MCMP 422: Immunology Class MWF 11:30-12:20 Instructors –Dr. Geahlen –Dr. Harrison –Dr. Hazbun (RHPH 406D, , Objectives Course Policies Grading

The Immune System Second Edition Chapter 1 Elements of the Immune System and their Roles in Defense Copyright © 2005 by Garland Science Publishing Peter Parham

Chapter 1 Summarizes all of immunology Get a good Foundation Before class: Read the textbook in general and try to understand all the terminologies in bold. During class: Take good notes because I will be adding information that will be tested After class: Review material to commit to long-term memory

What components make up the immune system? Cells, organs, cytokines and molecules involved in the immune system What is the goal of the immune system? To clear pathogens and cancer cells 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 Lecture Concepts

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

Part of body Bacteria Head (scalp) 1,000,000 /cm2 Surface of skin 1000 /cm2 Saliva 100,000,000 /g Nose mucus10,000,000 /g Faeces over 100,000,000 /g How Clean are You?

Four Classes Opportunistic pathogens Pathogen-Host relationship Diversity of Pathogens

Defenses against Pathogens Physical Defenses 1. Skin 2. Mucosal surfaces Immune Defenses 1. Innate 2. Adaptive

Figure 1-4

Pathogen Recognition Signal Effector mechanisms Effector CellsComplement Innate immunity - “naïve” everyday immunity Acquired immunity - “specialized” immunity Immunity: Basic Parts (Binding event) (Foreign) (Self) Immune disorders

Figure 1-5 part 1 of 2 Complement Effector cell Endocytosis One way Immunity Works

Figure 1-5 part 2 of 2

Figure 1-6 Cytokines Inflammation Phagocytosis Inflammatory cells Innate Immunity

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

Figure 1-7 Characteristics of Innate vs Adaptive Immunity Lymphocytes - white blood cells that increase the immune response to ongoing infection

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

Figure 1-11 part 1 of 2 Flowchart of Hematopoiesis

Figure 1-11 Flowchart of Hematopoiesis

Myeloid Lineage

Figure 1-9 part 3 of 6 Neutrophils: 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 Granulocytes (Myeloid progenitor) Polymorphonuclear leukocytes (PMLs)

Figure 1-9 part 5 of 6

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Lymphoid Lineage Cells

Figure 1-9 part 2 of 6 Lymp

Figure 1-9 part 1 of 6

Erythroid Lineage

Figure 1-9 part 6 of 6

Figure 1-11 part 2 of 2 LymphoidMyeloidErythroid

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

Figure 1-16 Draining Lymph node Edema Afferent and Efferent

Figure 1-17 part 1 of 2

B-cell area (follicle)

Figure 1-19 Anatomy of immune function in the Spleen

Figure 1-19 part 1 of 2

Figure 1-19 part 2 of 2

Figure 1-20

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 like to bind to a structure

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) Small lymphocyte sub-types

Recognition modules of Adaptive immunity B cellsT cells

B-cellsT-cell

Figure 1-25 Intracellular pathogens Extracellular pathogens

Figure 1-26 MHC class I communicates with Tc cells

Figure 1-27 MHC class II communicates with T H cells

Parasite + Mast cell Inflammation Mast cell activated Expel and/or destroy pathogen Neutralization Opsonization 1.Inflammation Parasitic infection

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

Figure 1-22

Figure 1-30

Figure 1-31

Figure 1-28 Mechanism of Self-tolerance

Immunodeficiencies Inherited deficiencies Stress induced Pathogen caused deficiencies

Figure 1-32 IgG CD4 T H 1 CD8 CTL

Figure 1-33 Insulin-Dependent Diabetes Mellitus

Figure 1-34

Figure 1-10

Figure 1-29 part 1 of 2

Figure 1-29 part 2 of 2

Figure 1-31 part 1 of 3

Figure 1-31 part 2 of 3

Figure 1-31 part 3 of 3