9. How do Microbes Cause Disease? Flashcards
What do normal flora and pathogens compete for?
Can normal flora also cause disease?
What are the stages in microbial infection?
Colonisation sites.
Yes if they get to sites where they don’t normally live.
Attachment to and/or entry into body. Local/general spread. Evasion of host defence. Multiply and reproduce. Damage host. Shedding (exit).
List 5 specific portals of entry for most pathogens, and explain how.
1) Skin: cuts, abrasions, surgery, war (contaminated soil)
2) GI tract: contaminated food/water, faecal-oral route
3) Respiratory tract: direct inhalation, inhalation of food/vomit
4) Genito-urinary tract: commensals from perineum, STDs
5) Infected blood: transfusion (hep, malaria), needlestick (hep A, B, C, HIV), organ transplants, vertical (mum -> baby - viruses, syphilis)
Distinguish between horizontal and vertical transmission, and list the types of each.
Horizontal: from host to host of same generation. 1. Direct: host to host by contact (skin lesions (papillomavirus), saliva (rabies, HIV), mechanical trauma, aerosols). 2. Indirect: host to fomites (food, water, needles, vector-mediated) to host (e.g. hep A/B, polio, yellow fever).
Vertical: from host to progeny. Congenital transmission e.g. rubella, cytomegalovirus, HIV. 1. Transplacental:** CMV, parvovirus B19 cross placenta and can cause foetal infections. **2. Parinatal:** infection wiht HIV/HSV can occur during birth. **3. Breast Milk: vehivle for HIV1/HTLV1 transmission.
How can microbes spread throughout the body? What are 3 different types?
Describe the course of viral infection.
If gain access to lymphatics of bloodstream. Bacteraemia (bacteria in blood), viraemia (virus in blood), septicaemia (microbes in blood with evidence of host damage). Once in blood/lymph, most exposed to host immune defences (complement, Ab, polymorphs etc.)
Primary replication (place where virus replicates after gaining initial entry, determines whether infection will be localised/systemic). Systemic spread (via blood stream and CNS). Secondary replication (at susceptible organs/tissues following systemic spread).
Describe the disease mechanism of the following:
a) smallpox (variola virus)
b) rabies (lyssavirus, rabies virus)
What are some symptoms of measles?
a) transmitted by respiratory tract secretions, spreads through lymph and blood. Zoonoses transmitted by contact. Sequential infection of multiple organs. Cell-mediated and humoral immunity important to resolve infection.
b) transmitted by saliva via bite or by aerosols in bat caves. Replicates in muscle at bite site. Weeks-months incubation. Infects peripheral nerves and travels to brain, where replication causes seizures, hydrophobia, hallucinations, paralysis, coma and death. Spread to salivary glands from where it’s transmitted. Postexposure immunisation can prevent disease (due to long incubation).
Fever, cough, coryza, conjunctivitis, Koplik’s spots, measles rash
What might cause direct cell damage and death from an infection?
What might cause indirect cell damage from an infection?
Diversion of cell’s energy. Halt of cell macromolecular synthesis. Competition of viral mRNA for ribosomes. Competition of viral promoters and transcriptional enhancers for cellular transcriptional factors e.g. RNA pols, and inhibition of interferon defence mechanisms. Toxins (bacterial). Cell transformation (viruses).
Integration of genome (transformation, viral). Induction of mutations in host genome. Inflammation. Host immune response.
Give some examples of direct death by microbes.
Distinguish between necroptosis, apoptosis and autophagy regulation.
Viruses can induce histological changes/characteristic cytopathic effect in some cell lines e.g giant cells, or cause cells to enter apoptosis (HIV). Some bacteria thrive intracellularly causing granulomas e.g. M. tuberculosis. Physical presence e.g. obstruction of lymphatics/gut/bile ducts by worms. Direct cell destruction e.g. RBC’s with malaria.
Necroptosis: programmed form of necrosis due to trauma etc. Apoptosis: programmed cell death, natural in growth and development. Autophagy: intracellular degradation system that delivers cytoplasmic constituents to the lysosome
Describe the 2 different types of microbial toxin.
List some important exotoxins.
What are some clinical features of endotoxin?
Exotoxins: proteins produced by gram +ves and -ves
Endotoxins: the lipopolysaccharide component of gam -ve cell wall
Toxins that: help bacteria spread in tissues (e.g. hyalronidase, collagenase), lyse cells - cytolysins (phospholipases or pore forming proteins), block protein synthesis/cell function (e.g diptheria toxin inhibits protein synth., cholera toxin stimulates cAMP)
Fever, hypotension, disseminated intravascular coagulation, multi-organ failure, death
Virus-transformed cells have an altered phenotype - what characteristics can they display?
What can HBV cause?
How can host defences be evaded?
Loss of anchorage dependance/contact inhibition, colony formation in semi-solid media, decreased requirement for growth factors e.g HPV, HBV, HCV, herpes. [ONCOGENES!]
Hepatocellular carcinoma (HCC)
Stealth (disguise), avoid destruction (capsules etc.), inactivate Ab, evasion (mimicry - adsorb host acute phase proteins onto surface), hide in protected sites, antigenic variation, latency. Viruses that escape immune: herpes, pox, papova, retro.
How can phagocytes be evaded?
How can antibodies be destroyed?
What ‘protected sites’ can microbes hide in?
Bacterial polysaccharide capsule (hides cell wall and prevents binding of membrane attack complexes and complement lysis). M proteins in Streptococcus pyrogenes inhibit phagocytes. Production of antiphagocytic enzymes (S. aureus: leucocidin, Step pyogenes: streptolycin)
IgA proteases (e.g. in Heamophilus influenzae) degrade IgA at mucosal surfaces.
In cells (e.g. HSV, malaria), in eye (rubella), stones in urinary/biliary tract, dead tissue (poor blood supply)
What is antigenic variation? Give examples of how this is used to microbes advantage.
What is latency?
Constant DNA rearrangement causes expression of different surface proteins. Immune response develops to initial antigens but is ineffective once proteins change leading to relapsing fever. May vary from strain to strain (e.g. strep pyogenes), or within the same strain (e.g. trypanosomes)
Viruses may remain in dormant form following infection, viral nucleic acid is incorperated into host DNA. At times of stress, the virus may re-acitvate e.g. herpes
Describe the impacts of the host immune response on the infection outcome.
Distinguish between the roles of cellular and humoral immunity.
What mechanisms could enhanced viral injury be due to?
Usually microbe cleared completely from body -> recovery. Sometimes it’s unable to clear the pathogen completely. In some infections the immune response plays a large pathological role in the disease.
Cellular- plays major role in clearing infections (e.g. T-cells) whereas humoral protects against reinfection (e.g. B-cells).
Increased secondary response to T-cells e.g. HBV. Specific ADCC or complement mediated cell lysis. Binding of un-neutralised virus-Ab complexes to cell surface Fc receptors, and thus increasing number of cells infected e.g HIV. Immune complex deposition in organs like skin, brain or kidney (e.g. rubella, measles).
What is indirect damage via inflammation?
What is oncogenesis? Give examples of agenst that cause this.
Immune response may damage host iteslf if it’s inappropriate or overactive. Polymorphs may release enzymes at sites of infection leading to abcess formation. BV damage -> ischaemia. Hypersensitivity reactions.
Some microbes cause development of cancers by chronic inflammatory processes e.g. H. pylori. Some incorperate their nucleic acid into host genome which may cause development of cancers (onco/cancerogenesis). Causes: HBV (hepatocellular carcinoma), EBV (Burkitts lymphoma), HIV (lymphoma), HPV (cervical carcinoma)
Differentiate between host damage by bacteria and viruses.
By bacteria: intracellular infection may kill/alter function of host cell. Endo and exotoxins. Bacterial metabolic products. Physical presence. Nutrient consumption. Neoplasia (don’t alter genome but chronic infection promotes chronic inflammation and neoplasia). Hypersensitivity (type 2 (Abs), type 3 (immune complexes), type 4 (granulomas).
By viruses: kill/alter function of cell infected. Cause specific histological features (syncytia, giant cells etc.). Neoplastic change in cells they infect (genome alteration). Hypersensitivity (type 2 (auto Abs), type 3 (immune complexes).
