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Chapter 2: Hematopoiesis and Cells of the Immune System

This chapter explores the process of hematopoiesis, the regulation of gene expression in hematopoietic cells, and the different cell types involved in the immune system. It also delves into the functions of lymphocytes, including B cells, T cells, and Natural Killer cells, as well as other leukocytes like macrophages and granulocytes.

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Chapter 2: Hematopoiesis and Cells of the Immune System

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  1. Chapter 2 Cells and Organs of the Immune System Dr. Capers Immunology

  2. Hematopoiesis • All blood cells (erythrocytes and leukocytes) arise from Hematopoietic Stem Cells (HSC) • Study of these cells is difficult • Scarce • Difficult to grow in vitro • Can isolate using monoclonal antibodies and flow cytometry

  3. Hematopoiesis • Early in hematopoiesis, stem cell differentiates to either • Lymphoid progenitor cell • Myeloid progenitor cell • Progenitor cells have lost ability for self renewal and are committed to particular cell lineage (it is then a multi-step process to the production of one cell type) • Most complex stem cell system in the mammalian body

  4. Hematopoiesis • Regulated at gene level • Transcription factors play important roles in hematopoiesis • Studies using “knockout” mice • Gene inactivated, if RBC or a particular WBC fails to develop, it is concluded that protein was involved in development of that cell • Ikaros – transcription factor needed for lymphoid development • Notch – transcription factor needed for choice between B and T cell development • Notch signaling is evolutionary conserved pathway in multicellular organisms that regulates cell fate determination during development and maintains adult cell homeostasis

  5. Hematopoietic Homeostasis • Erythrocyte • Average life span: 120 days • Phagocytosed by macrophages in spleen • WBC - LEUKOCYTES • Life spans from 1 day to 20-30 years • Apoptosis – programmed cell death

  6. Normal WBC WBC going through apoptosis

  7. Watch this video on Apoptosis: • https://www.youtube.com/watch?v=-vmtK-bAC5E

  8. Cells of the Immune System • Lymphocytes • 20-40% of WBC • 3 populations • B cells • T cells • Natural Killer Cells

  9. Lymphocytes • B cells and T cells • Adaptive immunity • Small cells • Those that have not interacted with antigen are called naïve • Interaction with antigen – proliferation into effector cells (i.e. plasma cells) and memory cells

  10. Lymphocytes • Once they have encountered antigen that they are specific for, they will proliferate, making an army of B and T cells that are specific for that antigen • Plasma or effector cells • Plasma B cells – actively secrete antibody against the antigen • Effector T cells – actively search cells presenting the antigen they are specific for • Memory B and T cells – will now last for decades, watching for that same antigen to come back • What causes a cell to become a plasma or memory cell after activation is not yet known

  11. Lymphocytes • B and T cells

  12. Lymphocytes • B Lymphocytes (B cells) • Site of maturation • Bursa of fabriscus in birds • Bone marrow in mammals • Display membrane-bound immunoglobulin (antibody) • Once antigen is encountered: • Differentiation • Plasma cells – antibody can be secreted, die within 1-2 weeks • Memory B cells – same membrane-bound antibody as parent B cell, longer life span

  13. Lymphocytes • T Lymphocytes (T cells) • Site of maturation • Thymus • T cell receptor • Only recognize antigen that is bound to cell membrane proteins called major histocompatibility complex (MHC) • Once antigen in encountered with MHC: • Differentiation • Effector T cells • Memory T cells • 2 subpopulations • T helper (TH) • T cytotoxic (TC) • And now T regulatory (Treg)

  14. Lymphocytes • T helper cells • CD4 glycoprotein • Recognizes antigen presented in MHC Class II • “help” activation of B cells, TC cells, macrophages in immune response

  15. Lymphocytes • T cytotoxic cells • CD8 glycoprotein • Recognizes antigen presented in MHC Class I • Eliminates infected cells or cancerous cells

  16. Lymphocytes • T regulatory cells • CD4 and CD25 glycoproteins • Help suppress the immune system after it’s been upregulated, after the infection is cleared • It is thought that there are many other subpopulations of T celsl

  17. Lymphocytes • Natural Killer Cells • Innate immune response • Large, granular • Recognize tumor or virus-infected cells • CD16 – which can recognize a region of antibody that has attached to cell infected by virus

  18. Other Leukocytes • Mononuclear phagocytes • Monocytes circulate in blood and then migrate into tissue and differentiate into specific macrophage • Macrophages • Intestinal macrophages in gut • Alveolar macrophages in lung • Histiocytes in connective tissue • Kupffer cells in the liver • Mesangial cells in the kidney • Microglial cells in the brain • Osteoclasts in bone • Activated macrophages are more effective than resting ones

  19. Macrophage and bacteria

  20. Other Leukocytes • Granulocytes • Neutrophils • Eosinophils • Basophils

  21. Other Leukocytes • Granulocytes – Neutrophils • Multi-lobed nucleus, light granules • 1st to arrive at site of inflammation • High #’s is 1st indication of infection • Phagocytize • Generate antimicrobial agents • Neutrophils are very short lived when compared to macrophages • Come out of blood vessels ready to kill, would cause too much damage to tissues if long lived

  22. Other Leukocytes • Granulocytes – Eosinophils • Phagocytize • Play a role in parasitic organisms

  23. Other Leukocytes • Granulocytes – Basophils • Nonphagocytic • Play a role in allergic reactions

  24. Other Leukocytes • Mast cells • Play important role in development of allergies

  25. Other Leukocytes • Dendritic cells • Long membranous extensions, look like dendrites on nerve cells • Antigen presentation • Take a “snapshot” of what is happening in the tissues and carry this image to the lymph node • Dendritic cells imprint regional identity • 4 major groups: • Langerhans DC • Interstitial DC • Monocyte-derived DC • Plasmacytoid-derived DC • Follicular dendritic cells • Involved with B cell maturation

  26. Organs of the Immune System • Primary • Thymus and bone marrow • Place of maturation of lymphocytes • Secondary • Lymph nodes, spleen, mucosa-associated lymphoid tissues such as gut-associated lymphoid tissues • Mature lymphocytes interact with antigen

  27. Primary Lymphoid Organs • Bone marrow • Lymphocytes arise there, T cells go to thymus to mature • B cells mature here • 90% of plasma IgG and IgA comes from B cells in the bone marrow

  28. Primary Lymphoid Organs • Thymus • T cell development and maturation • Bilobed organ above heart • Surrounded by capsule and divided into lobules • Outer part of lobule is cortex, inner is medulla • Network of epithelial cells, dendritic cells, and macrophages • Thymus will induce death of those T cells that can’t: • Recognize self-MHC molecules • Those that interact with MHC molecules too strongly (could produce autoimmune disorder) • Function decreases with age

  29. Lymphatic System • Interstitial fluid (the portion that doesn’t enter venous system) is returned to circulatory system by lymphatic vessels • Largest lymphatic vessel – thoracic duct • Enters left subclavian vein • Lymph from right arm and right side of head enters through right lymphatic duct, drains into right subclavian • Antigen is carried by lymph to lymph nodes

  30. Secondary Lymphoid Organs • Primary follicle • Unactivated lymphoid follicle • Secondary follicle • Follicle that is activated by antigen • Germinal center – area of activated B cells • B cells here will proliferate, go through hypermutation and will class switch

  31. Secondary Lymphoid Organs • Lymph Nodes • Encapsulated • 3 regions: • Cortex • B cells, macrophages, dendritic cells • Primary follicles • Paracortex • T cells, dendritic cells • Medulla • Plasma cells secreting antibody

  32. Secondary Lymphoid Organs • Spleen • Filters blood, traps blood-bourne antigens • Important in systemic infections • Blood enters through splenic artery • Encapsulated • Structure: • Projections from capsule form trabeculae • Compartments: • Red pulp • Macrophages, red blood cells • White pulp • Surrounds branches of splenic artery • Forms PALS (periarteriolar lymphoid sheath) • Primary follicles rich in B cells

  33. Secondary Lymphoid Organs • Mucosa-Associated Lymphoid Tissue • MALT • Organized areas along digestive, respiratory, and urogenital tracts • Very well organized areas in intestine are referred to as Peyer’s patches • Includes tonsils and appendix

  34. Cross-section of small intestine

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