Structure of Immune System

Structure of Immune System Structure of immune system 1. Lymphoid Organs: Consist of central and peripheral lymphoid organs Central or Primary lymphoid organs- Examples include thymus and bone marrow- They host the development of immune cells (hematopoiesis) Peripheral or Secondary lymphoid organs- Examples include lymph node, spleen, and MALT (Mucosa associated lymphoid tissue) 2. Lymphoid Cells Consist of lymphocytes such as T cells, B cells and NK cells Structure of immune system 3.Other cells of immune systemInclude phagocytes such as macrophage and microphages (neutrophil, eosinophil & basophil), dendritic cells, mast cells and platelets. 4.Cytokines• • They are the soluble products secreted from various cells of immune system Include interleukins, interferons, tumor necrosis factors, colony stimulating factors, etc. Central lymphoid organ - Bone marrow • All the cells in blood are originated from pluripotent hematopoietic stem cells of bone marrow and the process is called a hematopoiesis. • In early fetal life, hematopoiesis occurs in liver; gradually the stem cells migrate to bone marrow. • By birth, the stem cells occupy most of the bone marrow space of large bones. Central lymphoid organ - Bone marrow • As the individual ages, hematopoietic activity in large bones decreases and after puberty hematopoiesis is mostly confined to axial bones such as pelvis, vertebrae, sternum, skull & ribs. • Progenitor T and B cells originate in bone marrow. o Further development of B cells occurs in bone marrow itself. o Progenitor T cells migrate to thymus for further proliferation. Central lymphoid organ - Thymus • Site of proliferation and maturation of T cells. • Development: o Developed in the embryonic life (third month) from third/fourth pharyngeal pouch. o Highly active at birth, continues to grow for many years, reaches its peak size at puberty, and then it degenerates. • Structure: Thymus has two lobes surrounded by a fibrous capsule. Septa arising from capsule divide thymus into lobules, and each lobule is differentiated into an outer cortex & an inner medulla Thymus -Cortex • Densely populated and contains: o Thymocytes- Lymphocytes of thymus (immature and many in number). o Cortical epithelial cells and o Nurse cells (specialized epithelial cells with long membrane extensions that surround many thymocytes) Thymus -Medulla • Sparsely populated and contains: o Thymocytes which are relatively more mature and fewer in number o Medullary epithelial cells o Interdigitating dendritic cells o Hassall’s corpuscles (concentric layers of degenerating epithelial cells) Thymic hormones • Produced from the epithelial cells of thymus. • They are believed to attract the precursor T cells (progenitor T cells) from bone marrow. o Thymulin o Thymopoietin o Thymosin Maturation of T cells • Cell to cell interaction between thymocytes & thymic stromal cells (including epithelial cells, dendritic cells & macrophages) • Effect of thymic hormones. Central tolerance • Only 2-5% of the developing T cells become mature and released out from thymus. • Remaining T cells are destroyed as they are either not capable of recognizing MHC or are believed to be self-reacting in nature. • Destruction of such self-reacting T cells prevents development of autoimmunity (immune response against self-antigens). • Such tolerance to self-antigens mediated by thymus that occurs in embryonic life is called as central tolerance. Defect in thymus • Leads to defect in maturation of T lymphocytes that in turn results in severe life threatening cell mediated immunodeficiency disorders. • DiGeorge syndrome (immunodeficiency disorder) - congenital aplasia of thymus. • Nude mice- Mice with congenital absence of thymus. PERIPHERAL LYMPHOID ORGAN - Lymph Node • Small bean shaped organs. • Occur in clusters or in chains, distributed along the length of lymphatic vessels. • Lymph nodes act as physiological barriers - filter the microbial antigens carried to lymph node by activating the T and B cells. Lymph Node - Structure • Thymus is divided into three parts: o Cortex o Medulla (both are B cell areas) o Paracortex (T cell area). • Bears the lymphatic vessels (efferent and afferent) and blood vessels. Lymph Node - Structure • Thymus is divided into three parts: o Cortex o Medulla (both are B cell areas) o Paracortex (T cell area) • Bears the lymphatic vessels (efferent and afferent) and blood vessels. Lymph Node - Cortex • Contains lymphoid follicles that are composed of: o B cells o Few special type of dendritic cells (called follicular dendritic cells) o Occasional T cells. • Lymphoid follicles are mainly of two types: o Primary lymphoid follicles o Secondary lymphoid follicles Primary lymphoid follicles • Found before the antigenic stimulus. • Smaller • Contain resting B cells. Secondary lymphoid follicles • Following contact with an antigen resting B cells starts dividing and become activated. • Activated B cells differentiate rapidly in to plasma cells and memory B cells. • Follicles become larger called secondary lymphoid follicles. Secondary lymphoid follicles • Has two areas: o Central area - germinal center o Peripheral zone - mantle area; contains activated B cells. Lymph Node – Paracortical area and Medulla • Paracortical are: o Present in between cortex and medulla. o T cell area of lymph node (rich in naive T cells). o Contains macrophages and interdigitating dendritic cells, which trap the antigens and present to T cells. • Medulla: o Innermost area of lymph node. o Rich in B-lymphocytes (mainly plasma cells). Spleen • Largest secondary lymphoid organ. • Acts as physiological barrier similar to lymph node in clearing the microbial antigens through the antigenic stimulation of T and B cells. Spleen - Structure • Situated below the diaphragm on left side of the abdomen. • Adult spleen measures about 5-inch in length & weighs around 150gm. • Divided into two compartments: central white pulp and outer red pulp, surrounded by capsule and intervened by trabeculae. Spleen - Structure • White pulp: o Central densely populated area. o Contains T cells and B cells. o It has two parts:  Periarteriolar lymphoid sheath (PALS), which is T cell area Marginal zone is located peripheral to the PALS and is populated by B cell lymphoid follicles Spleen - Structure • Red pulp: o Area that surrounds the sinusoids. o Filled with red blood cells (RBCs). o Older and defective RBCs are destroyed here. Defect in spleen • Increased incidence of bacterial sepsis caused primarily by capsulated bacteria such as: o Streptococcus pneumoniae o Neisseria meningitides o Haemophilus influenzae. Mucosa Associated Lymphoid Tissue (MALT) • Defense mechanisms in the mucosal sites to prevent the microbial entry. • Group of lymphoid tissues lining these mucosal sites are collectively known as mucosa associated lymphoid tissue (MALT). Mucosa Associated Lymphoid Tissue (MALT) • Structurally, MALT may be arranged in two typeso Loose clusters of lymphoid cells (usually found in the lamina propria of intestinal villi) o Lymphoid tissues arranged as organized structures (such as tonsils, appendix and Peyer’s patches) MALT in intestinal mucosa • Submucosa - Peyer’s patches: o Nodules of 30-40 lymphoid follicles (both primary and secondary follicles similar to that of lymph node). • Lamina propria: o Loose clusters of lymphocytes (B cells, plasma cells, activated T helper cells). o Macrophages. MALT in intestinal mucosa • Epithelial layer contains few specialized lymphocytes: o Intraepithelial lymphocytes (IELs) - γδ T cells. May encounter the lipid antigens that enter through the intestinal mucosa. o Secretory IgA (dimeric): Present in the submucosa as well as in the lining epithelium. Prevent the microbial entry at the mucosal sites (local immunity). o M cells M cells • Specialized flattened epithelial cells. • Do not have microvilli; instead they bear deep invaginations or pockets in the basolateral side. • Contains B cells, T cells and macrophages. • Portal of entry of a number of microbes such as Salmonella, Shigella, Vibrio, and Poliovirus. Cutaneous-Associated Lymphoid Tissue • Similar to MALT. • Skin also contains a few loose lymphocytes and specialized antigen presenting cells in epidermis called Langerhans cells. LYMPHOID CELLS • Lymphocytes are the major components of cells of immune system. • Approximately 1011 lymphocytes in the body, accounting for 2040% of the total white blood cells (WBCs) in blood and 99% of Tissues T cell B cell NK cell the cells in the lymph. Bone marrow 5-10 80-90 5-10 Thymus 99 <1 <1 Lymph node 70-80 20-30 <1 Spleen 30-40 50-60 1-5 Peripheral blood 70-80 10-15 10-15 CD molecules • CD (cluster of differentiation) molecules are cell surface markers useful for the identification of cells of immune system. • Thumerous functions, often act as surface receptors or some CD proteins may help in cell adhesion. • As of 2015, CD molecules for humans are numbered up to 364. Types of lymphocytes • Based on function and cell membrane structure: o T lymphocytes o B lymphocytes o NK (natural killer) cells. • Lymphocytes can also be classified into: o Naive lymphocytes o Lymphoblasts. Naive lymphocytes • Resting B and T lymphocytes that have not interacted with antigen (unprimed lymphocytes). • Also known as small lymphocytes (6µm); having thin rim of cytoplasm, larger nucleus with dense chromatin; fewer mitochondria, ribosomes, and lysosomes. • Short life span (1-3 months). Lymphoblasts • Naive cells interact with antigen in the presence of cytokines Activated and transform into lymphoblasts Effector cells Memory cells. Effector cells • Function in various ways to eliminate antigen. • Short life span (few days to few weeks) • Large lymphocytes (15 µm in size), having wider rim of cytoplasm with more organelles. o Effector B cells - Antibody producing plasma cells o Effector T cells - Helper T cells and cytotoxic T cells. Memory cells • Remain dormant like naive cells. • Capable of transforming into effector cells rapidly on subsequent antigenic challenge. • Longer life span; providing long term immunity to may pathogens. Differences between naive, effector and memory cells Location (present mostly in) Cell cycle Morphology Life span Function Naive cell Secondary lymphoid organs Dormant (G0 phase) Small lymphocyte Short Transforms to effector cell on primary exposure to antigen; Occurs slow due to lag period Effector cell Inflamed tissues & mucosal surfaces Active Memory cell Both the locations of naive & effector cell Dormant (G0 phase) Large lymphocyte Small lymphocyte Short Long Eliminate antigen Transforms to effector cell on secondary exposure to antigen, Occurs fast without lag period Differences between naive, effector and memory cells Naive cell Effector cell Memory cell CD127 (IL-7R) High Low High CD45 isoform CD45RA CD45RO CD45RO CD25 (IL-2R α) on T cells No Yes Yes CD27 on B cells No Yes Yes B cells producing Ig types & their affinity IgM and IgD Low affinity IgG, IgA, IgE High affinity IgG, IgA, IgE High affinity Surface markers