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CoolNitrogen

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Noel A. Brownlee, M.D., Ph.D.

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immunology biology blood composition medical science

Summary

This document is a set of lecture notes on immunology, covering topics such as blood composition, the classification of leukocytes, the formation of blood cells, and patterns of infection/inflammation. The notes are suitable for an undergraduate level course.

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IMMUNOLOGY 101 Help with all of that immunity stuff!!! Course Professor: Noel A. Brownlee, M.D., Ph.D. MABS Microbiology Powerpoint by: Cathleen J. Ciesielski. Ph.D. COURSE INSTRUCTIONAL OBJECTIVES MCRO 1.1 The student will explain the composition of blood, including the which leukocytes (white b...

IMMUNOLOGY 101 Help with all of that immunity stuff!!! Course Professor: Noel A. Brownlee, M.D., Ph.D. MABS Microbiology Powerpoint by: Cathleen J. Ciesielski. Ph.D. COURSE INSTRUCTIONAL OBJECTIVES MCRO 1.1 The student will explain the composition of blood, including the which leukocytes (white blood cells) are granulocytes vs non-granulocytes; polymorphonuclear vs mononuclear and phagoctyes vs non-phagocytes. MCRO 1.2 The student will explain the formation of blood cells including the leukopoiesis (genesis of leukoctyes). MCRO 1.3 The student will characterize the difference between neutrophils vs eosinophils vs basophils, including their histology. MCRO 1.4 The student will characterize the difference between innate and acquired immunity. MCRO 1.5 The student will describe the difference between T-cell (T-lymphocytes) including MHC vs B-cells (B-lymphocyte); including that activated B-cells are plasma cells that produce antibodies. MCRO 1.6 The student will describe the shape of an antibody and explain the difference in the five types of antibodies/immunoglobulins. COMPOSITION OF BLOOD Centrifuged blood § Erythrocytes • lower layer of centrifuged blood • 44% of sample § Buffy coat • middle slightly gray-white layer • composed of leukocytes and platelets • less than 1% of sample § Plasma • straw colored liquid at top of tube • remaining sample MCRO 1.1 COMPOSITION OF BLOOD MCRO 1.1 LEUKOCYTES CLASSIFICATION Non- Granuolcytes: Monocyte Lymphocyte Granuolcytes: Neutrophil Basophil Eosinophil MCRO 1.1 LEUKOCYTE CLASSIFICATION § Granulocytes – 65% Non- Granulocytes • Neutrophils – 62 % - Monocytes – 5.3% • Eosinophils– 2.3% - Lymphocytes – 30% • Basophils– 0.4% § Polymorphonuclear Mononuclear • Neutrophils - Monocytes • Eosinophils • Basophils - Lymphocytes § Phagocytes Non-phagocytes • Neutrophils, monocytes - Lymphocytes • Macrophages, eosinophils - Basophils MCRO 1.1 FORMATION OF BLOOD CELLS Hematopoiesis: development of the formed elements of blood from bone marrow stem cells. Cells below the horizontal line are found in normal peripheral blood. The principal cytokines that stimulate each cell lineage to differentiate are shown. (EPO, erythropoietin; TPO, thrombopoietin; CSF, colony-stimulating factor; G, granulocyte; M, macrophage; IL, interleukin; SCF, stem cell factor.) See Table 6–1 for details. (Redrawn, with permission, from Ganong WF. Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005.) MCRO 1.2 FORMATION OF BLOOD CELLS Leukopoiesis MCRO 1.2 GENESIS OF LEUKOCYTES (WBC) § Granulocytes and monocytes develop in the bone marrow, and most remain there until needed peripherally (number in marrow ~3x blood; 6-day supply) § Lymphocytes develop mostly in the peripheral lymphoid organs (thymus, spleen, tonsils, lymph nodes, Peyer’s patches) § Megakaryocytes develop and reside in the red marrow, fragment to release platelets MCRO 1.2 PATTERNS OF INFECTION/INFLAMMATION § Bacterial Infection: increased neutrophil count (neutrophilia) • Pus, purulence, suppurative, abscess are terms associated with bacterial infection • Bacterial infections may have increased numbers of circulating immature neutrophils known as “bands” § Viral Infections: increased lymphocyte count (lymphocytosis § Parasitic infections: increased eosinophil counts MCRO 1.2 FORMATION OF PUS Composition of Pus § Necrotic tissue § Dead neutrophils § Dead macrophages § Tissue fluid § Eventually absorbed into the tissues MCRO 1.3 EOSINOPHILS § ~ 2% of total white blood cells § Weak phagocytic activity § Exhibit chemotaxis § Active against parasites (worms) • schistosomiasis • trichinosis • Immunomodulatory – attach to juvenile forms of parasite 1. Granules (lysosomes) – hydrolytic enzymes 2. Reactive forms of oxygen 3. Major basic protein - larvacidal § Decrease inflammation from basophils and mast cells in allergic reactions MCRO 1.3 BASOPHILS § ~ 1.5 -0.5% of total white blood cells § Basophils similar to mast cells § Release primarily histamine • • • • some bradykinin, serotonin heparin slow-reacting substance of anaphylaxis lysosomal enzymes § Release of chemicals • IgE antibody attached to the cell • Binding an antigen to the antibody causes cell rupture MCRO 1.3 Immunity Innate Defenses = non-specific defenses § Ability to resist damaging organisms and toxins § Barriers (skin/gastric acid) § Cells (neutrophils & macrophages) § Chemicals (lysozyme, complement) § Processes (fever, phagocytosis, inflammation) Acquired Immunity = specific defenses § Humoral (antibody-mediated) ----> circulating antibodies § Cellular (cell-mediated) ----> activated T cells MCRO 1.4 T- CELLS § Lymphocytes processed by the thymus • Cells divide rapidly • Extreme diversity – each lymphocyte will react to only one antigen • Thousands of antigens § Surface cell receptor proteins (T-cell markers) – react with specific antigens § Activation causes clone proliferation – some lymphocytes remain in the tissues – T-lymphocyte memory cells MCRO 1.5 B-CELLS § Bone marrow – late fetal life and after birth § B lymphocytes • Secrete antibodies • Large protein molecules • Combine with and destroy antigenic substances § 100,000 antibody molecules on the cell surface MCRO 1.5 PLASMA CELLS Activated B lymphocytes enlarge 1. Plasmablasts – – – Form plasma cells Proliferate – 500 cells per precursor Gamma globulin antibodies – 2000/sec MCRO 1.5 Antibodies antigen binding site heavy chain light chain IgG: bivalent antibody 75% of antibodies Fab fragment Variable portion Specificity of antibody Fc fragment Constant portion -diffusivity into tissues hinge region -adherence to tissues -pass through membranes Attachment to complement complex IgA, IgD, IgE, IgG, IgM: at least 2 and as many as 10 heavy-light pairs MCRO 1.6 ANTIBODIES/IMMUNOGLOBULINS (Ig) § IgG (immunoglobin G) • 75% total, cross placenta, opsonization § IgM • first produced, 10-15% total, activate complement § IgD • not known, may help CD4 T cell § IgA • body fluid, tears, bronchiole secretions, saliva § IgE • allergic reactions, histamine release MCRO 1.6 T-CELL & MHC MHC-I: present foreign peptides to cytotoxic T cells MHC-II: present foreign peptides to helper T cells Cytoxic Cells: kill infected cells Helper Cells (two types): activate macrophages and B-cells Suppressor Cells: regulate activity MCRO 1.5 20 CYTOTOXIC T CELLS § Killer cells – direct attack on microorganisms § Figure 1. Secretion of perforins – cell membrane 2. 3. Fluid flows into the cell Cytotoxic substances injected into the cell 4. Killer cell pulls away from its victim § Kill tissue cells invaded by viruses § Kill cancer cells § Heart transplant cells MCRO 1.5

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