Lec 12: Primary and secondary lymphoid organs Flashcards
What is more important, B cell or T cells?
T cells
these drive and coordiante the immune response
can you survive without either B or T cells? What would be the consequeces?
nopeee youd be bubble boy
Primary lymphoid organs
Thymus= development
and the bone marrow
where the immune cells develop
secondary lymphoid organs
spleen
lymph nodes= activation
= tonsils, adenoids, etc…
wher the adaptive immune responses are initiated
Tertiary lymphoid tissue
site of active infection and or immune activity
de novo lymphoid organs at the site of infection
Immune cell trafficing
know where the cells develop, where they further develop and which organs they develop in
CLPs and the Bone Marrow
required for B cell development
seat of hematopiesis
HSCs =hematopoietic stem cells
stromal cells= support HSCs
Osteoblasts = bone formation and control HSCs
endotheliad cells = line the blood vessel and regulate HSC differentiation
Reticular cells = connect bone and vessels
sympathetic neuron = control the release of HSCs form the bone marrow (central nervous system cross talk)
What is one reason that hematopoeisis decreases with age
with age, fat cells replace 50% of the bone marrow
B lymphocytes develop in the bone marrow
Cytokines involved in B cell differentiation
chemokine CXCL12 is essential for the generation of pre-pro-b and pro-b cells
Il-7 is essential for the generation of pro-B and pre-b cell differentaion
CXCL12 is also involved in homing antibody producing plasma cells to the bone marrow
-> plasma cells take up long-term residence inteh bone marrow and produce ig from within the bone marrow
Development of B cells from the bone marrow to the periphery
HSCs begin their life in close contact with osteoblasts. Once they differentiate into pre-pro-B cells they get the CXCL12 signal from stromal cells as well as a the secretion of IL7 from another stromal cell subset.
rearrangement of the immunoglobulin locus results in pre-BcR receptor and finally a mature BcR
at immature stage, selceiton process to eliminate self ractive B cells
The B cells then mature into follicular B cells (aka marginal zone b cells) in lymph nodes and the spleen
activate antigen specific B cells develop into either plasma cells (anti-body secreting) or memory B cells
negative selection of B cells in movement fromt he bone marrow to the periphery
selection process are in place to kill self-reactive B cell (by apoptosis in the bone marrow)
Thymus
T cells develop initially in the bone marrow but then migrate to the thymus to achieve full maturity
T cell Trafficking in the thymus
circulating T cell progenitors enter vi athe vasculature in teh corticory-medullary junction
CD4-CD8 double negative (DN) thymocytes migrate inot the capsule due to CXCR4 and CCR7 mediated chemotaxis
migration into the subcapsular zone mediated by CCR9 signals (deeper and deeper into the tissue)
CD4+CD8+ double positive (DP) thymocytes interact with cortical thymic epithliad cells (cTEC) for positive and negative selection
Positively selected DP tymocytes differentiate inot CD4+ or CD8+ single positive cells (SP) increased CCR7+ allows for migration towrds the medulla expressing CCR7 ligands
Further selection of SP thymocytes includes the deltion of tissue specific antigen-reactive T cells and the generation of regulatory T cells
matrue SP T cells expression sphingosine-1-phosphate receptor 1 (S1P1) guiding them to the circulation
Purpose of cTEC
these are cortical thymic epithelial cells
they aid in positive and negative selection of T lymphocytes
the are APCs that present self-antigens and will kill T-cells if they react to those self-antigens
corticor-medullary junction
where the circulating T cell progenitors enter the thymus
What cytokine induces double-negative T cells to migrate in the capsule
CXCR4 and CCR7 mediated chemotaxis
what is a double negative T cell
Lacks CD4 and CD8
What cytokine triggers DN T cells to migrate into the subcapsular zone
CCR9