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Immunology > T cell activation and generation of effector T cells > Flashcards

T cell activation and generation of effector T cells Flashcards

1
Q

What is humoral immunity mediated by?

A

Mediated by B lymphocytes and the antibodies they produce

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2
Q

What does humoral immunity target and why?

A

Target extracellular microbes because they’re located on the surface of the cell

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3
Q

What is cellular immunity mediated by?

A

Mediated by T lymphocytes

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4
Q

What does cellular immunity target?

A

Target intracellular microbes/pathogens which have found their way in

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5
Q

What do B and T lymphocyte circulate between once they mature and to find what?

A

Once B and T lymphocyte mature, they circulate between peripheral lymphoid organs and blood to find their antigens

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6
Q

Life stages of T lymphocytes

A
  • T lymphocytes are generated in the bone marrow and undergo maturation in thymus
  • Mature naïve T cells are released from thymus into blood
  • Recirculate between blood and lymphoid organs
  • If they encounter antigens that they recognise it leads to lymphocyte activation, proliferation and differentiation into effector and memory cells
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7
Q

What is the main purpose of T cells and what does this include?

A

• Main purpose is to defend against intracellular microbes including:
○ Intracellular bacteria in phagosomes of phagocytes
○ Viruses free in cytoplasm of cells
○ Mutated proteins from cancer cells

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8
Q

When do T cells only recognise antigens after?

A

•T cells only recognise antigens after processing and presentation

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9
Q

What do most T cells have?

A

Most T cells have alpha-beta TCR

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10
Q

What do T cells only recognise and when bound to what?

A

• T cells only recognise peptides from foreign antigens when bound to MHC molecules

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11
Q

What does TCR consist of and what does each one have?

A

• TCR consists of 2 chains, each one has 1 variable domain and 1 constant domain

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12
Q

What is antigen binding to TCR formed by?

A

Antigen binding is formed by the combination of the variable domain from each chain

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13
Q

What do MHC molecules bind and display from what and for recognition by what?

A

• MHC molecules bind and display peptides from antigens for recognition by TCR

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14
Q

How many types of MHC are their and what are they?

A

○ MHC I

○ MHC II

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15
Q

What do MHC I present on what and what are they composed of?

A

MHC I presents peptides on CD8 T cells which are composed of alpha and beta2 microglobulin

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16
Q

What are MHC I expressed on?

A

• MHC I expressed on all nucleated cells

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17
Q

What do MHC II present peptides to and what are they composed of?

A

• MHC II presents peptides to CD4 T cells which are composed of alpha and beta chain

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18
Q

What are MHC II expressed on?

A

• MHC II expressed on APCs, mainly macrophages and dendritic cells

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19
Q

What are antigen presenting cells?

A

• Are cells that specialise in the capture and presentation of antigen to CD4 T cells

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20
Q

What do professional APCs include?

A
  • Dendritic cells

- Macrophages

21
Q

What are dendritic cells the only type of APCs to activate?

A

○ Dendritic cells are the only APCs that can activate naïve T cells

22
Q

What do macrophages present to?

A

○ Macrophages present to previously activated effector T cells

23
Q

Where are dendritic cells found?

A

Dendritic cells are found in the skin, mucosa and tissues

24
Q

What are langerhan cells?

A

Langerhans cells are dendritic cells in the skin

25
Q

What do dendritic cells capture and how does it process?

A

• They capture microbes process them into antigens and transport them to draining lymph nodes where they present to and activate naïve T cells

26
Q

What must dendritic cells undergo and what are they?

A

• Dendritic cells must undergo three stages to result in T cell activation:

1. Antigen recognition 
	i. T cell activation
2. Co stimulation
	i. T cell activation
3. Cytokines
            i. Type of effector T cell
27
Q

What happens if there’s no co-stimulation to T cells?

A

• Without co-stimulation, it will result in the lack of T cell response or anergy of T cell

28
Q

What is co-stimulation more critical for?

A

• Co-stimulation is more critical for naïve T cells than previously activated effector/memory T cells

29
Q

What do APCs exposed to infection increase expression of?

A

APCs exposed to infection, increase the expression of co-stimulatory molecules and MHC which increases the antigen presenting functions of APCs

30
Q

What do cytokines regulate the differentiation of?

A

Cytokines regulate the differentiation of activated T cells into the right type of effector T cells

31
Q

What do macrophages do?

A

• Phagocytose microbes

32
Q

What do macrophages present and to what?

A

• Present antigens to effector CD4 T cells

33
Q

What do macrophages activate?

A

Activate effector Th1 which in turn activate mechanisms within the macrophage to kill ingested microbes

34
Q

What can all nucleated cells get infected with and what do they present to CD8 T cells?

A

All nucleated cells can get infected by viruses and present peptides from their cytosol, to CD8 T cells

35
Q

What do CD8 T cells specialise in?

A

• CD8 T cells specialise in:
○ Recognising viral antigens and mutated proteins
○ Eliminating cells infected by viruses/malignant cells

36
Q

Steps involved in antigen processing and presentation to CD8+ T cells

A

○ Virus can infect any cell and produce cytosolic antigen proteins within the cells
§ This causes cells to develop proteasomes
○ Proteasomes takes up viral protein and breaks it down into peptides
○ Peptides are recruited to lumen of ER by TAP
○ In the ER, there is also the generation of MHC-I with a free peptide groove which binds to a peptide that fits in its groove
○ MHC-I/peptide complex travels to the Golgi where it is transported out using an exocytic vesicle which fuses with plasma membrane and is presented
○ Recognised by CD8 T cells

37
Q

What do CD4 T cell effectors help macrophages and B cells with?

A

• CD4 T cell effectors help macrophages and B cells eliminate extracellular bacteria

38
Q

Steps involved in antigen processing pathway to CD4+ T cells

A

○ Bacteria taken up into endosome which fuse with lysosome to produce endo-lysosome where it is cleaved into peptides
○ At same time, MHC-II is synthesised in ER and MHC-II unstable if there is a lack of
peptide in its groove. This will cause degradation so needs to be conjugated with
invariable chain so it fills the groove to prevent breakdown
○ MHC-II/invariable chain complex leaves ER, travels to Golgi and is transported out
using an exocytic vesicle
○ Whilst exocytic vesicle is travelling to the membrane, it encounters and fuses with
the endo-lysosome
○ Lysozymes in the endo-lysosome cause the pH to be low and invariable chain is broken down and only small fragment remains = CLIP
○ This compartment also expresses HLA-DM (another MHC-II molecule) = not involved in antigen presentation but has a high affinity for CLIP
○ CLIP can now be removed from the MHC-II and it can bind to a peptide from the
endo-phagosome, that fits in its groove
○ MHC-II is now stabilised and leaves in a vesicle, fuses with plasma membrane and is
presented and can be recognised by CD4 T cells

39
Q

Different type of effector T cells

A
  1. T helper cells
  2. Cytotoxic T lymphocytes
  3. Cytotoxic T lymphocytes
  4. Regulatory T cells
40
Q

What induces differentiation into Th1?

A

○ IL-12 and IFN-gamma are released by APCs to induce differentiation into Th1

41
Q

What does Th1 help?

A

○ Help phagocytes to kill ingested microbes which causes increased destruction of intracellular pathogens

42
Q

What does Th1 stimulate?

A

Also stimulates the production of IgG antibodies which increases phagocytosis of microbes and activate complement

43
Q

What induces differentiation into Th2?

A

○ IL-4, IL-25, IL-33 released by APCs/cells infected with helminths to induce
differentiation into Th2

44
Q

What cytokines does Th2 produce?

A

○ Th2 then produce the cytokines IL-4, IL-5 and IL-13

45
Q

What do Th2 work with to produce and what does this play a role in?

A

○ Work with B cells to produce IgE which plays a role in allergic reactions/asthma and activating eosinophils/mast cells to kill parasites

46
Q

What does Th17 play a role in?

A

○ Role in defence against bacteria and fungi

47
Q

What does Tfh help B cells undergo?

A

○ Help B cells undergo class switching and affinity maturation

48
Q

What do cytotoxic T lymphocytes kill?

A

Kill cells infected by microbes that grow free in the cytosol

49
Q

What do effector CD8 T cells leave via and migrate to in order to perform their effector functions?

A

• Effector CD8 T cells leave PLO via blood and migrate to site of antigen entry to
perform their effector functions and eliminate antigen

Immunology (8 decks)

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