PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson Immunology: Categorization of Leukocytes Action SIAMAK BADIE, SALIMAH CHAMPSI, FANYA GAO, DANIELLE PORTER Leukocytes 5 Classes: Neutrophils (40% - 75%) Eosinophils (1% - 6%) Granulocytes Basophils (less than 1%) Monocytes (2% - 10%) Lymphocytes (20% - 45%) Agranulocytes Neutrophils – Mechanism of Action Characteristics: - Innate immune response - Most abundant - First responders - Granulocytes Damaged Cells Cytokines Phagocytosis Degranulation Oxidative burst: use energy from NADPH to form oxygen free radicals Release anti-microbial compounds NETs Trap microbes Basophils – Mechanism of Action Allergic Response Degranulation B-phil Th cell B cell Produce antibodies Eosinophils – Mechanism of Action Cell Activation Degranulation Degranulation E-phil Host Defense (Peroxidase + Rnase) Monocytes – Mechanism of Action Hematopoietic Stem Cells LP MP Bone Marrow Blood Tissue Ly6C Monocyte Macrophage - Phagocytosis MDP CDP Ly6C+ Monocyte MonocyteDerived DC - Process and present antigen to T cell Pre-CDC PDC Classical DC PDC - Process and present antigen to T cell - Respond to viral infection - Act as APC and control T cell responses Lymphocytes– Mechanism of Action Adaptive Immune Response Antigen Innate Immunity: NK Cells -Non specific attack on tumours and infected cells -Release cytotoxic granules to induce cell apoptosis Macrophage MHC Helper T cell Cellular: Cell-Mediated Humoural: Antibody-Mediated B cell T&B Memory T cell Suppressor T Cells Antibodies: Signal destruction pathways Granules: breakdown cell membrane of pathogens Summary Neutrophils: Phagocytosis: use energy from NADPH to form oxygen free radicals Degranulation: secrete antimicrobial compounds Formation of neutrophil extracellular traps: trap microbes Eosinophils: Work mainly to counter infections Granules produce ROS/RNS and ribonucleases Basophils: Work mainly in allergic responses Granules contain histamine, heparin, and antiparasitic molecules Monocytes: Circulate in blood and differentiate into macrophages and dendritic cells in tissues during inflammation Digest pathogens and stimulate antibodies Lymphocytes: Adaptive immunity: antibody mediated B cells and cell mediated T cells attack antigen and provide antigen memory Innate Immunity: natural killer cells attack non-specifically through release of cytotoxic granules References 1. Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Helper T Cells and Lymphocyte Activation. Available from: http://www.ncbi.nlm.nih.gov/books/NBK26827/ 2. Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A. Neutrophil function: from mechanisms to disease. Annu. Rev. Immunol. 2012; 30: 459-489 3. Bandeiro-Mela, C., & Weller, P. Mechanisms of eosinophil cytokine release. PMC. 2005; 100(1), 73-81 4. Falcone, F., Hass, H., & Gibbs, B. The human basophil: A new appreciation of its role in immune responses. Blood Journal. 2000; 96(13): 4028-4038 5. Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages and dendritic cells. Science. 2010;327(5966):656-661 6. Maddaly, R., Govind, P., Balaji, S. et al. Receptors and signalling mechanisms for B-lymphocyte activation, proliferation and differentiation- Insights from both in vivo and vitro approaches. FEBS Letter. 2010; 584(24): 4883-4894