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Immunology (aimen n) - use these > T-Cell Activation and Generation of Effector T-Cells > Flashcards

T-Cell Activation and Generation of Effector T-Cells Flashcards

1
Q

What are the 2 types of adaptive immune responses?

A
  • Humoral immunity

- Cellular immunity

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2
Q

What is humoral immunity?

A

B lymphocytes produce antibodies targeting extracellular pathogens

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3
Q

What is cellular immunity?

A

T lymphocytes target intracellular pathogens

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4
Q

Where are lymphocytes produced?

A

T and B Lymphocytes are generated in the bone marrow

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5
Q

Where are T cells located in the body?

A

T cells mature in the thymus and naive cells circulate in the blood to peripheral lymphoid organs such as lymph nodes, spleen and mucosal tissues

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6
Q

What happens when naive T cells encounter antigens?

A

Naive T-cells encounter antigens that they recognise = lymphocyte activation, proliferation & differentiation into effector/memory cells

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7
Q

What are the roles of activated T cells?

A

Effector T cells => specialised functions

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

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8
Q

Describe the life stages of mature T lymphocytes

A

Naïve mature T cell recognises antigen = activates, proliferates and differentiates into: effector T cells & memory T cells => effector function

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9
Q

What is the role of T cells in the immune response?

A

Designed to fight intracellular microbes -intracellular bacteria in phagosomes of phagocytes

  • Viruses: free in cell cytoplasm (phagocytes/non-phagocytes e.g. epithelial cells)
  • Cancer cells (mutated proteins from cancer cells)
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10
Q

When do T cells recognise antigens?

A

T cells recognise antigens when they are processed and presented
(by MHC I on nucleated body cells/MHC II on APCs)

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11
Q

What kind of antigens do T cells recognise?

A

Most T cells (αβ TCR T cells) recognise cell-bound Ags (peptides)

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12
Q

How are antigens processed for T cell recognition?

A

T-cells only recognise peptide antigens when they are bound to MHC = self-MHC-restriction (positive selection)

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13
Q

How do T cells recognise antigens?

A

T cells recognise antigens via their T cell receptor (TCR)

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14
Q

Describe the structure of TCRs

A

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

  • each chain: 1 variable (V) domain + 1 constant (C) domain
  • V and C domains of TCR and BCR are homologous
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15
Q

Where do antigens bind on the TCR structure?

A

Antigen binding site formed by: Vα + Vβ

The N terminus contains the variable domains α and β which act as the antigen binding site

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16
Q

Which end of the TCR is the constant terminus domain located?

A

The constant terminus is where the receptor is inserted in the plasma membrane
The transmembrane region is the constant domain

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17
Q

Describe the role of MHC I molecules

A

MHC I:

  • presentation of peptides to CD8+ T cells
  • composed of α chain + β2-microglobulin
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18
Q

What is the role of MHC II molecules?

A

MHC II:

  • presentation of peptides to CD4+ T cells
  • composed of α chain + β chain
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19
Q

Which cells express MHC I molecules?

A

MHC I: all nucleated cells

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20
Q

Which cells express MHC II molecules?

A

MHC II: antigen presenting cells: dendritic cells and macrophages

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21
Q

What are the different types of MHC I molecules in humans?

A

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

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22
Q

Outline the different MHC II molecules in humans

A

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

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23
Q

Describe the structure of MHC I molecules

A

Consists of 2 chains: α and β2m

N terminus domains (α1 and α2) form a groove between each other where antigenic peptide is held for CD8+ TCR presentation

24
Q

Describe the structure of MHC II molecules

A

Also consists of 2 chains: α and β2m

N terminus domain structures of MHC II also form a groove for antigenic peptide presentation for CD4 T cells

25
Q

What are professional APCs?

A

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

26
Q

Name 2 professional APCs

A

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

Macrophages => present to previously activated effector T cells

27
Q

Where are dendritic cells found?

A

Skin, mucosa, tissues

28
Q

Outline the different functions of dendritic cells

A
  • 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
29
Q

What do Naïve T cells require to be activated?

A

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

Recognition of Ag (peptide:MHC complex) on APC
=> not sufficient to induce T cell activation

30
Q

What signal occurs to activate Naïve T cells?

A

B7 ligates to CD28 on naïve T cells

Together with signal 1 => activation of naïve T cells

31
Q

How does infection effect rate of co-stimulation?

A

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

Infection increases the antigen presenting function of APCs

32
Q

What is co-stimulation?

A

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

33
Q

What is the result of costimulation?

A

This co-stimulatory signal drives signalling pathways that promote lymphocyte survival, proliferation and differentiation

34
Q

What are the roles of macrophages?

A

=> 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

35
Q

Describe the antigen presentation to CD8+ T cells

A

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

36
Q

Why can all nucleated cells present to CD8+ T cells?

A

=> all nucleated cells can get infected by viruses

=> all nucleated cells can get cancer-causing mutations

37
Q

What are the specialised roles of CD8+ T cells?

A

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

  • recognise viral antigens and mutated proteins
  • eliminate cells infected by viruses/malignant cells
38
Q

How are exogenous pathogens eliminated?

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)
39
Q

What are 3 ways antibodies help target exogenous pathogens?

A

Eliminated by antibodies via neutralisation, opsonisation and complement activation

40
Q

How do CD4+ T cells aid exogenous pathogen phagocytosis?

A

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

41
Q

Outline the process of exogenous pathogen processing and presentation

A
  1. Uptake of extracellular proteins into APC vesicles
  2. Processing of internalised proteins in endosomal / lysosomal vesicles
  3. Biosynthesis + transport of MHC II molecules to endosomes
  4. Association of processed peptides with MHC II molecules in vesicles

5, Expression of peptide-MHC complexes on cell surface

42
Q

How are cytosolic pathogens processed?

A

Cytosolic Ags (e.g. viruses, mutated proteins in cancer cells) are processed and presented by MHC I to CD8+ T cells

43
Q

Outline the antigen processing to CD8+ T cells of cytosolic pathogens

A
  1. Proteins produced in cytosol
  2. Proteolytic degradation of proteins
  3. Transport of peptides from cytosol to ER
  4. Assembly of peptide-class I complexes in ER
  5. Surface expression of peptide-class I complexes
44
Q

What are cytosolic pathogens?

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

45
Q

Name the different effector Th cells?

A

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

Th1: help phagocytes to kill ingested microbes

Th2: help eosinophils/mast cells to kill helminths

Th17: role in defense against bacteria & fungi

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

46
Q

What are the different types of effector T cells?

A
  • Th cells
  • Cytotoxic T lymphocytes
  • Regulatory T cells
47
Q

What are the roles of CTL?

A

Cytotoxic T lymphocytes (CTL):

  • express CD8 (CD8+ T cells)
  • kill cells infected by microbes that grow free in cytosol
48
Q

What is the role of regulatory T cells?

A

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

- immune tolerance & inhibition of immune responses

49
Q

What is the role of cytokines?

A

Regulates differentiation into different effector T cells

Ensure the right type of effector T cell is generated

50
Q

Where are cytokines produced?

A

produced by APCs & other cells in response to infection

51
Q

Which cytokines induce differentiation into Th1 cells?

A

IL-12 and IFN-γ

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

52
Q

What is the main cytokine produced by Th1 cells?

A

Main cytokine produced by Th1: IFN-γ

53
Q

What are the roles of Th1 cells?

A

Main role Th1: activate phagocytes (macrophages)
=> ↑ destruction of intracellular pathogens

Other roles: stimulate production of IgG Abs
=> ↑ phagocytosis of microbes

54
Q

Describe the process of Th1 differentiation

A

Naïve CD8+ T cell activated by APC due to bacteria presence

IL-12 and IFN-y drives the differentiation of the activated T cell into Th1

55
Q

Which cytokines induce differentiation into Th2?

A

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

from APC/cells infected with helminths

56
Q

What are the main cytokines produced by Th2 cells?

A

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

57
Q

What is the role of Th2 cells?

A

Main role Th2: help B cells produce IgE

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

Immunology (aimen n) - use these (14 decks)

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