Microbio Lecture Slides 1.4 PDF

Host Pathogen Interactions Pt. 1I  WHY DO WE CARE? HOST-PATHOGEN INTERACTIONS I  Before we learned about how the immune system fights pathogens  Now we will elaborate on what happens when pathogens thwart the immune system  Host-pathogen interactions play a critical role in the e...

Host Pathogen Interactions Pt. 1I  WHY DO WE CARE? HOST-PATHOGEN INTERACTIONS I  Before we learned about how the immune system fights pathogens  Now we will elaborate on what happens when pathogens thwart the immune system  Host-pathogen interactions play a critical role in the establishment AND stages of infectious disease  As physicians, you need to understand these complex interactions in order to treat and/or prevent disease depending on what stage of infectious disease  CLASS OBJECTIVES  Differentiate between the 6 Stages of Establishment of Infectious Disease & 5 Stages (Periods) of Infectious Disease  Define and give examples of virulence factors  Further breakdown RON & learn about transmission to new hosts  Define what is needed for nutritionally compatible niche (i.e. oxygen- aerobe v. anaerobe, facultative v. obligate; & iron)  Identify mechanisms of cell death and how microorganisms perform them  Identify the three types of bacterial toxins & give examples of each  Compare & contrast antigenic drift & antigenic shift FIVE STAGES (PERIODS) OF INFECTIOUS DISEASE From DITKI Host Pathogen Interactions I  VIRULENCE FACTORS HELP ESTABLISH INFECTION/DISEASE  VIRULENCE FACTORS- enable pathogen to replicate and disseminate inside a host by either subverting or eluding host defenses.  Every pathogen has their own combination of virulence factors; some unique, & some shared  Shared by multiple strains:  Adhesins- Surface proteins that bind to host cells  Capsules that inhibit phagocytosis  Toxins- e.g. Lipopolysaccharide (LPS)  Unique:  Toxins: e.g. Botulinum toxin  Gp120- facilitates HIV entry into host cells  Etc. (we’ll learn a ton of these over the semester)  GOAL: SURVIVAL  3 demands of free-living microbes: RON  Avoid being washed away (colonize the surfaces of host cells). (Occupancy)  Find a nutritionally compatible niche. (Nutrition)  Survive innate and adaptive defenses. (Resistance) *I wanted to spell RON to help you remember, but we’re going to go a bit out of order today- NOR  Transmit to a new host  NUTRITIONALLY COMPATIBLE NICHE  Nutritional requirements often reflect ecological habitat (i.e. soil is minimal, human body is complex)  Will select for environments that support their nutritional requirements  Human body ideal microenvironment for microbes: sugars, vitamins, minerals, etc.  Oxygen  Anaerobes (“an”-without + “aero”- air + “bios”- life)  Aerobes (“aero”-air + “bios”- life)  Facultative- occurring optionally in response to circumstances  Obligate- restricted to a particular function  Iron  Bacteria need iron for synthesis of cytochromes & enzymes  Human body (low free iron) & bacteria compete  Body decreases free iron concentration in bacterial infection  Bacteria excrete siderophores, iron-chelating agents, to steal iron from host  OCCUPANCY- SURFACE COLONIZATION  Adhesins-cell-surface components of bacteria that facilitate adhesion  Type of virulence factor  Bind to special receptors- highly specific  Gram- bacteria  Fimbrial adhesins  Invasin (nonfimbrial surface protein) bind to integrin  Gram+ bacteria  Surface proteins that bind to fibronectin  *Remember*- hospitalized patients deficient in fibronectin= >Gram- infections  Both (but not all can have)  Capsules- composed of polysaccharides that cover the cell wall; principal antiphagocytic that prevents access of *rare exception of Gram+ bacteria having fimbriae, but the leukocytes to the underlying cell wall elements know it’s “unique” to Gram- bacteria for exam RESISTANCE- SURVIVING THE CONSTITUTIVE & INDUCED DEFENSES  How do microbes evade the host’s first line defenses? 1. Defending against complement 2. Subverting phagocytosis 3. Surviving inside phagocytes 4. Becoming intracellular 5. Immunosuppression 6. Diversion of Lymphocyte Function 7. Proteolysis of Antibodies 8. Latency 9. Antigenic Variation (& Antigenic Drift & Shift)  1. DEFENDING AGAINST COMPLEMENT  Complement- Circulating plasma proteins that recognize molecular components of pathogens & become activated  Causes opsonization & killing of bacteria  Opsonization= antibodies attached to surface of pathogen to mark them for destruction  Classical, Alternative, and Mannose- Binding Lectin activation pathways Figure 8-1 MMD 2. SUBVERTING PHAGOCYTOSIS  Phagocytosis- the ingestion of bacteria or other material by phagocytes (like macrophages & neutrophils)  Killing phagocytes  Avoiding neutrophil extracellular traps (NETS)  Escaping ingestion- capsules  3. SURVIVING INSIDE PHAGOCYTES  Inhibition of lysosome fusion with phagosomes  Escape into the cytoplasm  Resistance to lysosomal enzymes  Inhibition of phagocytes oxidative pathway 4. BECOMING INTRACELLULAR  Some cells thrive inside the phagocytes  Can trigger infected cells to fuse with uninfected neighbor cells so they can spread  Some use host’s cytoskeleton & actin to spread into adjacent cells  Ex. Listeria monocytogenes (what I studied in undergrad); facultative intracellular bacteria 5. IMMUNOSUPPRESSION  Immunosuppression  Damage immune cells like T cells, or inhibiting cytokine secretion  Ex. HIV  6. DIVERSION OF LYMPHOCYTE FUNCTION  Diversion of lymphocyte function: Superantigens  Type of antigen that results in excessive activation of immune system  Non-specific activation of T-cells & widespread cytokine release  Ex. Certain streptococci  7. PROTEOLYSIS OF ANTIBODIES  Proteolysis of antibodies  Make proteases (protein that breaks down proteins) that cleave a specific antibody, immunoglobulin A (IgA)  Sometimes a piece of IgA remains (antigen binding fragment- Fab), which prevents other antibodies from binding- fabulation  Found in pathogenic bacteria  8. LATENCY  Latency  Pathogen is present in the body, but exists in a resting state without producing more of itself  Not affected by immune system, long-lasting  Can reactivate in times of stress or decreased immune function  Herpes virus, HIV, tuberculosis 9. ANTIGENIC VARIATION  Changing surface antigen  Trypanosomes- Trypanosoma brucei  Variable surface glycoprotein  Hundreds of genes code for different antigens  When antibodies are created, they switch to a different antigen  N. Gonorrhoeae  Changes surface pilin (protein that makes pili)  Influenza viruses  Hemagglutinin-binds cell surface receptors, Neuraminidase- changes the receptors  Antigenic Drift- every 2-3 years.  A/Wisconsin/67/2005 (H3N2)-like virus & A/Hong Kong/4801/2014 (H3N2)  Antigenic Shift- every 10 years.  2009 swine flu- H1N1 with swine, avian, and human genes TEST YOUR KNOWLEDGE #1  How do microbes evade the host’s first line defenses?  Defending against complement  Subverting phagocytosis  Surviving inside phagocytes  Becoming intracellular  Latency  Antigenic variation  Immunosuppression  MECHANISMS THAT DAMAGE THE HOST DURING INFECTION 1. Pathological Alterations of Metabolism  Produce toxin that mimic hormones or other pharmacologic effectors 2. Mechanical Causes of Damage  Mechanical obstruction due to buildup or blockage of lymphatics  Common with parasites like roundworm 3. Damage Caused by Host Response  Cytokine storm  Overactivation of complement system  Superantigens MECHANISMS THAT DAMAGE THE HOST DURING INFECTION- CELL DEATH 4. Lysis- disintegration of cell by rupture of cell wall or membrane  Produces toxin to damage cell membrane  Clostridia lyse red blood cells & cause gas gangrene  Multiplies inside cell & leads to lysis from inside  Rickettsiae produces peroxide  Multiplies inside host, but immune cells eradicate the cell  Mycobacteria 5. Apoptosis (ahp-uh-toe-sis)-Programmed cell death  Part of normal cell cycle  HIV & herpes- premature apoptosis  Epstein-Barr block apoptosis to make immortal host cell  MECHANISMS THAT DAMAGE THE HOST DURING INFECTION- BACTERIAL TOXINS  A range of proteins that alter the normal metabolism of host cells with deleterious effects on the host  Can have intracellular, extracellular, or extracellular matrix targets 1. Intracellular Intracellular Extracellular  Exotoxins  Type III cytotoxins  Type IV to VII cytotoxins 2. Extracellular  Endotoxin (LPS)  Membrane-damaging toxins  Superantigens 3. Extracellular matrix  Exoenzymes TEST YOUR KNOWLEDGE #2  Which is not a mechanism that damages the host during infection (and why?)? A. Brugia malayi filaria blocking lymph node B. Cytokine storm in Covid-19 C. Exotoxin production by Clostridium perfringens D. Phagocytosis of Rhinovirus TEST YOUR KNOWLEDGE #3  You are working in a microbiology lab and receive a blood sample from a patient suffering from a bacterial infection. As you are gram staining, you notice the bacteria seem to be dying off quite quickly and you hypothesize that this is due to the presence of oxygen. What type of bacteria is your most-likely culprit? A. Obligate aerobe B. Obligate anaerobe C. Facultative aerobe ALSO A SCIENTIST Abigail Salyers, PhD (1942-2013) - Nuclear Physics, PhD, George Washington University (switched to Micro during postdoc at Virginia Polytechnic)  “Mother of human microbiome research”  First female tenured professor at University of Illinois, Champaign-Urbana (1983)  Authored 5 books & >200 scientific publications  Revenge of the Microbes- PopSci book on antibiotic resistance  President of the American Society for Microbiology during US anthrax epidemic (2001) so she developed public policies & educated postal workers about biosafety  For funzies: https://www.youtube.com/watch?v=xf2PbVHgdEM