’Granzymes activate caspases => apoptosis
β†’Granzyme B: can trigger mitochondrial apoptotic pathway

β†’ FasL (on CTL) ligates Fas receptor (on target cells) => activation of caspases => apoptosis

β†’Killing of infected cells by CTL => eliminates reservoirs of infection

34

what do NKT cells do?

β†’Express T cell markers and NK cell markers.
β†’Large cell population (20% mouse liver lymphocytes) β†’Restricted TCR usage (Va14/Va24) Antigenic specificity? β†’Respond to glycolipids such as a-galactosyl-ceramide β†’Restricted through CD1d