Bacterial Pathogenesis Flashcards
What are bacterial pathogens?
Bacteria that are able to cause disease. Pathogens have some key attributes: colonisation, invasion, multiplication & tissue damage
What are Koch’s postulates?
rules that determine if a bacteria is a pathogen.
- organisms found in all patients with the disease - distribution corresponds to lesions - cultivate outside the host for several generations - reproduce the disease in other species - demonstrate a specific immune response
What defenses must a bacteria face at the mucosal surface?
Mucosal surfaces are overcome with competition from commensals. Infecting pathogens have to move through mucus, resist mucosal defenses and adhere to the epithelial cells competing against those commensals.
How does Bacterial Adherence occur?
Occurs via surface proteins using either fimbrial or non-fimbiral adhesions.
What are some components that contribute to the virulence of a bacteria?
There is evidence for fimbriae in virulence that stems from the virulence of fimbriate and non-fimbriate bacteria. Anti-fibrial immunity can be either passive or active. (ETEC)
There is evidence for capsules in virulence stemming from virulence of capsulated and unencapsulated bacteria as well as anti-capsular antibodies and immunity (passive immunisation with anti-capsule antibodies and active immunisation with capsular antigens)
What are some advantages of capsules in bacteria?
Capsules can electrostatically repel immune cells (they can enhance the electrostatic charges of the host), resemble host components (such as strep. pyogenes that has a capsule that is non antigenic that the Immune system doesn’t recognise as foreign and meningococcus group B) and mask underlying structures to enhance virulence.
Bacterial structures such as capsules can be classified according to letters to indicate the protein structure/type of virulence factor. Such as O and H antigens in influenza or group A/group B Meningococcal strains. Similarly there are various types of vaccines for different serotypes of pneumococcal and meningococcal strains.
How does bacterial entry occur?
Bacterium penetrate the epithelium both through cells and between cells.
Penetration of Epithelial cells is often via pathogen-mediated endocytosis and initiated by bacterial surface proteins.
(Yersinia going between M-cells in gut)
How do some bacteria overcome phagocytosis?
Extracellular pathogens overcome phagocytosis through strategies such as direct effects on phagocytes or by interfering with opsonins (antibodies, complement). LPS is often activates the alternative complement pathway and the bacteria become coated with C3b, which is an opsonin. This enhances phagocytosis.
Direct evasion of Phagocytosis: Via production of leukocidins, production of anti-inflammatory toxins and enzymes and carriage of surface anti-phagocytic structures.
Capsulated bacteria can mask underlying structures such as LPS or peptidoglycan thus not inducing opsonisation.
As protected as bacteria are with their capsules, antibodies are able to overcome those capsules. Antibodies for specific bacteria can fix opsonins to the bacterial surface via the classical pathway.
Explain the process of opsonisation
Antibodies and Complement both have opsonic function.
- IgM coated bacteria bind to the C3b receptor and activate the phagocytes via the classical pathway.
- IgG coated bacteria bind to IgG & C3b receptors inducing phagocytosis (Receptors bind to the Fc region of the IgG)
How does phagocytosis occur?
Intracellular pathogens resist killing by phagocytes by inhibiting respiratory bursting, preventing phagolysosome formation, escaping from phagocytic vacuoles (such as Salmonella) and resisting bactericidal systems (such as TB because it is acid fast and the enzymes cannot destroy them - reason for latency of TB)
Chemotaxis draws phagocytes toward to bacteria (ie. C3a, C5a).
ROS oxidase: gram positive components and lipid layer of bacteria.
How are bacteria able to overcome the adaptive immune system?
Bacteria are able to overcome the adaptive immune system by:
- direct immunosuppression (HIV, Measles) - expression of weak antigens - antigen diversity (pneumococcus has 90 serotypes and requires different vaccines for each serotypes. They are able to change their capsules and therefore their antigens) - antigen modification (antigens can be changed during the course of infection, resulting in relapses)
How do bacteria induce tissue damage?
Tissue damage is usually a result of direct toxicity mediated by bacterial toxins, induction of cytokines, or induction of immunopathology.
What are some features of Bacterial toxins?
They can be broken down bacteria, toxins produced by the bacteria, secreted toxins of the bacteria etc.
There are two broad categories of toxins: Exo- and Endo- toxins.
Endotoxins: classified according to the site of action (intra/extracellular), mechanism of action (cytotoxic or cytotonic/stimulatory - cholera) or tissue specificity (such as neurotoxins like tetanus or cardiotoxins).
Tissue specificity can arise due to the site of infection as well as distribution of the receptors that the toxin binds to.
Endotoxins are essentially released by dying cells. It is a part of the cell wall (LPS) and thus is highly resistant to heat. This is important because if something is heat resistant then traditional methods of sterilization involve heating. If something is pyrogen free then it means that there were no toxins that caused fever in test subjects. Antibodies are not able to neutralise the toxin itself as it is a lipid toxin with a non specific mechanism of action.
Exotoxins: are produced by the bacteria and are generally made up of proteins that are highly antigenic. (Clostidium tetani - causes tetanus/lock jaw; gram positive rods that are anaerobic and spore forming, particularly on rust as this is a micro anaerobic environment. Tetanus can only be immunised against by vaccine which comprises of tetanus toxoid which is just the toxin with a neutralised toxic component.) Toxins are able to transport from the site of infection to other regions of the body. The mechanisms of action for exotoxins are highly specific and vary between different types of toxins.
What are some differences and examples of intracellular acting toxins and extracellular acting toxins?
Extracellular-acting toxins have many targets:
- intact host cells such as haemolysin, leucocidins
- extracellular matrix such as hyaluronidase, collagenase
- other host molecules such as lipid, fibrin, nucleic acids etc.
Intracellular-acting toxins can be either cytotoxic which kills the cells (diphtheria toxin, shiga toxin) or cytotonic which are stimulatory (cholera enterotoxin, heat stable enterotoxin). They can be either simple (uncommon) for example the heat stable enterotoxin or bi-functional (A-B type - A is the active fragment and the B fragment is the binding fragment which is the part that antibodies target) such as the diphtheria toxin or the cholera toxin.
