Cells of the Immune System PDF

Stem Cell: Cells with ability to self renew and differentiate to diverse cell types Embryonic Stem Cell: Pluripotent cells with capacity to generate all cell type in organism Adult Stem Cells (Somatic Stem Cells): Organs harboring stem cells, that can only differentiate to diverse cell types o...

Stem Cell: Cells with ability to self renew and differentiate to diverse cell types Embryonic Stem Cell: Pluripotent cells with capacity to generate all cell type in organism Adult Stem Cells (Somatic Stem Cells): Organs harboring stem cells, that can only differentiate to diverse cell types of a particular tissue. Example: Hematopoietic Stem Cells (HSC), Mesenchymal Stem Cells (MSC) in bone marrow (dedifferentiation, trans-differentiation, IPSc) Hematopoietic Stem Cell (HSC): Cells that can differentiate into all types of blood cells. Present less than 1 in 5x105 bone marrow cells Generally quiescent, but in need displays immense proliferative ability. Hematopoeisis: Process of HSC differentiation into different blood cells Rate of Hematopoeisis as well as production of specific cell lineages is environment deoendent Human Blood Corpuscle Types Hematopoiesis Overview CMP CLP  Cells of Myeloid-erythroid Lineage lineage Cells of this lineage act as first responders to Infection Common Myeloid Progenitor (CMP) differentiates into: Erythroid Progenitor Erythrocytes Platelets Myeloid progenitor Granulocytes Neutrophils Basophils Eosinophils Mast cells Myeloid Antigen Presenting cells Monocytes Macrophages Dendritic cells  Granulocytes Neutrophils: Life span of few days Dominant first responders to infection and major cellular component of pus Leukocytosis: Number of circulating neutrophils significantly increase during infection Recruited to site of infection in response to chemokines secreted by innate cells Kills by phagocytosis as well as release proteins with antimicrobial and tissue remodeling effects Basophils: Contains large granules filled with basic proteins (Histamine is best example responsible for vasodilation) In response to circulation antibodies, basophils release granule contents Like neutrophils can secret cytokines Has role in allergies Mast cells: Found in variety of tissues including skin, digestive, genitourinary tracts etc. Released into blood as undifferentiated cells, but differentiate in blood. Performs mostly similar functions to basophil Eosinophils: Phagocytotic cells, that can also secrete cytokines that can regulate lymphocytes Thought to play important role against defense of multicellular organisms. Also contribute to asthma and allergy symptoms  Myeloid Antigen-Presenting cells Group of phagocytic cells that have antigen presentation ability Act as bridge between innate and adaptive immunity Monocytes: Heterogeneous group of cells that differentiate into diverse tissue resident phagocytic cells Can be categorized into two broad categories: Inflammatory monocytes and Patrolling monocytes Inflammatory monocytes enter tissue in response to infection whereas Patrollling monocytes lie along blood vessel that act as reservoir of tissue resident monocytes Macrophages: Tissue resident monocytes Tissue resident macrophages play role in repair and regeneration Others are inflammatory macrophages that can engulf pathogens as well as act as APC Examples are Osteoclasts, Microglial cells and Alveolar Macropahges Dendritic cells: Arise from Both myeloid and Lymphoid lineage Cells have large membranous extension like nerve cells, that help it to have increased surface area Most efficient activator of T cells Different from follicular dendritic cells  Cells of Lymphoid lineage Lymphocytes- Key Players to adaptive immunity Represent 20-40% of circulating lymphocytes in blood and 99% of blood cells of lymph Broadly subdivided into 3 Types: 1. B cells 2. T cells 3. Natural Killer cells (NK Cells) Unlike other WBCs, they are difficult to differentiate morphologically Usually differentiated by the signature of Surface proteins expressed on the surface, often referred as Cluster of Differentiation (CD) In addition to CD signature on surface, B and T cells Express BCR and TCR respectively  Cells of Lymphoid lineage B- Lymphocytes Site of maturation: Bursa fabricus in Birds and Bone marrow in mammals Mature B-cells are distinguished from other lymphocytes by the presence of BCR. BCR and B-Cells maturation to be read in detail. Mature B cells differentiate to Plasma cells (effector; antibody secreting) cells, whereas few develop into Memory cells T- Lymphocytes Site of maturation: Thymus Express TCR on its surface Differentiated into 3 Types: 1. T- Helper Cells 2. T cytotoxic cells 3. T regulatory cells  Cells of Lymphoid lineage T cytotoxic Lymphocytes (TC) Express CD8 on its surface that recognizes antigen-MHC1 complex, after which they activate to form effector cells called Cytotoxic T-Lymphocytes (CTL) Functionally eliminate infected cells, cancer cells, foreign graft etc. T helper Lymphocytes (TH) Express CD4 on its surface that recognizes antigen-MHCII complex, after which they proliferate to T- Helper Type 1 (TH1) or T- Helper Type 2 (TH2) cells TH17- secrete IL-17 and play role in cell mediated immunity to provide defense against Fungi T follicular Helper Cells (TFH) play role in B-cells development in germinal centers. T Regulatory Lymphocytes (TREG) Inhibit an immune response Identified by presence of CD4 and CD25 on cell surface and expression of FoxP3 transcription factor Natural TREG- Arise during maturation in Thymus from auto-reactive T cells Induced TREG- Arise at the site of immune response in response to antigen  Cells of Lymphoid lineage Natural Killer cells (NK cells) No antigen specific receptors on surface and considered part of innate immune response Comprise 5-10% of circulating Lymphocytes Express surface marker NK1.1 and contain cytotoxic ganules Kill abnormal cells (tumour cells, virus infected cells), by recognizing the absence of MHC-1 molecules on target cells. Also express receptor for Immunoglobulins that help it to recognize infected cells. NKT cells Share feature of T cells and NK cells Like T cells they express TCR (some even express CD4), hat recognize specific lipids/Glycolipids presented on CD1. Like NK cells, they also have surface antibody receptors and release contents of cytotoxic granules to kill cells.