Lecture 8 Flashcards
Primary Lymphoid Organs
Sites of Immune Cell Development
1. Bone Marrow: genesis of all immune cells
a. B-Cell maturation
2. Thymus:
b. T-Cell maturation
Secondary Lymphoid Organs
Sites where Adaptive Immune Cells are activated and initiate function (mature-naïve to activated)
1. Spleen: filters the blood
2. Lymph Nodes: keeps from going systemic
3. MALTs: screen lymphatic tissue
Tertiary Lymphoid Organs
- Peripheral sites with persistent infection
- Immune cells take up residence
Vascular and Lymphatic Vessels
- Connect the Immune system
- Vascular System: deliver immune cells throughout the body
- Lymphatic System: drain peripheral tissue effluent through lymph nodes; return to blood
Bone Marrow
Bones with greatest level of RBC/WBC synthesis
1. ileum: hip
2. femur: leg
3. sternum: chest
4. humerus: arm
Bone Marrow
Specialized environment that promotes the homing, proliferation, and differentiation of hematopoietic stem cells
Developmental Niches (Cues from Four Cell Types in Bone)
- Osteoblasts: generate bone matrix
a. signal and moderate HSC differentiation - Endothelial Cells: line vascular spaces
a. signal and moderate HSC differentiation - Perivascular and Reticular Cells: cellular processes bridge bone to blood vessels
a. signal and moderate HSC differentiation - Sympathetic Neurons: moderate release of hemopoietic cells from marrow
Hematopoietic Stem Cells (HSC)
Give rise to all cell types in the immune system
Endosteal Niche
Leukocyte precursors are sequestered prior to development
Osteoblasts
Interact with stem cells to promote quiescence
Vascular Niche
HSCs Induced to proliferate and differentiate
Reticular Cells
Cellular ‘Mesh’; traffic HSCs between sites
Bone Marrow
Immature lymphocytes
Thymus
Thymocytes
Thymus
Mature Naïve T-Cells
2o Lymphoid Organs
Mature Naïve T-Cells
Thymus Cortex
Site of Thymocyte proliferation and selection
Thymus Medulla
Reserve of Mature (Naïve) T-Cells
T-Cell Development, Differentiation, and Selection
- Immature lymphocytes are delivered to the subcapsular cortex (thymocytes)
- Thymocytes are induced to undergo proliferation
- Thymocytes develop T-Cell receptors on their surface
T-Cell Development, Differentiation, and Selection
- Thymocytes interact with the stromal epithelial reticular cells
- Thymocytes migrate toward the medulla while undergoing selection
- Functional but NOT ‘self-reactive’ thymocytes are selected to be mature T-cells
- Mature T-Cells reside in the medulla
- Cytokines signal for their medullary release and migration into the vasculature
DN
Double-negative cells
DP
Double-positive cells
SP
Single-positive cells
Negative Selection
Thymocytes bind with too high an affinity to stromal cells expressing MHC: Self-Antigen Complexes