MECHANISMS OF INFECTION

what are pathogens

• disease causing organisms

• fully virulent - possess virulence factors i.e. structures and systems that help pathogens cause disease via infection and damage of host tissues

• show clonality

what are opportunistic pathogens

• possess some virulence factors i.e. structures and systems that help pathogens cause disease via infection and damage of host tissues

• often commensals

• tend to cause problems in immunocompromised or a susceptible area e.g. wound

iceberg concept of disease

• only a small portion of a disease is visible and detected e.g. in death, hospitalisation

• the majority of people w a disease are asymptomatic and hidden/ undetected

routes of transmission (6)

• respiratory/ salivary

• fecal/ oral

• venereal spread - sexual contact

anthropod-borne infections and zoonoses

• vector e.g. malaria

• vertebrate reservoir e.g. rabies

• vector-vertebrate reservoir e.g. yellow fever

define horizontal transmission and vertical transmission

• horizontal transmission: microorganism is passed between individuals who are not related as parent and offspring (same generation) e.g. plague, influenza

• vertical transmission: microorganism is passed from a parent to its offspring e.g. HIV, Hep B

what is colonisation and how does it lead to a bacterial infection

• when bacteria are present on/ in body wo causing disease/ illness

• colonisation » bacterial infection if balance between host and bacteria is disrupted, if opportunistic pathogens exploit host nutrients, if host has a weak immune system

requirements for colonisation and infection (6)

• successful transmission

• adhere to susceptible cells/ surface by pilli/ fimbriae, polysaccharide/ protein adhesins

• grow on/ in host

local/ systemic spread

• evade host defences

• invade by subversion of the endocytic system

• infectious dose threshold must be reached

how do bacteria adhere to human cells

• via pilli/ fimbriae

• ^ have adhesin molecules located at the tip

colonisation and infection: surface protein adhesion

• surface proteins on pathogens help bacteria to adhere to host cells’ proteins/ glycoproteins and invade them

• e.g. HIV binding to CD4 receptors

colonisation and infection: surface polysaccharide adhesion

• polysaccharides act as molecular glue helping bacteria stick to surfaces and each other

• important in biofilm formation - bacteria produce polysaccharides that help them adhere to surfaces

biofilms

heterogenous film of bacteria coating surfaces

• primary colonisation: surface such as a plastic catheter

• secondary colonisation: increased by extracellular polysaccharide and cell interactions

clinical significance of biofilms

• causes increased antibiotic and immune resistance

• resistance to macrophage enzymes

increased localised enzyme concentration promotes tissue damage

colonisation and infection: motility

• motility aids colonisation

• allows bacteria to spread from biofilm microcolonies and colonise other tissues

• penetrates mucous blanket - moist, mucus-covered lining in the nose that traps harmful particles and moves them out of the body

• penetrates intercellular junctions - special regions of contact between plasma membranes of adjacent cells

what is the endocytic system

• series of processes involving uptake and delivery of materials into and out of a cell

• main types: pinocytosis, phagocytosis, receptor-mediated endocytosis

colonisation: subversion of the host’ endocytic system

• bacterial ligand binds to host receptor causing plasma membrane to zipper around bacterium

E.coli:

• bacteria pilli binds to glycolipids on host cell surface - helps bacteria generate biofilm-like structures on and inside host

• when pilli binds, a pedestal (actin-rich protrusion) is formed beneath which anchors E.coli to host

• cell effectors (virulence factors) are injected via pedestal using secretion needles

colonisation: what is an infectious dose threshold

the minimum number of pathogens required to cause an infection - varies between diseases

evasion of host defences (4)

• blocking and degradation of immune molecules

• avoid phagocytic killing

• hide from adaptive immune response

• combat physical barriers

complement molecules

complement molecules work together to identify and eliminate pathogens:

• opsonization: complement molecules coat pathogens with opsonins to mark them for phagocytosis 

• inflammation: complement molecules generate proinflammatory mediators to attract immune cells and activate mast cells 

• lysis: complement molecules assemble membrane attack complexes (MACs) that damage the plasma membranes of pathogens

evasion of host defences: blocking and degradation of immune molecules by Gram +ve and Gram -ve bacteria

• Gram -ve: antigens block complement access to membrane

• Gram +ve: capsule blocks complement access to membrane by masking surface components

evasion of host defences: avoid phagocytic killing (5)

• organism releases toxins e.g. leukocidin produced by staphylocci causing phagocytes to die

• organism possesses a capsule which prevents contact w phagocyte

• organism escapes from phagolysosome into cytoplasm and replicates within phagocyte

• organism resists killing within phagosome by producing antioxidants

• organism inhibits fusion of phagosome and lysosome to form a phagolysosome e.g. TB so it survives for longer in macrophages

evasion of host defences: hide from adaptive immune response (6)

• organisms can incapacitate T-cells e.g. HIV

• organisms can vary their surface antigen e.g. influenza, meningitis, gonorrhoea - difficult to make vaccines for

• organism can coat itself w host protein, alter their surface proteins, imitate general structure of host i.e. mimicry

• organism can hide in privileged sites - areas of the body that are less likely to trigger immune response

• organism can produce a protein which prevents opsonization - coating of pathogens w opsonins to help immune cells identify

• organism can degrade/ inhibit complement - network of proteins that work together to destory pathogens e.g. C5a protease of S.pyogenes stops signal to phagocytes

evasion of host defences: combat physical barriers

• stomach acid is an example of a physical barrier

• Helicobacter pylori activates its urease to convert urea » ammonia + CO2

ammonia neutralises stomach acid

• many pathogens have an acid tolerance response (ATR) meaning they can survive in extreme acidic environments

• E.coli uses amino acid decarboxylases (AADC) to keep cytoplasmic pH above dangerous levels