Chapter 1. Chapter 1 Concepts. MCMP422 Immunology and Biologics Immunology is important personally and professionally!

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1 MCMP422 Immunology and Biologics Immunology is important personally and professionally! Learn the language - use the glossary and index RNR - Reading, Note taking, Reviewing All materials in Chapters 1-3 are examinable (with exceptions) plus extra material from class Chapter 1 Elements of the Immune System and their Roles in Defense Summarizes all of immunology Foundation for the rest of the course The rest is all details Chapter 1 Concepts What components make up the immune system? Cells, organs, cytokines and other molecules involved in the immune system What is the goal of the immune system? To clear pathogens in our body How do we classify immune responses? Innate and adaptive immune responses What are the side effects of the immune system? Autoimmune diseases, Allergies, Transplantation Rejection 1

2 Immunology: the science of how the body responds to foreign organisms (e.g. pathogens) or substances (e.g. allergen) Immune system: the organs, cells and molecules that defend and respond to pathogens/allergens 1. Tissues/organs 2. Cells 3. Blood borne proteins Origin of Immunology - individuals who survived a disease seemed to be untouched upon re-exposure Vaccination/Immunization - procedure where disease is prevented by deliberate exposure to infectious agent that cannot cause disease. Figure 1-2 2

3 Diversity of Pathogens Four Classes Opportunistic pathogens Pathogen-Host relationship How Clean are You? Part of body Bacteria Head (scalp) 1,000,000 /cm2 Surface of skin 1000 /cm2 Saliva 100,000,000 /g Nose mucus 10,000,000 /g Faeces over 100,000,000 /g Defenses against Pathogens Physical Defenses 1. Skin 2. Mucosal surfaces Immune Defenses 1. Innate 2. Adaptive 3

4 Physical Barriers Figure 1-4 Innate and Adaptive responses Innate Pathogen independent Immediate (hours) Neutrophils NK cells Macrophages Mast cells Eosinophils Basophils Adaptive Pathogen-dependent Slower (days) Dendritic cells B cells T cells (CD4 or CD8) Both systems talk to each other to modulate response 4

5 Immunity: Three Basic Parts Pathogen (Foreign) Recognition (Binding event) Immune disorders (Self) Effector mechanisms Signal Effector Cells Complement Innate immunity - naïve, immediate, everyday immunity Acquired immunity - specialized, late, immunity One way Immunity Works Figure 1-5 part 1 of 2 Complement Effector cell Endocytosis Figure 1-5 part 2 of 2 5

6 Innate Immunity Figure 1-6 Cytokines Inflammation Phagocytosis Inflammatory cells What if Innate Immunity is not Enough? Innate immunity keeps us healthy most of the time Some pathogens escape the innate immune process Need a specific system to adapt to a specific pathogen Adaptive immune response Characteristics of Innate vs Adaptive Immunity Figure 1-7 Lymphocytes - white blood cells that increase the immune response to ongoing infection 6

7 Innate vs Adaptive Molecular Recognition Most important difference: Receptors used to recognize pathogens Innate immunity: Receptors recognize conserved structures present in many pathogens Pathogen-associated Molecular Patterns: LPS, peptidoglycan, lipids, mannose, bacterial DNA and viral RNA Adaptive immunity: Receptors recognize a specific structure unique to that pathogen Flowchart of Hematopoiesis Figure 1-11 part 1 of 2 7

8 Flowchart of Hematopoiesis Figure 1-11 Myeloid Lineage Granulocytes (Myeloid progenitor) Polymorphonuclear leukocytes (PMLs) Neutrophils: Figure 1-9 part 3 of 6 Most abundant Phagocyte Effector cells of Innate Immunity Short-lived - Pus Eosinophils: Worms/intestinal parasites Amplify inflammation Bind IgE Very Toxic - Pathogen and host Chronic asthma Basophils: Rare Unknown function Bind to IgE 8

9 Figure 1-9 part 5 of 6 Figure

10 Lymphoid Lineage Cells Figure 1-9 part 2 of 6 Lymp Figure 1-9 part 1 of 6 10

11 Erythroid Lineage Figure 1-9 part 6 of 6 Lymphoid Myeloid Erythroid Figure 1-11 part 2 of 2 11

12 Figure 1-12 Figure 1-14 Sites of Lymphoid Tissue Figure 1-15 Primary and Secondary GALT, BALT, MALT Lymph Recirculation 12

13 Figure 1-16 Draining Lymph node Edema Afferent and Efferent Figure 1-17 part 1 of 2 B-cell area (follicle) 13

14 Anatomy of immune function in the Spleen Figure 1-19 Figure 1-19 part 1 of 2 14

15 Figure 1-19 part 2 of 2 Figure

16 Adaptive Immunity 1. Vertebrates only 2. Specificity - recognition modules - BCR, Ab and TCR - gene rearrangement is the source of diversity - clonal selection 3. Small lymphocytes - types and sub-types - functions Recognition concept Receptor or Antibody molecule Antigen - structure recognized by an Ab, BCR or TCR Epitope - particular sub-structure of the Ag that is bound Affinity - how much a molecule likes to bind to a structure Small lymphocyte sub-types B-cells BCR is Immunoglobulin (Ig) Plasma cells - effector cells that secrete Ab T-cells T c = cytotoxic (CD8+) T H = helper T-cells (CD4+) Th1 (inflammation) Th2 (help B-cells make AB) 16

17 Recognition modules of Adaptive immunity B cells T cells B-cells T-cell Figure 1-25 Intracellular pathogens Extracellular pathogens 17

18 MHC class Figure I communicates 1-26with Tc cells MHC class II communicates with T H cells Figure 1-27 Parasitic infection Parasite + Mast cell Inflammation Mast cell activated Neutralization Opsonization 1. Inflammation Expel and/or destroy pathogen 18

19 Principles of Adaptive Immunity Diversity Specificity Memory Self-tolerance Gene Rearrangement is the source of Diversity Germline configuration Diversity 1. Alternative combinations 2. Imprecise joints 3. Different types of chains 4. B-cells - somatic hypermutation In the absence of antigen Clonal Selection 1. Each cell = one receptor 2. Millions of lymphocytes are generated 3. Small subset will recognize a pathogen 4. Proliferation and differentiation 5. Acquired immunity - the adaptive immunity provided by immunological memory 19

20 Figure 1-22 Figure 1-30 Polio Vaccine - Inactive vs Oral live version 20

21 Figure 1-28 Mechanism of Self-tolerance Immunodeficiencies Inherited deficiencies Stress induced Pathogen caused deficiencies Figure 1-32 Cells and molecules involved in Hypersensitivity Diseases IgE IgG CD4 T H 1 CD8 CTL 21

22 Insulin-Dependent Diabetes Mellitus Figure 1-33 Figure