Bacterial & Viral Pathogenesis Flashcards
Define epidemiology
Study of occurrence, distribution and control of diseases in populations
What are the basic stages of pathogenesis for microbial Disease
- Entry into the body
- attachment/adhesion to cells
- infection/colonisation and growth
- pathological alterations of host = symptoms
Name some non-specific virulence factors
Extracellular proteins
Polysaccharide capsule (protection)
Toxins - damage inducing substances
Give some examples of pathogenic extracellular proteins
Hyaluronidase Processes, Nucleases, Lipases etc. Collagenase Streptokinase Coagulase
What is Glycocalyx
Glycoproteins and glycolic is covering that surrounds cell membrane of some bacteria
What are the 3 types of Toxin
Exotoxins
Endotoxins
Enterotoxins
What are the 3 types of exotoxins
Cytolytic, A-B and superantigen toxins
Describe the function of Cytolytic toxins
Lose host cells by enzymatically degrading cellular components
Describe the function of A-B toxins
Consist of two Covenanter bonded subunits, A(ctive) and B(inding). B subunit usually binds to cellular surface to allow transport of A through membrane to damage cell
Describe function of superantigen toxin
Stimulate large amounts of immune response cells that lead to massive inflammatory reactions
Describe enterotoxins
Exotoxins affecting host small intestine
- produced by food poisoning and intestinal pathogens, bacteria including staph, clostridium, bacillus, vibrio chlorae, E. coli, salmonella etc.
Describe endotoxins
Produces only by gram negative organisms
- located in the outer layer of cell envelope of lysed gram negative bacteria
Describe the effect of endotoxins
- released when lysed
- causes diarrhoea,rapid decrease in leukocyte and lymphocyte and platelet numbers, release of cytokines and systematic inflammation
- haemorrhagic shock and tissue necrosis (after high doses of endotoxins)
What is bloat
Uncontrolled increase of body size due acc. Of gases in body as a result of pathology or death
What is putrefaction
The decomposition of proteins by putrefying (anaerobic) resulting in the formation of polyamines with putrid odour - putrescine
What is gnotobiology
raising mammals under germ-free environments, or conditions with controlled spectra and numbers of microorganisms
Reasons for gnotobiology
Use genetically modified model systems
Study establishment and maintenance of immune system
Provide new insights on aetiologies
Health and disease are two different states of the body, what is the word for health —> disease
Pathogenesis
Health and disease are two different states of the body, what is the word for disease —> health
Convalescence
Define pathogenesis
Set of mechanisms by which an etiological factor causes a disease
Define epidemiology
The study of occurrence, distribution and control of diseases in populations
What are the 3 types of human-microbe interactions
Parasitic: one organism lives and benefits at expense of other
Symbiotic: both organisms benefit from each other
Commensals (Maybe opportunistic): neither organism particularly benefits or suffers or one can benefit with no obvious harm to other
Define virulence
Extent of pathogenicity expressed by pathogens
Define pathogenicity
Ability of pathogens to cause disease
Define attenuation
Long cultivation of pathogens in culture
Define ID50
Infectious Dose 50%: number of pathogens cells needed to cause 50% of host cells to show signs of infection
Define LD50
Lethal Dose 50%: the number of pathogen cells needed to cause 50% of host cells to die
Define infection
The colonisation of host by a pathogen
Define incubation period
The time between infection and symptoms of disease
Define acute period
Height of disease with pronounced symptoms
define Decline period
Symptoms subside
define Convalescence period
Returning to normal
How are microbes like E. Coli aides during adhesion
They produce adhesins that bind to host receptors on specific sugars present in fimbriae and pili
What is sepsis
Viraemia
Bacteraemia
Parasitaemia
What is toxicity in terms of pathogenicity
Aiding disease by different toxins that inhibit or kill host cells
What is invasiveness in terms of pathogenicity
Growing in a tissue to such amounts of cells that inhibit host functions and cause disease (even in the absence of toxins)
The action of toxins can be:
Direct: causing lysis or apoptosis to cells
Indirect: triggering biological activities that harm the host systematically
What is the significance of a polysaccharide capsule in terms of virulence
It takes over 10,000 unencapsulated bacteria to kill a mouse but it the bacteria is encapsulated then it can take less than 10.
What is mycolic acid
Each material in cell walls of mycobacterium that can inhibit phagocytosis by antibiotics
True or false: exotoxins and enterotoxins are proteins
False: ENDOtoxins and Enterotoxins are
True or false: Exotoxins are lipopolysaccharides
True
True or false: exotoxins are less potent than endotoxins
False, other way around
Do bacteria secrete endo or exotoxins
Exotoxins
What does Anthrax result in
Reduction of RNCs especially and and leads to destruction of surrounding tissue
- spores are highly resistant to physical and chemical agents
What 3 toxins are the cause of anthrax development
Protective antigen: which mediates entry is the two other proteins, Oedema and Lethal factor) which are all encoded by a plasmid
Describe the appearance of anthrax colonies
Gram positive, with characteristic squared ends and ellipsiidal central endospores (resistant to staining and refactor to light)
- Large cells
- older colonies have ground glass phenotyoe
What does oedema factor (EF) do
Ca2+ and calmodulin dependant.
Increases cAMP —> upsets water homeostasis —> liquid accumulation
What does lethal factor (LF) do
Inactivated MAPK kinase —> fall in cellular signalling —> impaired macrophage function —> distorted immune system
What are the 3 main types of anthrax
Gastrointestinal
Inhalational
Cutaneous
How quickly can death account after inhaling anthrax bacilli
Inhalation of spores will lead to haemorrhagic pneumonia and death within 24 hours after the flu like stage that lasts for 2-4 days
Characteristics of Botulism
Flaccid paralysis of muscles and respiritory failure
- caused by botulinum toxin of anaerobic bacterium Clostridium botulinum
- usually through contaminated food
Characteristics of Clostridium botulinum
Anaerobic organism, heterogenous group, spire forming
- under anaerobic conditions, spores can germinate under salt
- at least 7 antigenicallu distinct botulinum exist A - G.
- Types A, B, E and F are associated with human botulism
What is the most poisonous substance known
Botulinum toxin, 1 gram can kill 10 Million people
Characteristics of infant botulism
Most common form associated with consumption of contaminated food (usually honey or corn syrup)
Flaccid paralysis and respiratory arrest can develop, with rare death.
How is botulism diagnosed
Search for Clostridium bacteria
- toxin bioassay works in mice, not in infant or wound botulism.
- demonstrate toxin presence in serum or stool by injecting either into mice and searching for botulism
How is botulism treated
Early diagnosed food borne and wound can be treated with horse derived antitoxin which blocks the action of toxin
- removing contaminated food from gut
- wounds should have bacteria surgically removed
- NOT with antibiotics as they promote paralysis
Characteristics of Diphtheria infection
Caused by corynebacterium diphtheriae
- bacteria multiply on epithelial cells of pharynx and cause local damage
- local inflammation with false membrane, sometimes bleeding
- life threatening complication is respiratory obstruction, myocarditis, fever and exhaustion
Characteristics of cutaneous diphtheria infection
Bacteria colonised skin and subcutaneous tissue, developed Papua’s evolves into bronco ulcer that doesn’t heal. The exotoxins May cause systemic disease
Treatment and control of respiratory diphtheria infection
- Early administration of antitoxin
- Penicillin and erythromycin
- Immunisation with toxoid vaccine is recommended in childhood with boosters ever decade
- immunity determines by Schick test
True or false: staph epididimis secretes coagulase
False: Steph coccus does
Describe enterotoxins
Endotoxins that cause gastrointestinal distress when ingested. Cause massive secretion if fluid in SI lumen —> vomiting and nausea
- mostly superantigen that activate T cells —> prod cytokines and stim macrophages
When toxic shock syndrom usually occur
After infection during surgery By toxic shock syndrome toxin-1 (TSST-1) which is released by growing cells of s aureus
What is leukocidin
A protein (produced by staph aureus) that destroys leukocytes. The process cause pus prod in skin boils
What do carotenoids of staph aureus do
Destroy phagocytes like macrophages
Name some reasons for antibiotic resistance (of staph aureus)
- plasmids as well as chromosomes provide resistance against aminoglycosides, penicillins and chloramphenicol
- use of antibiotics causes natural selection against it
What is the usual reason for MRSA being resistant
Due to a mobile element-derives chromosomal mecA gene encoding a Penicillin Binding Protein with altered (reduced) affinity to penicillin beta-lactam rings
Characteristics of a carbuncle
Infection involves several adjacent hair follicles, central necrotic core forms large ulcer requiring antibiotics.
- local invasion of staph aureus
- outer layer of fibroblasts
Characteristics of endotoxins
- NOT located inside bacterial cell
- NOT a protein
- Lipopolysaccharide component in Outer leaflet of cell membrane
- released from the outside of cell when lysed
- consist of 3 subunits: Lipid A, a core polysaccharide and O-polysaccharide
Describe the 3 subunits of Lipopolysaccharides
Lipid A: responsible for toxicity
Core polysaccharide
O-polysaccharide: makes complex soluble and immunogenic
True or false: endotoxins are produced by gram negative bacteria only (with possible exceptions)
True
True or false: exotoxins are bound to the outside of the bacteria cell
False: they are metabolic products secreted from inside the cell
True or false: endotoxins are more heat resistant than exotoxins
True: stable up to 1 hour at autoclave temp (121 degrees)
Exotoxins up to 60 degrees
Describe the effects on the host of an endotoxins
Fever, malaise, shock, blood coagulation
Describe the variable effect of exotoxins on the host
Could be a neurotoxin, cytotoxic, enterotoxins
True or false: exotoxins are fever inducing
False, endotoxins are
What are some representative diseases of exotoxins
Botulism Diphtheria Cholera Plague Tetanus
What are some representative diseases of endotoxins
Typhoid fever
Endotoxic shock
Urinary tract infection
True or false: endotoxins activate nearly every non specific defence mechanism
True
- complement in alternative pathway
- coagulation
- inflammation
- cytokines and macrophage release
- B cells etc.
Characteristics of a retrovirus
Virus containing RNA that use reverse transcriptase for its replication
What family does HIV (human immunodeficiency virus) belong to
Retrovirus
How does HIV interact with the immune system
Destroys it by releasing HIV particles infecting and killing white blood cells, particularly CD4 surface protein expressing cells
Characteristics of HIV virions
Lipid Bilayer: apx. 72 viral envelope GP spikes
Core Proteins
- RT: Reverse Transcriptase
- MA (Matrix Protein P17) forms shell to inner side of membrane to ensure integrity of virion
- CA (Capsid Protein P24) assemble in hexameric rings to constitute to capsid
- NC (nucleocapsid protein or P7) is needed for RNA stability and nucleocapsid assembly
- Gp41 and Gp120 are needed to enter cell
Outline HIV replication in a CD4 host cell
- Entry of virion into cell
- conversion of RNA to DNA by RT
- Integration of viral DNA into host DNA by viral integrase
- Activation of T-cells leads to transcription and translation of viral genome
- assembly of new virions
Common features of HIV patients
WEight loss Fatigue Fevers Weakness Lower CD4 count
Diagnosis of HIV
Direct identification is hard as often integrated into host chromosome and could be kept as provirus for years. Serological tests - ELISA - HIV Enzyme immunoassay - Western blot
True or false: presence of HIV antibody doesn’t necessarily mean patient is infected with HIV
True, just means they have been exposed to it
Name some manifestations of HIV infection
Shingles: limited painful skin rash one one side of body with blisters
Disseminated herpes
Kaposi’s sarcoma: rare cancer of blood vessels AIDS associated
Major routes of HIV infection
- unprotected sexual inter course
- intravenous drug abuse
- blood transfusions, organ transplants, haemophilic therapy, tattooing, contaminated needles
- mother to baby at birth, breastfeeding milk
Treatment of HIV
No effective vaccine or cure for HIV or AIDS
Post exposure prophylactic is needed
HAART is a prescription medicine used
Describe the HAART prescription drug
Cocktail of 3-4 antiviral drugs including inhibitors of RT, Protease inhibitors, Nucleotide analogues
Characteristics of HAART
Stops HIV replication (coz they can’t develop multi-resistance to it)
Infected Cells can potentially live up to 60 years before they die
Describe Enfuviritide (anti-HIV Drug)
Fusion inhibitor composed of a synthetic peptide chain that acts by binding to the Gp41 membrane protein of HIV
Explain Kochs postulate
- the suspected pathogenic organism should be present in ALL cases of disease and absent in healthy animals
- suspected organism should be pure cultured
- cells from pure culture should cause disease in healthy animal
- organism should be reisolated and shown to be the same as the original
Examples of some pathogens that can’t be cultured in a lab
Mycobacterium leprae
Tryponema pallidum
True or false: some diseases aren’t virulent by them selves
True, some are caused by combinations of factors e.g. liver cancer can be a product of Hepatitis B and D
What did the discovery of slide media for cultivation allow
- basic studies on biology of individual species and strains
- diagnostic purposes
- gene cloning and vaccine making
- Recognising emerging infectious diseases
Name the portals of entry
Skin, placenta, conjunctiva and mucous membranes of the respiratory, GI, urinary and reproductive tracts
- parenteral route is through skin puncture
Difference between vertical and horizontal spread of infection
Vertical is from generation to generation e.g. through gametes
Horizontal is from person to person e.g. airborne
Name some pathogens that can cross the placenta
Toxoplasma gondii
Treponema pallidum
Lentivirus (HIV)
Rubivirus
Characteristics of the epidemiological triangle
Who what (when) where Host, Agent [virus, bacteria etc.], (Time), environment (blood etc.)
