Blood Cells PDF

Agranulocytes Single non-lobulated nucleus Granules in cytoplasm are too small to see (nonspecific granules, azurophilic granules, primary granules, lysosomes) 2 types based on structure (not cell lineage): – Lymphocytes – Monocytes  Monocytes Largest leukocytes...

Agranulocytes Single non-lobulated nucleus Granules in cytoplasm are too small to see (nonspecific granules, azurophilic granules, primary granules, lysosomes) 2 types based on structure (not cell lineage): – Lymphocytes – Monocytes  Monocytes Largest leukocytes Bluish cytoplasm (frosted glass appearance) & a large C-shaped nucleus Highly motile and phagocytic Travel through bloodstream to reach connective tissues, where they transform into macrophages (large phagocytic cells) Dr. Heba Kalbouneh Are precursor cells of macrophages, osteoclasts, microglia, and other cells of the mononuclear phagocyte system in connective All monocyte-derived cells are tissue antigen-presenting cells  Monocytes and macrophages are the same cells at different stages of maturation Dr. Heba Kalbouneh Microglia Kupffer Cells CNS Liver MONONUCLEAR PHAGOCYTIC SYSTEM Macrophages Monocyte Dendritic cells Bone marrow Lymph node Connective tissue Dust cells Spleen Lung Osteoclasts Bone ( all characterized by phagocytic activity) Langerhans cells resorption Epidermis  Lymphocytes Smallest leukocytes Round nucleus occupies most of cell volume Cytoplasm is light clear blue Increased numbers are commonly seen in viral infections Lymphocytes vary in life span according to their specific function, some live for a few days and some live for many years Cell mediated immunity T cells – Has different types, some directly kill foreign or infected cells; others activate phagocytes to destroy microbes Humoral immunity B cells Dr. Heba Kalbouneh – Differentiate into plasma cells – Secrete antibodies that bind to specific antigens and mark them for destruction by phagocytic cells Long term immunity Lymphopoiesis: the process by which lymphocytes are formed Precursor cells in bone marrow Dr. Heba Kalbouneh Thymus Directly into blood BM T Lymphocytes Natural killer lymphocytes B Lymphocytes  Morphologically lymphocytes can be classified into: The amount of cytoplasm depends upon state of activity of the lymphocyte In circulation blood there is predominance of Large small inactive lymphocytes Small (9-18 m) (6-9 m) Active lymphocyte Inactive lymphocyte Different types express specific cell surface proteins Dr. Heba Kalbouneh CD4 or 8 B lymphocyte T lymphocyte Natural killer lymphocyte  Small Large (6-9 m) (9-18 m) Inactive lymphocyte Active lymphocyte Darkly stained cell Lightly stained cell Dr. Heba Kalbouneh  Immunohistochemistry Direct method Anti-CD4 labeled with fluorescent tag CD4 Immunohistochemistry Using CD 4 Antibody ??????? CD 4 + Dr. Heba Kalbouneh T Helper lymphocyte  Neutrophils and monocytes are highly The small lymphocyte has phagocytic and engulf scanty cytoplasm (contain few microorganisms and cell debris in a Dr. Heba Kalbouneh organelles but large number of NON-SPECIFIC manner (Innate ribosomes ) immunity) While Account for basophilic The activity of lymphocytes is always cytoplasm directed against SPECIFIC foreign agents (Adaptive immunity)  Lymphocytes B Lymphocyte T Lymphocyte Natural killer cells (NULL Lymphocyte) Kill virus-infected, Memory cell Plasma cell transplanted and neoplastic cells Produces antibodies (innate immunity) Large granular lymphocytes Activated lymphocytes Cytotoxic Suppressor Kill virus-infected, Suppresses immune response to self Ag transplanted and Suppresses immune response of T and B lymphocytes neoplastic cells (adaptive immunity) Helper Help cytotoxic T Dr. Heba Kalbouneh cells and B cells in their immune functions Innate immunity: We are born with innate immunity. It is non-specific, which means that the innate cells are not able to distinguish one type of pathogen from another. Cells of innate immunity: Neutrophils, Basophils, Eosinophils, Mast cells, Monocytes (macrophages and Suppressor T cells switch off the dentritic cells), natural killer cells immune response when the stimulus is removed Adaptive (acquired) immunity is the body's ability to recognize and respond to specific foreign substances (antigens: microbes, parts of microbes, or non-microbial substances, such as pollen) Damage to suppressor cells can Cells of adaptive immunity: B and T result in autoimmune disease lymphocytes Memory cells allow a more rapid response if the antigen appears again later Natural killer cells and T which allows a very rapid response upon cells play a major role in subsequent exposure to the same antigen. graft rejection Basis of immunity/vaccination The retrovirus that produces acquired immunodeficiency Dr. Heba Kalbouneh syndrome (AIDS) infects and rapidly kills helper T cells. Reduction of this key lymphocyte group cripples the patient’s immune system rendering them susceptible to opportunistic bacterial, fungal, protozoan, and other infections that usually dealt with easily in immunocompetent individuals.  Different types express specific cell surface proteins TCR CD8 CD4 TCR B cell Cytotoxic T cell Helper T cell Note: Receptors of B cells are immunoglobulins that bind antigens directly; those on T cells react only with antigen on MHC molecules and this requires the additional cell surface proteins CD4 or CD8. Dr. Heba Kalbouneh T lymphocytes are said to be MHC restricted "CD" stands for "cluster of differentiation”: are surface molecules that help differentiate one cell type from another  Major histocompatibility complex MHC Glycoprotein on cell membrane Two classes: MHC-I On surface of all nucleated cells Coupled to peptide formed within the cell MHC –II On surface of APCs If the MHCs on cells Coupled to peptide product of proteins of a tissue graft are not similar to those that T the cells had ingested (peptide product of lymphocytes encountered during their Ag digestion) development, the grafted cells will induce a strong immune reaction by T cells of the recipient. To these lymphocytes, the unfamiliar MHC Dr. Heba Kalbouneh epitopes on the graft’s cells are recognized as markers of “non-self ” cells that they must eliminate.  Self- peptide bound to MHC-1 MHC-1 MHC-1 mRNA Self-peptide is derived from the proteins that are synthesized by the cell (Self Antigen) Endogenous protein mRNA Dr. Heba Kalbouneh Peptide fragment Normal cell  Viral- peptide bound to MHC-1 MHC-1 MHC-1 mRNA Viral peptide is derived from the viral proteins that are synthesized by the viral infected cell (non-self Viral mRNA Antigen) Dr. Heba Kalbouneh viral peptide fragment Viral infected cell  Mutant peptide bound to MHC-1 MHC-1 MHC-1 mRNA Mutant peptide is derived from the mutant proteins that are synthesized by the Mutant protein cancerous cell mRNA (non-self Antigen) Dr. Heba Kalbouneh Peptide fragment Cancerous cell  Cytotoxic CD8 T cells: Antigen in virus infected, transplanted or neoplastic cells bind to MHC-I molecules Ag-MHCI complex Ag/ MHC-I complex Viral peptide MHC-I Dr. Heba Kalbouneh virus CD8 TCR Viral infected cell Cytotoxic T cell  Cytotoxic T cell When the Ag- MHCI complex binds to receptors on cytotoxic CD8 T cells They TCR CD8 Proliferate Ag/ MHC-I complex Activate Release Perforins and granzymes (proteases) Dr. Heba Kalbouneh virus Perforins form pores in the cell membrane through which granzymes can enter, inducing apoptosis Viral infected cell  Ag/ MHC-II complex Antigen presenting cell (macrophage, dentritic cell, B lymphocyte) Phagolysosome Lysosome Phagosome MHC-II Dr. Heba Kalbouneh Ag Ag Macrophage Ag (APC) Dr. Heba Kalbouneh Helper CD4 T cells: When Ag is phagocytosed by antigen presenting cells (APCs) e.g macrophages, dentritic cell and B lymphocytes It binds to MHC-II molecules Ag-MHCII complex Ag/ MHC-II complex MHC-II Phagosome phagolysosome Ag CD4 TCR Macrophage (APC) T Helper cell Dr. Heba Kalbouneh T Helper cell When the Ag- MHCII complex binds to receptors on Helper CD4 T cells IL-1 They Proliferate Activate Secrete Lymphokines (cytokines) to Stimulate T and B cells Macrophage (APC)  When a B lymphocyte is stimulated by T helper cells B cell Proliferate Activate Dr. Heba Kalbouneh Activated B lymphocytes: plasma cells memory cells 1- differentiate into plasma cells (secrete antibodies) 2- differentiate into memory cells (Rapid response on the 2nd exposure to the same Ag) Life long immunity (vaccination)  B cells: When the specific Ag binds to receptors on B cells Dr. Heba Kalbouneh receptor-mediated endocytosis and fragments of the Ag bind to MHC-II molecules Ag-MHCII complex Ag/ MHC-II complex Ag MHC-II Free Ag B cell (APC)  T Helper cell T Helper cells bind to Ag-MHCII complex on the B cells Stimulates proliferation and differentiation (activation) of B cells TCR CD4 Ag/ MHC-II complex B cells Dr. Heba Kalbouneh Proliferate Activate Activated B lymphocytes: 1- differentiate into plasma cells (secrete antibodies) 2- differentiate into memory cells (Rapid response on the 2nd exposure to the same Ag) B cell (APC) Life long immunity (vaccination) Never Let Monkeys Eat Bananas Most common to least Dr. Heba Kalbouneh Thrombocytes (Platelets) Small non-nucleated cytoplasmic fragments Formed by fragmentation of the cytoplasm of megakaryocytes in the bone marrow Number: 200,000-400,000/mm3 Shape: biconvex discs Cytoplasm: purple, granular In stained blood smears, platelets often Diameter: 2-4 um appear in clumps Lifespan about 10 days Control the bleeding by plugging the defects in blood vessels and activating blood clotting cascades Platelete has 2 zones  Outer pale basophilic (clear) peripheral zone: hyalomere  Central dark granular zone: granulomere Dr. Heba Kalbouneh Hyalomere: contains cytoskeleton and membranous channels Have thick glycocalyx Cytoskeletal elements  Microtubule Microtubule and microfilament  Actin filaments Maintain shape and help Dense tubular contractions of platelets and system Open canalicular squeezing, clot retraction system Membrane channels Open canalicular system Dense tubular system Granulomere: contains granules and organelles Alpha granules: clotting factors, growth factors Dense (delta) granules: serotonin (absorbed from plasma), ATP, ADP Delta granule Alpha granule Lambda granules: lysosomes (aid in clot resorption) Lambda granule Dr. Heba Kalbouneh  Their main function is to continually monitor the vascular system and detect any damage to the endothelial lining of the vessels. If the endothelial lining breaks, the platelets adhere to the damaged site and initiate a highly complex chemical process that produces a blood clot Thus preventing blood loss Dr. Heba Kalbouneh