1-Doschak PH310-Elements of the Imm System (2023) Ver 2.pdf

Pharmacy 310 Elements of the Immune System Dr. Michael R. Doschak Professor Faculty of Pharmacy & Pharmaceutical Sciences University of Alberta Email: [email protected]  Immunology Study of physiological mechanisms and def...

Pharmacy 310 Elements of the Immune System Dr. Michael R. Doschak Professor Faculty of Pharmacy & Pharmaceutical Sciences University of Alberta Email: [email protected]  Immunology Study of physiological mechanisms and defenses humans (and animals) employ against invading microorganisms Immune System: Cells and humoral factors dedicated to defend the body against infection  Triumphs of Immunology Protective Immunity: Vaccination or immunization – Severe disease prevented by prior exposure to attenuated infectious agent Tissue and Organ Transplantation – Bone marrow – Immunosuppression Antibody diagnostics and therapeutics Figure 1-1 Elements of the Immune System Innate Immunity (passive) – Physical barriers, cells, soluble factors Adaptive Immunity (acquired, protective) – Cell-mediated immunity – Humoral immunity  Infectious Organisms Pathogen: any organism with the potential to cause disease Opportunistic Pathogen: take advantage of an individual’s weakened body’s defenses and cause illness Figure 1-2  Figure 1-3 part 4 of 4 Bacteria: Bacteria: Bacteria: Listeria monocytogenes Salmonella enteritidis Streptococcus pyogenes  Figure 1-3 Ringworm fungus: part 2 ofInfluenza Retrovirus: 4 virus: Epidermophyton floccosum HIV Orthomyxovirus  Figure 1-3 Helminth worm: part 1 of 4Fungus: Protozoan: Schistosoma mansoni Trypanosoma brucei Pneumocystis carinii  Physical Barriers to Infection Skin and mucosal surfaces – Layers of keratinized cells – Mucus: thick fluid (acidic glycoprotein) containing enzymes (lysozyme) – Ciliated epithelial cells (lungs) When barriers breached, pathogens readily gain access Figure 1-4 Innate Immunity: Soluble Factors Bactericidal factors – Hydrochloric acid (stomach parietal cells) – Phagocyte cell lysosomes (superoxide and H2O2 production, a.k.a. “Respiratory burst”) – Lysozyme, lysosomal defensin proteins Complement proteins Interferon cytokines Innate Immunity: Soluble Factors Bactericidal factors Complement proteins – Group of serum glycoproteins – Activated during innate immune reponse – Induce cytotoxicity of foreign organism Interferon cytokines Innate Immunity: Soluble Factors Bactericidal factors Complement proteins Interferon cytokines – Group of antiviral glycoproteins (16-27kDa) – Released from virus-infected cells  Inflammatory Response Overall effect of the innate immune response Characterized by five cardinal signs: – Rubor (redness) – Calor (heat) – Dolor (pain) – Tumor (swelling) – Functio-laesia (loss of function) Figure 1-6 part 1 of 2 Figure 1-6 part 2 of 2 Figure 1-7  Adaptive Immunity Results when innate immune response overwhelmed Mediated by white blood cells (lymphocytes) Highly specialized defence against one pathogen at a time (takes up to one week) Mediated by cell surface receptor molecules coded for by genes that are cut & spliced to produce billions of variants  Leukocytes: Cells of the Immune System Common progenitor (pluripotent haematopoietic stem cell) Gives rise to differentiated lineages: – Lymphoid – Myeloid – Erythroid Figure 1-11 Figure 1-9 part 1 of 6 Figure 1-9 part 2 of 6 Figure 1-9 part 3 of 6 Figure 1-9 part 4 of 6 Figure 1-9 part 5 of 6 Figure 1-9 part 6 of 6 Peripheral Blood Count Red Blood Cells and Leukocytes Leukocyte proportions change depending on the type of Immune Response invoked Figure 1-12 Sites of Hemopoietic Activity in Humans Figure 1-10 Neutrophils – the predominant phagocytic cell of Innate Immunity Figure 1-13  Primary Lymphoid Organs Where lymphocytes develop and mature Bone Marrow Thymus Secondary Lymphoid Tissues Where mature lymphocytes are stimulated and respond to pathogens Spleen Adenoids Tonsils Appendix Lymph nodes Peyer’s patches Secondary Lymphoid Tissues GALT: Gut-associated lymphoid tissue – Tonsils, adenoids, appendix, Peyer’s patches BALT: Bronchial-associated lymphoid tissue – Aggregates of less-organized lymphoid tissue MALT: Mucosa-associated lymphoid tissue – Mucosal aggregates of lymphoid tissue Principal Lymphoid Tissues Figure 1-15  Lymph nodes & Lymphatics Lie at the junctions of anastomosing lymph vessels, or lymphatics Lymphatics originate in connective tissues Collect extracellular fluid that leaks from blood vessels Return fluid (via thoracic duct to subclavian vein in neck) to venous circulation Mature lymphocytes “recirculate”, from: 1o organs – blood stream – populate 2o organs – then use lymphatics to get back to the blood circulation, and to tissue sites where needed Lymphocytes-pathogens meet in lymph nodes 4 Figure 1-16 1 3 2  Lymph Node Structure and Cellular Organization Figure 1-17  Splenic Structure and Cellular Organization Figure 1-19 part 1 of 2 NB. Spleen has no lymphatic connections. It filters circulating blood, removes old red blood cells, bacteria, site of Aby production as well (lymphoid organ) Figure 1-20  Adaptive Immunity Immunoglobulin (Ig, or antibody) – Protein with binding activity, synthesized by B-lymphocytes (secreted by plasma cells) – Identify and neutralize foreign objects – Found in serum, body fluids, and tissues – Cell-surface tethered and secreted forms T-cell receptors (TCRs) – Cell surface molecules that recognize antigen – Found only on T-cells  Antigen (Ag) (Definitions): Any substance capable of inducing a specific immune response Any molecule recognized and bound by an immunoglobulin or T-cell receptor Antigenic determinant (or “epitope”) is the part of the antigen surface that is bound TCRs and Igs have “specificity” for Ag Figure 1-21 Specificity of Adaptive Immunity Figure 1-22 Figure 1-8  Key Attributes of Adaptive Immunity Specificity – reacts to each antigen Memory – remembers encounter with Ag; next response quicker and greater Amplification – clonal expansion Modulation – switching of Aby isotypes Figure 1-30  Resource Materials Parham P: The Immune System, 2nd Edn., Garland Science, New York, 2005. Shen W-C, Louie SG: Immunology for Pharmacy Students, Harwood Academic, Netherlands, 1999. © Copyrighted material contained herein is reproduced under ss. 29-29.4 of the Canadian Copyright Act. This document is available for your individual use; further distribution may infringe copyright.