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Cells and Organs of the Immune System Chapter 2

Cells and Organs of the Immune System Chapter 2. Hematopoiesis. HSC (Hematopoietic Stem Cell) Reside in Bone Marrow Pluripotent 1 HSC Per 50,000 BM Cells (~3x10 8 cells in Mouse Bone Marrow) Extremely Proliferative If Need Arises

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Cells and Organs of the Immune System Chapter 2

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  1. Cells and Organs of the Immune SystemChapter 2

  2. Hematopoiesis • HSC (Hematopoietic Stem Cell) • Reside in Bone Marrow • Pluripotent • 1 HSC Per 50,000 BM Cells (~3x108 cells in Mouse Bone Marrow) • Extremely Proliferative If Need Arises • HSC Differentiates to LPC (lymphoid progentor cell) or MSC (myeloid stem cell) • Growth Factors and Cytokines Determine Path • Once LPC or MSC, Committed • Stromal Cells Are Supporting Cells In BM (endothelial, fat cells, fibroblasts, macrophages)

  3. Hematopoietic Growth Factors • Colony Stimulating Factors • 4 types • Multi-CSF (IL-3) • M-CSF (Macrophage CSF) • G-CSF (Granulocyte CSF) • GM-CSF (Granulocyte Monocyte CSF) • EPO (erythropoietin) • Induces production of RBCs

  4. Cell Death • Orderly Self Destruction and Disorderly • Neutrophils (5.0 x 1010) Last For a Few Days • Aberrant Apoptosis Can Give Rise To Leukemia • Apoptosis (orderly) • Reduction In Cell Volume • Chromatin Condensation • DNA Degradation • M Ingest Membrane Bound Bodies • No Inflammation • Necrosis • Bursting of Cell Due To Injury • Contents Released To Environment • Inflammation

  5. Genes Regulating Apoptosis

  6. Detecting Apoptosis Using Flow Cytometry Ceramide Treatment Propidium Iodide Annexin V-FITC

  7. Cells of the Immune System • Lymphoid Cells • B-cells, T-cells and Null cells (NK cells) • 20-40% of body’s leukocytes • 99% of lymph node • If inactivated said to be naïve • Nucleus occupies almost entire cell • 6 m diameter

  8. Lymphoid Cells

  9. Lymphoid Cells

  10. Identifying Cell Using the CD Nomenclature • CD Cluster Of Differentiation • Over 300 CD Markers • T cells, CD4 or CD8 and CD3 • B cells, CD19 • NK cells, CD56 • Monocytes/Macrophages CD14 • Dendritic Cells, CD1c (Human), CD11c (mouse)

  11. Null Cells • Do Not Express Classical Lymphocyte Markers • Predominantly NK Cells (CD56) • Eliminate Tumor Cells and Virally Infected Cells • Express Low Affinity FcRIII (CD16) • Using CD16 They Can Carry Out ADCC • Reduction of MHC I Can Activate Them

  12. Mononuclear Cells Mononuclear Cells • Monocytes in Blood, M in Tissues • Monocytes 5-10 times smaller than M • M Increases Phagocytic Ability • Secretes cytokines and Produces Hydrolytic Enzymes • Named Based on Tissue They Reside • Alveolar (lungs), Kupffer (liver), Microglial (brain), Osteoclasts (bone) • Activated By Phagocytosis or Cytokines (IFN) • Antigen Presenting Capacity Thru MHC II

  13. Monocyte vs M

  14. M Effective APC

  15. M Capturing Bacteria

  16. Dendritic Cells • Professional APCs • Several Types • Langerhans (LC) found in skin • Circuilating DCs • Myeloid (MDC1 and MDC2) • Plasmacytoid • Interstitial DCs, populate organs such as heart, lungs, liver, intestines • Interdigitating DCs, T-cell areas of lymph nodes and Thymic medulla

  17. Dendritic Cells • Scarce Cell Type • Discovered in 1972 • Early 90s Using GM-CSF/IL4 and Later flt-3 limitation Was Overcome • Intense Area of Research • Seemed Promising for Tumor Treatment • Maybe Better for Tolerance

  18. http:www.coleypharma.com Dendritic Cells

  19. Developmental Pathway of DCs

  20. Follicular DCs • Do Not Express MHC II Molecules • Found in Lymph Follicles (Rich in B Cell) • Express FcR For Antibodies and Complement • Ag-Ab Complex Shown To Last Very Long (weeks to months)

  21. Organs Of Immune System • Primary Lymphoid Organs • Bone Marrow and Thymus • Maturation Site • Secondary Lymphoid Organs • Spleen, lymph nodes, • MALT (mucosal associated lymph tissue) • GALT (gut associated lymph tissue) • Trap antigen, APC, Lymphocyte Proliferation

  22. Thymus • Bilobed Organ on Top of Heart • Reaches Max. Size During Puberty • 70g infants, 3 g in adults • 95-99% Of T Cells Die in Thymus • self reactivity or no reactivity to Ag • Consists of Cortex and Medulla • Rat Thymocytes Sensitive to Glucorticoids

  23. Thymus

  24. Lymphatic System • Plasma From Blood Seeps Into Tissue • Interstitial Fluid Either Goes Back or Becomes Lymph • Lymph Enters Lymphatic Vessels • Thoracic Duct Is Largest Lymphatic Vessel Empties Into Left Subclavian Vein • Lymphatic Vessel Depends On Muscle Contractions For Movement • One Way Valves Ensure One Direction • Lymph Nodes Act As Filters For Antigens

  25. Lymphatic System

  26. Lymph Node

  27. Lymph Node • Multiple Afferent Lymphatics • Cortex • B-cells, Follicular DCs, M, GCs, Primary Follicles • Paracortex • TH, M, DCs • Medulla • Plasma Cells • Post Capillary Venule • Allow Lymphocyte Migration From Circuilation Into Lymph Node • One Efferent Lymphatic • Rich In Abs and Lymphocytes

  28. Mucosal Associated Lymphoid Tissue (MALT) • Mucous Membranes S.A=400m2 • Mucous Membr. Most Common Pathogen Entry Site • M.M Protected by MALT • Organization Varies (most organized P.P, Tonsils, appendix • GI Tract, IEL Unique  TCRs • Lamina Propia (below epithelium) M, B cells, TH • M Cell Allows Ag Entry, Unique Architecture

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