Lecture 5: The lymphatic system Flashcards Preview

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Flashcards in Lecture 5: The lymphatic system Deck (35)
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1
Q

What is the function of the lymphatic vasculature?

A
  • Primary role is in fluid homeostasis, the draining of fluid (lymph) from interstitial space
  • Provides a conduit for the trafficking of immune cells and antigens
  • Lipid Transport
2
Q

Describe the lymp is formed.

A
  • 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. Here it is known as lymph
3
Q

Describe lymph drainage;

A

Lymph drains from capillaries into precollecting vessels and collecting vessels

Specialised valves prevent backflow and ensure unidirectional flow of lymph

4
Q

Describe the structure of lymphatic capillaries

A
  • Unidirectional fluid flow
  • Highly permeable vessels
  • No smooth muscle or pericytes
  • Little or no basement membrane
  • Attached to matrix by anchoring filaments
5
Q

Describe how lymph returns to the blood stream;

A

All lymph flows into one or two lymphatic trunks; The thoracic duct and the right lymphatic duct.

These connect via specialised lymphovenous valves to the left and right subclavian veins respectively

6
Q

What do lymphatic vessels develop from?

A

Veins

7
Q

Describe lymphatic vessel development;

A

Vein
- contains lymphatic progenitor cells which express an array of genes importantly VEGFR3 and VEGF-C*(not sure if this isnt or is)

This encodes lymphatic specification

  • Lymphatic sprouting
  • Lymph sac formation and proliferation
  • Lymphatic plexus remodelling and maturation
8
Q

Describe evolutionary conservation of the lymphatics;

A
  • Lymphatic development is highly conserved among vertebrates
  • The thoracic duct develops from lymphangioblasts that sprout from cardinal veins
  • Lymphangioblasts are lymphatic precursor cells, derived from veins
9
Q

Describe how during lymphatic development receptors are upregulated

A

As lymphatic cells become specialised in the veins, they upregulate the expression VEGFR3 (receptor).

10
Q

Describe the importance of VEGFr3

A

Vegfr3 is acitvated by a ligand VEGFC present in the tissues and this causes the lymphatics to become migratory and sprout from the cardinal vein
- Mutations of knockdown of these genes prevent lymphatic development

11
Q

What causes lymphoedema?

A

Lymphatic dysfunction causes fluid accumulation, particularly in the limbs.

Milroys disease is a type of lymphoedema and is caused by mutations in VEGFr3

12
Q

Describe lymphatic vessel and lymph node interplay;

A

Lymph nodes are wired into the lymphatic system.

13
Q

Where are there clusters of lymph nodes?

A

There are clusters of lymph noes in key regions such as;

  • Cervical
  • Axillary
  • Intestinal
  • Inguinal
  • Popliteal
14
Q

How do lymph nodes collect antigens?

A

Directly in the lymph or by cells that travel along the afferent lymphatics (DC)

A variety of lymphocytes within the nodes are able to interact with these antigens

15
Q

What is the problem with lymphocytes and circulation?

A

The number of lymphocyte specificities is large, only a small population of individual cells are able to deal with a particular infection

Therefore, recirculation of cells from blood to secondary lymphoid organs, into lymph and back to blood increases the likelihood that lymphocytes interact with their target antigens

16
Q

Describe how circulating lymphocytes can enter lymph nodes?

A

Circulating lymphocytes can enter lymph nodes through specialised blood vessels (High Endothelial Vessels)

HEVs are present in all secondary lymphoid tissue

17
Q

What happens to lymphocytes once they enter secondary lymphoid tissues via HEV?

A
  • Can potentially antigens presented by DC in the node

- Majority of lymphocytes do not meet their target antigens and exit via efferent lymphatic vessel

18
Q

Do DC capture antigens in the node?

A

DC may have captured the antigens in the tissue and migrated to the node via afferent lymphatics or captured the antigen in the node itself

19
Q

How do lymphocytes exit the circulation into tissue when they are needed?

A

IN a process called extravasation

20
Q

What are the two broad stages of extravasation?

A

Margination

Diapedesis

21
Q

What is the first step in leukocyte extravasation?

1/4

A

Infection or trauma causes localised release of inflammatory cytokines

  • TNFa, IL1
22
Q

What is the second step in leukocyte extravasation?

2/4

A

TNFa and IL1 activate local venous endothelial cells

These upregulate expression and activating cell surface proteins such as selectins and intracellular adhesion molecules (ICAMS)

23
Q

What is the third step in leukocyte extravasation?

3/4

A

Tethering-rolling of leukocytes in the blood is mediated by interactions between activated selectins and cell surface glycoproteins

As these are weak they only slow the leukocytes

24
Q

What is the final step in leukocyte extravasation?

4/4

A

During rolling, integrins are activated in the leukocyte and the endothelial cells that allow it to bind to ICAMS

These interactions are strong enough to cause arrest and flattening of the leukocyte

The leukocyte then migrates between endothelial cell junctions in the issue (diapedesis)

25
Q

Describe selectin binding:

A

Selectins- mediate weak binding between cells.

They bind to glycoproteins with sialylated carbohydrate groups

26
Q

Give example 1/2 of selectins;

A

I.e L-Selectin on leukocytes binds to glycosylation-dependant cellular adhesion molecule 1 (GlyCAM-1) on endothelial cells

27
Q

What is the function of integrins?

A

Mediate strong binding between cells. Are expressed on leukocytes and endothelial cells. They bind to immunoglobulin superfamily molecules.

28
Q

Give example 1/2 of integrins;

A

I.e Lymphocyte function-associated antigen 1 (LFA-1) is an integrin that binds to ICAM-1 , ICAM-2, ICAM-3

29
Q

Give example 2/2 of integrins;

A

I.e Lymphocyte payers patches adhesion molecule 1 (LPAM-1) is an integrin that binds to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on HEVs

30
Q

Give example 1/2 of selectins

A

i.e E-Selectin on endothelial cells binds to E-Selectin Ligand One (ESL-1) on neutrophils

31
Q

What is lymphocyte homing?

A

Different types of lymphocytes display tissue specific recirculation through lymphoid tissues.

32
Q

Describe B lymphocyte homing;

A

B cells tend to enter mucosa associated lymphoid tissues better than t cells

33
Q

Describe naive t cell homing;

A

Naive t cells enter into lymph nodes better than effector and memory t cells

34
Q

What does lymphocyte homing do?

A

Lymphocyte homing ensures that the correct population of lymphocytes are present at various sites in the body.

35
Q

How is homing achieved?

A

Homing is achieved due to the differential expression of various cell surface molecules on lymphocytes (homing receptors) and on the endothelial cells of HEVs in different lymphoid tissues (vascular adhesion)