MEDS2004 Notes - Microbes, Infection and Immunity (University of Sydney) PDF

lOMoARcPSD|28574464 MEDS2004 - Notes - Everything in Course Microbes Infection and Immunity (University of Sydney) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university...

lOMoARcPSD|28574464 MEDS2004 - Notes - Everything in Course Microbes Infection and Immunity (University of Sydney) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 MEDS2004 – MICROBES, INFECTION AND IMMUNITY LECTURE 2 – INTRODUCTION TO MICROBIOLOGY 2 LECTURE 3 – INTRODUCTION TO VIRUSES 4 LECTURE 4 – BASIC IMMUNOLOGY 8 LECTURE 5 – INTRODUCTION TO IMMUNOLOGY 12 LECTURE 6 – MICROBIAL DISEASE 16 LECTURE 7 – THE HOST-PATHOGEN RELATIONSHIP 21 LECTURE 8 – THE GENITOURINARY SYSTEM  MICROBES AND DISEASE 24 LECTURE 9 – THE IMMUNE RESPONSE TO HSV 28 LECTURE 10 – RESPIRATORY SYSTEM PT2  STRUCTURE AND MICROORGANISMS 33 LECTURE 11 – THE RESPIRATORY SYSTEM  MICROORGANISMS AND DISEASE 38 LECTURE 12 – THE RESPIRATORY SYSTEM  IMMUNE RESPONSE 41 LECTURE 13 – THE RESPIRATPORY SYSTEM  IMMUNE RESPONSE 45 LECTURE 14 – THE GASTROINTESTINAL SYSTEM  STRUCTURE AND MICROORGANISMS 49 LECTURE 15 – THE GASTROINTESTINAL SYSTEM  DISEASES 52 LECTURE 16 – THE GASTROINTESTINAL SYSTEM  IMMUNE RESPONSE 56 LECTURE 17 – THE GASTROINTESTINAL SYSTEM  IMMUNE RESPONSE 60 LECTURE 18 – VACCINES 64 LECTURE 19 – THE SKIN SYSTEM  STRUCTURE AND MICROORGANISMS 67 LECTURE 20 – THE SKIN SYSTEM  MICROORGANISMS AND DISEASE 71 LECTURE 21 – THE SKIN SYSTEM  IMMUNE RESPONSE 74 Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 LECTURE 2 – INTRODUCTION TO MICROBIOLOGY MICROORGANISM  Simplest terms  An organism that is too small to be seen with the naked eye.  Cellular microorganisms  Fungi, protists, bacteria, archaea o Prokaryote  Have membrane bound organelles (Fungi, Protists) o Eukaryote  Generally lack membrane-bound organelles (Bacteria) o Have features common to prokaryote and eukaryotes (archaea)  currently no known pathogenic species  Acellular Microorganisms  Viruses, Viroids, Satellites, Prions BACTERIA (PROKARYOTE)  Single-celled organisms  Generally, 0.5 um) o Triggered by binding to pattern recognition receptors (PRRs) or phagocytosis receptors o Membrane closes around the particle o Internalised into phagosome o Phagosome fuses with a lysosome  phagolysosome o Reactive oxygen species (ROS), nitric oxide (NO) and lysosome enzymes kill the microbe ACUTE INFLAMMATION  The process of recruiting immune cells and plasma protein to sites of infection and injury  Typically result in heat, redness and swelling  Essential step in activating the adaptive immune response THE INNATE IMMUNE RESPONSE  Global recognition system (patter recognition receptors)  Rapid  Repetitive  Interactive  Does not react to self  Needed for initiation of adaptive immune response ADAPTIVE IMMUNE RESPONSE Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 NAÏVE LYMPOCYTES REQUIRE ACTIVATION  Naïve lymphocytes require activation  Naive T cells cannot perform effector function  Need antigens recognition and other signals – co-stimulation – to proliferate and become effector cells COMPNENTS OF THE ADAPTIVE IMMUNE SYSTEM  Humoral immunity o B Lymphocytes  Produce anti-bodies immunoglobulins: IgA, IgG, IgM, IgE, IgD o Block infections and eliminate extracellular microbes  Cell mediated immunity o T lymphocytes  Cytotoxic (CD8+)  deal with intracellular microbes (viruses)  Kill infected cells and eliminate reservoirs of infection  Helper T cells (CD4+)  Help phagocytosed microbes in macrophages – Secrete cytokines to aid elimination of phagocytosed microbes  Th1  Th2  Th17  Serology: study or antibodies in the blood  Serotype: a subset of a species that can be recognised by the same antibody ANTIGEN, EPITODE AND PEPTIDES  Antigen  derived from “antibody generator” but now we refer to antigens as anything that a B cell or T cell receptor binds to: o Proteins o Lipids o Polysaccharides  Epitope  the specific region of the antigen that the lymphocyte receptor recognises  Cognate T and B cells recognise the same antigen  T cell receptor can only recognise proteins B CELLS VS T CELLS  B cells ‘see’ free antigens  T cells looks for a complex on the cell surface o Major histocompatibility complex (MHC) + foreign peptide  T cells work with other host cells – by directly killing infected (or damaged) cells (CD8+) or providing ‘help’ (CD4+) CLONAL SELECTION AND IMMUNOLOGICAL MEMORY Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  We maintain a vast supply of T and B cells each with unique antigen recognition receptors  When we encounter a pathogen only those T or B cells that recognise the pathogen are triggered to respond – multiple in number  clonal expansion  Some convert to memory cells – poised to attack again if we re- encounter the pathogen THE ADAPTIVE IMMUNE SYSTEM  Takes days to mount a response o Requires activation  Highly specific recognition o Recognises distinct parts of a molecule (antigens, epitopes)  HUGE diversity  Clonal expansion  Memory  Does not react to self THE IMMUNE SYSTEM VS THE PATHOGEN  Its complex, integrated and coordinated response  The response to tailored to each different pathogen  The pathogen fights back LECTURE 5 – INTRODUCTION TO IMMUNOLOGY  Identify features and cells of the innate immune response  Identify feature and cells of the adaptive immune response  Compare and contrast the main features of the innate and adaptive immune systems  Outline how immune cells are recruited into sites of infection and lymph nodes  Discuss the role of lymph nodes in the immune response Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 THE INNATE IMMUNE RESPONSE  Rapid  Repetitive  exactly the same response each time.  Global recognition system (pattern recognition receptors)  Does not react to self *  Normal healthy self  Needed for initiation of adaptive immune response  Interactive HOW DO IMMUNE CELLS TRAFFIC TO THE SITE OF INFECTION RECRUITMENT OF CELLS  Leukocytes need to leave the blood to migrate to sites of infection  Step wise process: o Infection is sensed and resident cells respond by producing cytokines and chemokines o Cytokines increase adhesion molecules selectins (E- and P-selectin), on endothelial cells o Leukocytes express selectin ligand o Leads to initial interaction between leukocytes and endothelial cells  Chemokines displayed on endothelial cells by proteoglycans  Leukocytes express chemokines receptors which bind to high affinity state  Induce integrins (LFA-1 and VFA-4) to change from a low to a high affinity state  Integrin ligands (ICAM-1 and VCAM-1) are also upregulated on the endothelial cells  Strengthens the interaction between the leukocyte and endothelial cell, leading to arrest  Cells squeeze through junctions between endothelial cells  Migrate towards chemokine gradients and complement fragments in the tissue. THE ADAPTIVE IMMUNE SYSTEM  Takes days to mount a response Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 o Requires activation  Highly specific recognition o Recognises distinct parts of a molecules (antigens, epitopes)  HUGE diversity  Clonal expansion  Memory  Does not react to self  needs education THE ADAPTIVE IMMUNE RESPONSE REQUIRE ACTIVATION  Naïve T and B cells responses to foreign antigens are initiated and develop in secondary lymphoid tissue LYMPHOID TISSUE  Primary o Provide growth signals and educate lymphocytes  Bone marrow (B cells mature)  Thymus (T cells mature)  Secondary o Lymph nodes o Spleen o Mucosal and cutaneous associated lymphoid tissue THE LYMPHATIC SYSTEM  Lymphatics: specialised vessels, drain fluids from tissue into lymph nodes  Essential for tissue fluid homeostasis and the immune response.  Antigen presenting cells such as Dendritic Cells capture antigens and travel via lymphatics to lymph nodes  Free antigens can drain to lymph nodes in fluid o Picked up by macrophages and DCs in the lymph node LYMPH NODES  Specific B and T cell zones  Lymph fluid and migrating DCs enter via afferent lymphatic vessels  Naïve lymphocytes enter via high endothelial venules and migrate to their zones NAÏVE LYMPOCTYES  Naïve lymphocytes cells circulate through secondary lymphoid tissue NAÏVE T CELL TRAFFICKING  Naïve T cells enter lymph node via high endothelial venules (HEV) – T cell zone o HEV express selectin ligands, ICAM-1 and chemokines o Naïve T cells express L-selectin LFA-1 and CCR7  binds to CCR19 and CCR21  T cells leave via efferent lymphatic vessels Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 ANTOGEN, EPITOPE AND PEPTIDES  Antigen  derived from “antibody generator” but now we refer to antigens as anything that a B cell or T cell receptor binds to: o Proteins o Lipids o Polysaccharides  Epitope  the specific region of the antigen that the lymphocyte receptor recognises  Cognate T and B cells recognise the same antigen  T cell receptor can only recognise proteins B CELLS VS T CELLS  B cells ‘see’ free antigens  T cells looks for a complex on the cell surface o Major histocompatibility complex (MHC) + foreign peptide  T cells work with other host cells – by directly killing infected (or damaged) cells (CD8+) or providing ‘help’ (CD4+) MHC-1 AND CD* T CELLS  CD8 T cells recognises peptides on MHC-I o MHC-I derived peptides come from inside the cell  Activated CD8 T cells are cytotoxic T cells o Destroy infected cells o MHC-I is expressed on all nucleated cells MHC-II AND CD4 T CELLS  CD4 cells recognised peptides on MHC-II o MHC-II derived peptides come from outside the cell, following phagocytosis  CD$ T cells provide help to other cells e.g., macrophages and B cells  MHC-II is expressed on DCs, macrophages and B cells APC PROVIDE SIGNALS TO T CELLS TO ACTIVATE THEM  Naïve T cells can’t perform effector functions  Activated by mature APCs in secondary lymphoid tissue o MHC recognition o Co-stimulatory signals  Drives proliferation and gain of effector function  Antigen specificity unchanged CLONAL SLECTION AND IMMUNOLOGICAL MEMORY  We maintain a vast supply of T and B cells each with unique antigen recognition receptors  When we encounter a pathogen only those T or B cells that recognise the pathogen are triggered to respond – multiply in number  clonal expansion  Some convert to memory cells – poised to attack if we re-encounter the pathogen Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 LECTURE 6 – MICROBIAL DISEASE  distinguish the various causative agents of disease  explain the links in the infectious disease chain and appreciate how they interrelate to increase incidence of disease  explain how breaking any link will control an epidemic outbreak  compare differences in occurrence of disease: terms in the science of epidemiology  understand how epidemiologists recognise epidemics  explain how spread of disease can be controlled EVOLUTION OF MICROBIAL DISEASE CONCEPTS  Ancient peoples recognised the relationship between the disease Malaria and living near swamps, “mal” – “aria” (Latin) literally means bad air.  Understood the concept of quarantine to control spread of disease  “Miasma Theory” (Hippocrates, 4th Century BC) suggested contagious disease caused by a Miasma  a noxious form of “bad air” from rotting organic matter  Germ theory of disease  1800s: o Fungus (Phytophthora infestans) cause of Irish Potato blight, fungal infection of cereal crops, etc. o Louis Pasteur  work around fermentation and pasteurisation recognised microbial relationship o Joseph Lister: antiseptic surgery MICROBIAL DISEASE CONCEPTS  Causal relationship between microbe and a specific disease o 1890  Robert Koch – “Koch’s postulates” o 1988  Stanley Falkow developed “Molecular Koch’s Postulates” INFECTIOUS DISEASE CHAIN PRINCIPLE EXPOSURE TO INFECTIOUS DISEASES: RESERVOIRS AND EXPOSURE  Inanimate objects  water , food, cups, towel  Animals (zoonoses)  Cow with TB via milk, rabies via bite  Contagious humans  Symptomatic with active disease o Temperature, cough, sore throat, vomiting, diarrhoea, etc.  Human Carrier (asymptomatic) Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 o Acute: incubation stage o Chronic recovered from disease, possibly shed > infective for years TRANSMISSION Direct  Contact: usu. skin to skin: shaking hands (staphylococci), kissing (streptococcal sore throat); STI's (chlamydia, gonorrhoea, syphilis, HIV-AIDS, trichomoniasis, HSV)  Air-borne: aerosols: coughing, talking, sneezing ('flu, chicken pox, mumps, measles etc)  Vectors: insect: mosquito (malaria), tsetse fly (trypanosomiasis sleeping sickness), flea (plague)  Mother to baby in utero: microcephaly (Zika virus), AIDS (HIV)  Trauma: tattoo, burn, bite, injury (polymicrobial / staphylococci) Indirect  Vehicles: contaminated food/water: cholera, food poisoning (Salmonella, Listeria etc)  Fomites: dust/linen: hospitals = nosocomial infection (staphylococci) CONTROL TRANSMISSION  People: o Physical barriers -> wear masks, condoms o Physical distancing  COVID-19 1.5 meters o Isolation/Quarantine  Isolation of cases/carriers/contacts (cholera, plague, rabies, smallpox, yellow fever, SARS, HPAIH, Viral haemorrhagic fevers, Ebola, COVID-19 in some countries)  Animals o Control disease in animals: zoonoses o (Rodent fleas = plague; dogs/canines (unvaccinated) = rabies; cattle = brucellosis, mad cow disease)  Water o Treat sewage to reduce water contamination (Vibrio cholerae = cholera; round worm = ascariasis; Giardia lamblia = giardiasis) o Provide safe drinking water: chlorination, filtration; eliminate water-borne pathogens  Food  safe good practices: manufacturing, manage food poisoning risks o Pasteurise milk; food handling; food storage  Eliminate Vectors  mosquito: malaria  Use therapeutics  antibiotics: penicillin: Syphilis: Yaws  Infection control  practices in hospitals THE INFECTIOUS DISEASE CHAIN  Change behaviour; wear masks; wash hands  Quarantine  Destroy animal carries/control animal vectors  Eliminate contaminated food or water  Destroy insect vectors  Use therapeutics  Infection control Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 EPIDEMIOLOGY  Epidemiology  how do diseases move through a population  An Epidemiology investigation needs to find out: o What caused the disease o Where is came from o How it got into the population o Why it became a problem  Goals of an epidemiological study include: o Control transmission/speed of spread o Eliminate pathogen from population HERD IMMUNITY HERD IMMUNITY THRESHOLDS Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 CLASSIFCATIONS OF DISEASES  Endemic  disease is constantly present in a population usu. At low frequency  Epidemic  disease suddenly increases in a population  Pandemic  disease increases within a large widespread population usu. Worldwide EPIDEMICS  Epidemics are shown at three main peaks that lie outside the predicted cases  Disease suddenly increases within a population EPIDMEIC TYPES: COMMON-SOURCE VS PROPAGATED Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 LECTURE 7 – THE HOST-PATHOGEN RELATIONSHIP Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  critically comment on what causes the shift to parasitic relationships in the symbiosis spectrum  distinguish commensals from pathogens  build on Lecture 6 outcomes to explain the links in the infectious disease chain and appreciate how they interrelate to increase incidence and spread of disease  explain how breaking any link will control an epidemic outbreak  understand how microbial strategies and/or products allow them to: colonise, invade, evade the immune response and damage the host  understand the role of the host immune system in responding to infection THE NORMAL HUMAN MICROBIOTA A COMMENSAL YET SOMETIMES A PATHOGEN – ENDOGENOUS  Example: Staphylococcus Aureus  Commensal: normal microbiota, carried in noses of 20-40% of a population  Pathogen: causes impetigo, boils, bone and blood infection … in susceptible people “ALWAYS A PATHOGEN – EXPGENOUS (AND ENDOGENOUS)  Example: smallpox  Worldwide vaccination program  Symptoms obvious  Quarantine effective  No other host THE SYMBIOSIS SPECTRUM Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 PARASITIC RELATIONSHIP  A constant battle between Host and Microbe  Parasitic relationship  Example: Trypanosomiasis (African sleeping sickness) HOST/MICROBE (PARASITE/PATHOGEN) INTERACTION FACTORS GOVERNING SYMBIOSES  Virulence of microorganisms  i.e., increase virulence = shift to parasitism  Host susceptibility  i.e., decreased immunocompetence = shift to parasitism  Load of microorganisms  i.e., increased load (e.g., poor hygiene habits, chemotherapeutic agents) = shift to parasitism. MICROBIAL VIRULENCE  Microbial Virulence: Degree or intensity or pathogenicity of a microbe o pathogenicity  the ability to cause disease  Increase virulence= increased likelihood to cause harm  therefore moving parasitism  Indicated by fatality rates, and the ability to invade host tissue and cause disease symptoms Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 WHAT ARE VIRULENCE FACTORS?  Microbial strategy/traits that contribute to virulence = virulence Fm  There is a clear connection. Between virulence and infection  Virulence is influence by microbial traits (i.e., genes) that mainly fall in four categories: 1. Those that affect the ability of the pathogen to replicate 2. Those that affect host defence mechanisms (i.e., immune-evasion mechanisms) 3. Those that affect tropism, spread throughout the host and transmissibility 4. Those that encode products that directly damage host cells  Can include “housekeeping” functions, i.e., deriving nutrients/energy for survival in host What do Virulence Facts do?  Aid Colonisation  Allow penetration of host tissue  Prevent/reduce host response: evade immune system o Evade phagocytosis and immune clearance o Encapsulation  Cause direct damage to host o Toxic metabolism and products: acid and gas o Proteins: cytosines, degradative enzymes o Exotoxins: A-B, membrane disrupting, superantigens o Endotoxins: Gram -ve: LPS; Gram +ve: peptidoglycans, LTA, TA  Induce inflammation o Pathogenicity islands  PLUS, antibiotic resistance HOST SUSCEPTIBILITY  IMPACTED BY:  Host factors  age, socio-economic status, occupation, sex, also inherited factors  Non-specific host defence and barriers to infection  physical, chemical and biological  Immune status  immunocompromised INFECTIOUS DOSE (LOAD)  Successful infection results from: o Initial inoculum/virulence or microbe/host susceptibility  Infectious Dose = ID50 o = no. microbes required to cause disease in 50% inoculated hosts  For example: o Dental Caries: polymicrobial LIMITATIONS OF HOST-PATHOGEN RELATIONSHIP  Cohort selection  what happens in a Caucasian male (or a mouse model) is not always relevant to other races and sexes  Ethical considerations  The integrated aspects of health and our world  multifactorial o The One Health Concept o Understanding holobionts (holobiont = the network formed by a host and the many other species living in or around it, which together form a discrete ecological niche) Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 LECTURE 8 – THE GENITOURINARY SYSTEM  MICROBES AND DISEASE THE GENITOURINARY SYSTEM – OVERVIEW  There is significant difference in the structure and function between sexes MICROBIOME OF THE GENITOURINARY TRACT  The bladder and urethra are continuously flushed by urine  Very low number of normal microbiotas in males  In healthy individuals, microbiota consist of resident microbes found on the skin, e.g., Staphylococcus  Complex and dynamic normal microbiota  Lower reproductive tract dominated by Lactobacillus species  Major role in non-specific defence against infections o Low pH (lactic acid) o Bacteriocins o Competition for nutrients and binding sites Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 THE GENITOURINARY SYSTEM – SEXUALLY TRANSMITTED INFECTIONS (STI) CAUSATIVE MICROORGANISMS  Over 30 different bacteria, viruses and parasites are known to be transmitted between humans via sexual contact o Neisseria Gonorrhoeae o Treponema Pallidum o Chlamydia trachomatis o Trichomonas vaginalis NEISSERIA GONORRHOEAE  Diseases  Gonorrhoea, pelvic inflammatory disease, urethritis  One of the most common STI, ~82 million cases globally (2020)  Gram negative diplococci bacteria, can infect the urethra, cervix, throat, anus and eyes  Obligate human pathogen  Transmitted via sexual contact with penis, vagina, mouth or anus  Can also be transmitted from mother to child during vagina childbirth  Many people with Gonorrhoea are asymptomatic (female and male)  When symptoms appear, they can include: o Males, penile discharge, irritation or pain when urinating, anal discharge or discomfort, conjunctivitis and eye inflammation o Female: unusual vagina discharge, irregular vaginal bleeding, pain when urinating, pelvic pain, especially during sex, anal discharge or discomfort, conjunctivitis and eye inflammation.  Suite of virus mechanisms o Type IV pill – adhesion, immune evasion (antigenic/phase variation) natural transformation o PorB – outer membrane protein, immune system evasion (suppression) o IgA protease – immune evasion (direct damage to immunoglobulin), tissue invasion  Infection with Neisseria Gonorrhoeae increases susceptibility to HIV infection  Can be cured with antibiotics  ceftriaxone, azithromycin  Penicillin, Tetracycline, Cefixime, Ceftriaxone – inhibits bacterial cell membrane synthesis  Ciprofloxacin – inhibits DNA replication  Azithromycin - inhibits protein synthesis, binds 50S ribosomal subunit) CHLAMYDIA TRACHOMATIS  One of the most common STI, 129 million cases globally (2020)  Gram-negative obligate intracellular bacterial parasite, only found in humans  Intracellular lifestyle means they avoid detection by immune system  Sexually transmitted, can also be transmitted from mother to child during vaginal childbirth  Silent epidemic as up to 70% of infections in women are asymptomatic  Suite of virulence mechanisms: o Type III secretion system - effector protein delivery o TARP - host cell remodelling for pathogen survival o Pgp3 - immune evasion (suppression)  Can be cured with antibiotics  e.g., azithromycin, doxycycline, erythromycin (all inhibit protein synthesis, binds 50S or 30S ribosomal subunit)  Antibiotic resistance is uncommon but increasing in prevalence TREPONEMA PALLIDUM  One of the most common STI, 7.1 million cases globally (2020)  Gram-negative bacteria, distinct spiral cell shape, motile Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  Sexually transmitted, can also be transmitted from mother to child during pregnancy and vaginal childbirth (congenital syphilis)  4 stages of disease - primary, secondary, latent, tertiary  Suite of virulence mechanisms: o Shape of the bacteria - entry & movement o TprK - surface protein, attachment, immune evasion (antigenic variation) o Outer membrane sheath - immune evasion (masking)  Can be cured with antibiotics e.g., benzathine benzylpenicillin o (Inhibits bacterial cell membrane synthesis)  Recent global shortage of this antibiotic is contributing to rises in incidence.  Antimicrobial resistance is not common but is increasing. TRICHOMONAS VAGINALIS  One of the most common STIs, 156 million cases globally (2020)  Single-celled protozoan, parasite exerts mechanical stress on host cells and then ingests cell fragments after cell death, only found in humans  Sexually transmitted, also spread via genital touching  Can cause pregnancy complications e.g., pre- term delivery and low birth weight.  Some virulence mechanisms: o AP65, AP51 and AP33 - adherence, immune evasion (mimicry) o CP65 - cysteine protease, tissue damage, o Dysbiosis - phagocytosis of protective normal microbiota  Infection is resolved after one dose of metronidazole o (Inhibits protein synthesis by interacting with DNA, causes a loss of helical DNA structure and strand breakage)  Antimicrobial resistance is not common but is increasing in prevalence MAJOR VIRAL PATHOGENS OF THE GENITOURINARY SYSTEM  Human immunodeficiency virus o Disease = acquired immunodeficiency (AIDS)  Human Papillomavirus (200+ strains, 40 responsible for STI) o Disease = genital warts or cervical cancer (also vaginal, anal, vulvar and penile cancers) o Vaccine available to protect against strains 6, 11, 16 and 18  Herpes Simplex -1 and -2 o Genital Herpes HERPES SIMPLEX VIRUS  Herpesviridae family  Alphaherpesvirus subfamily o Herpes Simplex virus type 1 (HSV-1) o Herpes Simplex Virus type 2 (HSV-2) o Varicella Zoster Virus (VZV) HSV-1 AND HSV-2  Double stranded DNA viruses  Viral genome replication occurs in the host cell nucleus  HSV-1 and 2 share a high degree of genome sequence homology  HSV-1 more commonly associated with cold sores  HSV-2 more commonly associated with genital infections  However, both can cause frequent and painful genital lesions  Can be distinguished serologically (by antibodies) Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  ~22% of Australians seropositive to HSV-2  As serology tests for antibodies, can't distinguish between an infection which causes cold sores or genital lesions HSV PATHOGENESIS  Primary infection: o Break the skin, virus accesses the mucosa, infection established in epithelial cells o Virus replication in oral or genital mucosa o Newly made virus particles released from infected cells access sensory nerve endings  Latent Infection: o Viral genome is sequestered in a non-replicating state in primary sensory neurons o No virus proteins or particles being made o Hidden from the immune system  Recurrent infection: o Viral genomes reactivate from the latent state o Enter replication cycle again o New infectious virus particles made o Trigger/s for reactivation unclear, immune suppression plays a role  Herpes for Life! The virus is never cleared from sensory neurons  HSV establishes latency in the ganglia that innervates the site of primary infection  It will then reactivate from that same ganglion, meaning that if you get cold sores the virus cannot suddenly travel and cause genital lesions GENITAL HERPES: TRANSMISSION AND SYMPTOMS  Transmitted during sexual intercourse, oral genital  More common in females  suggests female genital tract more permissive to infection  Only 10-25% of infected people are aware of the infection  Blisters visible 4-7 days after transmission  Associated with pain, itching and Burning sensations  Asymptomatic shedding of the virus can occur, this is a large driver of transmission PREVENTION AND CONTROL OF PATHOGENS OF THE GENITOURINARY SYSTEM – STI  Best to prevent initial infection o Comprehensive education about STIs o Counselling and support particularly for at risk popula1ons o Promotion of barrier protection - use of condoms o Development of vaccines - currently no vaccine for any bacterial or protozoan STIs  Easy to control these pathogens after infection, however, STIGMA o MUST have de-stigmatisation of STIs o education about symptoms and importance of early diagnosis & control of spread to sexual partners o Access to health care and timely and effective treatment Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 LECTURE 9 – THE IMMUNE RESPONSE TO HSV IMMUNE RESPONSE IN GENITOURINARY GLAND IMMUNE RESPONSE IN THE FEMALE REPRODUCTIVE TRACT  Hormone fluctuations occur  Tissue remodelling, cyclic shedding and regeneration  Balance between tolerance to infection and immunity to infection  During pregnancy the mother must tolerate foreign antigens TYPICAL IMMUNE RESPONSE TO VIRAL INFECTIONS  Interferons (IFN) and proinflammatory cytokines produced o By local immune cells e.g., tissue residents’ dendritic cells, as well as keratinocytes and epithelial cells  Natural killer cells  CD8+ T cells  B cells and CD4+ T cells IMMUNOPATHOLOGY OF HERPES LESIONS  HSV replication in mucosa/skin causes cell death, leads to blisters containing cellular debris, immune cells and virus particles  Generally, the primary infection is the most severe o Lack of adaptive immune response  Secondary lesions heal faster o Memory T cells quick to act to control STARTING THE IMMUNE RESPONSE  Before the immune response can begin, we first need a way to detach the pathogen  Distinguish: self from non-self, danger from harmless  Need receptors at all possible sites where pathogens could be Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 HOW DOES THE HOST CELL INITIALLY RECOGNISE A PATHOGEN? Pattern Recognition receptors Recognise Pathogen Associated Molecular patterns (PAMPs) PATTERN RECOGNITION RECEPTORS (PRRS)  Expressed by virtually all cells o But not all cells express all the receptors, each different cell type express a certain subset  High levels on resident and innate immune cells such as macrophages  PRRs found on the cell surface, in endosomes and in the cytoplasm and nucleus  Five major families: o Toll-like receptors (TLRs) o C-type lectin receptors (CLRs) o Nod-like receptors (NLRs) o RIG-like receptors (RLRs) o Cytosolic DNA sensors (CDSs) PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPS)  PAMPs (pathogen associated molecular patterns) o Structures common to many different pathogens which are not present in healthy cells  Components of bacteria, fungi or viruses which are generally essential e.g., nucleic acids, cell wall lipids, carbohydrates and proteins  DAMPs (damage associated molecular patterns) o Released from damaged/dying cells  In the wrong place at the wrong time PAMPS VS ANTIGEN  Common structure shared by different microbes e.g., LPS  Recognised by innate receptors – germline encoded  Features unique to each individual pathogen  Recognised by specific adaptive immune cell receptors – arise through gene recombination - unique PRRS TRIGGER INFLAMMATION AND ANTIVIRAL DEFENCE 1. Engagement of PRR 2. Signalling cascade 3. Drives:  Production of proinflammatory cytokines (e.g., TNF, interleukins IL-6, IL-1B)  Production of type I interferons  Programmed cell death (apoptosis)  Stimulation of adaptive immunity 4. This Kick starts the immune system Interferons (IFN) Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 WHAT DO THE RECEPTORS SENSE DURING A VIRAL INFECTION  Viruses replicate using host cells  limited targets for PPRs  Viral PAMPs: o Viral RNA (e.g., double-stranded RNA) o Viral DNA o Viral Glycoproteins  Major response to PRR recognition of viral PAMPs: Type 1 interferon production  Secondary response: cytokines – e.g., TNF, IL-12, IL-1B HSV PAMPS  Different PRRs trigger different responses  Pathogens trigger multiple PRRs  HSV-1 PAMPs: o Viral glycoproteins o DNA genome o Viral RNA TYPICAL IMMUNE RESPONSE TO A VIRAL INFECTION  Type I interferon (IFN) and proinflammatory cytokines produced o By local immune cells e.g., tissue resident dendritic cells as well as keratinocytes and epithelial cells  Establish an ‘anti-viral state’ and recruit immune cells INTERFERONS (IFN)  3 types of IFNs: o Type I interferon; alpha and beta o Type II interferon: y o Type III: gamma  Main sources of IFNs: o IFN-alpha: dendritic cells and macrophages o IFN-beta: Fibroblasts o IFN-y: Natural Killer cells, T cells  Type I IFN (Alpha and beta) can be secreted from virally infected cells and induce an ‘anti-viral’ state in surrounding uninfected cells o Induce interferon stimulated genes  Anti-viral enzymes  Shut-down host cells metabolism  IFNs increase MHC-1 expression  increased changes of CD8+ T cells detecting infected cells HSV LESIONS AND INTERFERON PRODUCTION  Infected keratinocytes, epithelial cells, tissue resident immune cells, dendritic cells and macrophages can all produce type 1 interferon in response to HSV infection  (Lymphocytes can produce type II interferon/IFN-g ) HSV INVASION AND TYPE 1 IFN RESPONSES  HSV encodes numerous gene products that inhibit the induction of Type 1 IFN and IFN signalling Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 NATURAL KILLER CELLS  Innate lymphocyte  Circulate in the blood  Recruited to sites of infection by chemokines  Found in HSV lesions  People who lack NK cells are extremely susceptible to severe HSV infections  Express a mosaic of activating and inhibitory receptors  Can recognise and lyse virally infected cell  Decision to Kill: o Summation of positive and negative signals  Use same cytotoxic mechanisms as CD8+ T cells to induce cell death  Release cytokines- IFN-gamma, helps adaptive immune response, and macrophages NK CELL ACTIVATION  Cell stress (e.g., infection) drives expression of activator ligands  Some viruses cause a down-regulation of MHC-I o Missing self-hypothesis  If activation signal is engaged, and the inhibitory receptor Is not, this leads to NK cell activation ADAPTIVE IMMUNITY REQUIRES RECOGNITION OF ANTIGENS  T cells are crucial in controlling most viral infections  Need innate response to activate the adaptive response  Activated effector CD8+ T cells then recognise and directly kill virally infected cells and CD4+ T cells produce cytokines and provide help to B cells to generate antibody responses  Antibody responses are important, particularly for preventing reinfection with viruses Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 IMMUNE RESPONSE TO BACTERIAL STIS  Chlamydia trachomatis o Infects epithelial cells o Can cause mucopurulent cervicitis, pelvic inflammatory disease and non-gonococcal urethritis o Immune response largely responsible for symptoms  Neisseria gonorrhoea: o Very strong immune response leads to symptoms- pus/discharge, and potentially scarring of tissue, can lead to infertility o Neutrophils recruited to phagocytose bacteria, bacteria can survive inside neutrophil, may facilitate transmission  Treponema pallidum: o Chancre contains replicating spirochetes surrounded by immune cells (T cells, plasma cells, macrophages). o Immune response can clear local infection- macrophage phagocytose bacteria, but T. pallidum spreads systemically, antigenic escape  Trichomonas vaginalis: o Triggers inflammation, can be broken down and killed by neutrophils LECTURE 10 – RESPIRATORY SYSTEM PT2  STRUCTURE AND MICROORGANISMS Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 ANATOMY AND FUNCTION OF THE RESPIRATORY SYSTEM WHY DO WE BREATHE?  Cellular metabolism requires Oxygen and produces carbon dioxide (1kg/day) according to the reaction  A typical person requires 550L of oxygen/day  Failure to expel carbon dioxide leads to decrease in pH (respiratory acidosis) and high carbon dioxide trigger inhalation ANATOMY OF THE RESPIRATORY SYSTEM  Intake of oxygen and release of carbon dioxide is the function of the respiratory system  You take 20,000 breaths/day (10,000L) of atmospheric air (21% oxygen, trace carbon dioxide) and expelled air is 15% oxygen and 5% carbon dioxide  You inhale >8 microorganism/minute or 10,000 a day  Each lung weighs about 1.3 kg and combined have a total surface area of 140m 2 RESPIRATORY SYSTEM AS AN ENTRY ROUTE FOR MICROORGANISMS  The surface area and magnitude of gas exchange in the respiratory system (RS) makes this structure a major route for infection by viruses, bacteria (a bacterial spores) and fungi (and fungal spores)  Microbes can access the RS through inhalation: directly (environmental sources) or associated with aerosol droplets (from infected individuals); or through fomites. Alternatively, commensal microbes (mostly bacteria) may cause under certain conditions. Fomites are any object contaminated with an infectious microbe that can transfer disease  A single sneeze may produce up to 40,000 droplets (at speeds of 100 m/s), while a cough may produce 3000 droplets ANATOMY AND INFECTIONS OF THE RESPIRATORY SYSTEM  The upper respiratory tract includes the nose, nasal cavities, sinuses, pharynx and the part of the larynx above the vocal folds  Most URTIs are of viral aetiology and include rhinovirus, coronaviruses (each 25% of common colds); influenzavirus, parainfluenza virus, respiratory syncytial virus, and adenovirus  URTIs also have bacterial causes such as by mycobacterium tuberculosis (tuberculosis), Haemophilus influenza type B (epiglottitis, laryngotracheitis), and streptococcus pyogenes (bacterial pharyngitis)  Lower respiratory tract includes trachea, bronchi, bronchioles, alveoli ducts and alveoli. Alveoli are cupped in a dense capillary network where exchange of gases takes place  LRTIs typically have viral and bacterial causes. Influenzavirus, rubella virus, measles virus, Bordetella pertussis, Haemophilus influenzas and streptococcus pneumoniae contribute to bronchitis and bronchiolitis.  Pneumonia (inflammation primarily of the alveoli) has many viral and bacterial causes, but the major cause of community-acquired pneumonia is streptococcus pneumonia. Also, fungal causes such as Aspergillus fumigatus (aspergillosis) MICROBIOTA OF THE RESPIRATORY SYSTEM  Different physiological environments along the RS dictate the presence of resident microbes, Access to the lower RS is restricted to small particles of 1-2um in diameter.  The establishment of a stable, healthy microbiota (microbiota of healthy individual) is heavily influenced by birth mode and feeding type.  Exposure to antibiotics can disrupt the composition of the RS microbiota (reduce Dolodigranulum spp. And Corynebacterium spp.) leading to increased susceptibility to infection and inflammation  Commensals are an important source of infection (endogenous infection): Staphylococcus and Streptococcus spp. ANTOMICROBIAL DEFENSES OF THE RESPIRATORY SYSTEM Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  Multiple lines of defence prevent infection of the RS  Mucus secreted by goblet cells is a physical barrier that immobilises microbes, which are trapped and transported by cilia to the pharynx where they are swallowed. Mucus also has lysosome activity (breaks down bacterial cell walls), expresses lactoferrin (bactericidal, fungicidal) and has a variety of antimicrobial chemical properties. Mucus also accommodates non-pathogenic commensal bacteria.  The mucociliary blanket coats the lower RS and ciliary action transports microbes and foreign objects towards the mouth.  The humid environment also swells microbes preventing them penetrating deeper regions of the RS  The alveoli lack cilia and here macrophages are a key line of defence  Secreted IgA (primarily in the lower respiratory tract, found in mucus), and IgG (primarily in the upper respiratory tract) also provided protection through the adaptive immune response ASPERGILLUS FUMIGATUS INTRODUCTION TO FUNGI  Fungi are eukaryotic organisms and include single celled yeasts and filament moulds  They are abundant and ubiquitous in the environment and as they cannot photosynthesise, they thrive as heterotrophs by absorbing nutrients from the environment often by secreting enzymes (which can cause tissue damage during infections.  Fungi possess a rigid cell wall, primarily composed of chitin Z(polysaccharide) that offers protection against environmental conditions, and other microbes. FUNGAL INFECTIONS OF THE RESPIRATORY SYSTEM  A fungal infection of humans is referred to as a mycosis and are usually the result of compromised immunity; generally, fungi are not highly virulent and are opportunistic pathogens.  Populations most at risk from RSS mycoses are immunocompromised: cancer patients, those on immunosuppressive drugs, and the very young.  They are generally acquired from the environment although commensals are also a possible source of infection.  Most fungi produce spores that are resilient and small enough (5-20um) to penetrate the deeper levels of the RS (alveoli) FUNGAL INFECTIONS OF THE UPPER RESPIRATORY SYSTEM  In the upper RS, candida Albicans is responsible for most mycoses, including oropharyngeal candidiasis (thrush). C. Albicans grows as a yeast but can switch to a filamented growth (dimorphic), which may be a virulence mechanism promoting tissue penetration during pathogenesis.  Newborns are at risk from thrush via vaginal transmission as they have yet to establish their oral microbiota. FUNGAL INFECTIONS OF THE LOWER RESPIRATORY SYSTEM  Fungal pneumonia has a variety of causes (over 100 have been recovered from lung infection) but prominent aetiologists are: o Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Paracoccidioides braziliensis, Candida albicans (includes yeasts, moulds). Commonly AIDS and cancer patients. o Aspergillus spp, particularly Aspergillus fumigatus. Commonly tuberculosis, and neutropenia (low white cells).  Pulmonary mycoses have very high associated mortality rates following invasion and spread (up to 80%) ASPERGILLUS FUMINGATUS  A. Fumigatus is common in decaying matter and is the dominant fungus in garden soil. The fungus is resistant across range of pH and can grow at 37 degrees Celsius. Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  Spores are cells produced sexually or asexually and are adapted for dispersal and are resilient to harsh environmental conditions. ASPERGILLUS FUMINGATUS CONIDIA  Small: 2um in diameter, therefore able to escape mucociliary clearance (65 are most at risk. VIRULENCE FACTORS OF STREPOCOCCUS PNEUMONIAE Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  S. pneumoniae colonises the mucus of the nasal epithelium, facilitated by bacterial capsule  Source of infection can be transmission from an acute infected individual or resident microbiota (30-60% children and 10% adults).  The bacterium expresses pgdA to resist mucosal lysozymes breakdown and adhesion factors to promote adhesion to the RS epithelium COMPLICATIONS OF STREPTOCOCCUS PNEUMONIA INFECTION  S. pneumonia infection can spread to lower RS and lead to pneumonia: enter the blood stream and lead to bacteraemia and meningitis, or spread locally of the inner ear (otitis media) PREVENTING AND TREATING S. PNEUMONIAE INFECTION  The pneumococcal vaccine ‘Prevenar-13’ protects against 13 stereotypes of S. Pneumoniae (of 97 known serotypes, although not all pathogenic) and is part of the NSW immunisation schedule.  Penicillin is used to treat S. Pneumoniae but rising rates of resistance has been observed, the ability of S. Pneumoniae to take up exogenous DNA contributes to the spread of antibiotic resistance and evasion of vaccine-induced immunity. LECTURE 11 – THE RESPIRATORY SYSTEM  MICROORGANISMS AND DISEASE DEFINITIONS Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  Pneumonia inflammation of the lung involving the alveoli, infections causes (bacteria, fungi, virus) and non-microbial causes  Respiratory tract infection are infections of the upper and lower respiratory tract  Pulmonary infections are infections of the lung  Commensal means close association but commonly used to describe bacteria (and fungi) that are part of the endogenous microbiota without causing disease. Infections from commensals are termed endogenous infections. INFLUENZAVIRUS – INTRODUCTION  PA, PB1, PB2 viral RNA polymerase involved in mRNA synthesis and replication of the genome  HA surface protein involved in virus entry  NA surface protein involved in virus exit  M matrix protein involved in virus assembly  NP nucleocapsid protein, protects genome CHARACTERISITCS OF INFLUENZAVIRUS  Infleunzaviruses are RNA viruses that belong to the family of Orthomyxoviridae and includes four genera influenzavirus A (IAV), B (IBV), C and D. only IAV and IBV cause significant disease in humans. IBV is exclusive to humans; in addition to humans, IAV is also found in aquatic migrating birds, poultry, pigs, horses, dogs, seals and bats.  Genome is segmented, negatived-sense, single stranded RNA with a total size of about 13.5kb, which encodes 8 proteins  Virions is the extracellular form of a virus particle that is sufficient to productively infect the host cell. NOMENCLATURE OF INFLUENZAVIRUS  IAv and IBV are named according to the following scheme: type/town isolated/# isolates/year isolated/major HA and NA (IAV inly)  A/Switzerland/8060/2017 (H3N2)  B/Colorado/06/2017 like virus  There is 18 HA (only H1, H2 and H# are found in humans IAV) subtypes and 11 NA subtypes (only N1 and N2 are found in humans IAV).  IAV tends to cause more severe infections in humans and H1N1, H2N3 and 209 H1N1 are currently circulating TRANSMISSION OF INFLUENZA VIRUS  Influenza virus is transmitted through fomites and respiratory droplets generated through speaking, coughing and sneezing.  A significant seasonality is observed in flu notifications and a range of factors are thought to contribute to this observation (low humidity and cold temperature enables transmission, social factors). Virions can be stable for 24-48 hours.  Those most at risk are young children, adults over 65m infants, pregnant women, peoples with weakened immune systems, people with chronic illness such as asthma, diabetes or heart disease. SYMPTOMS OF INFLUENZAVIRUS  Most cases of flu infection are mild and will resolve without intervention in less than two weeks.  It is generally more severe and with more sudden onset compared with a cold (range of aetiologies including rhinovirus, coronavirus, adenovirus and others).  Upper respiratory symptoms nasal stuffiness, runny nose, sore throat, sneezing, earache (58%) Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464  Lower respiratory symptoms coughing, breathing difficulties (21%)  Fever above 37.8 degrees Celsius (35%)  34% of infected participants were asymptomatic despite shedding virus CLEARING AN INFLUENZA VIRUS INFECTION  An effective adaptive immune response to influenzavirus will involve the generation of neutralizing antibodies to the surface envelope proteins HA and NA. This exerts selective pressure for mutation in HA and NA that are able to evade immune clearance. Over years, strains evolve and adapt (antigenic drift) allowing them to infect people who have had prior infection with ancestral strains or protecting from vaccination. POTENTIAL COMPLICATIONS  Pneumonia, bronchitis, asthma and ear infection are potential complications of influenzavirus infection  Pneumonia results from direct damage to cells as virus replication kills cells or induces apoptosis.  Cytokine production can compromise the integrity of the respiratory epithelium leading to alveoli filling with fluid (compromising their function.  Although antibiotics are ineffective against viral infection, in severe cases of influenzavirus infection they may be administered for this reason. INFLUENZAVIRUS: REPLICATION AND CONTROL ENTRY OF INFLUENZA  Trimers of HA on the surface of the virus bind to sialic acid, a carbohydrate group commonly attached to many cells surface proteins  Tropism of influenza from the upper respiratory tract is a combination of the presence of sialic acid and availability of cellular furin-like proteases that are required for influenza to be infectious  Sialic acid (SA) can be attached to a carbohydrate chain through either a 2-3 or 2-6 linkage  HA from human influenza is specific for 2-6 while HA from avian influenza bind to the 2-3 configuration  SA is present and abundant in the human upper respiratory tract  Once attached to the surface of cells in the respiratory epithelium , influenzavirus is internalised through a process of receptor mediated endocytosis, forming an endosome  A drop in the pH of the endosome triggers a membrane fusion event that exposes the segment viral genome to the cytoplasm. REPLICATION OF INFLUENZA  Genome segments are transported to the nucleus where viral RNA polymerase (present in virions) synthesise mRNA and copies the genome EXIT OF INFLUENZA  Viral mRNAs are translated by cellular ribosomes and viral transmembrane proteins are processed through the rough endoplasmic reticulum and Golgi apparatus.  Finally, virus particles assemble at the plasma membrane and released via a budding mechanism with genome segments loaded into nascent virions; the viral envelope derives from the plasma membrane  NA promotes release of influenza from the surface of infected cells by cleaving sialic acid residues between the virus and the host membrane, facilitating their dispersal CONTROL OF INFLUENZA BY ANTIVIRALS  Neuraminidase inhibitors are structural mimics of SA that are effective against IAV and IBV if used within 48 hours of the appearance of symptoms  Use of NA inhibitors leads to resistance mutations in NA Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 CONTROL OF INFLEUNZA BY VACCINATION  The most effective means to control influenzavirus is through vaccination. Each year for the Northern and southern hemispheres, an inactivated vaccine is developed (6 months lead time) that is composed of two IAV and two IBV strains (quadrivalent) and is delivered by an intramuscular injection.  Virus cultivated in chicken eggs and is inactivated  The vaccine has been shown to reduce the incidence, severity and spread of influenzas virus.  Alternative vaccines are available, such as live attenuated influenzavirus vaccine that is delivered by a nasal spay  2019 vaccine: o A/Brisbane/02/2018 (H1N1)pdm09-like virus o A/Kansas/14/2017 (H3N2)-like virus o B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) o B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage)  Specifically recommended for children >6 months, pregnant women, health care workers, Aboriginal and Torres Strait Islanders, and anyone >65 years. Annual vaccination due to waning immunity and updating of composition. SEASONAL EPIDEMICS AND PANDEMICS  Seasonal epidemics are outbreaks of human influenzavirus while pandemics are large scale, worldwide outbreaks of novel flu strains that derive (partially) from animal flu strains.  These novel flu strains derive from a reassortment of viral genome segments from strains of different origins in a process called antigenic shift.  As the human population has little to no pre-existing immunity (novel HA and NA) to these new strains, high morbidity and high mortality rates may result.  H1N1/09 (Swine flu) was the most recent flu pandemic and has a particular complex origin from swine, avian and human flu strains. H1N1/09 was not highly virulent but 2009 saw a surge in the number of flu cases.  Following a pandemic, the novel flu strain becomes one of the repertoires of circulating human flus. H1N1/09 descendants are now a component of the vaccine. SPANISH FLU  The 1918 flu pandemic (or Spanish flu) was the most fatal epidemic of any infectious disease and thought to be responsible for 50-100 million deaths. The case-fatality rate was thought to be 2-20% and most deaths were caused by associated bacterial infections and pneumonia. Environmental and social factors may have played an equally or more important role as virulence. DIAGNOSIS AND DETECTION OF INFLUENZAVIRUS  Influenza virus can be detected from. nasopharyngeal swabs through a number of different techniques including: o Rapid influenza diagnostic tests for detecting viral antigen in 1000 species of bacteria have been found on the skin; there are also yeasts and viruses NORMAL SKIN MICROBIOTA  Normal skin colonised by huge numbers of microbes depending on local skin environment  Could cause infection but generally don't due to: o Intact stratum corneum and epidermis o Shedding of stratum corneum o Host immune system  Pathogens further prevented by o Low skin pH (5.5) and high salt o Resident microbes o BE ABLE TO DESCRIBE THE MOST COMMON BACTERIAL PATHOGENS THAT CAN CAUSE SKIN INFECTION, AND THE RESULTING DISEASES. SKIN INFECTIONS  Skin infection occurs when the stratum corneum is disrupted by o Trauma o Inflammation o Maceration due to excess moisture  Or in the skin pores and follicles BACTERIAL SKIN INFECTIONS  Various bacteria infect the skin but two species most commonly implicated:  Staphylococcus aureus Downloaded by Caleb Zhou ([email protected])  lOMoARcPSD|28574464 o Present in anterior nares of 20-40% of people o Can spread person-person; usually colonises nose first then spreads to skin  Streptococcus pyogenes (= group A Strep) o Present on mucous membranes (mouth, respiratory, GU tract) in