T- cells

Question 1

describe the lymphoid progenitor cell

Answer 1

→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.

Question 2

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

Answer 2

→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.

Question 3

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

Answer 3

→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 for ILs)

Question 4

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

Answer 4

→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

Question 5

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

Answer 5

→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

Question 6

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

Answer 6

→TCR formed of g/d chain

→recognize lipid antigens

Question 7

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

Answer 7

→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

Question 8

what are properties of αβ T cells?

Answer 8

→ 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

Question 9

what are properties of γδ T cells?

Answer 9

→ 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

Question 10

what is MHC?

Answer 10

→ surface expressed molecule which bind peptides derived from antigens and present to T cells
→ MHC encodes for the human leukocyte antigens

Question 11

what are the two types of MHC?

Answer 11

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

Question 12

what are MHC I and MHC II made of?

Answer 12

→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 .

Question 13

what is the process of antigen presenting to CD4 cells?(8)

Answer 13

→Uptake of extracellular proteins into vesicular compartments of APC

→Processing of internalized proteins in endosomal/lysosomal vesicles

• MHC is being synthesised and regulated by chaperone proteins

To stop the MHC molecule binding the peptide in the right place, it binds to invariant change.

→Biosynthesis + transport of class II MHC molecules to endosomes

• Antigen binds to the MHC11. HLA DM takes away the CLIP part of invariant chain allowing the peptide to bind into it. prevent the degradation of MHC II dimers before antigenic peptides bind

→Association of processed peptides w/class II MHC molecules in vesicles

→Expression of peptide-MHC complexes on cell surface

Question 14

what is the process of antigen processing and presentation to CD8 cells?(6)

Answer 14

→Production of proteins in cytosol

→Proteolytic degradation of proteins via ubiquitination

→Transport of peptides from cytosol to ER
using TAP(transporter associated antigen processing protein) and they encounter MHC-1 molecule. 

The peptide binds and it is modified by ERAP(endoplasmic reticulum aminopeptidase). This trims down the peptide to fit the MHC-1. Beta 2 stabilises the structure

• MHC-1 presents on the surface and it is presented to CD8+

Question 15

describe dendritic cells

Answer 15

→Irregularly-shaped cells in most tissues

→DC usually myeloid derived (can be myeloid/lymphoid) →Only APC that can present to naïve T cells

Question 16

what happens when dendritic cells are immature?

Answer 16

→DCs capture Ag (foreign material) and migrate to

→LYMPHOID TISSUES where they mature and effectively ‘present’ or ‘show’ antigen to T cells (T lymphocytes)

Question 17

What is cross presentation?

Answer 17

Antigen presenting cells need to activate CD8+ without themselves being killed.
They take viral peptides and take it through the endosome through MHC-1 pathway.

Question 18

what are the subtypes of dendritic cells?

Answer 18

Langerhans cells (skin),
→Interdigitating
→plasmacytoid
→‘follicular DCs’ (actually fibroblasts)

Question 19

what are other APC?

Answer 19

Tissue specific DC:
→Langerhans cells in skin
→Interstitial DC in dermis
→Blood myeloid DC
→Plasmacytoid DC
→Blood monocyte derived DC

Macrophages
B-cells
Endothelial cells under some conditions

Question 20

what are the 3 signals to get correct T cell activation?

Answer 20

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

Question 21

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

Answer 21

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+
• They rearrange T-cell receptors molecules. If this doesn’t happen- apoptosis
→Are positively selected to bind to molecules called MHC

→negatively selected if bind self peptides (‘education’)

Question 22

what do CD4 T cells do?

Answer 22

→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.

Question 23

what do CD4+ Th1 cells do?

Answer 23

Express the co-receptor CD4
→Help to activate the cellular immune response
→Produce gamma-interferon
→Activates Macrophages and cytotoxic T cells

Question 24

what is the Th1 response effective against?

Answer 24

→ intracellular infections, bacterial, protozoal and viral

Question 25

what do CD4+ Th2 cells do?

Answer 25

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

Question 26

what is the Th2 response effective against?

Answer 26

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

Question 27

what do CD4+ Th17 cells do?

Answer 27

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

Question 28

what is Th17 response effective against?

Answer 28

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

Question 29

what do CD4+ Treg cells do?

Answer 29

→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

Question 30

what do Tregs inhibit the effector functions of?

Answer 30

CD4+ and CD8+ T cells.

→Also inhibit antigen presentation function of B cells and other APC.

Question 31

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

Answer 31

→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.

Question 32

what are CD8+ cytotoxic T-cells killing mechanisms?

Answer 32

→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

Question 33

what are CTL cytolytic proteins?

Answer 33

→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

Question 34

CTL killing mechanisms 2

Answer 34

→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

Question 35

what do NKT cells do?

Answer 35

→Express T cell markers and NK cell markers.
→Large cell population (20% mouse liver lymphocytes) →Restricted TCR usage (Va14/Va24) Antigenic specificity? →Respond to glycolipids such as a-galactosyl-ceramide →Restricted through CD1d

Question 36

How is autoimmune disease prevented

Answer 36

T-cell has to recognise MHC. To avoid autoimmune, they should not bind too strongly.