L94: Adaptive Immunity I

Question 1

What are the two components of adaptive immunity?

Answer 1

1. Cell-mediated response;

2. Humoral (antibody) response.

Question 2

Which cells carry out the responses of adaptive immunity?

Answer 2

T and B cells

Question 3

What is the role of T cells in adaptive immunity?

Answer 3

T-cells drive cell-mediated immunity, this includes activation of macrophages, natural killer cells (NK) and antigen-specific cytotoxic T-lymphoctyes.

Question 4

What is the role of B cells in adaptive immunity?

Answer 4

B-cells drive the humoral response through the production of antibodies.

Question 5

What is the main difference between innate and adaptive immunity?

Answer 5

In adaptive immunity, there is an immunological memory.

Question 6

What is immunological memory?

Answer 6

Where each pathogen is ‘remembered’ by a specific T-cell receptor and/or B-cell receptor.

Question 7

Describe the kinetics of adaptive immunity:

Answer 7

1. ‘Establishment of infection’ occurs as a microorganism has entered and reaches the antigen threshold level to initiate an adaptive immune response (innate immune response happens here too);
2. Once threshold has been reached, ‘induction of adaptive response’. At this point the level of microorganism continues to increase;
3. Once the ‘adaptive immune response’ has been initiated, the level of microorganism begins to clear;

(area under the graph from 1-3: duration of infection)

4. After clearance, ‘immunological memory’ is achieved. (up to 20 years).

Question 8

With regards to genetics, what is the difference between innate and adaptive immunity?

Answer 8

Innate immunity is regulated by one gene, adaptive is regulated by multiple genes leading to many signature patterns for immunity.

Question 9

What are the three main molecules involved in recognition of foreign antigens? (adaptive)

Answer 9

• T-cell Receptor (TCR);
• B-cell Receptor (immunoglobulins [Ig]);
• Major histocompatibility complex (MHC proteins).

Question 10

What are the two classes of T-cells?

Answer 10

• CD4+ (helper);

- CD8+ (cytotoxic).

Question 11

What does CD stand for?

Answer 11

Cluster of differentiation (cell surface markers involved in signalling)

Question 12

What does MHC stand for?

Answer 12

Major histocompatability complex (cell surface markers involved in signalling)

Question 13

Which MHCs do CD4+ cells interact with?

Answer 13

MHC Class II

Question 14

Which MHCs do CD8+ cells interact with?

Answer 14

MHC Class I

Question 15

What is CD3?

Answer 15

A co-receptor involved in the binding and activation of both CD4 and CD8 (also co-receptors) to MHCs

Question 16

Describe the structures of T-cell receptors (TCR):

Answer 16

• Two classes of TCRs: ab chains and gd chains (antigen binding sites);
• Majority are ab;
• Each chain, a and b (or g and d) have a variable and a constant region;
• For an a-chain, two gene segments encode the variable region of the chain;
• V (variable) and J (joining);
• For b-chains, three gene segments encode for the variable region of the chain;
• V (variable), D (diversity) and J (joining);
• This leads to millions of T-cells, each specific to one antigen.

Question 17

What process (genetic) leads to variation within TCRs?

Answer 17

Somatic recombination (mutation)

Question 18

Which part of the TCR is specific to different antigens?

Answer 18

The antigen binding site

Question 19

In the body, where are B and T cells produced?

Answer 19

The bone marrow

Question 20

In the bone marrow, lymphocytes are…

Answer 20

Undifferentiated

Question 21

Where are B-cells processed (differentiated)?

Answer 21

The bone marrow

Question 22

After differentiation of lymphocytes to B-cells, where are B-cells transported to?

Answer 22

The blood stream and lymphatic organs

Question 23

Give two examples of lymphatic organs

Answer 23

• Lymph nodes;
• Lymphatic ducts;
• Spleen

Question 24

Where are T-cells processed (differentiated)?

Answer 24

The thymus gland

Question 25

What is the name of the process given to differentiation of lymphocytes to T-cells?

Answer 25

Thymic Education

Question 26

Explain the process of Thymic Education:

Answer 26

• Lymphocytes (from bone marrow) transferred to thymus;
• Low expression of CD4+, CD8+ and TCRs;
• As cells mature, they move to the cortex region and adhere to epithelial cells;
• Positive selection as to whether they bind to MHC I or II and therefore CD8+ and CD4+, respectively;
• From this point they will express either CD4+ or CD8+;
• If no binding, apoptosis;
• Negative selection to determine whether T-cells bind to self-antigens;
• If they bind to self antigens, apoptosis;
• If no binding, ‘fully educated’;
• Released as naive T-cells.

Question 27

What is meant by naive T-cells?

Answer 27

After thymic education, T-cells are described as naive until they have been exposed to a foreign antigen

Question 28

After differentiation of lymphocytes to T-cells, where are T-cells transported to?

Answer 28

The blood stream and lymph nodes

Question 29

Why are lymph nodes (secondary lymphatic organs) important sites for the adaptive immune response?

Answer 29

They contain numerous B and T cells, and also dendritic cells

Question 30

What are the three signals required for CD4+ T-cells to become activated and differentiate?

Answer 30

• Signal 1: APC presents antigen on MHCII, binding of CD4+ with this MHC;
• Signal 2: CD28 interacts with CD80/86 expressed on mature dendritic cells;

(if signal 1 but no signal 2, anergy)

• Signal 3: Cytokines direct differentiation.

Question 31

What is the major role of TH1 cells?

Answer 31

Heighten ongoing immune response by supporting macrophage function

Question 32

What is the major role of TH17 cells?

Answer 32

Expression of IL-17 to dictate innate immune response

Question 33

What is the major role of TH2 cells?

Answer 33

Support humoral (B-cell) response, mainly in adaptive immunity. Lead to production of lots of anti-inflammatory cells (mast cells and eosinophils).

Question 34

What is the major role of Tfh cells?

Answer 34

Largely reside in lymph nodes and promote B-cell activation

Question 35

What is the major role of Treg cells?

Answer 35

To regulate immune response, turn cells ON and OFF and also programme cells to undergo apoptosis

Question 36

What is involved for the activation of CD8+ cells?

Answer 36

• APC presents antigen on the MHC I to TCR;
• CD8 acts as a co-receptor;
• This directs differentiation to CD8+ and memory cells.

Question 37

What is an alternative name for CD8+ cells?

Answer 37

Cytotoxic T-cells

Question 38

How do viruses infect cells?

Answer 38

They require genetic machinery for replication

Question 39

How are viruses removed from infected cells?

Answer 39

CD8+ cells induce the host cells to undergo apoptosis

Question 40

What is apoptosis?

Answer 40

• Programmed cell death;
• Requires energy (ATP);
• Contents remain inside of cell;
• No unwanted bi-response (i.e. no inflammation).

Question 41

What is necrosis?

Answer 41

• Cell death;
• No energy required;
• Spilling out of contents;
• Bi-response, inflammation.

Question 42

What do granules contain?

Answer 42

• Granzyme: Proteases that induce apoptosis*;

- Perforin: Pore-forming protein to direct granzyme into target (infected) cell.

Question 43

• Which apoptic signalling pathways do granzymes target?

Answer 43

• Caspase-3;

- Disrupts mitochondrial membrane releasing cytochrome c.