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BDS1 > Adaptive immunity 1 > Flashcards

Adaptive immunity 1 Flashcards

1
Q

What is the adaptive immune system?

A

the specific and acquired branch of the immune system which provides immunological memory

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2
Q

How are both the innate and adaptive immune system further divided?

A

Into cellular (e.g. B and T cells) and humoral aspects (proteins, antibodies, soluble mediators)

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3
Q

How does adaptive immunity provide immunological memory?

A

B and T cells are primed to respond to specific pathogens

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4
Q

Which cells mediate the adaptive immune system?

A

B and T cells (but still requires innate immune cell involvement e.g. APCs)

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5
Q

What are the 3 receptors of the adaptive immune system?

A

T cell receptor, B cell receptor, Major Histocompatibility Complex

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6
Q

What is the difference between innate receptors and adaptive immunity receptors?

A

Innate receptors are highly conserved (same amongst individuals and species) whereas adaptive receptors have variable structures to recognise specific pathogens

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7
Q

How do adaptive immune receptors (TCRs, BCRs, MHC) change structure?

A

genes encoding the receptors can be rearranged to form a diverse range of receptors with wide specificity.

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8
Q

Where do T cells originate?

A

From haemopoietic stem cells in bone marrow

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9
Q

What happens to immature T cells (thymocytes) after they have differentiated in bone marrow?

A

They travel to the thymus to mature and be educated

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10
Q

Term to describe immature T cells

A

thymocytes

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11
Q

After maturation in the thymus, where do T cells travel?

A

circulate in the lymph and stored in lymph nodes

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12
Q

Function of T cells

A

drive cellular immunity and recognise peptides (e.g. on antigen presenting cells)

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13
Q

Name of receptor used by T cells to recognise antigens

A

T cell receptor (TCR)

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14
Q

How are T cells able to respond to any antigen?

A

TCRs are very diverse as their genes can be rearranged

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15
Q

When does TCR diversity arise?

A

during thymic education

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16
Q

Which processes ensure T cells only respond to foreign antigens and not ‘self peptides’?

A

Negative and positive selection during thymic education

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17
Q

What are the 2 main types of T cells?

A

CD4+ helper T cells and CD8+ cytotoxic T cells

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18
Q

How many subsets of CD4+ T helper cells exist?

A

5 subsets

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19
Q

When are T cells negative for both CD4 and CD8?

A

When they are thymocytes (immature T cells) entering the thymus

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20
Q

What are CD4 and CD8?

A

proteins and coreceptors for the T cell receptor (TCR)

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21
Q

Which coreceptor do cytotoxic T cells express?

A

CD8

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22
Q

Which coreceptor are T helper cells positive for?

A

CD4+

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23
Q

Which MHC does CD4 bind to?

A

MHCII (only present on APCs)

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24
Q

Which MHC do CD8 bind to?

A

MHCI (present on all nucleated cells)

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25
Q

What is the main type of T cell receptor?

A

alpha-beta chain receptors (consist of constant and variable region)

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26
Q

What are the 2 components of T cell receptors (TCRs)?

A

Constant region and variable region (can change to bind to any antigen)

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27
Q

What is the variable region of the TCRs also known as?

A

antigen binding site

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28
Q

How to T cells bind to antigens?

A

The variable region of the T cell receptors binds to antigen via MHC (on APC/nucleated cell)

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29
Q

Which genes are responsible for the transcription and translation of the variable region of the TCR?

A

V (variable), D (diversity), and J (joining) genes

30
Q

What is VDJ rearrangement?

A

the process by which T cell receptors have different antigen binding sites / variable regions.

31
Q

What are the 2 terms used to describe the rearrangement of the VDJ genes to change the antigen binding site of the TCR?

A

VDJ rearrangement / somatic recombination

32
Q

How does VDJ rearrangement / somatic recombination give rise to extreme variable region diversity?

A

Each gene segment (V, D, J) has multiple parts that can be transcribed. E.g. V segment has >45 different parts, D segment has 2 parts and J segment has 50 parts for alpha chains. Therefore selecting just one part of each gene segment gives rise to 10^15 (45x2x50) combinations for the alpha chain.

33
Q

What happens once T cells have expressed their receptors (VDJ rearrangement)?

A

T cells undergo thymic education

34
Q

What are the 2 processes that occur during thymic education?

A

Positive and negative selection

35
Q

Which cells present self-antigens to the T cells via MHC during thymic education?

A

thymic epithelial cells

36
Q

What are the 2 types of thymic epithelial cells?

A

Cortical and medullary epithelia

37
Q

What is the first stage of thymic education?

A

Positive selection

38
Q

What is the purpose of positive selection?

A

To ensure that all the TCRs of the T cells that leave the thymus can recognise and interact with the MHC (which presents antigens to the T cell). If TCRs cannot interact with MHC the T cell is useless.

39
Q

What happens during positive selection of thymic education?

A

The thymic epithelial cell presents a self peptide to the TCR via a MHC. If there is moderate binding to the MHC, this means there are TCR-MHC interactions so the T cell is positively selected.

40
Q

What happens if there is no binding during positive selection?

A

The T cell will undergo apoptosis and is phagocytosed by a macrophage (TCR does not interact with MHC)

41
Q

Function of negative selection during thymic education

A

Ensures no self-reacting T cells leave the thymus and starts recognising/attacking self peptides/antigens.

42
Q

How do self-reactive T cells arise?

A

By chance, VDJ rearrangement has produced a variable region on the TCR that recognises self antigens

43
Q

What happens during negative selection of thymic education?

A

A thymic epithelial cell presents a self peptide to the TCR via MHC. If there is strong binding of the TCR to the self peptide this means the T cell is self-reactive and is negatively selected by undergoing apoptosis.

44
Q

What happens is self-reactive T cells leave the thymus?

A

can lead to autoimmune diseases

45
Q

Where do T cells go after thymic education?

A

leave the thymus and migrate to lymph nodes and spleen

46
Q

What are the T cells that leave the thymus known as?

A

naive T cells (even though they have been educated they haven’t yet encountered antigens/microbes)

47
Q

What process drives T cell activation?

A

Antigen presentation via MHCI or MHCII

48
Q

Which cells can undergo antigen presentation?

A

all nucleated cells (not just special APCs)

49
Q

Function of MHCI receptors

A

presents endogenous proteins (viral, tumour cells)

50
Q

Where are MHCI receptors found?

A

all nucleated cells

51
Q

Function of MHCII receptors

A

present exogenous proteins (post-phagocytosis therefore only on phagocytes/special APCs)

52
Q

Which T cells are activated by antigen presentation via MHCI receptors (on all nucleated cells)?

A

CD8+ T cells

53
Q

Which T cells are activated by antigens presented by MHCII receptors (on phagocytes)?

A

CD4+ T cells

54
Q

How does antigen presentation occur?

A

APCs (e.g. DCs) phagocytose pathogens at epithelial barrier. DCs migrate to the lymph nodes and mature en route by increasing their costimulatory activity. This allows the APC to activate CD4+ T cells. (CD4+ due to MHCII on APC)

55
Q

What happens as the APC is maturing on the way to the lymph node after phagocytosis?

A

APC upregulates its costimulatory receptors/proteins which will allow it to interact with the costimulatory receptors on the CD4+ T cell during T cell activation.

56
Q

Examples of the costimulatory molecules on APCs

A

CD40 and CD80/CD86

57
Q

What is T cell activation also known as?

A

T cell priming

58
Q

Where does T cell activation/priming occur?

A

in the lymph nodes (after APC arrives)

59
Q

Function of T cell priming/activation

A

To select the CD4+ T cell with the complementary TCR to the antigen and initiate its division and differentiation into T helper cell subsets

60
Q

What are the 3 signals that drive T cell activation/priming?

A
  1. MHCII-TCR interaction (DC presenting antigen to CD4+ T cell via MHCII)
  2. Co-stimulatory receptors on CD4+ T cells and APC interact
  3. Secretion of cytokines by APCs
61
Q

What is the effect on the CD4+ T cell when cytokines are released from the APC in the final stage of T cell activation/priming?

A

The cytokine binds to the specific cytokine receptor on the CD4+ T cell which stimulates differentiation into a CD4+ T helper cell subset.

62
Q

Which T cells are activated by nucleate cells presenting the endogenous protein via MHCI?

A

CD8+ cytotoxic T cells

63
Q

How does CD8+ cytotoxic T cell activation/priming occur?

A
  1. MHCI-TCR interaction as the nucleated cell presents the endogenous peptide
  2. Co-stimulatory receptors on both the nucleated cell and CD8+ cytotoxic T cell interact
  3. Cytokines are released by the nucleated cell which instructs the T cell to degranulate, releasing enzymes for apoptosis of the infected nucleated cell.
64
Q

Which type of T cell has subsets?

A

Only CD4+ T helper cells (CD8+ cytotoxic cells don’t have subsets)

65
Q

What is responsible for inducing CD4+ T cells to differentiate into a specific subset?

A

The type of cytokine released by the APC determines which subset the T helper cell differentiates into e.g. IL-4 triggers differentiation into T helper 2 cell

66
Q

What are the subsets of CD4+ T helper cells?

A

Helper or regulatory - T regulator cells, T follicular helper cells, T helper 17, 1, 2 cells

67
Q

What are the different functions of the T helper cell subsets?

A

initiate phagocytosis by macrophages, stimulate antibody production by B cells, immune suppression by interfering with MHC-TCR, barrier and mucosal immunity.

68
Q

Functions of cytotoxic CD8+ T cells

A

produce different pro-inflammatory mediators (cytokines), degranulation, induce apoptosis of host cells

69
Q

What is clonal expansion?

A

the specific T cell (that targets the specific antigen) increases in number

70
Q

Where does clonal expansion occur?

A

Secondary lymphoid organs (lymph nodes, spleen, tonsils)

71
Q

Difference between effector and memory T cells

A

Effector T cells (majority) exert a particular function whereas memory T cells (minority) circulate and provide immunological memory

BDS1 (66 decks)

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