Microbes and Disease TBL cycle MCS

what are the stages of infection - transmission - entry into host - evasion of host defences - spread and colonisation of target site - establishment: multiplication of pathogenic organisms - damage to host - dissemination: exit from host and transmissibility to cause a disease what must a pathogen do - enter host and attach to target - spread from site of infection - multiply within host - evade host defences - be shed from body - cause damage what are the types of mechanisms of transmission - contact: direct, indirect, airborne - disease vehicles: medium in which disease can spread (blood, water, food, soil, air) - vectors: insects bites, faeces which type of transmission is the most effective and why human to human transmission - due to sexual and social habits of humans - respiratory route: lungs - faecal oral route: through ingestion of what are the 3 most common transmisfaecal derived organisms sion strategies in humans - venereal route: acquisition through sexual practices - number of pathogens shed what is the effectiveness of transmission - stability of organism in environment influenced by - virulence/pathogenicity or infectivity of the organism what does virulence mean the severity or harmfulness of a disease what is the infectious dose - the number of organisms required for 50% of population to show signs of infection 1 / 15 - eye: tears - ear: wax - nose: secretions - mouth: saliva, sputum - broken skin: blood - skin: flakes - mammary glands: breast milk - placenta - vagina: secretions, blood - urethra: urine - anus: feces - seminal vesicle: semen what are the entry and exit sites of pathogens a pathogen won't be able to successfully - effectively avoid predation by the hucolonise a patient to cause disease if man immune response they can't - adherence mechanisms using microbial adhesions: molecules which bind strongly to host cell surface what are the evolutionary adaptations - active interference with removal mechpathogens have in order to colonise body anisms: mucociliary escalator (achieved sites by production of toxins) - resistance to immune attack and destruction ( covering and cell wall adaptations achieve this) cilia that transport mucus and foreign material out of the respiratory tract mucociliary escalator - first avoid the non specific responses of what are the two main parts of the imthe innate immune response mune response that pathogens have to - then avoid adaptive immunity which avoid uses antibodies what passive mechanisms do pathogens use as defensive mechanisms 2 / 15 - be resistant to immune attack - have blocking layers (cell wall) - be undetectable - camouflage - grow within the immune system - survive and divide inside cells - infect where it can't get you - interfere immune response using toxins what active mechanisms do pathogens - kill immune cells by making immune use as offensive mechanisms chemicals that trick them into over or under activity what are viruses - chemical complex of protein and nucleic acid - may have a layer of phospholipid surrounding it - obligate pathogen: can't survive or replicate without a host virus structure: genome - contains genetic info as double stranded or single stranded - RNA or DNA virus structure: capsid - protective protein coat made of capsomers (protein subunits) - gives virus its shape - shape icosahedral (spherical) - shape rod (helical) - shape complex (mixture of the two) virus structure: envelope lipid bilayer around capsid. - structure derives from host cell membranes on exit of the intact virus - contains viral proteins: receptors for host interaction what must a virus do to enter the body - reach mucous membrane (eye, lung, gut) - enter through cuts/abrasions - vectors (insects, needles) - attachment: to a call that permits replication of that virus - penetration: directly via cell membrane, or by endocytosis followed by fusion or what are the 6 stages of virus replication fusion of viral membrane with host memin host cells brane - uncoating: release of genome form capsid - subversion: viral genes take over host 3 / 15 cell machinery to make new virus - expression of viral genes - assemble: at sites of release under cell surface on cytoplasmic side - release: of virus particle as mentioned above - interaction with the host cellular biosynthetic machinery how do viruses cause damage and how - symptoms of viral infection are caused are symptoms caused by immune response to the virus and not the virus itself - pathogen gaining entry into circulatory system has potential to spread to any part of body through body as circulatory system has networks of arteries and explain the spread of pathogens through veins the circulatory system - as lymphatic and circulatory system and connected, pathogens spreading through circulatory system can gain entry into lymphatic system vice versa what diseases are caused by pathogens which spread through the blood and lymph to various organs - meningitis - malaria - plague - bacteraemia - septicaemia explain malaria - "black water fever" - caused by species of parasitic protozoan plasmodium - transmitted by bite of female anopheles mosquito 1. female anopheles mosquito bites someone infected with malaria 2. the male and female gametocytes circulating in blood of human enter gut of mosquito where they fuse forming zygote 3. zygote is deposited on gut wall of mosquito and develops into an oocyst 4 / 15 4. thousands of sporozites form inside oocyst which eventually ruptures to release them explain the life cycle of plasmodium fal- 5. some migrate to salivary glands of ciparum in mosquito mosquito 6. when mosquito bites a healthy person the sporozoites are transmitted into blood stream 1. sporozoites reach hepatocytes of liver and each produces daughter cells called merozoites 2. infected hepatocytes rupture releasexplain the life cycle of plasmodium faling the merozoites which then enter red ciparum in man blood cells and destroy them 3. some merozoites develop into gametocytes which can be sucked up when bitten by a mosquito what are the symptoms of malaria - high fever - chills - haemolytic anaemia - haemoglobin in urine due to rupture of RBC explain the plague - "black death" - caused by: bacterium Yersinia pestis - disease of rodents and transmitted to human when a rat flea from an infected rodent bites humans what does the plague do in the body - when in blood it secretes a virulence factor, F1 protein, which forms protective gel capsule around bacteria helping it to escape phagocytosis - then reaches lymph nodes where they multiply rapidly to produce buboes - bacterium spreads to the lungs and causes deadly form of disease called pneumonic plague leading to death by septic shock 5 / 15 buboes symptom of plague occur as painful swellings in the thighs, neck, groin or armpits explain bacteraemia - the transient appearance of bacteria in blood - bacteria staphylococcus epidermidis and staphylococcus aureus can enter through IV lines and cause bacteraemia explain septicaemia - results in septic shock characterised by flu symptoms, hypotension, changes in mental state and tachycardia leading to multiorgan failure and death - bacteria neisseria meningitidis causes sudden and fatal form of the disease called fulminating septicemia explain anthrax - caused by inhaling spores of bacillus anthracis present in soil of pastures - spores germinate to form bacilli in human tissues & are protected from phagocytes by secreted capsule allowing it to survive and multiply - it rapidly spreads to blood and CNS leading to death what are the symptoms of anthrax - causes malignant pustules on skin caused by accumulation of toxic material secreted by the bacilli followed by build up of necrotic tissue - symptoms: fever, non productive cough leading to respiratory distress and cyanosis explain leptospirosis - caused by spirochete leptospira interrogans - infects mammals (rats, dogs) - transmitted to human through contaminated food and drink - can enter through skin - reach blood and cause fever, flu symptoms followed by hepatitis and hemor6 / 15 rhages of liver and conjunctiva - weils disease, kidney and liver failure is severe form of leptospirosis - CNS is extensive network of nerves - pathogens use network to spread in explain the spread of pathogens through body the central nervous system - once traveled from CNS to body they cause localised infections - multiply in oral mucosal cells (in mouth) causing lesions which eventually ulcerate - virus particles enter sensory nerves and are transported to the dorsal root explain cold sores and herpes simplex ganglion where they lie dormant virus - activation of latent virus caused by stress, direct sunlight, mensuration - viral particles travel through sensory neurons and cause recurrent herpes lesions explain genital herpes -caused by herpes simplex virus - infects genital mucosa - causes lesions - can be transmitted through genital secretions - can go through a latent phase before reactivating to cause recurrent infections Although shingles and chickenpox are caused by the same virus, they are not the same illness. Chickenpox is usualdifference between shingles and chicken ly a milder illness that affects children. pox Shingles results from a reactivation of the virus long after the chickenpox illness has disappeared. The chickenpox virus stays in the body even after recovery explain chicken pox - CP caused by varicella zoster virus in children - viral particles infect upper respiratory 7 / 15 tract and lymph nodes causing rash and fever explain shingles - caused by varicella zoster in adults - virus travels through peripheral nerves to dorsal root ganglion and lies latent into late adult life - get reactivated in dults and multiplies in sensory neurons - causes rash localised along the infected sensory neuron (waist, upper chest, back) - also causes unilateral neuralgia: severe pain caused by lesions explain rabies - caused by rhabdovirus (bullet shaped) - enters epidermal tissue from bite of a rabid animal - spreads through peripheral nerves into CNS - gives neurological symtpks:agitation, hydrophobia, hallucinations, excessive salivation - rapid multiplication in gray matter of NS and involvement of respiratory center in brain causes fatal encephalitis and respiratory paralysis what is encephalitis inflammation of the active tissues of the brain caused by an infection or an autoimmune response. explain protozoan parasites parasitic amebic meningoencephalitis caused by amoebae: naegleria fowleri and acanthamoeba Castellani naegleria fowleri - found in natural springs - enters nose of swimmers and spreads through olfactory nerve to olfactory centre in brain - causes rapid onset of severe bifrontal 8 / 15 headache, seizures, abnormal taste and smell progressing to coma and death acanthamoeba Castellani - acquired from contaminated tap water and or saline used for washing contact lenses - causes damage to cornea and spreads via optic nerve to brain causing tissue damage and haemorrhage what are the treatments of these diseases - malaria: Quinine Chloroquine - plague: Streptomycin - anthrax: ciprofloxacin - unilateral neuralgia in shingles: Amitriptyline and duloxetine - cold sores: antiviral meds - direct interactions: productions and use of offensive virulence factors which destroy immune cells and tissues promoting spread, transmission and persishow can damage in the human host be tence mediated - indirect interactions: interactions with host immune responses that cause damage such as inflammation or blockages in organs such as kidneys - productions of effector proteins, degradative enzymes secreted from bacterial cells into extracellular environment what is a common mechanism used by or directly into cytoplasm of host bacterial pathogens to cause disease - why bacterial pathogens: hv broad secretory capacity and cell wall can cause symptoms of disease without being secreted what are the two types of microbial toxins - exotoxins - endotoxins explain exotoxins - secreted from cell to cause effects - soluble, heat labile secondary protein metabolites produced during growth 9 / 15 explain endotoxins - structural components of cell wall that interact with immune system causing severe disease - called A-B toxins. A = toxic part - consist of active or toxic portion and a moiety that helps translocat the toxic part bacterial exotoxins can be multi compointo the cytoplasm of host cell nent toxins - example: Corynebacterium diphtheriae --> inhibits protein synthesis & cause death of cells - only exert action on particular structures of body e.g. neurones, gut epithelia bacterial exotoxins can be site specific - some site specific toxins work at cell surface to either destabilise membrane in a detergent like way or form pores - neurotoxins prod. by clostridium botulinum and clostridium tetani work at nerve synapse - botulinum block release of excitatoimportant specific exotoxins: clostridium ry transmitters causing flaccid paralysis botulinum and clostridium tetani and respiratory collapse - tetanus toxin: block release of inhibitory neurotransmitters causing continuous contraction of muscles causing spastic paralysis - enterotoxin prod. by staphylococcus aureus important specific exotoxins: staphylo- works in gut causing vomiting coccus aureus and enterotoxin B - effects vagus nerve to induce vomittingreflex important specific exotoxins: vibrio cholerae - exotoxin prod. by vibrio cholerae - affects gut epithelial cells causing fluid loss - organism invades cells causing damage - is example of A-B toxin 10 / 15 - pore forming: leucocidins prod. by S.aureus - punches holes in membrane of WBC causing them to burst - detergent: alpha toxin of clostridium example of pore forming toxin and deter- perfringens gent like action - causes gangrene - which separates phosphate containing grp from the lipid grp in the phospholipids of cell membranes which in effect causes emulsification and destabilisation resulting in destruction what are super antigenic exotoxins - exotoxins that exert their effects through interaction with the immune response - example: TSS toxin prod. by T helper cells. produce cytokines that communicate instructions to other parts of the immune system and activates processes that help pathogen clearance. SAT activate these cells in unregulated way causing massive release of cytokines resulting in symptoms of shock explain bacterial endotoxins - cause damage indirectly through interaction with host immune response - most often released on death of organism as they are structural proteins that form part of the cell wall of the organism - work by activating inflammation and coagulation leading to organ failure and death what is epidemiology study of people and diseases through time and space - evaluates occurrence, causation, control of health and disease in a population What are nosocomial infections infections acquired in the hospital pathogens come from 2 sources: - from patient: from one site in the patient 11 / 15 to another - environment around patient: contaminated people and equipment - have natural or acquired antibiotic resistance or resistance to biocides - example: clostridium difficile -> form resistant spores which persist in envipathogens that cause nosocomial infecronment. shed in faeces of infected peotions ple and contaminate surfaces and equipment -can only be treated with metronidazole or vancomycin - process of complete destruction/elimination of all viable microorganisms in or difference between sterilisation and dis- on a substance being sterilized infection - disinfection: process of removing microorganisms including pathogens from surface of inanimate objects - compromise between good antimicrowhat compromise does the choice of the bial activity and maintaining product stasterilizing process depend on bility explain the process of filtration - removes both viable and nonviable particles and is used for clarification and sterilisation of liquid and gases - mechanisms: sieving, adsorption, entrapment - used in the sterilisation of heat sensitive injections, ophthalmic solutions, biological products, air and gases for supply to aseptic areas explain dry filtration - used to purify gases for sterile air supply to aseptic manufacturing units, hospital isolators and operating theatres - uses high efficiency particulate air filters (HEPA) 99% efficient in removing 0.3 micrometers particles - made of random fibre matrix made up of 12 / 15 paper/glass fibre/sintered ceramic product and the cells are either adsorbed or entrapped in the fibrous matrix explain wet filtration - used to clarify liquids - works by employing thin sieve like membrane filters made of cellulose esters or paper with a nominal pore diameter - filters aid removal of bacteria explain moist heat sterilisation - used for partial reduction of microorganisms - autoclave standard conditions: 15 psi, 121.6°c for 15 min - the microorganisms endure hydrolytic damage when exposed to moist heat explain dry heat sterilisation - hot air ovens at temps 160°c to 180°c for 2 hrs - used to sterilise glassware, metallic surgical instruments, nonaqueous thermostable liquids and thermostable powders - for removal of endotoxins and pyrogens from glass 250°c used explain thermal death of bacteria - bacteria will die when exposed to lethal temps - the higher the temp the less time it takes to kill population - D value -time taken at a fixed temp or radiation dose required to achieve a 90% reduction in viable cells thermal death of bacteria: decimal reduc- - calculated: plotting log10 of viable cell tion time number after exposing a microbial population to temp or radiation against time of exposure - d value causes a 10 fold reduction in viable microorganisms 13 / 15 thermal death of bacteria: z-value - the increase in temp needed to reduce the D-value of an organism by 90% explain gaseous sterilisation - destruction of microorganisms by gases - ethylene oxide and formaldehyde - work by alkylating sulfhydryl, amino, hydroxyl, carboxyl grps on proteins and nucleic acid - alkylating gases are carcinogenic and mutagenic - used to sterilise disposable medical devices, diagnostic and electrical equipment explain irradiation - gamma irradiation used to sterilise plastic pipettes, etui dishes, tissue culture flasks,syringes filters - more lethal than UV light as causes microbial damage y ionisation and free radical production - disinfectants, antiseptics, antibiotics explain the use of chemicals for sterilisa- used for destruction or inhibition of mition crobes with minimal damage to host or materials explain disinfection process of removing microorganisms from surfaces of inanimate objects or surfaces - too harsh to be used on living tissues what are the different types of disinfectants used for the control of microorganisms - alcohols - aldehydes - halogens - heavy metals - silver - soluble phenolics explain antiseptics - the destruction or inhibition of microorganisms on living tissues - prevent/limit infection - not toxic or irritating 14 / 15 - common types:ethanol, isopropyl alcohol explain antibiotics - substance prod. by microorganism which at low concs can kill or inhibit growth of microorganisms - hv selective toxicity - derived from bacteria and fungi or by chemical synthesis what is bactericidal - antibiotics that kill bacterial cells what is bacteriostatic antibiotics that inhibit growth - are reversible 15 / 15