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Fundamentals of P > T Cell Activation & Generation of Effector T Cells > Flashcards

T Cell Activation & Generation of Effector T Cells Flashcards

1
Q

The life stages of T lymphocytes

A

Generated in bone marrow => undergo maturation in thymus

Mature naïve T cells released from thymus into the blood

Recirculate between blood and peripheral lymphoid organs (lymph nodes, spleen, MALT)

If they encounter antigens that they recognise => lymphocyte activation, proliferation & differentiation into effector/memory cells

Effector T cells => specialised functions

Memory T cells => memory responses (faster, ⇧efficient)

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2
Q

T cell role

A

Designed to fight intracellular microbes:

  • intracellular bacteria in phagosomes of phagocytes
  • viruses: free in cytoplasm of cells (phagocytes or non-phagocytes e.g. epithelial cells)
  • cancer cells (mutated proteins from cancer cells)
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3
Q

When do T cells recognise antigens

A

T cells: do not recognise antigens directly

T cells: recognise antigens only after processing and presentation

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4
Q

Most T cells (αβ TCR T cells) recognise what

A

=> T cells recognise cell-bound Ags (peptides)

=> peptides from foreign Ags only when bound to major histocompatibility complex (MHC) molecules

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5
Q

Other subsets of T cells recognise what

A

Other subsets of T cells (γδ T cells recognise antigens that are not peptides

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6
Q

Describe structure of T cell receptor

A

=> 2 chains: α and β (most common TCR type)

γ and δ (TCR in γδ T cells)

  • each chain: 1 variable (V) domain + 1 constant (C) domain

Antigen binding site formed by: Vα + Vβ

  • V and C domains of TCR and BCR are homologous
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7
Q

MHC molecules display peptides from processed Ag - compare types

A

MHC I: presentation of peptides to CD8+ T cells
composed of α chain + β2-microglobulin

MHC II: presentation of peptides to CD4+ T cells
composed of α chain + β chain

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8
Q

γδ T cells recognise antigens that are what

A

γδ T cells recognise antigens that are not displayed by MHC I and MHC II (are not MHC restricted)

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9
Q

Expression of MHC molecules - compare types

A

MHC I: all nucleated cells

MHC II: antigen presenting cells: dendritic cells
macrophages

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10
Q

Human MHC molecules = HLA (human leucocyte Ags) - list all with MHC I/II

A

MHC I: e.g. HLA-A, HLA-B, HLA-C

MHC II: e.g. HLA-DP, HLA-DQ, HLA-DR

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11
Q

Antigen presenting cells (APC) - define

A

Cells that specialise in the capture and presentation of antigens (Ag) to CD4+ T cells

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12
Q

Professional APCs - give examples and describe roles

A

Dendritic cells => the only APCs capable to present to naïve T cells

Macrophages => present to previously activated effector T cells

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13
Q

CD8+ T cells - function

A

CD8+ T cells recognise Ags displayed by nucleated cells (not just APC but also cells that are not APCs)

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14
Q

Dendritic cells - distribution + function

A

skin, mucosa, tissues

capture microbes

transport microbes from tissues (e.g. epithelia) to draining lymph nodes

process microbes =>Ags

present Ags to naïve T cells

activate naïve T cells

Critical in the initiation (priming) of T cell responses

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15
Q

Naïve T cells need what for activation

A

Naïve T cells need signals in addition to Ag to get activated

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16
Q

Explain importance for combination of signals 1 and 2

A

Signal 1: recognition of Ag (peptide:MHC complex) on APC

=> not sufficient to induce T cell activation

=> without signal 2 => no response or anergy of T cell

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17
Q

Signal 2: co-stimulation - describe

A

=> binding of co-stimulatory molecules (B7 family, e.g. CD80/CD86) on APC by co-stimulatory receptor (CD28) on T cell

=> together with signal 1 => activation of naïve T cells

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18
Q

Signal 2: co-stimulation - effect on APCs

A

=> APCs exposed to infection increase the expression of co-stimulatory molecules (B7) and of MHC

Infection increases the antigen presenting function of APCs

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19
Q

Signal 3: cytokines produced by APCs (after infection) - functions

A

=> regulate the differentiation of activated T cells into different types of effector T cells

e. g. IL-12 and IFN-γ from APC => differentiation into Th1
e. g. IL-4 from APC => differentiation into Th2

=> ensure the right type of effector T cell is generated

e.g. effector T cell type that is most suited to respond to the infection that triggered the response

Th1 <=> macrophage co-operation

Th2 <=> B cell and eosinophils / mast cell co-operation

20
Q

Macrophages - functions

A

Macrophages

=> phagocytose microbes (e.g. Mycobacteria tuberculosis)

=> Ag presentation to effector CD4+ T cells (Th1)

=> activation of Th1 cells (see later slides)

=> Th1 cells activate macrophage to kill ingested microbes

21
Q

Antigen presentation to CD8+ T cells - which cells can do this

A

All nucleated cells can present peptides derived from proteins from antigens present in the cytosol to CD8+ T cells

22
Q

Nucleated cells can be affected by what

A

=> all nucleated cells can get infected by viruses

=> all nucleated cells can get cancer-causing mutations

23
Q

=> CD8+ T cells (cytotoxic T cells, CTLs) specialised to:

A
  • recognise viral antigens and mutated proteins

- eliminate cells infected by viruses/malignant cells

24
Q

Exogenous Ags - describe processing

A

Exogenous Ags (e.g. bacteria) taken up in cells, processed and presented by MHC II to CD4+ T cells

Exogenous pathogens (bacteria that grow outside cells)

=> taken up by phagocytes

=> eliminated via killing in phagocytes

=> eliminated by antibodies (via neutralisation, opsonisation and complement activation)

25
Q

CD4+ T cell effectors - function

A

CD4+ T cell effectors help macrophages (Th1) and B cells (Th2) to eliminate extracellular bacteria

26
Q

Treatment of pathogens in cytosol

A

Pathogens that grow free in the cytosol (viruses) or

Pathogens (bacteria, viruses) that are taken up in phagosomes but are then released into the cytosol

=> efficiently eliminated via killing by CD8+ T cells (CTLs)

27
Q

CD8+ T cells specialised to do what

A

CD8+ T cells specialised to eliminate cells infected by viruses and cancer cells

28
Q

Th (helper) cells: function

A

Th (helper) cells: express CD4 (CD4+ T cells)

29
Q

Th1: function

A

Th2: help eosinophils/mast cells to kill helminths

30
Q

Th17: function

A

Th17: role in defense against bacteria & fungi

31
Q

Tfh (T follicular helper); function

A

Tfh (T follicular helper); help B cells (class switch and affinity maturation)

32
Q

Cytotoxic T lymphocytes (CTL): function

A

Cytotoxic T lymphocytes (CTL):

express CD8 (CD8+ T cells)

kill cells infected by microbes that grow free in cytosol

33
Q

Regulatory T cells (CD4+CD25+FOXP3+): function

A

Regulatory T cells (CD4+CD25+FOXP3+):

immune tolerance & inhibition of immune responses

34
Q

Signal 3: cytokines - produced by what and regulates what

A

Signal 3: cytokines

=> produced by APCs & other cells in response to infection

=> regulate the differentiation of activated T cells into different types of effector T cells

=> ensure the right type of effector T cell is generated

e.g. effector T cell type that is most suited to respond and help eliminate the infection that triggered the response

35
Q

Cytokines that induce differentiation into Th1

A

Cytokines that induce differentiation into Th1

IL-12 and IFN-γ

from APC infected with bacteria (e.g. Mycobacteria, Listeria)

36
Q

Main cytokine produced by Th1

A

Main cytokine produced by Th1: IFN-γ

37
Q

Th1 - functions

A

Main role Th1: activate phagocytes (macrophages)

=> ↑ destruction of intracellular pathogens

Other roles: stimulate production of IgG Abs

=> ↑ phagocytosis of microbes

38
Q

Cytokines that induce differentiation into Th2

A

Less well defined (IL-4, IL-25, IL-33)

from APC/cells infected with helminths

39
Q

Main cytokines produced by Th2:

A

Main cytokines produced by Th2: IL-4, IL-5, IL-13

40
Q

Main role Th2:

A

Main role Th2: help B cells produce IgE

  • IgE => opsonise helminths
  • activate eosinophils & mast cells
  • eosinophil & mast degranulation and killing of helminths
41
Q

CD4+ T cell responses

A

Naïve T cells recognise Ags in peripheral lymphoid organs
Activation, proliferation, differentiation into effectors
Effector T cells leave activation site (PLO) via blood
Effector T cell migration to site of Ag entry
Effector T cells perform their effector functions to eliminate Ag together with other cells (macrophages, B cells, etc.)

42
Q

CD8+ effector T cells=cytotoxic T lymphocytes (CTL) - functions

A

Ag recognition by naïve CD8+ T cells in PLOs

activation, proliferation, differentiation into effectors

Effector CD8+ T cells leave activation site (PLO) via blood
Effector CD8+ T cell migration to site of Ag entry
Effector CD8+ T cells perform their effector functions to eliminate Ag/infection

43
Q

CD8+ T cells (cytotoxic T cells, CTLs) specialised to:

A
  • recognise viral antigens and mutated proteins

- eliminate cells infected by viruses/malignant cells

44
Q

CD8+ T cells (cytotoxic T cells, CTLs) - main mech

A

Main mechanism: kill infected cells

Killing is antigen-specific and contact-dependent

45
Q

CD8+ T cells (cytotoxic T cells, CTLs) - effect on healthy/unhealthy cells

A

Uninfected/healthy cells are not killed by CTLs!

Killing of infected cells by CTL => eliminates reservoirs of infection

46
Q

CD8+ T cells (cytotoxic T cells, CTLs) - mediated by

A

Killing mediated by cytolytic molecules:

Perforin: forms pores => delivery of granzymes

Granzymes A, B, C: initiate apoptosis

delivered at the site of contact between CTL:target !

=> prevents killing of neighbouring healthy cells

Killing mediated by death receptor pathway (Fas/FasL)

Fundamentals of P (62 decks)

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