Innate Immunity Chapter 2 PDF

6/26/2024 Chapter 2 I N N AT E I M M U N I T Y Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ◦ PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for...

6/26/2024 Chapter 2 I N N AT E I M M U N I T Y Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. ◦ PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  6/26/2024 External defense system Physical, chemical, and biological barriers Chapter Internal defense system Pattern-recognition receptors Overview Acute-phase reactants Inflammation Phagocytosis and killing of pathogens Natural killer (NK) cells Innate lymphoid cells Defenses that act immediately when a host is attacked by a pathogen Nonspecific Innate External defense system ◦ Anatomical barriers to keep Immune microorganisms from entering the System body Internal defense system ◦ Cellular responses that recognize specific molecular components of pathogens 2  6/26/2024 External Defense System PHYSICAL, CHE MICAL, AND B I O L O G I C A L B A R R I E R S T H AT P R E V E N T I N F E C T I O U S AG E N T S FRO M E NTE RING THE BODY External Defense System (continued_1) Skin Physical barrier to pathogen entry Epidermis: tightly packed epithelial cells coated in keratin Dermis: connective tissue with blood vessels, hair follicles, sebaceous glands, sweat glands, and white blood cells (WBCs) Secretions discourage microorganism growth Lactic acid and fatty acids maintain the skin at a pH of ~ 5.6. Proteins with antibacterial effects (e.g., psoriasin) 3  6/26/2024 Mucous membranes Line respiratory, digestive, and genitourinary tracts Serve as a physical barrier to pathogen entry External Mucous secretions contain surfactants that Defense block bacteria from adhering to epithelial System cells. (continued_2) Respiratory tract Cilia in nasopharyngeal passages clear deposited material. Coughing and sneezing remove pathogens. External Defense System (continued_3) Microbiota (normal Digestive tract Genitourinary tract flora) Stomach’s urine flushes out Help to keep hydrochloric acid pathogens pathogens from keeps the pH as low lactic acid keeps establishing as 1, prohibiting vagina pH at ~5. themselves in the microorganism growth. body Lysozyme in tears and saliva attacks cell walls of gram-positive bacteria. 4  6/26/2024 Internal Defense System Composed of cells and soluble factors that nonspecifically defend against foreign invaders ◦ Pattern-recognition receptors ◦ Acute-phase reactants ◦ Inflammation ◦ Phagocytic cells ◦ Natural killer (NK) cells ◦ Innate lymphoid cells Found on macrophages and dendritic cells, neutrophils, eosinophils, monocytes, mast cells, T cells, and epithelial cells Pattern Recognize molecules unique to infectious organisms called pathogen-associated molecular patterns (PAMPs) Recognition Receptors When bound to a pathogen, activate phagocytic cells (PRRs) Examples are TLRs, CLRs, RLRs, NLRs 5  6/26/2024 Toll-Like Receptors (TLRs) 10 types found in humans ◦ Some on cell surfaces ◦ Some in cytoplasm ◦ Glycoproteins that bind to microbial substances, activating cytokine and chemokine production and other processes ◦ Phagocytosis is enhanced and adaptive immunity is triggered, destroying pathogens before disease sets in C-type lectin receptors (CLRs) bind to mannan and β-glucans in fungal cell walls to activate cytokine and chemokine Retinoic acid–inducible gene-I-like receptors Other PRRs (RLRs) recognize RNA from RNA viruses and induce production of inflammatory cytokines/ type I interferons Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) 6  6/26/2024 Acute-Phase Reactants Soluble factors normally found in serum Increase rapidly in response to infection, injury, or tissue trauma Facilitate contact between microbes and phagocytic cells Limit host tissue destruction caused by proteolytic enzyme release and phagocytosis Bind to, and recycle, important proteins and minerals during inflammation Examples of Acute-Phase Reactants PROTEIN RESPONSE TIME NORMAL CONCENTRATION INCREASE FUNCTION (HOURS) (MG/DL) C-reactive protein 4–6 0.5 1,000X Opsonization, complement activation Serum amyloid A 24 5 1,000X Activates monocytes and macrophages Alpha1-antitrypsin 24 200–400 2–5X Protease inhibitor Fibrinogen 24 200–400 2–5X Clot formation Haptoglobin 24 40–290 2–10X Binds hemoglobin Ceruloplasmin 48–72 20–40 2X Binds copper and oxidizes iron Complement C3 48–72 60–140 2X Opsonization, lysis 7  6/26/2024 Process of Inflammation The body’s overall reaction to injury or invasion by an infectious agent Cardinal signs and symptoms Redness (erythema) Swelling (edema) Heat Pain Major Events Involved in Acute Inflammation Know these 5 steps! 8  6/26/2024 Process of Phagocytosis Phagocytic cells attracted to site of inflammation ◦ Neutrophils ◦ Monocytes ◦ Macrophages ◦ Dendritic cells Process is enhanced by opsonins like CRP. Know these 7 steps! Killing of Pathogens Oxidative burst — HMP shunt converts NADP to NADPH; O2 is converted to O2-; O2- to H2O2 and OH- O2 independent pathway — pH of cell is altered, leading to activation of lytic enzymes such as defensins 9  6/26/2024 Natural Killer (NK) Cells First line of defense against cells that are virally infected, cells infected with other intracellular pathogens, and tumor cells Recognize altered structures on damaged cells and can eliminate them without prior exposure NK activity is enhanced by certain cytokines. NK cells produce other cytokines that recruit T cells and aid in development of granulocytes and macrophages. Natural Killer (NK) Cells (continued_1) MEC HAN I S M OF CY TOTOXI C I T Y 10  6/26/2024 Innate Lymphoid Cells (ILCs) Develop from the CLP but do not express markers of the lymphoid lineage Found mainly at mucosal sites Release immunoregulatory cytokines such as interferon gamma in response to infectious agents Summary Innate immunity encompasses the body’s normally present defense mechanisms. Innate immunity is characterized by: ◦ Lack of specificity ◦ No need for a prior exposure ◦ A similar response with each exposure External defenses include structural barriers such as the skin and secretions that keep microorganisms from entering the body. 11  6/26/2024 Summary (continued_1) Internal defenses include: ◦ Cells capable of phagocytosis and killing of foreign invaders (e.g., neutrophilis, macrophages) ◦ Acute-phase reactants like C-reactive protein that enhance phagocytosis ◦ Reflexes such as coughing or sneezing to remove pathogens ◦ The inflammatory process Pattern recognition receptors (PRRs) are molecules on host cells that recognize substances found only on pathogens called PAMPs (pathogen-associated molecular patterns), which allow host cells to distinguish them from self. Acute-phase reactants are serum proteins that increase rapidly in response to infection or injury. Summary (continued_2) Inflammation is the body’s response to injury or invasion by a pathogen. Inflammation is characterized by increased vasodilation and vasopermeability, and migration of neutrophils and macrophages to the injured area. Following phagocytosis, killing of microbes can occur through oxygen-dependent and - independent mechanisms. 12  6/26/2024 Summary (continued_3) NK cells kill target cells that are infected with a virus or other intracellular pathogen without prior exposure. NK cells are a link between the innate and adaptive immune defenses. Innate lymphoid cells rapidly secrete cytokines that can activate other innate cells and influence the adaptive immune response. Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 13