Lecture 6

Question 1

What are the functions of the lymphatic vasculature found in vertebrates?

Answer 1

Its primary role is in fluid homeostasis with the draining of fluid from interstitial spaces, in addition to this it also provides a conduit for the trafficking of immune cells and antigens as well as playing an important role in lipid transport

Question 2

How does fluid enter the lymphatics?

Answer 2

Blood pressure causes plasma to leak out of blood capillaries, this interstitial fluid is taken up by lymphatic capillaries along with leukocytes, large macromolecules and microbes at this point the fluid is known as lymph
This lymph drains from capillaries into precollecting vessels and collecting vessels, specialized valves prevent backflow of fluid

Question 3

What are the structural features of lymphatic capillaries?

Answer 3

Allow unidirectional fluid flow
Highly permeable vessels
No smooth muscle or pericytes
Little or no basement membrane
Attached to matrix by anchoring filaments

Question 4

Where do the lymphatics connect up to the bloodstream?

Answer 4

Fluid in the lymphatics reenters the bloodstream through two ducts, the thoracic duct and right lymphatic duct which connect via specialized lymphovenous valves to the left and right subclavian veins respectively

Question 5

How do lymphatic vessels develop?

Answer 5

These develop from veins where there is lymphatic specification given to produce lymphatic progenitors, these will then give rise to lymphatic sprouting leading to formation of a lymph sac and proliferation finally resulting in the lymphatic plexus remodelling and maturation

Question 6

How does the thoracic duct develop?

Answer 6

The thoracic duct develops from lymphangioblasts which sprout from the cardinal vein

Question 7

What is the role of vegfr3 in lymphatic development?

Answer 7

As lymphatic cells become specified in veins they upregulate this receptor which is activated by the vegfc ligand in the tissue causing the lympahtics to become migratory, sprouting from the cardinal vein

Question 8

What is lymphoedema?

Answer 8

A condition where there is fluid accumulation particularly in the limbs, this can be caused by things such as Milroy’s disease which is a result of mutations in vegfr3

Question 9

Where are there clusters of lymph nodes located?

Answer 9

Cervical, axillary, intestinal, inguinal and popliteal

Question 10

What is the cause of hennekam syndrome?

Answer 10

Loss of CCBE1

Question 11

How can antigen be collected by the lymph node?

Answer 11

Antigen flows into the lymph node through the afferent lymphatic vessel this can be through direct transport of the antigen or through cells such as dendritic cells which carry the antigen

Question 12

What is the problem solved by lymphocyte recirculation?

Answer 12

The number of lymphocyte specificities is large resulting in their being only a few individual cells capable of dealing with a particular infection and there is a low a probability of these cells encountering the antigen
Lymphocyte recirculation moves cells from the blood into the secondary lymphoid organs back into the blood giving them a higher probability of encountering their antigen

Question 13

How do lymphocytes enter lymph nodes?

Answer 13

Circulating lymphocytes can enter lymph nodes through high endothelial vessels which are present in all secondary lymphoid tissue except the spleen
These lymphocytes can potentially interact with antigens presented by dendritic cells in the node which may have captured antigens in the tissue and migrated or captured it in the node itself
However the majority of the lymphocytes will not meet with their antigen and will exit the lymph node via the efferent lymphatic vessel

Question 14

What is extravasation?

Answer 14

The process where leukocytes exit blood vessels, this is made up of two stages margination and diapedesis

Question 15

How does extravasation occur?

Answer 15

The infection or trauma causes the release of inflammatory cytokines such as tumour necrosis factor and interleukin 1
These activate local venous endothelial cells to upregulate the expression of selectins and intracellular adhesion molecules
These molecules mediate tethering-rolling of the lymphocytes slowing them down
This process causes leukocytes to up regulate integrins allowing them to bind to intracellular adhesion molecules in a strong interaction which results in arrest and flattening of the leukocyte allowing it to migrate between endothelial cell junctions and into the tissue

Question 16

What are selectins?

Answer 16

These mediate weak binding between cells by binding to surfaced glycoproteins with sialylated carbohydrate groups
They are expressed on both leukocytes and endothelial cells for example L-selectin on leukocytes which binds to glycosylation-dependent cellular adhesion molecule 1 on endothelial cells and E- selectin on endothelial cells which binds to E-selectin ligand on neutrophils

Question 17

What are integrins?

Answer 17

These mediate strong binding between cells by binding to immunoglobulin superfamily molecules they are expressed on both leukocytes and endothelial cells for example
Lymphocyte function associated antigen 1 is an integrin on lymphocytes which binds to ICAM-1,2 and 3
Lymphocyte Peyers patches adhesion molecule 1 is an integrin which binds to mucosal addressin cell adhesion molecule 1 on high endothelial vessels

Question 18

What is lymphocyte homing?

Answer 18

Different types of lymphocytes display tissue specific recirculation through lymphoid tissues with B cells tending to enter mucosa ssociated lymphoid tissue better than T cells and naïve T cells entering into lymph nodes better than effector and memory T cells
This is called lymphocyte homing and it ensures that the correct population of lymphocytes are present at various sites in the body, it is achieved through differential expression of cell surface molecules on lymphocytes known as homing receptors and differential expression on endothelial cells in different lymphoid tissues known as vascular addressins