Learning Objectives from Lectures 9-16

Learning Objectives from Lectures 9-16 Lecture 9: ➢ Introduce and define the immune system ○ The immune system is divided into the innate/natural immunity and the adaptive/ acquired immunity ○ Innate includes the first and second line of defense (nonspecific) ■ First line of defense: skin, mucous membranes and secretions, normal flora ■ Second line of defense includes innate immune cells, inflammation, complement, and antimicrobial substances ○ Adaptive is the third line of defense (specific) ■ Includes specialized lymphocytes ■ B cells and T cells ➢ List the major components of the innate 1st line of defense ○ Skin ■ Physical barrier ■ Keratin ■ Sebum ■ Dendritic cells ■ Sloughing cells ○ Mucous membranes and secretions ■ Mucociliary escalator ■ Tears and saliva ■ Crevicular fluid ■ Gastric juice ■ urine/vaginal secretions ○ Normal flora ■ E. coli produce vitamin K and fill receptors in GI tract ➢ List and define the cell types involved in the 2nd line of defense ○ Neutrophils: first to arrive, form nets when they die ○ Eosinophils: parasitic infections, secretes cytolytic enzymes ○ Basophils: releases histamine from granules ○ Mast cells: most abundant in submucosal tissue, allergic reactions, releases histamine ○ Monocytes: baby macrophages in the bloodstream ○ Macrophages: professional phagocyte, antigen presenting cell ○ Dendritic cells: professional antigen presenting cell, phagocytic, carries antigen to lymph glands for memory ○ Natural killer cells: nonspecific killers with no memory ➢ Describe the mechanisms involved in diapedesis, chemotaxis, and phagocytosis ○ Diapedesis: the migration of cells into blood vessels ○ Chemotaxis: the movement of cells based on a concentration gradient and chemokine release ○ Phagocytosis: engulfing of cells ➢ Discuss complement activation ○ 3 pathways: classical, alternative, and lectin pathways ○ Activated complement produces MAC which pokes holes into cell membranes causing lysis ➢ Identify the most important activated complement products and their biological activity including neutralization and opsonization ○ C3b: opsonization ○ C5a: chemoattractant ○ C3a & C5a: anaphyatoxins ○ C5-C9: MAC ➢ Differentiate between MHC I and MHC II ○ MHC I ■ Nucleated cells ■ Presents endogenous peptides ■ CD8+ cytotoxic T lymphocytes ■ MHC I is used to display “self” and “non-self” proteins so that basic cells can kill the bad ones ○ MHC II ■ Found only on antigen presenting cells (macrophages, dendritic cells and B lymphocytes) ■ Presents exogenous peptides ■ Activates CD4+ T helper cells ■ Helps with adaptive immune response to specific antigens that are in memory Lecture 10: ➢ Outline the elements of the adaptive (or acquired) immune system ○ Specialized immune cells ○ Specific response (antigen recognition) ○ self/non-self recognition ○ Memory generation ➢ Describe the functions of the adaptive response ○ Antigen-dependent ○ Lag response ○ Antigen specific ○ Generates memory ➢ List the 5 types of antibodies and their functions ○ IgG: most abundant, can be transferred to fetus through placenta ○ IgM: first antibody produced in primary response, more efficient to activate complement ○ IgA: predominant in external secretions (breast milk, tears, saliva), prevents attachment of bacteria and viruses ○ IgE: responsible for allergies, neutralization of parasites ○ IgD: possible mucosal immunity, expressed on cell surface of B cells ➢ Define serum and plasma ○ Serum ■ Yellow liquid separated from coagulated blood ■ No active blood clotting proteins ○ Plasma ■ Yellow fluid obtained by treating blood with anticoagulant ■ Blood clotting proteins present and not yet activated ➢ Explain how a defect in T cells can cause immunodeficiency ○ Partial immunodeficiency: loss in function or numbers of T cells ○ Auto-immunity: T cells unable to differentiate self from non-self ○ Severe immunodeficiency: SCID, immune system does not work properly at all, no T cells ○ Acquired immune deficiency syndrome: HIV hijacks the T cells ➢ Differentiate between necrosis and apoptosis ○ Necrosis: cell death from illness or injury (very messy and causes inflammation) ○ Apoptosis: programmed cell death Lecture 11: ➢ Describe the 4 types of hypersensitivity and give an example of each ○ Type 1 hypersensitivity: “allergy” ■ Peanut allergy ■ Hay fever ○ Type 2 hypersensitivity: “cytotoxic” ■ Transfusion reactions ■ HDN ○ Type 3 hypersensitivity: “immune complex mediated” ■ Serum sickness ■ SLE ○ Type 4 hypersensitivity: “delayed cell-mediated” ■ Tuberculin test, contact hypersensitivity ➢ Describe the different vaccine formulations ○ Attenuated whole agent ■ Living but changed (weakened) microbes ■ Mimics real infection ■ Can revert to wildtype and cause disease ■ Not for pregnant women or immunocompromised ■ Long term immunity ○ Inactivated whole agent and sub unit ■ Made from parts of the organism ■ Cannot revert to wildtype ■ Safe for pregnant women and immunocompromised ■ Doesn’t last as long, requires boosters ○ Toxoids ■ ■ Toxin isolated and treated to be non functional Vaccine used to stop toxin production from the microbe, not the microbe itself ■ Requires boosters ○ Conjugated ■ Used for organisms with capsules ■ Not good for young children ■ Fools the immune system ○ Nucleic acid (DNA) ■ ○ Nucleic acid (RNA) ➢ List a use for each vaccine formulation ○ Listed above ➢ Identify the function of immunoglobulin in passive immunity ➢ Discriminate between the four types of immunity ○ Naturally acquired active immunity ■ Individual exposed to antigens or disease in normal life ○ Naturally acquired passive immunity ■ Transfer of antibodies from mother through placenta ○ Artificially acquired active immunity ■ vaccines ○ Artificially acquired passive immunity ■ Introduction of antibodies from animal/person who is immune to the disease Lecture 12: ➢ Define pathogenicity and virulence ○ Pathogenicity: ability to cause disease by evading or overcoming host defenses ○ Virulence: the extent of pathogenicity of the organism ➢ Distinguish between primary and opportunistic pathogens ○ Primary pathogen: causes the disease in all cases ○ Opportunistic pathogen: causes disease in immunocompromised or when conditions are right ➢ Define virulence factor ○ Molecules or structures that help with the organisms pathogenicity ➢ Describe and least 3 virulence factors used to evade the immune system ○ Out of these listed below, capsules, biofilms, enzymes, toxins, antigen variation, intracellular growth ○ Capsules: hard to opsonize ○ Cell wall components: ■ Fc receptors prevent opsonization ■ M protein helps attachment and heat and acid resistant ■ Mycolic acids resistant to digestion ○ Biofilms: community of bacteria, reduces antibiotic effectiveness and WBC ➢ ➢ ➢ ➢ penetration ○ Enzymes ■ Leukocidin: destroys WBC ■ Kinase: breaks down fibrin and dissolves clots ■ Hemolysin: breaks down RBC ■ Coagulase: creates clots to stop WBC ■ Collagenase: breaks down collagen ■ Lecithinase: destroys plasma membranes ■ Proteases: inactivates antibodies ○ Invasins ■ Surface proteins that rearranges and facilitates bacterial engulfment into the host cell eg. pedestal formation ○ Superantigens ■ Also called type 1 exotoxins ■ Stimulate an abnormally large immune response that leads to excessive inflammation that leads to tissue damage ■ Eg. TSST-1 toxin that causes toxic shock ○ Toxins ■ Primary virulence factor ■ Endotoxin in G- (lipid A in cell wall) leads to shock ■ Exotoxins like superantigens ● Cytotoxins, neurotoxins, enterotoxins ● Sensitive to heat ● Carried by bacteriophages or plasmids ○ Secretion systems ■ Genes on the chromosome that encode for pathogenic characteristics ■ Pathogenicity island ○ Antigenic variation ■ Pathogens mutate and change their antigens so they are no longer recognized by the immune system ○ Intracellular growth ■ Growing inside host cells to evade the immune system defenses Describe at least 3 virulence factors used by bacteria to enter host cells ○ Listed above (specifically secretion systems, invasins, enzymes) Define toxins and provide at least 2 examples ○ Endotoxins like lipid A in G- cell membranes ○ Exotoxins like tetanus toxin Define superantigens and provide an example ○ Exotoxins that cause an abnormally large immune response ○ TSST-1 toxin Describe multiple ways bacteria use to share virulence factors between them ○ Conjugation: exchange of plasmids ○ Transduction: acquiring genes by a bacteriophage ○ Transformation: absorbing naked DNA ➢ List some effects viruses can exert on host cells to cause disease ○ Downregulate MHC I ○ Syncytium formation ○ Inhibit protein synthesis ○ Deregulate cell function ○ Necrosis ○ Chromosomal changes ○ Uninhibited cell growth Lecture 13: ➢ Describe the differences between normal flora and transient flora ○ Normal flora: usually in the GI tract that you develop after birth and do not normally cause you any harm. Takes part in microbial antagonism (competition) and prevents overgrowth eg. lactobacilli in vagina ○ Transient flora: flora that is introduced to you system temporarily and can be pathogenic or nonpathogenic ➢ Define terms used to describe disease ○ Local infection: infection limited to one site ○ Systemic infection: infection is spread throughout the body ○ Focal infection: after a systemic infection the organisms stay in specific areas ○ Primary infection: acute and quick initial infection ○ Secondary infection: appears after a complication of a primary infection ➢ Describe how diseases are transmitted ○ Contact transmission ■ Direct contact: person-person ■ Indirect contact: transferred by fomites ■ Droplet transmission: sneezing ○ Vehicle transmission ■ Through food or water or ingestion ■ Includes airborne transmission ○ Vector transmission ■ Mechanical transmission: passive transport on vectors body ■ Biological transmission: like how mosquitoes transmit malaria by biting you ➢ Define epidemiological terms ○ Study: when and where diseases occur ○ Purpose: to control disease transmission ○ Notifiable diseases: required to report to Public Health ○ Incidence: number of diseases within a specific time period ○ Prevalence: number of diseases at a specific point in time ○ Morbidity: incidence of specific diseases ○ Mortality: number of deaths from diseases ➢ Describe different types of infections including nosocomial infections ○ Nosocomial infections are hospital acquired infections most often due to the urinary tract ➢ List hazards you face as a health professional ○ infection/diseases ■ From patients ■ Soiled bedding/towels, dressings, fomites ■ Contaminated needles ■ Surgical equipment that's not sterile Lecture 14: ➢ Describe why skin is a good barrier to infection ○ Poor environment for microbial growth ■ Dry, high salt, lysozyme, antimicrobial peptides ➢ Identify the normal flora of the skin and give reasons why they survive on the skin ○ Can be anaerobic or aerobic because theres oxygen present ○ Dominating flora is Staphylococcus epidermidis ■ Also micrococci sp ■ Diphtheroids: ● Corynebacterium ● Propionibacterium ■ Yeasts like Malassezia purpur ➢ Identify common eye infections, their causes, and the results of disease (i.e. styes, blepharitis, conjuntivitis, keratitis, trachoma, inclusion conjunctivitis, opthalmia, neonatorum) ○ Viral conjunctivitis ■ Caused by inflammation of the conjunctival membrane ■ Results in pink eye ○ Eyelids infected with Staphylococcus aureus ■ Blepharitis ■ Styes ○ Acanthamoeba keratitis ■ Keratitis ■ Caused by inflammation of the cornea ■ Results in pus within the cornea (more pus in bacterial, less in viral) ○ Chlamydia trachomatis ■ trachoma ➢ Define terms used to describe rash lesions (i.e. macular, vesicle… etc) ○ Vesicle: fluid less than 1 cm ball in dermis ○ Bulla: fluid larger than 1 cm blob in epidermis ○ Macule: no fluid, flat red rash ○ Pustule/Papule: ball of pus smaller than 1 cm in dermis ➢ Identify characteristics of Staphylocooccus aureus and Streptococcus pyogenes that make them major skin pathogens ○ Staphylococcus aureus ■ Produces coagulase ● Converts fibrinogen to fibrin to remove clots ■ Adhesion molecules ■ Exotoxins and superantigens ■ DNase ■ Membrane damaging toxins ■ Sometimes capsules ■ Protein A (because its G-) ○ Streptococcus pyogenes ■ M protein ■ Beta hemolytic ■ Streptokinase ■ Hyaluronidase ■ Deoxyribonucleases ■ Proteases ■ Erythrogenic toxin ■ Spe toxins ➢ Describe common skin diseases and their causes ○ Impetigo ■ Caused by staphylococci or streptococci ○ Scalded skin syndrome ■ Caused by S. aureus exfoliative toxin or as a secondary infection to toxic shock syndrome ○ Erysipelas ■ Caused by group A streptococcus ○ Necrotizing fasciitis ■ Caused by G+ Streptococci ○ Warts ■ Caused by HPV ➢ Describe the diseases caused by measles virus and 5th disease (B-19) ○ 5th disease (B-19) is parvovirus ○ Maculopapular rash ○ Kopliks spots ○ Causes immunosupression ○ Symptoms are respiratory: fever, malaise, anorexia, conjunctivitis, photophobia, myalgia ○ Reduced macrophage activation Lecture 15: ➢ Identify some common causes of pharyngitis including the common cold ○ Virus ○ Bacteria ○ Chylamidia pneumoniae ○ Mycoplasma pneumoniae ○ unknown ➢ Identify the causes and discuss the disease “infectious mononucleosis” (HHV IV) ○ Epstein barr virus ○ More severe when older ○ Systemic effects on cardiovascular and lymphatic systems ○ Produces heterophile antibodies that are practically useless ○ Ampicillin rash as a complication if given beta-lactams ➢ Discuss S. pyogenes pathogenicity in the respiratory tract ○ Cannot be differentiated from other infections without laboratory tests ○ Must treat all S. pyogenes pharyngitis with antibiotics to prevent sequelae (complications after an infection) ➢ Explain how C. diphtheriae causes disease ○ Produces exotoxin that inhibits protein synthesis ■ Death of epithelial cells leads to lots of inflammation ○ Pseudomembrane at back of throat ➢ Identify the causes of otitis media (middle ear infection) ○ Streptococcus pneumoniae ○ Haemophilus influenzae ○ Moraxella catarhalis ○ Staphylococcus aureus ○ Streptococcus pyogenes ○ Cold viruses ➢ Discuss pathogenic mechanisms of Bordatella pertussis causing whooping cough ○ Produces many exotoxins ○ FTA filamentous hemagglutinin for adherence ○ Pertussis toxin (systemic effects) ○ Tracheal cytotoxin: damages ciliated cells in respiratory tract ○ Lethal toxin: causes tissue necrosis ○ Adenylate cyclase: reduces phagocytic activity ○ LPS Lecture 16: ➢ Describe M. tuberculosis pathogenicity, latent infection and active disease ○ Pathogenicity ■ Mycolic acid forms an impermeable barrier to entry of molecules into the bacillus to kill it ■ Cord factor causes bacteria to clump together to prevent phagocytosis ○ Latent infection ■ MTB present ■ Tuberculin skin test positive ■ Chest x-ray normal ● because it cannot replicate in granulomas ■ Sputum smears negative ■ No symptoms ● Because it is not actively causing disease ➢ ➢ ➢ ➢ ➢ ■ Not infectious ■ Not defined as a case of TB ○ Active disease ■ MTB present ■ Tuberculin skin test positive ■ Chest x-ray reveals lesions ● Many granulomas have calcified to stop the spread ■ Sputum smears and cultures positive (in your juices) ■ Symptoms: cough, fever, weight loss ■ Infectious before treatment ■ Defined as a case of TB Describe pneumonia caused by S. pneumoniae and the major virulence factor for the organism ○ Capsule is main virulence factor ○ Cell wall: lipoteichoic acids and peptidoglycan ○ Autolysins: self-destruction, aids inflammation ○ Pneumolysis: damages lungs ○ Symptoms: fever, rust coloured sputum, breathing problems, chest pain ○ Can lead to sepsis Identify and discuss characteristics of some viral causes of LRTI: RSV Parainfluenza, Influenza ○ Transmitted by mostly direct contact, but also droplet sometimes ○ Seasonal epidemics common ○ Symptoms are coughing and wheezing ○ Most susceptible are infants and babies under 5, as well as the elderly ■ Premature babies are at highest risk because their lungs arent fully developed Identify the major cause of epiglottitis, a life-threatening infection ○ Bacterial infections? Define antigenic shift and antigenic drift for Influenza A ○ Antigenic shift: ■ recombination of viral RNA segments that changes the surface antigens of the cell that the body is not used to ● Leads to pandemics because we have no cross immunity or immunity at all to it because it is completely new ○ Antigenic drift: ■ Point mutations in the viral genome that slightly changes the virus ● Leads to new strains of yearly infections, but we have some previous immunity from the year before because its not completely new Describe Covid-19 and mechanism of pathogenicity ○ New enveloped RNA virus ○ Glycoprotein spikes responsible for tropism and attachment to host cell ■ S1 used to bind to receptors on host cells ○ ○ ○ ○ ■ S2 used to fuse host cell and virus envelope Main receptor for Covid-19 is the angiotensin enzyme 2 (ACE2) ■ Found on many of our tissues so it can easily cause systemic effects Lymphopenia Increased plasma concentration of chemokines and cytokines Elevated D-dimer and fibrinogen (increased clotting)