Lymphoid Tissues

Question 1

What are the hallmarks of adaptive immunity?

Answer 1

Specificity and Memory - Can identify and respond to specific threats + remember previous encounters for a prolonged period, providing rapid protection to subsequent exposures, at any site in our bodies.

Question 2

What are characteristics of proteins expressed on the membrane of each individual T/B-cell?

Answer 2

1. Can only express a single unique TCR/BCR
2. Each individual T or B cell produced has the ability to express only a single TCR or BCR that is unique, both in the genetic sequence that encodes it and the antigen it can recognise.

Question 3

How is diversity in B-cell variable region created?

Answer 3

While still at the B-cell progenitor stage in the bone marrow, B cells randomly rearrange their variable (V), diversity (D), and joining (J) genes to form the blueprint for the variable regions of their antibodies. There are multiple copies of the V, D and J genes that can be joined together in different combinations. In a majority of mammals, each antibody molecule is composed of both a heavy and light chain, which each have their own V and J genes to rearrange (only the heavy chain has D genes). Further diversity is added to the variable region genes by an enzyme called terminal deoxynucleotidyl transferase (TdT) that adds extra nucleotides between the V, D and J regions, changing the structure of the variable regions that will be produced.

Question 4

How is further specifity produced by B-cells when they meets an antigen that it recognises?

Answer 4

B cell can undergo a process called somatic hypermutation. Here an enzyme called activation-induced cytidine deaminase (AID) makes random mutations in the antibody variable region genes. If the mutations result in an antibody that more strongly binds to their targets then these B cells will survive and may differentiate into antibody-producing plasma cells with the new specificity.

Question 5

How do T-cells create diversity in their variable region?

Answer 5

The T cell receptor genes e.g. TCRA and TCRB which encode the heterodimeric TCRαβ that the majority of T cells in the body express, use a similar process to create diversity

Question 6

What is primary lymphoid tissue?

Answer 6

Where lymphocytes are produced; Lymphopoiesis

E.g. Thymus, Bone Marrow, Foetal Liver

Question 7

Name lymphocytes and what response they are involved in?

Answer 7

Lymphocytes: B-cells, T-cells and NK cells. Former two comprise adaptive immune response while latter is non-specific response.

Question 8

Where does haematopoeisis occur?

Answer 8

In foetus: haematopoiesis occurs in all bones, liver and spleen. The marrow is very cellular.
In adults: haematopoiesis occurs mostly in flat bones, vertebrae, iliac bones, ribs, and ends of long limb bones.

Question 9

Where are B-cells made? Define repertoire.

Answer 9

The B cell “repertoire” is generated in the bone marrow but final maturation occurs in the periphery. Repertoire is the range of genetically distinct BCRs or TCRs present in a given host – with larger the repertoire the more threats can be recognized.

Question 10

How are T-cells made?

Answer 10

Immature T cells migrate from the bone marrow to the thymus as thymocytes. First, undergo positive selection where whether cell can signal is tested. If it can signal, cell then undergoes negative selection to test if cell reacts against self cells. If not, finally selected and exits the thymus.

Question 11

What is thymic involution?

Answer 11

The shrinking of the thymus with age. Associated with a change in structure and a reduced mass.

Question 12

What is the need for secondary lymphoid tissue?

Answer 12

Blood contains approximately 2% of total pool of T-cells and hence there are 3.75x10^11 different T-cells in the body. Thus how does a small population of cells, initially only one, find the foreign protein/antigen.

Question 13

What is the purpose of the secondary lymphoid tissue and where is it found?

Answer 13

Secondary lymphoid organs are where lymphocytes can interact with antigens and other lymphocytes. E.g. Spleen, lymph nodes, appendix, mucosal associated lymphoid tissue (MALT)

Question 14

What are the secondary lymphoid tissues?

Answer 14

Lymph nodes (LNs), Spleen, Peyer’s patches (PPs) and mucosal tissues- the nasal associated lymphoid tissue (NALT), adenoids, and tonsils. Distributed around the body Interconnected via the lymphatic system and the blood. Can be discrete organs (e.g. lymph nodes /adenoids) or distinct regions within a tissue (e.g. spleen). Highly organised and bring cells in close proximity to antigens.

Question 15

What are the properties of the lymph nodes and spleen?

Answer 15

Distinct T and B cell zones, Afferent (in) and efferent (out) lymph, Arterial and venous connection.

Question 16

What are the properties of epithelial barriers?

Answer 16

First line of defence against infection, Physical barrier, Extensive lymphatic network

Question 17

What is gut-associated lymphoid tissue and what are its properties?

Answer 17

Specialized secondary lymphoid tissues called Peyer’s patches. Found below the epithelium of the ileum of the small intestine. The follicle is highly enriched with B cells, and contains a high frequency of germinal centres.

Germinal centre: anatomically restricted site where B cells undergo mutation and selection to generate high affinity antibodies (affinity maturation)

Question 18

Where are the tonsils found?

Answer 18

Pharyngeal, tubular, palantine and lingual tonsils encircle the oral and nasal cavity – form the Waldeyer ring

Question 19

How do B-cells, T-cells and antigens in the blood get to SLOs?

Answer 19

Fluid drained from between tissue cells absorbed into lymph. 2 to 3 litres of lymph are returned to the blood each day (via superior vena cava).

Question 20

Describe cycle of T-cells moving through circulation and lymph

Answer 20

A naive T-cell passes into a lymph node without an antigen through a high endothelial venule from a blood vessel. It then moves between lymph nodes via an efferent lymphatic vessel and should it find a lymph node with an antigen, the T-cell is then activated. It then travels through an efferent lymphatic vessel into the thoracic duct, finally drained into the vena cava and reaches the bloodstream. The activated T-cell then circulates in peripheral blood vessels until site of damage/pathogen found. Eventually passes back into the lymphatic system via an afferent lymphatic vessel.

Question 21

Describe extravasation of T-cells into lymph nodes

Answer 21

1. Rolling - T-cell’s L-selectin binds to CD34 on epithelial cell surface of lymph node and rolls on PNAd.
2. Activation - chemokine binding occurs. Last stage of selectin binding.
3. Arrest/Adhesion - LFA-1 on T-cell binds to ICAM-1
4. Transmigration - Last stage of integrin binding where T-cell migrates into high endothelial venule

Question 22

What is antigen presentation and which cell does it?

Answer 22

Antigen presentation is the display of peptides in the major histocompatibility complex I or II proteins such that the T cell receptor can attempt to bind them. Dendritic cells are professional antigen-presenting cells and are of migratory and tissue-resident varieties.