adaptive immune system (T cells) Flashcards

(34 cards)

1
Q

describe the lymphoid progenitor cell

A

→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.

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2
Q

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

A

→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.

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3
Q

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

A

→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)

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4
Q

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

A

→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

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5
Q

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

A

→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

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6
Q

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

A

→TCR formed of g/d chain

→recognize lipid antigens

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7
Q

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

A

→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

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8
Q

what are properties of αβ T cells?

A

→ 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

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9
Q

what are properties of γδ T cells?

A

→ 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

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10
Q

what is MHC?

A

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

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11
Q

what are the two types of MHC?

A

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

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12
Q

what are MHC I and MHC II made of?

A

→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 .

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13
Q

what is the process of antigen presenting to CD4 cells?

A

→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

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14
Q

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

A

→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

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15
Q

describe dendritic cells

A

→Irregularly-shaped cells in most tissues

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

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16
Q

what happens when dendritic cells are immature?

A

→DCs capture Ag (foreign material) and migrate to

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

17
Q

what are the subtypes of dendritic cells?

A

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

18
Q

what are other APC?

A
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

19
Q

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

A

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
Q

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

A

→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’)

21
Q

what do CD4 T cells do?

A

→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.

22
Q

what do CD4+ Th1 cells do?

A

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

23
Q

what is the Th1 response effective against?

A

→ intracellular infections, bacterial, protozoal and viral

24
Q

what do CD4+ Th2 cells do?

A

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

25
what is the Th2 response effective against?
→extracellular cellular infections, bacterial, protozoal and viral. →Effective in production of IgE against helminth infection.
26
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
27
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.
28
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
29
what do Tregs inhibit the effector functions of?
CD4+ and CD8+ T cells. | →Also inhibit antigen presentation function of B cells and other APC.
30
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.
31
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
32
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
33
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
34
what do NKT cells do?
→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