MMI 528 Lectures 1-9 | Questions and Answers (Latest Version)

MMI 528 Lectures 1-9 | Questions and Answers (Latest Version) Immunity The body's ability to resist specific diseases Immune response A reaction to substances the body recognizes as foreign What are the 3 general goals of the immune system? Distinguish self from non-self Distinguish dangerous pathogens from harmless foreign substances. Identify cells that have become infected or cancerous. What are the 2 phases of the immune response? Innate and Adaptive What is the time scale of the innate immune response? Immediate; minutes to hours What is the time scale of the adaptive immune response? Days What is our first defense against microbes? Barrier-forming tissues List the barrier-forming tissues Skin Respiratory mucosa Gastrointestinal mucosa Urogenital mucosa List the immune components of the skin Cutaneous immune system Epithelial cell tight junctions Sweat Lipid secretions Antimicrobial compounds (defensins) What type of immune cells compose the skin's cutaneous immune system? Langerhans cells Macrophages T-cells Innate Lymphoid cells Langerhans cells Skin-resident dendritic cells specialized for pathogen detection Defensins Small, cationic, non-specific molecules that can disrupt microbial membranes List the immune components of the respiratory tract Ciliated epithelial cells Mucus Surfactants Lactoferrin Defensins How do ciliated cells contribute to respiratory immunity? Ciliated epithelial cells beating synchronously to expel microorganisms; contribute to physical clearance of pathogens How does mucus contribute to respiratory immunity? Mucus traps microorganisms; contributes to physical clearance of pathogens Lactoferrin A glycoprotein that sequesters metal ions needed by bacteria and fungi, inhibiting their growth List the components of gastrointestinal (GI) immunity. Epithelial cell tight junctions Microbiota Peristalsis Mucus Digestive enzymes Lactoferrin and defensins (antimicrobials) Peristalsis Wave-like movements that push material through the GI tract What role do cytoplasmic granules play in immunity? Damage pathogens Regulate cell trafficking Remodel tissues at the site of infection. What portion of circulating leukocytes do neutrophils make up? 50-70% (most common) Describe the function of neutrophils First migratory immune cell to arrive at site of infection or inflammation. Their primary function is phagocytosis and killing of pathogens. Increase significantly during bacterial infections. What portion of circulating leukocytes do eosinophils make up? 1-3% Describe the function of eosinophils Cluster around living parasites and release granules that damage the parasite's outer membranes. They also contribute to allergies and asthma. They can perform phagocytosis, but less efficiently. Elevated eosinophil counts often indicate parasitic infection. What portion of circulating leukocytes do basophils make up? less than 1% Describe the function of basophils Non-phagocytic cells that respond to multicellular parasites, bug bites, and antibodies. Release histamine. Also contribute to allergies and asthma through airway constriction. Primarily found in the blood. Describe the physiological effects of histamine Rapidly dilates blood vessels, making them leaky and causing redness. Can restrict airways. Contributes to itchiness. What portion of circulating leukocytes do mast cells make up? A lot less than 1% Describe the function of mast cells. Responds to multicellular parasites in tissues by releasing granules when their receptors bind antibody. Also release histamine, which contributes to asthma and allergies. Primarily found in the tissues, particularly barrier tissues. Similar to basophils. List the PMNs Neutrophils Eosinophils Basophils Mast cells List the key features of Monomorphonuclear Leukocytes/Mononuclear cells Single, round nucleus Expert phagocytes Present antigen to T cells, bridging the innate and adaptive immune systems Activate T cells Describe the function of professional antigen presenting cells (pAPCs) Mononuclear cells that make contact with a pathogen at the site of infection and present antigen to T cells in the lymph nodes; activate T cells Describe monocytes Precursor cells that migrate to tissues and differentiate into macrophages and dendritic cells. Increased monocyte counts indicate ongoing inflammation or infection requiring tissue repair What portion of circulating leukocytes do monocytes make up? 5-10% Describe the function of macrophages Highly phagocytic antigen-presenting cells that break down engulfed pathogens into peptides for presentation to T cells. Mostly tissue-specific. Become more phagocytic upon activation. Can activate T-cells. M1 Pro-inflammatory macrophages that kill pathogens and help activate other immune cells M2 Anti-inflammatory macrophages that help repair and regenerate tissues; play a role in cancer response. What portion of circulating leukocytes do dendritic cells make up? 0.15-0.5% Describe the function of dendritic cells (DCs) Antigen-presenting cells. Uptake molecules via phagocytosis, receptor-mediated endocytosis, and pinocytosis to sample the environment. Most efficiently activate T cells. Describe the physical barriers in the skin that contribute to immunity. Epithelial cells form a water-tight barrier Describe the chemical barriers in the skin that contribute to immunity. Sweat: washes away microbes and creates acidic conditions Lipid secretions: create an inhospitable environment for microbial growth Antimicrobial compounds, including defensins Describe the chemical defenses that contribute to respiratory immunity Surfactant: helps with microbe clearance Lactoferrin: denies microbes iron needed for growth Defensins: disrupt microbial cell membranes Outline the physical barriers that contribute to GI immunity Epithelial cells: form tight junctions that create a sealed barrier to block pathogen entry Mucus: layers of mucus trap microbes and foreign particles Peristalsis: prevents bacterial overgrowth Outline the chemical barriers that contribute to GI immunity. Digestive enzymes: break down pathogens Antimicrobial molecules: disrupt microbial membranes and microbial growth Describe how the location of the immune system's encounter with a pathogen shapes the response Microbes trigger different immune reactions, depending on the tissue where they're detected The unique molecular signatures possessed by microbes determine the type of immune response that is activated Immune-privileged tissues restrict immune cell access to prevent strong immune reactions Describe the innate phase of the immune response The immediate response to a pathogen/damage; uses generic responses that activate within minutes Describe the adaptive phase of the immune response Uses highly-specific, customized responses to pathogens; takes days to develop Leukocyte White blood cell Lymphocyte Refers to B cells, T cells, and NK cells; comes from common lymphoid progenitor cell List the characteristics of Polymorphonuclear Leukocytes (PMNs) AKA Granulocytes Size: small-to-medium Multi-lobed nucleus Contain cytoplasmic granules Use PRRs to recognize pathogens Circulating Lifespan: 1-3 days Name this cell! Mast cell (deep purple granules, round nucleus) How are subpopulations of lymphocytes distinguished from one another? Cluster of differentiation nomenclature based on the unique combination of surface proteins on cells Antigens Molecules that the adaptive immune system recognizes as foreign or harmful. Unique molecular fingerprints of individual pathogens. _____ composes antigens peptides/proteins External sources of antigens Bacteria, viruses, toxins, foreign substances Internal sources of antigens bodily tissues (in autoimmune disease), tumor cells Antigen receptors Proteins on B and T cells that bind specific antigens, enabling the adaptive immune system to recognize pathogens and foreign substances with specificity. Can distinguish between strains within a class of pathogen. B-cell receptors (BCRs) membrane-bound antibodies that bind directly to intact antigens T-cell receptors (TCRs) antigen receptor that recognizes antigen fragments (peptides) present by MHC molecules on the surface of tother cells Pathogen-associated Molecular Patterns (PAMPs) Shared molecular signatures across pathogen groups Pattern Recognition Receptors (PRRs) Receptors used to recognize PAMPs. Can distinguish general classes of pathogens, but not between strains. What portion of circulating leukocytes do lymphocytes comprise? 20-40% Naive cell Newly formed with no prior antigen exposure Effector cell Activated cell that is actively fighting pathogens Memory cell Long-lived cell that responds faster upon re-exposure to the same antigen Describe B cell function Target extracellular antigens via unique BCRs. Produce antibodies with different functional classes. Use affinity maturation to improve the strength of antibody binding to antigens over time. CD8+ Cytotoxic T cell function Detect foreign antigens presented by MHC-I molecules on any nucleated cell. Kill infected/tumor cells with cytotoxic molecules. Where do B cells mature? Bone marrow B cell CD expression Express CD19 and CD20 Plasma cells Activated B cells that secrete large quantities of antibody. Have a prominent Golgi apparatus. List the 5 classes of antibodies IgM, IgD, IgG, IgE, and IgA Where do T cell mature? Thymus T cell CD expression CD3 General T cell function Recognize processed pieces of antigen (peptides) presented by MHC molecules CD8+ T lymphocyte surface markers CD3 and CD8 Describe CD4+ T helper lymphocyte function Detect antigens presented by MHC-II molecules on pAPCs and direct other cells using cytokines and direct cell contact. Specialized subsets regulate/coordinate immune responses. How do CD4+ helper lymphocytes coordinate responses? Activate B cells to produce antibodies. Stimulate CD8+ T cells to kill infected cells. Recruit and activate macrophages and other immune cells. Suppress overactive immune responses. CD4+ T helper surface markers CD3 and CD4 MHC molecules Highly variable proteins essential for T cell surveillance of cellular contents Innate lymphoid cell (ILC) function Use non antigen-specific recognition of pathogens to respond faster than adaptive immune cells. First line of defense in skin and mucosal tissues. Uses helper and killer types to function similar to T cells. Which ILCs function as helper cells? ILC1, ILC2, ILC3, and ILCregs Which ILCs function as killer types? NK cells Natural Killer (NK) cell function Kill abnormal cells (infected, cancerous, stressed) How do NK cells recognize abnormal cells? A balance of activating and inhibitory receptors determine their activity. Recognize the absence of MHC-I on the surface of cells as a signal to kill cells. Hybrid immune cells Cells that have features of both innate and adaptive immune cells. Have T cell receptors with limited repertoires and express receptors classically associated with innate cells. i.e: NKT and MAIT cells Natural Killer T (NKT) cell function Recognize lipids presented by CD1d on target cells. Contributes to immune regulation and antimicrobial defense. Mucosal-associated invariant T (MAIT) cell function Recognize vitamin metabolites presented by MR1 on target cells. Contributes to antimicrobial defense at mucosal barriers. What technique can be used to distinguish lymphocytes from one another? Flow cytometry, uses forward and side scatter to distinguish cell size and granularity What are the 4 classes of immune system structure and organization? Primary lymphoid tissues/organs Blood and lymphatic vessels Secondary lymphoid tissues//organs Peripheral lymphoid tissues Describe the role of the primary lymphoid tissues/organs. These are highly organized tissues of distinct microenvironments where lymphocytes undergo education before migrating to secondary lymphoid tissues Primary lymphoid tissues/organs Thymus: site of T cell development Bone marrow: site of B cell development Lymphocyte education The process by which self-reactive B and T cells are eliminated and self-tolerance is developed. Only antigen-specific cells survive and pass to secondary lymphoid tissues. What systems do cells use to traffic between lymphoid tissues? Blood: active movement of cells by the heart with access to almost every organ and tissue & Lymphatic: passive movement of cells driven by muscle movement to drain the site of infection. Provides a route for immune cells and antigens in tissues to reach secondary lymphoid tissues. Describe how cells use blood and lymphatics to traffic between lymphoid tissues. Lymphocytes in circulation (in the blood) can enter secondary lymphoid or peripheral tissues. They return to the blood via lymphatic vessels when lymph drains through the thoracic and right lymphatic ducts. Lymph The fluid surrounding cells, originating from blood plasma that has leaked out of blood vessels. Contains various molecules and immune cells. Lymphatic system A network of thin-walled vessels that collect lymph. Plays a major role in transporting immune cells and antigens. Describe how fluid moves through the lymphatic system One-way valves and the movement of surrounding tissues Secondary lymphoid tissues Places where immune cells and antigens aggregate to initiate adaptive T and B cell responses How do lymphocytes locate their rare, specific antigen targets? B and T cells gather in specific regions of secondary lymphoid tissues. pAPCs bring antigens site of infection/inflammation to these tissues through the lymphatics. Ideally, this brings pAPCs with antigen into contact with B and T cells specific for that antigen, allowing lymphocytes to be activated. Draining lymph nodes The first lymph nodes to receive lymph containing proteins and cells from a specific area of the body. Typically the closest nodes to the site of infection/injury/tumor. List the lymph node microenvironments Follicle: B cell zone Paracortex: T cell zone, surrounding follicles Medulla: pathway for lymph and immune cells to exit from lymph nodes Germinal centers: site where activated B cells undergo antibody class-switching and affinity maturation. Form when a B cell is activated in the follicle Follicular dendritic cells (FDCs) Cells that act as antigen depots in the B cell zones of the lymph nodes. Play an essential role in antibody maturation. NOT an immune cell. Fibroblastic reticular cells (FRCs) Cells that create a conduit system in the T cell zones of lymph nodes and enable DCs to interact with T cells. NOT an immune cell. Spleen Secondary lymphoid organ that is highly structured into lymphoid and non-lymphoid compartments. Specializes in trapping and responding to blood-borne pathogens. Filters blood for antigens and old/abnormal blood cells. How is the spleen organized? White pulp: lymphoid tissue Red pulp: blood-filtering tissue. Removes old/damaged blood cells Marginal zone: area between the red and white pulp, contains specialized macrophages and B cells Lymphoid compartments follow pattern of B cells surrounded by T cells Not connected to lymphatic vessels Describe the sub-organization of the white pulp in the spleen Follicles: B cell zone PALS (Periarteriolar Lymphoid Sheath): T cell zone Marginal zone: where red and white pulp meet. pAPCs pick up antigen List the peripheral lymphoid tissues Tonsils Gut-associated Lymphoid Tissue (GALT) Appendix Tonsils Peripheral lymphoid organs that help monitor antigens entering your mouth and nose. Help stimulate antibody production to protect your oral cavity. Composed almost entirely of B cell follicles with a small population of T cells. MALT. MALT Mucosal-associated lymphoid tissues Peyer's patches