Primary and Secondary Lymphoid Organs Flashcards
What are the primary lymphoid organs? (PLOs) What is their function?
Bone marrow and thymus.
Development of the immune cells.
What are the secondary lymphoid organs?
Where adaptive immune responses are initiated like…
Spleen, lymph nodes, tonsilds, adenoids, bronchus, Peyer’s patches, etc.
Describe how a T/B cell would get from the bone marrow to the secondary lymphoid organs? (SLOs)
T cell precursor would go from the bone marrow to the blood vessel to the thymus to differentiate then it would go back to the blood vessels to recirculate and head to the target area.
B cells leave the bone marrow and circulate in the blood until they get to their target.
Briefly describe the function of the bone marrow. What happens with age?
It is the seat of hematopoiesis. With age fat replaces 50% of the bone marrow.
What is the function of... Stromal cells? Osteoblasts? Endothelial cells? Reticular cells? Sympathetic neurons
Support HSCs
Bone formation and control HSCs
Line blood vessel and regulate HSC differentiation
Connect bone and vessels
Control the release of HSCs from bone marrow
Where do B lymphocytes develop?
Where do T cells develop?
Bone marrow.
In the Thymus
B=bone marrow
T=Thymus
Briefly describe the cytokines involved in B cell differentiation.
Chemokine CXCL12 is essential for generating pre-pro-B and pro-B cells.
IL-7 is essential for cell differentiation.
CXCL12 is alo involved in homing Ab producing plasma cells to the bone marrow where they take up long term residence.
Briefly describe the B cell generation and differentiation.
Bone marrow:
- Pro-B cells have a straight rod for an Ig.
- Pre-B cells have an immature Ig due to rearrangement of Ig. Selection process to eliminate self-reactive B cells.
- Immature B cell has mature Ig/BcR.
Periphery:
- T1Bcell
- T2Bcell
- Mature B cell
- Mature B cells can differentiate into Pre-plasma/Plasma B cells or memory B cells by Ag activation.
Discuss, in detail, T cell trafficking and maturity in the thymus.
- Circulating pre-T cells enter cortico medullary junction
- Double negative (DN) T cells migrate to capsule via CXCR4 and CCR7
- Migration to subcapsular zone via CCR9
- Double positive (DP) T cells interact with cTEC for +/- selection
- Positively selected DP T cells become CD4/CD8 SP cells and CCR7 brings them towards medulla expressing CCR7 ligands.
- Further SP selection T cells includes deletion of tissue-specific Ag reactive T cells and generation of Tregs.
- Mature SP T cells express S1P1 and are guided into circulation leaving as naive T cells. Tregs also leave here to maintain tolerance.
What is cTEC?
Cortical thymus epithelial cells. APCs that present self Ag.
Describe T cell selection types and how they are expressed?
A positive selection is kept and is expressed by an affinity for the MHC.
Negative selection is when the DP has too strong an affinity for the MHC and the T cell is killed.
Death by neglect is when there is no interaction with the MHC and the T cell dies.
What is AIRE? What is its function? Where is it located.
AIRE is the autoimmune regulator and is a key transcription factor in the thymus. It expresses tissue restricted antigens in the medullary thymus epithelial cells (mTEC) that show the T cells other parts of ‘self’ without leaving the thymus so it will not self-react.
Describe SLOs.
How are SLOs connected?
Areas where lymphocytes encounter Ag, become activated, undergo clonal expansion, and differentiate into effector cells.
Connected via blood/lymphatic circulatory systems.
What are the chemokines responsible for T cell homing to the lymph nodes? For T cell return to circulation?
CCR7
S1PR1
What are HEVs?
How do T cells reach in HEVs?
High endothelial venules.
Rolling - sensing
Activation - via CCR7 and CCL21
Arrest - ICAM1