Lecture 4 - Adaptive immunity

Question 1

How long after the first encounter with a microorganism does the adaptive immune response take to become effective?

Answer 1

2-4 days

Question 2

What does a vaccination do to the immune system?

Answer 2

1. Initiates a primary immune response, generating memory cells without making the person ill
2. Later, if some similar pathogens invade the body, specific memory cells already exist
3. The memory cells recognise the agent and produce massive numbers of lymphocytes and immunoglobulin that overwhelm invaders

Question 3

What did Edward Jenner develop in 1798?

Answer 3

The jennerian vaccination for smallpox.

He observed that injecting fluid from cowpox pustules into the skin of children led to the acquisition of immunity to smallpox

Question 4

Which lineage of cells is the adaptive immune response mediated by?

Answer 4

Lymphocytes of the lymphoid lineage

Question 5

What is the role of T lymphocytes?

Answer 5

Kill virus infected and cancerous cells (CD8+/ cytotoxic t cells)
Activate other cells of the immune system (CD4+ helper T cells)

Question 6

What is the role of B lymphocytes?

Answer 6

Secrete immunoglobulins (antibodies)

Question 7

What is the role of Natural Killer (NK) cells?

Answer 7

Cells that are considered part of the innate immune system as they don’t require prior activation.
They lack antigen specific receptors and are capable of killing virus infected cells immediately, without clonal expansion.

Question 8

How are NK cells activated?

Answer 8

Binding of an activating receptor to surface molecules produced by cell damage, e.g. cancer, or that are encoded buy infecting viruses

Question 9

What is the definition off an antigen?

Answer 9

A molecule or parts of molecules recognised by the variable antigen receptors of lymphocytes

Question 10

What is the definition of a naive lymphocyte?

Answer 10

Mature Lymphocytes that have not yet encountered an antigen

Question 11

Once naive lymphocytes come into contact with an antigen, what do they differentiate into?

Answer 11

Effector cells

Question 12

What is the process prior to differentiation into effector cells that involves vigorous proliferation that selectively expands the numbers of lymphocytes with receptors for specific antigens known as?

Answer 12

Clonal selection

Question 13

Where does interaction between activated DCs and lymphocytes occur?

Answer 13

Lymphoid tissues, which they enter through the bloodstream

Question 14

How do T lymphocytes recognise antigens?

Answer 14

T cell receptors generated during their differentiation, interact with APCs via complementary ligands

Question 15

Are CD4+ t cells helper or cytotoxic?

Answer 15

Helper

Question 16

Are CD8+ t cells helper or cytotoxic?

Answer 16

Cytotoxic

Question 17

Does CD4 bind MHCI or II?

Answer 17

MHCI

Question 18

Does CD8 bind MHCI or II?

Answer 18

MHCII

Question 19

Where’re dendritic cells especially numerous?

Answer 19

Epithelia and mucosal surfaces

Question 20

What are Langerhans cells?

Answer 20

A subset of DCs that reside in the keratinised epidermis for several months

Question 21

What are dermal or interstitial DCs?

Answer 21

Skin resident DCs found in the dermal layer

Question 22

What are mucosal gut DCs and what are their roles?

Answer 22

Dos that are concentrated at specialised sites of antigen collection that overlie lymphoid tissues.
Some have specialised surface properties that enable them to extend their long dendritic processes between the cells of the epithelium and into the lumen to sample antigens

These cells are directly exposed to ingested antigens and to commensal bacteria as well as invading pathogens

These cells have a specialised role in preventing inflammatory responses to harmless gut residents

Question 23

What are M cells?

Answer 23

Specialised cells that deliver antigen from the lumen of the gut to the underlying tissue, where dendritic cells cluster

Question 24

What is the process of adaptive immune system activation? (7 points)

Answer 24

1. Dendritic cell engulfs pathogen
2. migration to lymph
3. Here the DC comes into contact with naive T cells, to which it presents its antigen and the T cell docks with the DC
4. T cells activate and proliferate thorough clonal expansion
5. These proliferated T cells differentiate into effector T cells
6. These effector T cells come into contact with macrophages or B cells and activate them
7. Active B cells will produce antibodies specific to the pathogen

Question 25

Whats the process of DC migration and activation of T cells? (5 steps)

Answer 25

1. DCs are generated from progenitors in the bone marrow. Here they lie and wait for pathogens entering the body through sites of injury for example. 2. DCs express PRRs which bind to and phagocytose these pathogens 3. Once bound they mature and migrate to the lymphatics, changing their behaviour to stop phagocytosing, starting to express immune stimulatory molecules 4. Here the T cells inspect the DCs for antigen 5. If they find one they recognise, T cells activate and proliferate differentiating into effector cells.

Question 26

What is the name of the process that allows T cells to alter their receptors in order to achieve a perfect fit with the antigen displayed on DC for example?

Answer 26

Somatic hypermutation

Question 27

How do T cells know which immune cells to interact with?

Answer 27

They recognise MHC surface proteins on DCs which display peptides for recognition. They then differentiate into effector cells, which are capable of killing cells or activating those displaying the same complex of MHC and antigen.

Question 28

What did Peter Medwar establish in 1944?

Answer 28

Established that the timing and vigor of rejection is related to differences between histocompatibility antigens of donor and recipient. Rejection within the first week = Major histocompatibility complex Slower rejection process = Minor histocompatibilty complex

Question 29

What are the two internal compartments of cells that need to be monitored for pathogens?

Answer 29

The cytoplasm Vesicles of the endosomal/ lysosomal pathway

Question 30

What class of MHC molecules monitor the cytoplasm?

Answer 30

MHCI

Question 31

What class go MHC molecules monitor vesicular compartments?

Answer 31

MHC II

Question 32

Which cell types express MHC class I?

Answer 32

Virtually all body cells

Question 33

Which type of molecules does MHCI bind?

Answer 33

Peptides generated by cytoplasmic proteases from cytoplasmic proteins

Question 34

Which cell types recognise molecules displayed on MHCI?

Answer 34

Cytotoxic T cells (CD8+)

Question 35

Which cell types express MHC class II?

Answer 35

Cells of the immune system, particularly B cells, macrophages and DCs

Question 36

Which cell types recognise molecules displayed on MHCII?

Answer 36

Naive helper T cells (CD4+)

Question 37

Which type of molecules does MHCII bind?

Answer 37

Peptides generated from internalised antigen in the | endosomal compartments of cells

Question 38

Upon activation, what do CD8 T cells produce?

Answer 38

Perfroins and Granzyme

Question 39

What are perforins?

Answer 39

Proteins that form pores in the membrane of target cells

Question 40

What are granzymes?

Answer 40

Proteases that induce programmed cell death on entry into target cells

Question 41

How do granzymes mediate cell death?

Answer 41

- Granzymes target proteins that regulate apoptosis such as BID and pro caspase 3 - Granzymes cleave bid which in its truncated form cause cytochrome c to release from miochondria into cytosol - Simultaneously granzyme b activates pro caspase 3 which in turn cleaves icad - CAD migrates into nucleus where it degrades dna ensuring death of cell

Question 42

What are the steps in the process of antigen-MHCII complex recognition on macrophages by T helper cells? (2 steps)

Answer 42

``` 1. Helper T cells recognise fragments of a pathogen that has been internalised by macrophages and are carried to the cell surface by MHC class II molecules. ``` 2. The helper cell is then stimulated to activate the macrophage to destroy the internalised pathogen.

Question 43

What are the steps in the process of antigen-MHCII complex recognition on B cells by T helper cells? (5 steps)

Answer 43

1. B cells internalise antigens bound to their surface immunoglobulin and deliver them to the endosomal compartments of the cell 2. Here they are digested into fragments. 3. The antigen fragments then bind to MHC class II molecules which carry them to the cell surface 4. Here they are recognised by helper T cells 5. Helper T cells activate the B cell to proliferate and differentiate into an antibody- secreting plasma cell

Question 44

The CD4 cell subset, Th1, are produced in order to stimulate which immune cell?

Answer 44

Macrophages

Question 45

The CD4 cell subset, Th2, are produced in order to stimulate which immune cell?

Answer 45

B cells and the production of antibodies

Question 46

What is the costimulatory pair for MHCII found on the T cell?

Answer 46

TCR with CD4 coreceptor

Question 47

What is the costimulatory pair for B7 (CD80/86) found on the T cell?

Answer 47

CD28 CTLA-4

Question 48

What is the costimulatory pair for CD40 found on the T cell?

Answer 48

CD40L