what are the secondary lymphoid organs and tissues? where are they located? | lymph nodes: throughout the body
spleen: underneath the left part of the diaphragm
mucosa-associated lymphoid tissue (MALT): throughout the body in submucosal sites; GI and respiratory tract, thyroid, breast, eye, skin |
what is the structure of a lymph node and which cells are present where? | cortex: outer layer containing mainly B cells in follicles
paracortex: middle layer containing mainly T cells and DCs
medulla: inner layer containing some B and T cells and plasma cells |
how does the lymph fluid flow? | into the lymph node -> subcapsular sinus -> cortical sinuses -> cortex -> medullary sinuses -> efferent lymph vessels -> out of the lymph node |
describe the structure of the spleen and where the lymphoid cells are located | the spleen consists out of trabecular arteries organized in a network of channels called sinusoids.
the spleen has red and white pulp;
red pulp: storage of red blood cells
white pulp: arterioles surrounded by lymphoid cells. T cells surround the arteriole in periarteriolar lymphoid sheaths (PALS) and B cells are located in follicles |
which cells are present in follicles? what happens in there? | naive B cells located in follicles
clonal expansion, proliferation and differentiation (isotype switching) takes place -> the naive B cells become plasma or memory cells |
which tissues/organs belong to MALT? | GALT -> gut (Peyer's patches, appendix)
BALT -> bronchus
NALT -> nasal (tonsils)
CALT -> conjunctival
LALT -> larynx
SALT -> skin
VALT -> vagina
TALT -> testis |
what are Peyer's patches, where are they located and what are they characterized by? | Peyer's patches are lymphoid follicles located in the small intestine. they are characterized by follicle-associated epithelium (FAE) and M cells |
what is the function of M cells and where are they located? | M cells or microfold cells are active in the GI tract.
their function is to bring microbes from the lumen to the lymphoid tissue in the epithelium. |
what is the function of regulatory T cells and how is this done? | to suppress the immune response to not harm commensal bacteria
this is done by;
- production of cytokines that inhibit activation of lymphocytes
- expressing CTLA-4 which block B7 molecules -> APCs cannot costimulate the T cells and T cells will not be activated
- binding to T cell growth factor, reducing the availability for the T cells |
what is the most important cytokine for the functioning of regulatory T cells? | IL-2 (also important is TNF-beta) |
what structures are present in the red and white pulp? | red pulp: sinusoids, splenic cords, marginal zone (which is the outer edge)
white pulp: malpighain corpuscles with B and T cells |
how do naive T cells migrate into the lymph nodes? | 1. rolling adhesion on high endothelial venules (HEVs) mediated by L-selectin
2. chemokines (CCL19, CCL21) from lymph node attach to CCR7 on the T cell
3. CCR7 activates leukocyte function-associated antigen 1 (LFA-1) on the T cell
4. binding affinity of LFA-1 to ligand ICAM-1 on endothelium is increased
5. firm binding
6. T cell exists the vessel through junctions into the lymph node |
how do T cells migrate out of the lymph nodes? | naive T cell: following the gradient of SIP into the lymph fluid
effector T cell: SIP receptor is reexpressed after differentiation, T cells loose L-selectin and CCR7 expression and follow the gradient of SIP into the lymph fluid |
how do effector T cells migrate to the site of infection? | 1. high levels of E- and P-selectin and integrins LFA-1 and VLA-4 are expressed on the T cell
2. the cytokine produced by the innate response (TNF, IL-1) act on endothelial cells to increase expression of E- and P-selectin and integrin ligands
3. rolling adhesion occurs
4. T cells express receptors for chemokines produced by the infection, this increases binding affinity and causes firm adhesion to the endothelium
5. T cells enter the tissue through the junctions
6. T cells follow chemokines to infection |
why are naive T cells unable to enter the site of infection? | they do not express E- and P-selectins or receptors that can bind the chemokines produced at an infection |
why can't effector T cells enter the lymph nodes? | they do not express CCR7 or L-selectin, which is needed for attachment of chemokines and rolling adhesion respectively |