W12 The adaptive immune response - focus on T cells Flashcards

1
Q

Lymphoid progenitor cell

A

Gives rise to Lymphocytes
20-30% peripheral blood white cells
6-10 microns in diameter with large nucleus, small halo of cytoplasm

Upon stimulation by Ag become EFFECTOR CELLS or MEMORY CELLS

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2
Q

2 main types of lymphoid progenitor cell: T cells and B cells

A

(T-lymphocytes and B-lymphocytes)

Early developmental stage, cells pass to Thymus – become T cells or stay in Bone marrow – become B cells

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3
Q

Role of the thymus in T cell development

A

T cells mature in the thymus

Immature T cells develop in bone marrow → migrate to thymus to encounter self-antigen

During this process many T cells die by apoptosis leaving just those that can generate a useful response to infection

thymus enlarges during childhood and then atrophies at pubert

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4
Q

Helper T cells (express CD4 and CD3)

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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5
Q

Cytotoxic T cells (express CD8 and CD3)

A

Cytotoxic T cells (express CD8 and CD3)
activated to kill infected targets or to become memory cells
usually cytotoxic in nature and kill via the release of the toxic
contents of granules or through induction of apoptosis

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6
Q

Regulatory T-cells

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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7
Q

Gamma/delta T cells

A

TCR formed of g/d chain recognise lipid antigens

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8
Q

The T cell receptor

A

Dimeric molecule; ab or gd 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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9
Q

alpha/beta

A

Makes up ~90% of peripheral blood MNC
Express CD4 or CD8
Restricted through MHC I or MHC II
a chain consists of germline Variable, Joining and Constant regions
b chain consists of germline Variable, Diversity, Joining and Constant regions
Total repertoire ~1017 possible ab TCRs

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10
Q

gamma/delta

A

Makes up ~10% peripheral blood MNC but up to 70% of mucosal T cells
Some express CD8 and few CD4, most double negative
Some gd T cells are restricted through CD1c
Some use the NK receptor family
Some recognise cells stress indicators (HSP, butyrophilin)
gd T cells can recognise a number of bacterial antigens

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11
Q

gamma/delta can also recognise…

A

Can also recognise small aliphatic molecules (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system
Extensive junctional diversity increases the gd TCR repertoire to ~1019 possible receptors

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12
Q

MHC: The Major Histocompatibility Complex

A

Surface expressed molecule which bind peptides derived from antigen and present to T cells.
MHC encodes for the human leukocyte antigens (HLA)
Two types: 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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13
Q

MHCII on APC

A

presents peptide to CD4+ T cells to qualify the immune response: cytotoxicity or humoral

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14
Q

MHCI on any nucleated cell

A

cell presents peptide to CD8+ T cells and is a signal for a cytotoxic response (except cross-presentation in APC)

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15
Q

Antigen processing and presentation 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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16
Q

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

17
Q

CLIP

A

CLass 2 associated Invariant chain Peptide

18
Q

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

19
Q

When dendritic cells 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)

20
Q

Dendritic cells - subtypes

A

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

21
Q

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

22
Q

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

23
Q

thymus: +ve and –ve selection

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

24
Q

CD4 T cells:

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.

25
Q

CD4+ Th1 cells

A

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

26
Q

Th1 response effective against

A

intracellular infections, bacterial, protozoal and viral

27
Q

CD4+ Th2 cells

A

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

28
Q

Th2 response effective against

A

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

29
Q

Leishmania major

A

Th1 and Th2 are mutually antagonistic

Respone in most mice = TH1

Respone in BALB/c mice = TH2

TH1 response = recovery

TH2 response = disseminated infection

30
Q

Mycobacterium leprae

A

Th1 and Th2 are mutually antagonistic

Some patients = TH1

Some patients = defective TH1 or dominant TH2

TH1 response = tuberculoid leprosy

TH2 response = lepromatous leprosy (high bac count)

31
Q

CD4+ Th17 cells

A

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

32
Q

Th17 response effective against

A

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

33
Q

CD4+ Treg cells

A

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

34
Q

Tregs inhibit the effector functions of

A

of CD4+ and CD8+ T cells. Also inhibit antigen presentation function of B cells and other APC.

35
Q

CD8+ cytotoxic T-cells (CTL)

A

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.

36
Q

CD8+ cytotoxic T-cells killing mechanisms

A

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

37
Q

CTL cytolytic proteins

A

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

38
Q

CTL killing mechanisms 2

A

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

39
Q

NKT cells

A

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