Microbio Lecture Slides 1.3 PDF

Host Pathogen Interactions Pt. 1  WHY DO WE CARE? HOST-PATHOGEN INTERACTIONS II  Last class, we learned about normal microbiota, dysbiosis, & ESTABLISHMENT of infectious disease  Today we’ll be discussing how the body fights back, aka immune system basics...

Host Pathogen Interactions Pt. 1  WHY DO WE CARE? HOST-PATHOGEN INTERACTIONS II  Last class, we learned about normal microbiota, dysbiosis, & ESTABLISHMENT of infectious disease  Today we’ll be discussing how the body fights back, aka immune system basics  Don’t worry, this is an intro… we’ll cover this ad nauseum next semester CLASS OBJECTIVES  Differentiate between innate & adaptive immunity  Be able to describe components of the innate immune system & their function  Be able to identify different immune cells based on job, role, and/or picture  Be able to describe how the innate immune system activates the adaptive immune response  Differentiate between the different lymphocytes of the adaptive immune response (how lymphocytes are activated & their roles)  Be able to describe what antibodies are and what immunological memory is  Distinguish between MHC class I & II  Antigen- a foreign substance which induces an immune response, especially antibody production INNATE VS. ADAPTIVE IMMUNITY  Innate Adaptive Cells of innate & adaptive immune system have common source- multipotent hematopoietic stem cell  INNATE IMMUNE SYSTEM  Early, generalized, first-line of defense  Recognize microbes that are encountered by the host  Prevent infection of the host by either eliminating the microbes or allowing them to exist on body surfaces as normal microbiota that is not harmful (and is often beneficial)  Initiate adaptive immune responses and influence the nature of those responses based on the type of the invading microorganism  Identifies “Non-Self” via pattern recognition receptors (PRRs) which recognize structures present in microbes but not in mammals known at Pathogen Associated Molecular Patterns (PAMPs)  COMPONENTS OF THE INNATE IMMUNE SYSTEM: CELLULAR  Skin, mucous membrane surfaces, nose hairs, flow of urine, coughing & sneezing- mechanical defenses  Phagocytic cells (neutrophils, macrophages)- ingest & kill bacteria  Pro-inflammatory cells (macrophages, mast cells, eosinophils, basophils, etc.)- induce host defenses & inflammation  Antigen Presenting Cells (APCs) (dendritic cells, macrophages)- recognize, process & present antigen to lymphocytes; initiate adaptive immune response-  Natural Killer Cells*- kill virus infected or damaged cells (like cancer cells) *also part of adaptive immune system  Neutrophil extracellular traps (NETs)- complexes of DNA, histones, & granule proteins released by neutrophils that “catch” extracellular microbes CELLS OF THE INNATE IMMUNE SYSTEM  COMPONENTS OF THE INNATE IMMUNE SYSTEM- HUMORAL  Bile, gastric acid, (low pH) mucous, tears (lysozyme), normal microbiota bacteria & fungi, produce antimicrobial peptides- kill & digest microorganisms  Complement- enhance phagocytosis/opsonization, induces inflammation, kills some organisms  Cytokines- small secreted proteins released by cells that are involved in signaling (pro-inflammatory, anti- inflammatory, attract leukocytes)  Chemokines- “chemoattractant cytokines” involved in signaling (pro-inflammatory, anti-inflammatory, attract leukocytes) COMPLEMENT- “COMPLEMENTS ANTIBODIES”  Makes invading microorganisms susceptible to phagocytosis (opsonization)  Promotes the inflammatory response  Produces substances that are chemotactic for white blood cells  Lyses some microorganisms directly (MAC)  Classical- triggered by antigen-antibody complexes  Alternative- triggered by bacterial lipopolysaccharides (LPS)  Lectin- triggered by mannose containing polysaccharides  Final product of all 3: membrane attack complex (MAC)-Binds to pathogen surface & makes membrane permeable to lyse cells *do not memorize this picture, you’ll freak out for no reason.  *LPS can block MAC* TEST YOUR KNOWLEDGE #1  If LPS can block MAC, what type of pathogens would most likely be able to avoid being killed via the complement pathway?  Gram Negative bacteria (because they contain LPS!)  CONSEQUENCES OF RECOGNIZING ANTIGEN: INDUCED INNATE IMMUNITY  Increased production of antimicrobial peptides- enhances the killing of microorganisms  Secretion of numerous mediators of inflammation, such as cytokines, chemokines, etc. by pro- inflammatory cells; induces inflammation  Activation of complement- enhance phagocytosis/opsonization, induces inflammation, kills some organisms  Activation of clotting cascade  Chemotactic attraction of phagocytic cells and lymphocytes to the site of infection  Acute phase response- greatly increased production of many defense proteins and proinflammatory mediators  Inflammation  Brings more Erythema-increased antimicrobial cells blood supply and proteins to the site of infection INFLAMMATION IS Brings more CHARACTERIZED BY: Inflammation Edema- Increased vascular permeability antimicrobial cells & proteins to the site of infection 1. REDNESS (RUBOR) Infiltration of Chemotaxis infection site with 2. HEAT (CALOR) white blood cells 3. SWELLING (TUMOR) 4. PAIN (DOLOR) LEADS TO LOSS OF FUNCTION (FUNCTIO LAESA) TEST YOUR KNOWLEDGE #2  What immune cell type is pictured below? A. Eosinophil B. Macrophage C. Monocyte D. Neutrophil PURPOSE OF ADAPTIVE IMMUNE SYSTEM  Steps in when innate immune system fails  Makes up immunological memory- provides body with the ability to recognize & remember specific pathogens through their antigens  Produces antibodies (Antibody-ody-odys: https://twitter.com/ravenscimaven/status/1376172066232225792?lang=en )  Humoral immune response-  Antibodies recognize and bind to microbial epitopes:  to prevent microbial spread by immobilization (agglutination)  prevention of microbial attachment to host cells (neutralization)  promotion of microbial phagocytosis and clearance (opsonization)  targeting of microbial destruction by soluble molecules (complement) or by leukocytes  Cell-mediated immunity- leukocytes destroy invading cells CELLS OF THE ADAPTIVE IMMUNE SYSTEM: LYMPHOCYTES  CD8 “Cytotoxic” T cell- kill virus-infected & damaged cells  CD4 “Helper” T cell- help cytotoxic T cells & B cells in their immune function  B cells (plasma cells)- make antibodies  Tregs- suppress/regulate immune response LYMPHOCYTE DEVELOPMENT, ACTIVATION, & ANTIGEN PRESENTATION  Both T & B cells must go through stages of development to make sure they can distinguish “self” from “non-self”  T-cells that wrongly identify “self” or identify self too-strongly are not selected- less than 2% of T-cells actually “graduate” and enter the periphery  Cells become activated when presented with antigen  When T cells are activated they divide & proliferate  Helper (CD4) T cells- secrete cytokines & activate other cells (CD8 T cells & B cells)  Cytotoxic (CD8) T cells- kill cells bearing the antigen (i.e virus infected or damaged cells)  When B cells are activated they divide & proliferate & synthesize immunoglobulins  B cells differentiate into plasma cells which secrete antibody  IMMUNOGLOBULINS  Immunoglobulin aka antibodies- glycoprotein molecules produced by plasma cells (white blood cells)  Immunoglobulins are bound to B cells, while antibodies are secreted into blood & tissue  INITIATION OF ADAPTIVE IMMUNE RESPONSES BY INNATE IMMUNITY AKA ANTIGEN PRESENTATION 1. Microbial antigen appears 2. Dendritic cell recognizes the microbial antigen via pattern recognition receptors 3. Dendritic cell takes up microbial antigen & migrates to lymph node & matures into an antigen presenting cell 4. Dendritic cell processes the antigen and loads it onto MHC class II molecules 5. Dendritic cell presents antigen + MHC class II molecule to CD4+ Helper T cells & activate them 6. Activated CD4+ T cells then activate B cells to differentiate into plasma cells to secrete antibody & eliminate the microbial antigen  MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)  Glycoproteins found on different cells and upregulated during innate immunity  Used in antigen recognition to activate T cells in adaptive immunity  MHC class I  Presents endogenous antigens (from cytoplasm)  Found on all nucleated cells  Presents antigen to Cytotoxic (CD8) T cells  MHC class II  Presents exogenous antigens (extracellular)  Found on antigen presenting cells (APCs) (dendritic cells, macrophages, B cells)  Presents antigen to Helper (CD4) T cells  IMMUNOLOGICAL MEMORY  Immunological memory- once an infectious organism stimulates an adaptive response, subsequent encounters with that organism produce mild or even unapparent effects because of the rapid and enhanced action of antibodies or effector T cell  Tolerance- responses to future exposures can be diminished TEST YOUR KNOWLEDGE #3  What are differences between MHC class I & class II?  MHC class I  Presents endogenous antigens (from cytoplasm)  Found on all nucleated cells  Presents antigen to Cytotoxic (CD8) T cells  MHC class II  Presents exogenous antigens (extracellular)  Found on antigen presenting cells (APCs)  Presents antigen to Helper (CD4) T cells ALSO A SCIENTIST Brigitte Askonas (1923-2013) -Biochemisty, PhD University of Cambridge  “Mother Figure” or “Grand Dame of Immunology”  Born to Jewish parents who converted to Catholism & fled Austria after Nazi takeover  Studied B cells and determined their role in producing antibodies as part of the immune response, and macrophages and their role in antigen presentation  “Good science gets recognition regardless of the sex of the scientist”