9. Adaptive Response: Where and When?

Question 1

Where do the lymphocytes and dendritic cells combine to activate T cells?

Answer 1

The secondary lymphoid tissue, then they may all go off and GSD (get shit done)

Question 2

What are the secondary lymphoid organs?

Answer 2

Lymph nodes, spleen and mucosa associated lymphoid tissue (MALT)

Question 3

What two pathways haematopoietic stem cells develop through? Which cells undergo which pathway?

Answer 3

Two pathways: myeloid, lymphoid

Myeloid: platelets, erythrocytes, dendritic cells, monocytes/macrophages, neutrophils, eosinophils, basophils

Lymphoid: B cells in bone marrow, T cells, NK cells, lymphoid dendritic cells

Question 4

What is the role of the blood and lymphatic systems?

Answer 4

Method of carrying cells from one place to another

Question 5

How do lymphocytes travel from the blood into the lymph nodes?

Answer 5

Through the high endothelial venues (HEV)

Question 6

What happens if an antigen for a lymphocyte is present in the lymph nodes?

Answer 6

Antigen will be processed by dendritic cells, presented to T cells which activate B cells and produce plasma cells

Question 7

Describe the structure of the lymph nodes

Answer 7

Consist of an outer capsule, cortex, paracortex, medulla

Question 8

What is the cortex and paracortex mostly composed of?

Answer 8

Cortex is mostly B lymphocytes

Paracortex is mostly T lymphocytes

Question 9

What occurs to the lymphocytes in the lymph nodes when antigen is present?

Answer 9

Lymphocytes divide and form primary follicles which then develop to secondary follicles then germinal centres

Question 10

What happens to dendritic cells if it is activated by a pathogen (activation-lymph node)?

Answer 10

1. Dendritic cell uses PRRs to recognises DAMPs or PAMPs of pathogen
2. Recognition activates dendritic cell and it becomes phagocytic, taking up and processing pathogenic antigens
3. Dendritic cell moves out of tissue and migrates through affluent lymphatics to the lymph node
4. Dendritic cell also vastly increases the amount of MHCII, CD80 and CD86 on cell surface making it a more potent antigen presenting cell
5. Reaches lymph node
6. MHCII presenting peptides and CD80 interact with CD28 to provide costimulation of T cells which become activated and leave lymph node

Question 11

How does the type of T cell activated affect the result?

Answer 11

If helper T cell activated then helps B cell differentiation

If cytotoxic T cell activated then goes to site of infection and murders

Question 12

What are germinal centres?

Answer 12

Structures in lymphoid tissue responsible for the maturation of B cells

Question 13

How do B cells mature through germinal centres?

Answer 13

Follicular dendritic cells show antigen to B cells

T follicular helpers also help B cell to differentiate

Question 14

What is the structure of germinal centres?

Answer 14

3 distinct zones (surrounded by a mantle): dark zone, basal light zone and apical light zone

Question 15

How does the names of the B cells vary as they travel through the germinal centre?

Answer 15

in dark zone = centroblast

in basal and apical light zone = centrocyte

Question 16

Why are plasma cells not produced in the germinal centres?

Answer 16

Because they produce antibodies which would cover up antigens and prevent responses

Question 17

What happens when the B cell mature?

Answer 17

Class switching, affinity maturation (proliferate and incorporate mutations), produce memory cells, produce plasma cell precursors

Question 18

Describe the lymphoid follicle/node

Answer 18

White pulp present within red pulp, contains PALS (periarteriolar lymphoid sheath), mostly T cells

Question 19

Which organ deals with blood infections?

Answer 19

The SPLEEEEEEEEEEEN

Question 20

How do most infections occur?

Answer 20

Through mucosal tissues

Question 21

How does IgA protect mucosal surfaces?

Answer 21

Present as a dimer (linked by J chain) and containing a secretory component (derived from poly Ig receptor) which protects mucosal surface, preventing pathogenic adhesion and infection

Question 22

How does IgA travel from underlying mucosal to mucosal surfaces?

Answer 22

Plasma cells which release the IgA are underlying mucosal so IgA must travel through the epithelial cells.

Polymerised Ig recognises and binds to J joining chain of IgA and transports it to mucosal surface. It is then endocytose to the mucosal side. A specific enzyme cleaves the poly Ig, leaving a bit of receptor to protect IgA from digestion

Question 23

What happens if pathogens get past IgA?

Answer 23

IgE ENTERS THE RING!

IgE activates Mast cells which cause neutrophils/eosinophils to leave blood and move to site of infection

Question 24

What are the Peyer’s patches?

Answer 24

Organised lymphoid nodules present in the intestinal epithelium, pathogens present here may also initiate an immune response.

Question 25

What is the role of the microfilm (m) cells in the Peyer’s patch?

Answer 25

transport antigen from outer mucosal surface and show it to lymphocytes underlying surface of gut (Peyer’s patch)

Question 26

What happens after lymphocytes are activated?

Answer 26

Undergo further round of activation by leaving Peyer’s patch and going to local draining lymph nodes (mesenteric lymph nodes), then they move back to the gut using homing molecules (such as MAdCAM-1 - mucosal addressin cell adhesion molecule 1) which act as a postcode for the lymphocytes

Question 27

What things are required for communication between cells?

Answer 27

Cell-to-cell contact, or release of soluble molecules (cytokines)

Question 28

What are cytokines?

Answer 28

Small proteins which act as messengers, controlling haematopoiesis and up/down regulating immune response, each cytokine has it’s own receptor (e.g. interleukin 1)

Question 29

What are the 6 groups of cytokines?

Answer 29

1. Interleukins - messengers between lymphocytes
2. Colony-stimulating factors
3. Chemokines (chemotactic cytokines that attract cells to site of infection)
4. Interferons (interfere with viral replication - stop viral spread)
5. Tumour necrosis factors (pro-inflammatory cytokines)
6. growth factors (cause growth of cells)

Question 30

What is pleiotropy of cytokines? Give an example

Answer 30

Where a single cytokine can do multiple things e.g IL-4 can act on B cells, activating them and causing proliferation and differentiation

Question 31

What is redundancy in cytokines? Give an example

Answer 31

Where different cytokines do exactly the same thing e.g. IL-2 may also cause B cells to proliferate

Question 32

What is synergy in cytokines? Give an example

Answer 32

Where cytokines work better together than on their own e.g. IL-4 can cause class switching to make IgE but if IL-5 around then the effect is increased

Question 33

What is antagonism in relation to cytokines?

Answer 33

If lots of gamma interferon around then it blocks the class switching of interleukin

Question 34

What effect increases the amount of cytokines produced?

Answer 34

Cascade effect

Question 35

What are the 6 functions of cytokines?

Answer 35

1. stimulate inflammation - IL-1, IL-17
2. immunosuppressive - IL-10, TGFbeta
3. antiviral - IFNalpha, IFNgamma
4. T cell proliferation/ differentiation - IL-2, IL-12
5. haematopoiesis - IL-2, IL-13
6. chemotaxis - IL-8, RANTES

Question 36

Describe the two types of interferons

Answer 36

Type I: IFNalpha, IFNbeta, produced by most nucleated cells

Type II: IFNgamma, produced by NK/T cells, important in regulating production of Th1 cells and in macrophage activation

Question 37

How else may cytokines be used (other than in the immune system)?

Answer 37

Therapeutically (e.g. IFNalpha for viral infections), or inhibited therapeutically (e.g. anti-TNFalpha for rheumatoid arthritis)