L02: Architecture and Haematopoiesis

Question 1

Lymphatic system composition and purposes (3)

Answer 1

1. Lymph vessels: drainage
2. Lymph nodes: filtration and defence
3. Lymph organs: filtration and defence

Question 2

Lymph composition (3)

Answer 2

1. Intercellular/interstitial fluid
2. Proteins
3. Particles (subcellular debris, pathogens and cancer cells)

Question 3

Lymphatic vessels

Answer 3

Drainage function. Lymph transport is slow in vessels and is maintained by skeletal muscle contractions. It is a one-way fluid flow to heart because lymphatic valves prevent back flow.

Question 4

Lymphatic system

Answer 4

Lymph vessels collect fluid, filtred through lymph nodes, drain into lymph ducts and returned to venous system through thoracic duct to the heart

Question 5

Lymphedema

Answer 5

Blockage of lymphatic drainage resulting in swollen limbs. Uncontrolled infections may develop. Lymphedema is caused by tissue scarring, surgery (e.g. breast cancer) and parasitic infection (e.g. elephantitis)

Question 6

Lymphocyte recirculation

Answer 6

Lymphocytes recirculate from blood to the lymph and back again. They recirculate from the bloodstream into the lymph via lymph nodes. Found in both lymphatic and cardiovascular system as they are interconnected. Postcapillary venules in lymphoid organs are composed of cuboidal high endothelial venules HEV) which are sites of lymphocyte extravasation. These cells express a variety of cell adhesion molecules - homing receptors to bind to endothelium.
Naive lymphocytes constantly recirculate, enter lymph nodes from blood. During an infection, Ag is taken up by dendritic cells taken to draining lymph node. In the LN, DCs display Ag to T cells while B cells are activated. Once T and B cells have undergone proliferation and differentiation period, they leave the LN as effector cells via efferent lymphatic vessel which drains into the thoracic duct and into bloodstream.

Question 7

Lymphoid organs

Answer 7

Lymphoid organs are organised tissues containing large numbers of lymphocytes in a framework of nonlymphoid cells. Divided into central (primary) or peripheral (secondary)

Question 8

Lymphoid and nonlymphoid cell interaction importance

Answer 8

Interactions important for lymphocyte development, initiation of the adaptive immune response, and lymphocyte sustenance

Question 9

Primary lymphoid organs

Answer 9

Location of where immune cells develop. Lymphocytes arise from stem cells in the bone marrow and differentiate in the central lymphoid organs (B cells in bone marrow, T cells in thymus)

Question 10

Thymus

Answer 10

Bi-lobed structure where maturation of T cells occurs, differs from other lymphoid organs because it doesn’t directly fight antigens and reaches maximum size at puberty then atrophies. Made up of several lobules consisting of cortex (outer layer) and medulla (inner layer)

Question 11

Cortex (outer layer)

Answer 11

Immature thymocytes closely associated with branched cortical epithelial cells and scattered macrophages. Immature proliferating thymocytes on outer cortex parts and immature T cells undergoing thymic selection on inner cortex areas

Question 12

Medulla (inner layer)

Answer 12

Mature thymocytes, medullary epithelial cells, macrophages and dendritic cells. In the medulla Hassall’s corpuscles are sites of cell destruction

Question 13

Peripheral lymphoid organs

Answer 13

Sites of lymphocyte activation. Lymph carries the antigen to the lymph nodes and recirculating lymphocytes from lymph nodes back into the blood.

Question 14

Lymph Node

Answer 14

Functions as a filter and active in immune response. Composed of outer fibrous capsule, cortex (B & T cells) and medulla (macrophages and B cells). Located at the points of convergence of the lymphatics system which collects extracellular fluid from the tissues and returns it to the blood.

Question 15

Lymph Node - Cortex

Answer 15

Contains lymphoid follicles containing B cells. During an immune response, these contain central areas of intense B cell proliferation and are called germinal centres

Question 16

Lymph Node - Paracortex

Answer 16

Area of diffuse T cells

Question 17

Lymph Node - Medulla

Answer 17

Medullary cords - macrophages and plasma cells

Question 18

Afferent lymphatics

Answer 18

Drain fluid from the tissues, carry Ags and phagocytic cells to LNs where they are trapped

Question 19

Efferent lymphataics

Answer 19

Exit of lymph and lymphocytes

Question 20

Spleen

Answer 20

Fist-sized organ behind stomach, collects Ag from blood and senescent RBCs. Red pulp is the site of RBC disposal and white pulp is site of lymphoid areas.
Periarteriolar lymphoid sheath (PALS): mainly T cells
Germinal centre: B cells plus dendritic cells/macrophages

Question 21

Gut-associated lymphoid tissues (GALT)

Answer 21

Comprised of tonsils, adenoids, appendix, peyer’s patches. Functions to collect Ag from the epithelial surfaces of the GIT. Highly dynamic structures: B cell follicles expand as germinal centres are formed, swelling the glands.

Question 22

Peyer’s Patches

Answer 22

Most important and organised GALT. Ag is collected by sepcialised epithelial cells - multifenestrated or M cells. Most of the tissue is B cells organised into a large, highly active domed follicle. T cells occupy areas between the follicles. Ag enters across a specialised epithelium of M cells.

Question 23

Lympho-haematopoietic system

Answer 23

In the embryo, Haematopoietic cells are generated at specific anatomical sites, first identified stem cells arise in blood islands of the yolk sac which migrate to foetal liver. At birth, cells migrate to colonise developing bones and establish haematopoietic lineages in bone marrow, and thymus.

Question 24

Stem Cells

Answer 24

All mature blood cells are derived from stem cells. Have the ability to self-renew. Majority are mature post-mitotic end cells and so in addition to proliferation, extensive amplification of various compartments must occur. Achieved via generation and subsequent proliferation of committed Progenitor Cells.

Question 25

Stem cell antigen (Sca-1)

Answer 25

Stem cells display a specific antigen on their cell surface, aiding identification and purification (Sca-1). CD34 is also found on stem cells and used in humans also.

Question 26

Regulating haematopoiesis (4)

Answer 26

Cytokines and growth factors
1. T cells: IL-2, 7, 12, 15
2. B cells: IL-3, 5, 6
3. Myeloid: IL-3, 6, GM-CSF, CSF-1
4. Erythroid: EPO, IL-3, GM-CSF
Haematopoietin family: IL-2, 3, 5, 7, GM-CSF, CSF-1 and EPO

Question 27

Colony stimulating factors

Answer 27

Stimulates committed particular lineages, many factors produced by stromal cells. Receptors for these factors form part of the haemopoietin receptor superfamily.

Question 28

Cytokine receptors: Class 1 (hematopoietin-receptor family)

Answer 28

alpha/beta chain: receptors for erythropoietin, GH and IL-13
beta chain/CD131: receptors for IL-3, IL-5 and GM-CSF,
gamma chain/CD132: receptors for IL-2, 4, 7, 9, 15

Question 29

Cytokine Receptor Signal Transduction (4)

Answer 29

1. Dimerisation of the receptor activates family of tyrosine kinases called JAK
2. JAK kinases phosphorylate receptor and STAT proteins (Signal transducers and transcription activators)
3. Upon phosphorylation, STAT proteins undergo dimerisation and translocate from the plasma membrane to the nucleus
4. In the nucleus STATS act as transcription factors, initiates gene transcription