UNIT X HUMAN IMMUNE SYSTEM & DISEASE Baby Campbell – Ch 9, 17, 24, 35 Big Campbell – Ch 12, 19, 27, 43

I. IMMUNE SYSTEM OVERVIEW 2

II. INNATE IMMUITY Barrier Defenses Skin Secretions Mucus Ciliated Epithelial Cells Lysozyme pH Normal Flora 3

II. INNATE IMMUNITY, cont Internal Defenses - Cellular Phagocytic Cells Detect pathogens using several types of receptors that are indicative of a type of pathogen Known as Toll-like receptors (TLRs) Recognize PAMPs – “Pathogen-Associated Molecular Patterns” 4

II. INNATE IMMUNITY, cont Internal Defenses - Cellular Phagocytic Cells Neutrophils 60-70% of WBCs Circulate in blood Respond to signals from infected tissue Macrophages 5% WBCs Begin as monocytes Migrate through body or reside in specific organs, tissues Dendritic Cells Found in tissues that are in contact with environment; skin Migrate to lymph nodes; stimulate adaptive immunity

II. INNATE IMMUNITY, cont Internal Defenses - Cellular Natural Killer (NK) Cells Lymphocytes Circulate throughout body Recognize lack of Class I MHC molecules – Class I MHC molecules are found in all normal cells; missing in virus-infected, cancer cells Trigger apoptosis by releasing perforins, other proteins

II. INNATE IMMUNITY, cont Internal Defenses - Cellular

II. INNATE IMMUNITY, cont Internal Defenses - Chemical Fever Interferon Proteins released by virus-infected cells Diffuse to healthy cells; stimulates production of proteins that inhibit viral replication

II. INNATE IMMUNITY, cont Internal Defenses - Chemical Complement System ~30 proteins that circulate in inactive form Activated by presence of pathogens Activation results in a cascade of biochemical reactions May result in lysis of pathogen, activation of inflammatory response

II. INNATE IMMUNITY, cont Internal Defenses - Chemical Inflammatory Response Histamine released by mast cells in response to injury, infection Causes blood vessels in area to dilate, increase permeability Macrophages, neutrophils in area respond, release cytokines Causes increased blood flow to region, resulting in redness & swelling 10

III. ADAPTIVE IMMUNITY Unique to vertebrates Based on function of white blood cells known as Four important properties of adaptive immunity Specificity Diversity Self from non-self Immunologic Memory Effector Cells Memory Cells

III. ADAPTIVE IMMUNITY, cont Lymphocytes further categorized based on mechanism for identification, response to pathogen/abnormal cell T Lymphocytes Mature in thymus Only capable of recognizing “displayed” antigens Respond by releasing toxic proteins to destroy infected cells B Lymphocytes Mature in bone marrow Bind to intact antigens in blood and lymph Antigens may be present on pathogen

III. ADAPTIVE IMMUNITY B and T Cell function based on interactions between… Receptor proteins Plasma membrane receptors on B and T cells Every receptor (~100,000) on a single cell is identical Binds to a specific foreign molecule Antigen Foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms, foreign cells) 13

III. ADAPTIVE IMMUNITY, cont Overview

III. ADAPTIVE IMMUNITY, cont Humoral Immunity & B Cells Activation of B cells Binding of B cell antigen receptor to epitope Triggers secretion of antibodies Antigen-binding immunoglobulin Soluble form of antigen receptor Composed of 2 heavy chains and 2 light chains joined by disulfide bridges Five classes of antibodies IgG is most abundant Effective against bacteria, toxins, and viruses free in the lymph and blood plasma 15

III. ADAPTIVE IMMUNITY, cont B Cells, cont

III. ADAPTIVE IMMUNITY, cont B Cells, cont Antibody Function

III. ADAPTIVE IMMUNITY Humoral Immunity, cont 18

III. ADAPTIVE IMMUNITY Humoral Immunity, cont

III. ADAPTIVE IMMUNITY Cell Mediated Immunity & T Cells T cells respond to displayed antigen on Antigen Presenting Cells (APCs) Antigen is bound to surface proteins found on virtually all cells known as Class I Major Histocompatibility Complex or Class I MHC Activated T cells are cytotoxic Secrete proteins that trigger cell death by causing lysis, destruction of cell membrane integrity T cells defend against cells infected with bacteria, viruses, fungi, protozoa, and parasites; nonself interaction

III. ADAPTIVE IMMUNITY Cell-Mediated Immunity, cont

III. ADAPTIVE IMMUNITY The Role of Helper T Cells Trigger both humoral and cell-mediated response Antigen is displayed on Class II MHC complex on “professional” Antigen Presenting Cells Include dendritic cells, macrophages, and B cells

III. ADAPTIVE IMMUNITY Clonal Selection Binding of antigen to receptor molecule activates particular lymphocyte Response is amplified by rapid division of B, T cells; known as clonal selection Effector cells are short-lived plasma cells that combat the antigen Primary Immune Response Memory cells are long-lived cells that bear receptors for the antigen Secondary Immune Response 23

IV. IMMUNIZATION Acquired Immunity Passive Immunity Conferred immunity by recovering from disease Immunization produces an immune response Passive Immunity Transfer of immunity from one individual to another Natural – Mother to fetus; lactation Artificial – Rabies antibodies

V. IMMUNE REJECTION ABO blood groups Rh factor Organ Transplants

VI. MISREGULATION OF IMMUNE SYSTEM Allergies Autoimmune Diseases

VI. MISREGULATION OF IMMUNE SYSTEM, cont Immunodeficiency Diseases SCIDS

VII. STRESS & IMMUNE SYSTEM

INFECTIOUS DISEASE

I. VIRUSES

I. VIRUSES, cont

II. HUMAN VIRAL REPLICATION Lytic Infection

II. HUMAN VIRAL REPLICATION, cont Latent Infection

II. HUMAN VIRAL REPLICATION, cont HIV Infection

III. PREVENTION & TREATMENT OF VIRAL DISEASES Containment

III. VIRAL DISEASES, cont Prevention Vaccination

III. VIRAL DISEASES, etc Treatment

IV. BACTERIA 38

IV. BACTERIA, cont Adaptations for Virulence Capsule Endospore Quorum Sensing 39

IV. BACTERIA Pathogenesis Direct Attack Toxin Production Exotoxins Bacterial proteins that can produce disease w/o the prokaryote present Examples include botulism, cholera Endotoxins Components of gram negative membranes Examples include typhoid fever, Salmonella food poisoning Hypersensitivity 40

V. PREVENTION & TREATMENT OF BACTERIAL DISEASE Normal flora

V. PREVENTION & TREATMENT OF BACTERIAL DISEASE

I. CANCER – AN OVERVIEW

I. CANCER OVERVIEW, cont Tumor versus Cancer Benign tumor Malignant tumor Metastasis

II. CELL CYCLE REGULATION Drivers Checkpoints G2 Checkpoint Is my DNA correctly replicated? Are chromosomes ready for separation? Mitosis Checkpoint Is environment ok? Is my DNA intact? G1 Checkpoint/ Restriction Point

II. CELL CYCLE REGULATION, cont G1 Driver Cyclin D S Driver 1 Cyclin E S Driver 2 Cyclin A G2/M Driver Cyclin B

III. A CLOSER LOOK AT CANCER Cancer-causing mutations can generally be placed in one of two categories: Oncogenes/Proto-oncogenes Tumor Suppressor Genes 48

III. A CLOSER LOOK AT CANCER, cont Oncogenes Examples HER-2/neu (erbB-2): a growth factor receptor. ras: a signal transduction molecule myc: a transcription factor src: a protein tyrosine kinase. hTERT: an enzyme that functions in DNA replication. Bcl-2: a membrane associated protein that functions to prevent apoptosis.

III. A CLOSER LOOK AT CANCER, cont Oncogenes, cont

III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes Encode for proteins that inhibit cell division therefore any mutation that inhibits activity of tumor-suppressor gene may lead to abnormal cell growth and formation of tumors. Act by producing proteins that repair damaged DNA, control density-dependent inhibition & anchorage dependence, or act as CDKs Examples INK proteins p53 Rb BRCA1 BRCA2 APC

III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont Gene that is most often defective in human cancers codes for transcription factor known as p53 Known as the “guardian angel of the genome” Serves as the master brake on the cell cycle when DNA damage has occurred p53 activates several genes with multiple effects Genes activated to halt cell cycle DNA repair genes turned on If DNA damage cannot be repaired, “suicide genes” are activated; results in apoptosis

III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont Apoptosis Nucleus Nucleus Nucleus blebs blebs The cell blebs Nucleus condenses Nucleus fragments The blebs are phagocytosed

III. A CLOSER LOOK AT CANCER, cont Tumor Suppressor Genes, cont BRCA 1 and BRCA 2 54

IV. CANCER & IMMUNOTHERAPY

IV. CANCER & IMMUNOTHERAPY, cont