Lecture 7- Lymphoid anatomy

Question 1

What are the 2 types of T cells?

Answer 1

Cd4- (helper) support innate cells to have particular function
Cd8- important in response to viral infections.

Question 2

How do you enhance the chances of rare antigen specific T and B cells of interacting with each other?

Answer 2

1. Have collections of T cells and immune cells in sites where infection is likely to happen
2. Have cells circulate throughout body and have specialised sites of antigen capture where lymphocyte/antigen interactions are enabled

Question 3

What does the anatomy enable?

Answer 3

To enable rare antigen-specific lymphocytes to encounter their antigen
To enable different types of antigen specific lymphocytes (e.g. T cells and B cells) to make physical contact
To enable cells to go where they are needed e.g. site of infection

Question 4

What are the two different types of lymphoid tissues that we think about?

Answer 4

1. Primary lymphoid tissue- where the B and T cells initially develop. This is antigen-independent. Bone marrow and then the Thymus where T cells are selected.
2. Secondary lymphoid tissue- where the immune cells are primed to respond during infection. 3 types of tissue: Lymph nodes, spleen and MALT (Mucosal associated lymphoid tissue )

Question 5

Describe lymphoid vessels?

Answer 5

• Not blood vessels! (but similar)
• Connect most body tissues with lymph nodes and eventually bloodstream
• Contains Lymph fluid, lymphocytes and tissue-dendritic cells
• Lymph not pumped by heart-muscles and valves. Just drainage of fluid from tissues.

Question 6

Describe the order of draining of lymph from tissue to lymph vessels?

Answer 6

Lymphatic capillaries, into lymphatic vessels, into afferent lymphatic vessels, into lymph node, into efferent lymphatic vessels,efferent and into blood stream

Question 7

How does lymphocyte activation occur in these lymph nodes?

Answer 7

1. When infection occurs in a site e.g. skin, free antigen and antigen–bearing dendritic cells travel from the site of infection through the afferent lymphatic vessels
2. Go to draining lymph nodes
3. T and B cells are activated (selection, differentiation, proliferation)
4. Once activated leave nodes via efferent lymphatic vessels
5. Then into blood
6. Back to tissue where infection is
7. This take 4-6 days if its a new antigen to immune system! If this is the first time your immune system has seen this particular pathogen. If second time, much quicker

Question 8

Describe 4 main structures of the lymph node

Answer 8

1. Cortex- where B cells are localised. Contains B cell follicles. Where they will proliferate during infection.
2. Paracortex- where T cells are. Spatially segregated from B cells.
3. Medulla- mix of different cells. Plasma cells (that differentiated from b cells), some t cells and some macrophages
4. Secondary follicle- where B cells proliferate during infection. These are transient structures. Disappear when infection has gone away.

Question 9

MALT contains how many lymphocytes?

Answer 9

Contains as many lymphocytes as rest of body!
examples:
-Gut associated lymphoid tissue (GALT)
-Nasal associated lymphoid tissue (NALT)
-Bronchus associated lymphoid tissue (BALT)
Also find specialised cells in e.g. liver and reproductive tract

Question 10

What are the payer’s patches?

Answer 10

Structures in small intestine full of lymphocytes

Question 11

Describe the Payer’s patch/ gut associated lymphoid tissue GALT

Answer 11

Lymphoid tissues Found in small intestine. Look similar to lymph node. Have Germinal centres, t cell regions etc.
Difference here is that the antigen presenting cells don’t need to drain from the tissue because this is localised in the tissue.
Singl epithelial layer. With payers patch under the epithelia. Specialised cells called Microphal? Cells. Cells allow lymph cells to drain from lumen of gut into germinal centre? Localised dendritic cells right next to this so can present them to the T cells right there. Avoids antigen-presenting cells having to drain from the tissue.

Question 12

Describe the structure of the M cells at payer’s patches?

Answer 12

Folded around all the immune cells. Allows close contact. So any antigens they pick up can be presented to them really quickly

Question 13

What’s the main difference with the spleen?

Answer 13

Nothing is being drained into spleen, no afferent lymphatics. Just blood stream.

Question 14

How does spleen help the lymphatic system?

Answer 14

Filter antigen from the blood. Can sense if there’s an infection. Allows us to respond to pathogens that enter the blood stream. Can also help with infected tissues because some will drain away from tissue and flow into spleen.

Question 15

What are the 2 structures of the spleen?

Answer 15

1. Red pulp= where red blood cells are being removed.
2. Periarteriole lymphoid sheath (PALS)= immune cells present, ready to pick up any antigen from the blood. (white pulp areas)

Question 16

What are High Endothelial Venules? (HEV)

Answer 16

Key areas in lymph nodes. Let lymphocytes leave blood stream and enter lymph node.

Question 17

Thoracic duct

Answer 17

Major lymphatic vessel. Allows cells to drain out of the lymph nodes into the blood stream

Question 18

Describe a cell’s route around the lymphatic system?

Answer 18

Cells drain to lymph node from tissue.
Activated in lymph node.
Cell move out of lymph node through lymphatic system and into blood stream via the thoracic duct
Circulate around blood system.
Usually get recruited to tissue if there’s an infection, to fight pathogen.

Question 19

What are the 2 key mechanisms for lymphocyte migration?

Answer 19

Adhesion molecules e.g. integrins and selectins

Chemokines

Question 20

What is the first step in migration process?

Answer 20

Selectin driven
In response to the inflammation, factors activate the endothelial cells in that area to upregulate specific adhesion molecules. E.g. P-selectin

Question 21

What is more detailed first step in migration process?

Answer 21

Selectin driven
P-selectin is induced on vessels in response to e.g. Leukotriene B4, C5a, histamine, TNFa, LPS
TNF and LPS also induce a 2nd selectin- E-selectin (few hours later)
Recognise sulphated sialyl-Lewis X structures on immune cells
Mediated reversible movement
“Rolling”- slowed down in that region

Question 22

What is the second step in the migration process?

Answer 22

Firm attachment
ICAM-1 (intracellular adhesion molecule) and ICAM-2 are induced on vessels by e.g. TNF
Bind to LFA-1 and CR3 on leukocytes
Rolling is stopped
Firm attachment

Question 23

What is the third step in the migration process?

Answer 23

Extravasation- from blood into tissue
Leukocyte crosses endothelial wall
“extravasation”
Involves LFA-1/CR3
CD31 (PECAM) interactions also facilitate this (on leukocyte and endothelial cells)
Movement also known as diapedesis

Question 24

Which chemokines are at the site of infection?

Answer 24

CXCL8 and CCL2 are produced at infection site
CXCL8 (il8) released by macrophages and attracts neutrophils
CCL2 produced by e.g. Epithelial cells and stromal cells and attracts monocytes
CXCL8 (IL8) produced by e.g. macrophages and epithelial cells and mobilises naive T cells

Question 25

What else is cell movement into tissues important for?

Answer 25

For getting cells to the right place when you don’t have inflammation.
Naïve t cells can get into lymph nodes to be ready to respond to dendritic cells when they drain into the lymph node.

Question 26

What is the specific mechanism of how naïve t cells get out of blood into nodes?

Answer 26

Via high endothelial venule HEV.
naive t cells have l-selectin (CD62L) and HEV express P- & E-selectin on their endothelium so can attach and get across