4.2 - Lymphoid tissues

Question 1

Lymphatic system and lymphoid tissue

Answer 1

Lymphatic system is comprised of:

1) lymphatic vessels
2) secondary lymphoid tissue

Lymphoid tissue is comprised of:

1) primary
2) secondary
3) tertiary

Question 2

Primary lymphoid tissue

Answer 2

• primary lymphoid organs are where lymphocytes are produced - lymphopoiesis
• lymphocytes: B cells, T cells, natural killer cells
• examples: thymus (T cell development), bone marrow (B cell development), foetal liver (foetus)

Question 3

Lymphocytes and adaptive immunity

Answer 3

• B and T cells comprise the adaptive immune response

Hallmarks of the adaptive immune system:

• specificity - provided by a vast range of unique T and B cell receptors
• memory - rapid expansion in response to secondary encounter

Question 4

Bone marrow

Answer 4

• primary site of haematopoiesis
• the B cell repertoire is generated in the bone marrow (maturation begins in the bone marrow)
• final maturation occurs in the periphery
• repertoire - the range of genetically distinct BCRs or TCRs present in a given host - the larger the repertoire, the more threats can be recognised

Question 5

Thymus

Answer 5

• immature T cells migrate from the bone marrow to the thymus (thymocytes)
• stepwise differentiation
• positive selection - selects functional T cells with TCRs that are signalling correctly
• negative selection - removes dysfunctional T cells that cause autoimmune disorders (react against healthy cells by recognising them as non-self)
• final selection and exit
• thymic involution = the shrinking of the thymus with age - thymus output declines with age - generation of T cells with new antigen receptors decreases. Associated with a change in structure and reduced mass

Question 6

Secondary lymphoid tissue

Answer 6

• our TCR and BCR repertoires vastly outnumber the number of T and B cells present in our bodies, so we need a specialised set of lymphoid tissues and vessels to allow rapid migration of these cells around our bodies and facilitate interactions with foreign antigens
• secondary lymphoid organs are where lymphocytes can interact with antigens and other lymphocytes
• allows T and B cells to be activated
• examples - PALMS: Peyer’s patches, appendix, lymph nodes, mucosal associated lymphoid tissue, spleen
• distributed around the body at strategic sites, especially at barrier surfaces e.g. lungs, GI tract and skin - especially prone to exposure to foreign antigens
• germinal centres - sites where antibody selection and maturation occur
• interconnected via a lymphatic system and the blood
• can be discrete organs (e.g. lymph nodes/adenoids) or distinct regions (e.g. spleen)
• generally highly organised structures
• brings cells in close proximity to antigen

Question 7

Lymph nodes

Answer 7

• distinct T and B cell zones
• afferent (in) and efferent (out) vessels to transport lymph
• arterial and venous connection

Question 8

Spleen

Answer 8

• distinct T and B cell zones
• afferent (in) and efferent (out) vessels to transport lymph
• arterial and venous connection
• red pulp, and white pulp (which contains lymphoid tissues)
• highly connected to blood - surveys circulation for foreign antigens and filters them out
• connection to splenic artery

Question 9

Epithelial barriers

Answer 9

• first line of defence against infection
• physical barrier
• extensive lymphatic network –> rapid response
• single cell epithelium

Question 10

Gut associated lymphoid tissue

Answer 10

• specialised secondary lymphoid tissues called Peyer’s patches
• found below the epithelium of the ileum of the small intestine
• drains from gut’s epithelial barrier to secondary lymphoid tissue
• rich in T and B cells
• the follicle is highly enriched B cells and contains a high frequency of germinal centres (anatomically restricted site where B cells undergo mutation and selection to generate high affinity antibodies)

Question 11

Tonsils

Answer 11

• pharyngeal, tubular, palantine and lingual tonsils encircle the oral and nasal cavity - form the Waldeyer ring
• continually exposed to foreign antigens
• tonsils are an important store of T and B cells, but they are still able to be removed since T and B cells can leave the tonsils

Question 12

How do lymphocytes enter secondary lymphoid organs?

Answer 12

• fluid drained from between tissue cells are absorbed into lymph
• 2-3 litres of lymph are returned to the blood each day via superior vena cava
• secondary lymphoid organs are connected to the circulation and the lymphatics
• lymphocytes circulate through the blood and lymph (SLOs connected to both = easy access) - each naive T cells recirculates once every 24 hours if they haven’t encountered an antigen
• extravasation (leakage) of naive T cells into lymph nodes - T cell rolls along endothelium, activated, adhesion, transendothelial migration into lymph node - via the high endothelial venule (naive lymphocytes from circulation –> secondary lymphoid tissue)

Question 13

How do antigens migrate to secondary lymphoid organs?

Answer 13

• dendritic cells - professional antigen presenting cells (display of peptides in the MHC I or II proteins such that the TCR can attempt to bind to them)
• range of migratory and tissue resident variety
• dendritic cells take up antigens and migrate to lymph nodes
• antigens traffic to the lymph node - dendritic cells migrate via the afferent lymphatic vessel into lymph nodes and present antigen to T cells
• regular flow of immune cells and fluid increasing chance of interactions