1. Immunology: Categorization of Leukocytes Action SIAMAK BADIE, SALIMAH CHAMPSI, FANYA GAO, DANIELLE PORTER PHM142 Fall 2015 Instructor: Dr. Jeffrey Henderson

2. Leukocytes 5 Classes:  Neutrophils (40% - 75%)  Eosinophils (1% - 6%)  Basophils (less than 1%)  Monocytes (2% - 10%)  Lymphocytes (20% - 45%) Granulocytes Agranulocytes

3. Damaged Cells Cytokines DegranulationPhagocytosisNETs  Oxidative burst: use energy from NADPH to form oxygen free radicals  Release anti-microbial compounds  Trap microbes Neutrophils Characteristics: -Innate immune response -Most abundant -First responders -Granulocytes – Mechanism of Action

4. Basophils – Mechanism of Action B-phil Th cell B cell Produce antibodies Degranulation Allergic Response Degranulation

5. Eosinophils – Mechanism of Action E-phil Host Defense (Peroxidase + Rnase) Cell Activation Degranulation

6. Hematopoietic Stem Cells Ly6C - Monocyte CDP MDP LP MP Ly6C+ Monocyte Macrophage Monocyte- Derived DC PDC Pre-CDC PDC Classical DC Bone Marrow Blood Tissue Monocytes – Mechanism of Action - Phagocytosis - Process and present antigen to T cell - Respond to viral infection - Act as APC and control T cell responses

7. Cellular: Cell-Mediated Humoural: Antibody-Mediated Adaptive Immune Response B cell T cell T & B Memory Suppressor T Cells Antigen Antibodies: Signal destruction pathways Granules: breakdown cell membrane of pathogens Macrophage Helper T cell MHC Innate Immunity: NK Cells -Non specific attack on tumours and infected cells -Release cytotoxic granules to induce cell apoptosis Lymphocytes– Mechanism of Action

8. 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

9. 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