BMS2045 1c Tissues of the Immune System 2024 PDF

Theme 1 Tissues of the immune system Aims To develop a knowledge of the structure and function of primary and secondary lymphoid organs/tissues Learning outcomes Identify and describe the structure of primary and secondary lymphoid tissues Describe the processes that occur in primary lymphoid tissue...

Theme 1 Tissues of the immune system Aims To develop a knowledge of the structure and function of primary and secondary lymphoid organs/tissues Learning outcomes Identify and describe the structure of primary and secondary lymphoid tissues Describe the processes that occur in primary lymphoid tissue leading to the development of naïve B and T cells Explain the processes that occur in secondary lymphoid tissue to promote a healthy immune response Discuss how lymphocytes circulate the body Lymphoid tissues Lymphocytes (T &B cells) are found in blood, but majority are either in discrete clusters or organised in specific tissues ⚫ These tissues are either primary, secondary or tertiary and are connected by the blood and lymphatics circulatory systems ⚫ Mucosal surfaces Primary lymphoid tissues Involved in development and differentiation (‘education’) of lymphocytes & include: Thymus (T cells) ‘Bursa equivalent’ tissues: foetal liver & adult Bone marrow in humans (B cells) Secondary lymphoid tissues Allow accumulation of antigen (Ag) with lymphocytes Allow presentation of antigen to both naïve & memory lymphocytes Include the lymph nodes, spleen and the mucosal associated lymphoid tissue (MALT) Tertiary lymphoid tissues Comprise all remaining lymphoid tissues in body (e.g. skin) Contain only few lymphocytes normally During inflammation may be invaded by unique subsets of memory lymphocytes Primary lymphoid tissues The Thymus First organ to produce lymphocytes & provides environment for T cell maturation and education Involutes (shrinks) with age 2 lobes divided into smaller lobules by trabeculae (or connective tissue walls) The Thymus cont. Each lobule has outer CORTEX and inner MEDULLA Cells enter as ‘Thymocytes’ and are surrounded by EPITHELIAL cells and others e.g. INTERDIGITATING dendritic cells & MACROPHAGES Cells pass from cortex to medulla while differentiating into T cells In cortex, THYMIC NURSE cells affect thymocyte development Those not leaving undergo apoptosis (programmed cell death) The Thymus cont. Only ??? % of original thymocytes make it through the thymus into the circulation as naïve T cells The Thymus cont. ….T cell differentiation/maturation Thymocytes enter not expressing either CD4 or CD8 (double negative), go through a stage of expressing both (double positive) followed by a decision be either CD4+ or CD8+ CD4CD8CD3TCRCD3low CD4+ TCRlow CD8+ Their expression of CD3 and TCR also increases as they pass through the thymus CD3high CD4+ TCRhigh CD8+ CD4+ CD3high CD8- TCRhigh Are positively selected to bind CD4CD8+ to molecules called MHC and negatively selected if bind self peptides (‘education’) B cell development Immature B cells (from bone marrow derived precursors) remain in bone marrow and mature under local influences such as a selection of growth factors (from stromal cells) ⚫ They are also educated not to respond or bind to self molecules whilst arranging their B cell Receptors (negative selection) and must respond to survival factors (positive selection) ⚫ ⚫…then released as naïve B cells which are still functionally immature….those that do not leave undergo apoptosis (about ??? %) The lymphatic system Blood components from capillaries enter tissues making extracellular fluid that provides food and gas exchange ⚫ ⚫ Extracellular fluid drains into vessels called the LYMPHATICS Lymphocytes and other leukocytes use this system to migrate around the body ⚫ Lymphocytes bind to adhesion molecules expressed by endothelial cells lining the blood vessels. These can be up and down regulated resulting in regulation of the movement of the cells ⚫ The lymphatic system Lymphocytes recirculate between tissues, primary and secondary lymphoid organs via the blood and a network of vessels called the lymphatics The Lymphatic System cont. How…? Arterial pressure due to close association with blood vessels Smooth muscle cell movement Backflow prevention valves Lymphocyte homing (migration) This movement is NOT random: Leukocytes have molecules called adhesion molecules (homing receptors) that allow binding to others expressed by endothelial cells lining blood vessels. E.g. LFA-1 on lymphocytes binds to ICAM-1 on endothelial cells ⚫ Lymphocytes adhere to, pass between endothelial cells into the tissues, from where they return, via the lymph, to the blood ⚫ This traffic of cells through body to specific areas is called migration or HOMING ⚫ Secondary Lymphoid Tissues (1) Lymph nodes Small, bean-shaped, tissue aggregates at junctions of major lymphatic vessels, 1-25mm diameter, becoming much larger in infection ⚫ Surrounded by a capsule & supported by a reticulum, 3 main areas: cortex, paracortical area, medulla ⚫ Lymphatics: Afferent vessels carries Ag and cells from tissues to lymph nodes allowing cells of the immune system to get together with antigen to start specific immune responses – exit is via Efferent vessels, which eventually drain back into the blood circulatory system via the thoracic duct ⚫ Blood: lymphocytes and Ag enter lymph nodes at High Endothelial Venules (HEV) ⚫ Lymph nodes cont. T cells collect in paracortical areas, B cells in outer cortex ⚫ HEV or Paracortical region contains antigen presenting cells and large lymphocytes & activated cells ⚫ (or HEV) Medulla contains plasma cells secreting Antibody ⚫ Lymph nodes cont. B cells form dense aggregates – FOLLICLES ⚫ Primary lymphoid follicle Primary follicles are very dense & uniform ⚫ Secondary follicles contain larger cells associated with macrophages forming GERMINAL CENTRES with lots of cell proliferation ⚫ After Ag exposure, lymph node shows increased turnover of lymphocytes ⚫ Secondary lymphoid follicle (2) The Spleen Secondary lymphoid organ/tissue with other nonimmunological functions Capsule with fibrous partitions (SEPTAE) Lymphocytes enter and leave mainly via blood stream 2 types of tissue: RED and WHITE PULP The Spleen cont. Red pulp: Non-immunological role: filters damaged or aged red cells White pulp: Immunological role: as for lymph nodes – to develop immune responses Cells & tissues surrounding major arterial branches form PERIARTERIOLAR LYMPHATIC SHEATH (PALS) and associated clusters of lymphocytes - the lymphatic follicles or nodules The Spleen cont. Follicles similar to those in lymph nodes B-dependent area consists of lymphoid follicles T-dependent area consists of the PALS (3) Mucosa-associated lymphoid tissue (MALT) Diffusely distributed lymphoid tissues in lining (mucosae) of gastrointestinal, respiratory and urinogenital tracts Gut-associated lymphoid tissue (GALT) and Bronchus ALT (BALT) are best characterised GALT made up of Peyer’s patches and isolated follicles in colonic submucosa Lymphocytes also found in lamina propria, intestinal epithelium and in lumen of intestine GALT Peyer’s patch Microfold/ Draining lymphatics Efferent lymphatic s GALT cont. Peyer’s patches Aggregates of lymphocytes; B cells form central follicle surrounded by T cells & macrophages/antigen presenting cells (APCs) ⚫ Have efferent lymphatics that drain into mesenteric lymph nodes, but no afferent lymphatics ⚫ Covered by specialised lymphoepithelium consisting of cells known as M cells (microfold cells) ⚫ Ag in gut enters via M cells that selectively take up particles and deliver them to lymphoid follicles also by specialised dendritic cells which ‘reach’ into the gut lumen! ⚫ Peyer’s patches cont. (Kuby, 6e, 2007) Peyer’s patches cont. BALT Similar to GALT; consists of collections of mostly B cells organised into aggregates & follicles with few germinal centres, some M cells but organisation is less defined than GALT ⚫ Contains network of capillaries, arterioles, venules, HEVs & efferent lymphatics ⚫ This suggests BALT may play role in sampling Ag not only from lungs but also from systemic circulation ⚫ See greater infiltration of white blood cells following infection (inducible BALT or iBALT) ⚫ Summary Tissues/organs are primary, secondary or tertiary Primary mainly concerned with the development or ‘education’ of lymphocytes B in the bone marrow and T in the thymus Secondary mainly involved in getting accumulating Antigen and immune cells together to activate immune responses Movement of leukocytes via the blood and lymphatics is guided by expression of and binding to adhesion molecules and is not random Theme 1 Further Reading Kuby 8th Edition Chapter 2 (main text; boxes optional), Chapter 14 (p511-522) Male, Brostoff, Roitt 8th Edition Section 1: Chapters 1&2