Principles of Infectious Diseases - Pathogenesis Flashcards
Define pathogen, pathogenecity, virulence, virulence factors
Pathogen: microbe that is able to cause disease
Pathogenicity: ability of an infectious agent to cause disease
Virulence: quantitative measure of pathogenicity (how pathogenic a microbe is)
Virulence factors (determinants of virulence)
- various genetic, biochemical or structural features of a pathogen which enable it to produce disease
- individual microbes can have many virulence factors
- Pili and spikes for attachment and entry
- enzymes to breakdwon tissue e.g. collagenase
What is Koch’s Postulates and what is its relationship with determining causation?
Koch Postulates: guidelines for linking specific organisms with specific diseases
- microbe must be present in every case of the disease
- microbe must be isolated from the diseased host frown in pure culture
- disease must be produced when a pure culture is introduced into a non-disease susceptible host
- microbe must be recoverable from an experimentally infected host
Very useful in early understanding of infectious disease but not applicable in modern medicine and not suitable to viruses
What is the biological response gradient
Microbes may not cause the same disease in all infected individuals
> Outcome can range from an asymptomatic to a lethal infection
What are the 6 steps that an infectious micro-organism takes to cause disease?
- Attachment (+- entry into the body) –> entry (infection)
- Local or general spread in the body –> spread
- Multiplication –> multiplication
- Evasion of host defences –> microbial answer to host defences (next set of palm cards)
- Shedding from body (exit) –> transmission
- Cause damage in host –> pathology, disease
How do pathogens enter the body through adherence factors?
Adherence factor = adhesins
- Attachment to a eukaryotic cell or tissue = adhesin and receptor
- Adhesin = macropmolecular component of the pathogen cell surface
>Bacteria - e.g, pili (fimbriae), capsule (not as specific)
>Virus - spikes on virion
- Receptor = usually a specific carbohydrate or peptide structure on the target eukaryotic cell surface
Describe the specifcity of adherence
- Specificity of adhesin binding means that bacteria adhere to and invade most efficient cells which express the target molecule –> tissues and species specificity
- Tissue tropism = specific bacteria bind most effectively to certain tissues –> streptococcus cell surface adhesins:
>S.mutans bind specifically to salivary glycoproteins(receptor) on teeth but is seldom found on the tongue
>S. salivarius binds to receptor expressed on tongue epithelium and is seldom found in plaque
- Viruses show a smilar tropism for different cells e.g. HIV for T helper cells
Describe how pathogens can spread through the host
- Some microbes may cause a superficial infection, which can then easily shed large numbers into environments –> avoids immune mechanisms –> e.g. viruses that cause colds, replicate in nasal epithelium
- Other microbes go deeper in the body and spread systemically –> reaches organs that enable replication and shed thorugh membranes and skin e.g. measles
- Many microbial and host factors influence whether an infection is localised or systemic
- Microbes that can multiply rapidly are extremely dangerous in systemic infections –> these generally cause local/superficial infections
- Slow replication can allow microbes to evade immune responses
What are bacterial invasins (spreading factors) and provide some examples
Localised production of enzymes by bacteria which degrade components of biological barriers e.g. intercellular spaces, tissue matrix
Examples of bacterial enzymes:
- Hyaluronidase: connective tissue
- Collagenase: collagen
- Neuramidase: intercellular junctions (sialic acid)
Invasins may also disrupt cell membranes (lecithinases, streptolysin)
What are systemic infections?
- Usually proceed in distinct steps –> especially in viral disease
- Microbes which are adpated to systemic infections –> adapted to avoid immunity –> complex course of entry, spread and transmission
- Symptoms frequently due to immune response
- Primary and often scondary parasitaemia
Explain the requirement of transmission for pathogens
- Pathogens must not only enter but must also successfully transmit to new hosts
Key factors affecting transmission
- Number of microorganisms shed
- Microorganism’s stability in the environment
- Number of microorganisms required to infect a fresh host (efficiency of the infection)
> Transmissibility of pathogen is a key factor in controlling infectious disease
>Stable microbes require less close contact while usntable microbes require more direct transmission
What are exotoxins (bacterial toxins)?
Proteins which are released into the extracellular environment
- Secreted by bacteria
- Gram-positive and Gram-negative
- Toxin production is often the major determinant of virulence e.g. tetanus toxin
- Among most potent poisons known
- Genes encoding toxin production generally located on plasmids or in lysogenic bacteriophage
- Genetic exchange via conjugation or transduction is significant in determining pathogenic potential
What is the biochemistry of bacterial exotoxins?
Exotoxins are similar to enzymes e.g.
- proteins
- denatured by heat,acid and proteolytic enzymes
- high biological activity (most are catalytic)
- neurotoxin, lueukocidin, hemolysin
Many protein toxins consist of two subunits (A + B)
- Subunit A is activated and responsible for toxicity
- Subunit B generally binds to specific receptor on target cell and mediates entrance to target cell (endoyctosis)
What are endotoxins? What does the structure look like
Lipopolysaccharides (LPS) associated with the Gram-negative cell wall
- LPS outer layer of the membrane
- Bacteriphage receptor sites
- Determines antigenic character
- Toxic in G-ve infections
Endotoxin structure
- Complex structure
- O polysaccharide (immune target, strain vaccination)
- Lipid A (toxic component, less toxic than extoxins, more stable)
- Released by bacterial lysis (autolysis etc)
Describe the toxicity of endotoxins
Endotoxins are toxic to most mammals
- Responsible for significant symptoms of Gram-negative bacteraemia and septicaemia
- Stimulate a systemic inflammatory response
>Fever
>Changes in white cell counts
>Disseminated intravascular coagulation (thrombosis)
>Hypotension
>Shock
>Death from massive organ failure
Describe the endotoxin toxicity mechanisms
- During severe gram-negative infections –> massive amounts of LPS can be released
- LPS triggers immune cells (macrophages and neutrophils) to release large amounts of inflammatory signalling molecules (cytokines)
- Overproduction of these cytokines and other molecules so they trigger a systemic shock response
- Under normal circumstances when bacteria levels in an infection are moderate, this response is useful to the host –> also gram positive septicaemia
What are the differences between exotoxins and endotoxins?
