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11. lymphoid dol29

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  • 1. Histology Lymphoid System
  • 2. Lymphoid System Basics • The immune system • Cells, tissues and organs that function to protect body from invasion and damage by foreign cells, microbes, viruses and parasites • The immune system is able to: – differentiate between self (own) and non-self (foreign & modified self) structures – specificity – respond: immune response fights against pathogens – remeber antigens over long periods of time
  • 3. Lymphoid System Basics • Cells of the immune system: – Lymphocytes •T •B • NK – Antigen presenting cells (APC): dendritic cells, macrophages, B lymphocytes – Other: neutrophils
  • 4. Lymphoid System Basics • The lymphoid tissue consists of: – numerous immune system cells (lymphocytes, APC) – stroma: reticular cells + reticulin fibres – reticular cells: cell body with oval euchromatic nucleus; long, thin processes that contact eachother (desmosomes)
  • 5. Lymphoid System Basics • Two main tissue architecture types: – Diffuse: uniform appearance – Follicular: consists of lymphoid follicles • Two types of lymphoid tissues: – Encapsulated: connective tissue capsule • spleen, thymus, lymph nodes – Unencapsulated (or partly encapsulated) • tonsils, Peyer’s patches, lymphoid nodules in GI tract, respiratory tract, urinary & reproductive tracts
  • 6. 2 Types of Lymphoid Organs • Central (primary) lymphoid organ: where lymphoid precursor cells undergo antigen independent proliferation and differentiation – T cells in thymus – B cells in bone marrow • Peripheral (secondary) lymphoid organ: where functional lymphocytes go including lymph nodes, spleen, Peyer’s patches, lymphoid nodules of GI and other tracts
  • 7. Peripheral Lymphoid Tissues • Lymphocytes contact antigens and divide and differentiate into effector B cells and T cells • Memory cells form that circulate for years to provide extended immunity
  • 8. Lymphocytes • Small cells • About 20% of the leukocytes in circulation. • These are the cells that recognize foreign antigen - they can distinguish self from nonself. They have surface antigen receptors. - Recognition of their specific antigen drives differentiation and proliferation to produce a highly specific and effective clone - memory lymphocytes can persist for many years. This is why vaccination works.
  • 9. T Lymphocyte
  • 10. B Lymphocyte
  • 11. T Lymphocytes T Lymphocytes (T cells) • A thymus-derived (or processed) lymphocyte. • ~75% of circulating lymphocytes • 6-15 mm diameter (red blood cell 7.2 mm diam.) • Small T lymphocytes – scanty cytoplasm • Large activated lymphocytes – more cytoplasm, azurophilic granules • 2 main subdivisions based on the expression of specific surface markers. • CD8 - cytotoxic T cells • CD4 - helper T cells
  • 12. T Lymphocytes  all express the T-cell antigen receptor (TCR) (alpha/beta TCR)  Helper T cell express CD4; these cells typically induce and coordinate the responses of the Cytotoxic T cell and other cells of the adaptive immune response - cytokine factories  Cytotoxic T cells express CD8; these cells kill their targets – virus-infected, tumour and foreign cells.  Lymphocytes recognize their specific antigens in association with major histocompatability antigens. Helper T cells (CD4+) recognize antigen that is presented in association with MHC class II Cytotoxic T cells see antigen presented via MHC class I
  • 13. MHC Class I & Class II Peptide Binding Groove α2 α1 β2 α1 α3 b2-microglobulin β2 α2
  • 14. B Lymphocytes B Lymphocytes • defined by expression of surface immunoglobulin - this acts as an antigenspecific receptor for the B lymphocyte (IgM and IgD). • ~5-15% of the circulating lymphoid pool. • Express MHC class II molecules which are important for presenting antigen to T cells. • The main function of B cells is the production of antigen-specific antibody (immunoglobulin). • Once activated B cells terminally differentiate into plasma cells.
  • 15. Cel. T LGL Small T lymph Large Granular Lymph - LGL
  • 16. B lymphocyte Centrocyte Plasma cell
  • 17. Antigen presenting cells Dendritic cell Macrophage B lymphocyte
  • 18. Dendritic cells • Interdigitating Dendritic Cells • Follicular Dendritic Cells • Germinal Center Dendritic Cell • Langerhans’cell •Located in peripheral tissues or lymphoid tissues •They can be activated in inflammatory conditions •Have the ability to uptake, process and present antigens to T cells. They are “professional” APC
  • 19. Thymus 1 • Central lymphoid organ, with double embryonuc origin: epithelial and mesenchymal • Thin capsule, lobular organization • Each lobule has cortex (greater cell density) with many T lymphocytes surrounding lighter-stained medulla • Epithelial reticular cells w/ large euchromatic nucleus • Hassal’s corpuscles (flattened epithelial reticular cells)
  • 20. Thymus: cortex and medulla
  • 21. Thymus cortex Thymus medulla
  • 22. Thymus • Cortex: many lymphocytes, macrophages, epithelial reticular cells • Medulla: more epithelial reticular cells and fewer lymphocytes – mature T lymphocytes leave from here to go to spleen and lymph nodes – Hassal’s corpuscles: concentric layers of epithelial reticular cells, core degenerated; function/significance unknown • After puberty thymus undergoes involution and increases in connective tissue and adipocytes
  • 23. Thymus • Thymocytes - precursor lymphocytes from the bone marrow which enter the thymus via blood vessels. • Thymocytes proliferate and mature in the thymus but only 1-3% survive the selection process that allows mature T cells to enter the peripheral circulation. • In this tissue, specialized APCs scan for T cells that may self-react; these cells are killed so as to prevent autoimmunity (negative selection). • Progenitor T cells (thymocytes) that recognize MHC class I molecules but not self antigen are positively selected for development • This is where the entire repertoire of antigen-specific T cells is generated (the variety of TCRs is created here)
  • 24. Thymic lobule cortical thymocytes cortical thymocytes subcapsular region cortical thymocytes apoptotic thymocytes outer cortical macrophages deep cortical septum reticuloepithelial cells cortico-medular junction dendritic interdigitated cells Hassall corpuscules medular epithelilal cells medular region
  • 25. Blood-thymus barrier •Blood supply and blood-thymic barrier - nonfenestrated endothelium, thick basal lamina and reticular cell sheath form the barrier found in the cortex separating proliferating thymocytes from the blood.
  • 26. Thymus • Major functions – supports the proliferation and programming of T lymphocytes. – It also secretes the hormone thymosin and thymopoietin that promotes the function and maintainence of T lymphocytes in particular.
  • 27. Lymphoid Follicles • Nodules of densely packed lymphocytes located in all peripheral lymphoid tissues. Most lymphocytes are B cells. • Two distinct areas – Mantle – darker stained, mainly small, resting lymphocytes – Germinal center (defines “secondary” or “reactive” lymphoid follicles): lighter stained, larger, activated B cells – centroblasts and centrocytes (latter with cleaved nuclei)
  • 28. Lymph follicle: -Mantle = cap (dark) -Germinal center (light) -centroblasts -centrocytes (cleaved nucleus)
  • 29. Lymph follicle: -Mantle (dark) -Germinal center (light) -centroblasts -centrocytes (cleaved nucleus)
  • 30. Lymph Nodes • Throughout body, along lymph vessels • Numerous in axilla, groin, cervical area and thoracic/abdominal mesenteries • Filter lymph before it returns to vasculature • Hilum, concave side, arteries, nerves enter; veins and efferent lymph vessels leave the organ • Afferent lymph vessels enter convex surface
  • 31. Lymph Nodes • Capsule of dense irregular connective tissue, with incomplete septa • Reticular fiber network • Lymph sinuses: subcapsular -> interfollicular -> medular
  • 32. Lymph Nodes • Cortex: – several primary and secondary (have germinal centers) lymphoid follicles – HEPV – high endothelium postcapillary venules: specific adhesion molecules that select lymphocytes that will enter the organ • Paracortical (deep cortical) – diffuse lymphoid tissue with many T cells; • Medula – cell chords (lymphocytes, plasma cells) – sinuses which join to form efferent vessels
  • 33. Lymph node Lymphatic vessel, lymph node
  • 34. Lymph node reticular stain Cortex of lymph node with lymphoid nodule
  • 35. Lymph node medulla Lymph node medulla with sinusoid and medullary cords
  • 36. Spleen • Largest lymphatic organ • Many macrophages; rbc phagocytosis • Thick capsule of dense irregular connective tissue w/ trabeculae dividing pulp incompletely • White pulp with lymphoid tissue • Red pulp found between sinusoids has cell chords (Billroth’s chords) with mainly macrophages, reticular fibers and reticular epithelial cells • Marginal zone - forms border between the red and white pulp. where lymphocytes leave blood to enter white pulp, and rbc’s and plasma cells to enter red pulp.
  • 37. White Pulp • Central arteries with encircling lymphoid tissue • Periarterial lymphatic sheaths (PALS) around small arteries, mainly T cells • Lymphoid follicles comprise mostly B cells • Reticular epithelial cells & macrophages
  • 38. Red Pulp • Reticular cells with cords of cells between sinuses • Cords have macrophages, monocytes, lymphocytes, plasma cells, rbc, granulocytes • Sinuses have irregular lumen, incomplete endothelium and basal lamina
  • 39. Spleen sinus - ME
  • 40. Spleen with red pulp and white pulp Spleen red pulp
  • 41. Spleen white pulp with surrounding red pulp
  • 42. Splenic circulation • Arterial supply - from the splenic artery it branches into several trabecular arteries that enter the hilum of the spleen. These branch to enter the parenchyma of the spleen as central arteries. The central arteries branch into marginal sinuses, then continues into the red pulp where it branches into several penicillar arterioles – Open circulation model – pa open into medullary sinuses – Closed circulation model - blood cells leave sinuses then reenter but is described as a continuous vascular channel
  • 43. Functions of Spleen Functions • Filtration of blood - removal of antigenic material and cellular debris by macrophages and dendritic cells, concentrated and presented to lymphocytes in the white pulp. • Lymphocyte activation - both T and B lymphocytes are activated in the spleen. Plasma cells migrate from the white pulp into the red where they secrete Igs into the venous blood. • Destruction of old/damaged RBCs - phagocytosed by macrophages and the hemglobin is broken down.
  • 44. Unencapsulated or Incompletely Encapsulated Lymphoid Tissue • Lymphoid nodules • Tonsils: palatine, pharyngeal, lingual • Peyer’s patches
  • 45. Tonsils • Incompletely encapsulated lymphoid nodules • Palatine: covered by stratified squamous nonkeratinized epithelium; crypts; underlying connective tissue barrier • Pharyngeal: covered by ciliated pseudostratified epithelium, no crypts • Lingual: smaller, at base of tongue; covered by stratified squamous nonkeratinized epithelium; one crypt in each nodule
  • 46. Palatine tonsil Pharyngeal tonsil
  • 47. Peyer’s Patches • Lymphoid nodules in the lamina propria of the ileum (covered in detail in the digestive tract section)
  • 48. Lymphocyte circulation