Lymphatic System, Antibodies and Class Switching

Question 1

Lymphoid organs?

Answer 1

Primary lymphoid tissues - thymus and bone marrow, antigen independent development

Secondary - MALT, spleen, lymph nodes

Question 2

Lymphoid vessels?

Answer 2

Like blood vessels, connect body tissues to lymph nodes
Hold lymph fluid, lymphocytes and tissue-derived DCs
Pressure regulated by tissue drainage, as no pumps

Question 3

Lymphocyte activation

Answer 3

Free antigen and antigen-presenting DCs drain thorugh lymph to lymph nodes, where B and T cells are exposed to the antigen and activate

Question 4

Lymph node regions

Answer 4

Cortex with follicles - affinity maturation site, B cells localise and differentiate to plasma cells
Paracortex - T cells
Medulla - plasma cells, some T cells and macrophages
Secondary follicle - B cells proliferate in infection, these are transient structures only present during this time for this purpose

Question 5

MALTs?

Answer 5

Mucosal-associated lymphatic tissue

Made up of gut-associated, nasal and bronchal tissues

Question 6

Peyer’s patch?

Answer 6

In GALT - have no afferent lymphatic vessels, but are directly beneath the epithelium so antigens enter directly
Can produce IgA outside of infection for gut health

Question 7

The spleen?

Answer 7

Also no afferent lymphatics, filter antigens from blood via arteriole transport through red pulp
Response to blood-borne pathogens

Question 8

Red/white pulp?

Answer 8

Red - filters old RBCs
White - immune function
Filter to periarteriole lymphoid sheath

Question 9

Naive lymphocyte entry?

Answer 9

Enter nodes through high endothelial venules (HEV) from bloodstream

Question 10

Lymphocyte adhesion molecules?

Answer 10

Help control migration
Lectins e.g. selectins
Ig superfamily
Integrins (dimers, alpha and beta chains)
CR3s
ICAMs - intracellular adhesion molecules
etc

Question 11

Migration of immune cells across endothelium

Answer 11

1. selectin driven rolling
2. firm attachment
3. extravasation

Question 12

Selectin driven rolling?

Answer 12

P-selectin induced on vessels by infection, which recognise sulphated sialyl-Lewis X structures
This slows down the immune cells where selectin is expressed

Question 13

Firm attachment?

Answer 13

ICAM 1 and 2 induced on vessels
Bind LFA-1 and CR£ on leukocytes
This stops the rolling motion for firm attachment

Question 14

Extravasation?

Answer 14

Leukocytes cross endothelial wall through tight junctions with LFA-1 and CR3
Also known as diapedesis
Aided by other interactions e.g. with CD31

Question 15

Role of chemokines in lymphocyte migration?

Answer 15

CXCL8 (IL8) and CCL2 produced at infection site
IL8 recruits neutrophils and mobilises naive T cells, CCL2 attracts monocytes in epithelial and stromal cells

Chemokine gradient dictates movement

Question 16

High endothelial venules?

Answer 16

Where width of lymphatic tissue increases so pressure drops = slower movement = better binding

Question 17

Naive T cell movement in MEVs?

Answer 17

Uses L-selectin (CDL62L) on naive T cells, plus P and E selectin on endothelial cells

CDL62L downregulated in activated T cells, so they move to infection sites instead

Question 18

Plasma cells?

Answer 18

‘cartwheel’ nucleus with lots of heterochromatin

Extensive RER and golgi for protein production

Question 19

When are plasma cells formed?

Answer 19

B cells that leave the bone marrow cannot secrete antibody, so must become plasma cells

Question 20

Activation of plasma cells?

Answer 20

Requires 2 signals - Ig membrane specific molecule recognition. and T cell helpers

Question 21

T-cell independent plasma activation?

Answer 21

Can occur if antigen is strong enough, but the antibody will be weak with reduced affinity

Question 22

Antigen-B cell interactions?

Answer 22

In lymph nodes and secondary antigens
Free antigen collected in marginal outer zone by macrophages, where naive B cells circultae
Cross-linking of BCRs (Ig) must occur for activation

Activated B cell migrates to cortex and paracortex

Question 23

B and T cell interactions?

Answer 23

Activated B cells at paracortex encounter CD4+ T cells, activated by MHCII DCs

Helper T cells interact with CD40 and MHCII on B cells

Directional interaction - cytoskeleton components re-orientate towards B cell

IL-4 released in the gap between cells

Question 24

Primary foci?

Answer 24

Where B and T cells merge, forming primary foci in the medullary cords for initial proliferation
Some cells migrate to the primary follicle to form germinal centres

Question 25

What signals clonal expansion of B cells?

Answer 25

Co-stimulaotry molecyles e.g. CD154/40L on T cells, CD40 on B
Cytokines from TfH cells

Question 26

Plasmablasts?

Answer 26

B cells that secrete IgM, non-specific and do not undergo affinity maturation

Question 27

Follicular dendritic cells?

Answer 27

Antigen-presenting, network in follicles to hold antigen/antibody complexes in iccosomes on their surface
Iccosomes internalised by B cells that recognise the antigens
Lead to germinal centres

Question 28

Germinal centres?

Answer 28

Where B activated B cells differentiate, and undergo affinity maturation

B cell entry = centroblast formation, where surface Ig of B cells goes down
(affinity maturation occurs during this)
Centroblasts then divide - H and L Ig chains hypermutate
Centrocyte formation - re-expression of surface Ig

Question 29

Centrocyte selection in germinal centres? (affinity maturation)

Answer 29

Interaction with FDCs expressing antigen - if affinity of binding is high enough, survival signals are released
Centrocytes compete for the antigens so only highest affinity survive

Question 30

Class switching in B cells?

Answer 30

Occurs during centroblast/centrocyte stage i.e. a second differentiation

Heavy chain constant region switches from IgM to IgG/A or E

Question 31

What controls class switching in B cells?

Answer 31

CD4+ Th - need CD40/CD40L interactions for anything other than IgM
Cytokines (e.g. IL4 - IgE)

Question 32

Plasma cells and memory cells?

Answer 32

Skips 4-6 days on Ig response, as no need for class switching or affinity maturation

Produced in apical light zone in germinal centres

Question 33

Production of memory cells?

Answer 33

Unclear
Thought to be:
CD154 on Tfh binds CD40 on B cells
Exit lymph nodes – circulation

Question 34

Localisation of memory cells?

Answer 34

Short/long-lived
Might stay in nodes/spleen, secreted over a few weeks
May migrate to bone marrow - months