Mechanisms of Infection
What are pathogens and their activities in vivo?
Pathogens are microbes capable of damage damage to a host
Infection is the invasion of host by pathogen
To cause an infection → establish foothold, evade host defences, proliferate, cause damage
How do bacteria establish/colonise an in vivo niche?
Bacterial adherence = to anchor, carry out cellular invasion or toxin production.
→ bind reversibly (most) via nonspecific adhesion molecules eg) Teichoic acids of Staphylococcus aureus &
Alginate capsule of Pseudomonas aeruginosa
→ bind via specific adhesions
eg) Pili, fimbriae, outer membrane adhesions of gram NEGATIVE (neisseria meningitidis) pili attach to the
receptor on nasopharyngeal surface and retract to allow adhesion.
eg) cell wall proteins MSCRAMMs bind to matrix proteins in gram POSITIVE (staphylococcus aureus)
lipoteichoic acids mediate initial attachment where MSCRAMMs mediate stronger attachment via interaction
with ECM fibronectin
What are the host defences against bacteria and how do pathogens evade them?
Host defences = skin barrier, antimicrobial secretions (lysosome, lactoferrin, sIgA), lack of iron, complement,
phagocytes, antibodies.
→ Masking & hiding = immune defenses cannot see invaders as non self as microbes hide beneath a barrier
via a capsule (streptococcus pneumoniae) which is immunogenic, preventing exposed antigens from being
recognised by Ab & stops complement being deposited. No capsule easily phagocytosed OR TB invades
macrophages where immune cells wont recognise
→ Host mimicking = appear as self where protein A of staphylococcus aureus binds to antibody Fc region
causing inhibition of complement, phagocytosis where the cell is now covered in layer of host proteins OR
MSCRAMMs bind to ECM which also allows coverage of cell in host protein OR binding of serum factor H to
sialic acid capsule of neisseria meningitidis & M protein of streptococcus pyogenes to evade complement
killing. Normally fH binds to our cells to degrade C3b from targeting.
→ Destruction of phagocyte = bacillus anthracis produces toxin in phagolysosome that kills phagocyte OR
detoxify phagocyte via ROI or prevent its fusion (tb) OR complement proteolysis by destroying chemotaxins
(pyogenes) via proteases or blockage of 5a receptors via secretion of CHIPS (aureus)
→ Mis-information = antigenic variation where antigen on bacteria mutate to a state that isn't recognised by the
Ab produced for them OR outer membrane blebs releasing LPS & membrane proteins that act as immune
decoys which confuses host defences allowing them to stay just out of reach
, How do pathogens acquire nutrients to grow?
Bacteria need iron to grow as it is a cofactor for essential enzymes. Iron restriction via Lactoferrin in secretions,
Transferrin in blood, Functional in enzymes - Hb, Stored as ferritin in cells.
Pathogens acquire iron → Siderophores (small iron chelators that find & bind), Specific binding proteins (for
transferrin), Increasing available iron (haemolysin, protease activities), Adapting to high iron niche of
phagosomes, Evolving enzymes that use other co- factors like Mn
Chronic Inflammation & Carcinogenesis
Peptide ulcer disease → a breaking in lining of stomach/SI where HCl & pepsin are present causing Upper
abdominal pain, Belching, Vomiting, Weight loss, Bleeding
1. To explain how Helicobacter pylori can persist and cause chronic inflammation leading to disease
They have flagellum & motility; they allow them to swim fast towards the mucus layer. Helical shape allows
penetration of mucus. Use urease to produce ammonia that neutralizes acid causing mucus to ‘de-gel’. It
attaches to gastric epithelium via Lewis b carb receptor with BabA adhesion allowing colonisation in the gut.
Immune evasion → H.pylori is gram -ve and secretes LPS that is poorly recognized by TLR4 resulting in low
cytokine production. Flagellin is poorly recognised by TLR5, also low in cytokine. It produces vacuolating toxin
A that inhibits phagosomal maturation, T B cell proliferation, iNOS generator & induces apoptosis of
macrophage. It is coated with plasminogen & cholesterol allowing host mimicry
Chronic inflammation → Infection of stomach pyloric antrum results in lack of somatostatin produced thus no
inhibition of acid production from parietal cells and gastrin from G cells. This acid leaks into duodenum causing
inflammation leading to duodenal ulcer & acid hypersecretion (peptic ulcer) // infection of corpus causes loss of
parietal cell function thus loss of acid secretion where intestinal like cells grow in stomach leading to
inflammation. This can result in gastric ulcer via acid hyposecretion (gastric cancer)
2. To explain how Helicobacter pylori infection can elicit mutations and cause cancer
CagA is an oncogenic protein that is phosphorylated in the gastric cell where CagA-P stimulates apoptosis,
barrier disruption, cytokine production, cell proliferation, ROS release thus stimulating oncogenic pathways.
This occurs via type 4 secretion allowing cagA to inject into the host cell which can lead to gastric cancer
What are pathogens and their activities in vivo?
Pathogens are microbes capable of damage damage to a host
Infection is the invasion of host by pathogen
To cause an infection → establish foothold, evade host defences, proliferate, cause damage
How do bacteria establish/colonise an in vivo niche?
Bacterial adherence = to anchor, carry out cellular invasion or toxin production.
→ bind reversibly (most) via nonspecific adhesion molecules eg) Teichoic acids of Staphylococcus aureus &
Alginate capsule of Pseudomonas aeruginosa
→ bind via specific adhesions
eg) Pili, fimbriae, outer membrane adhesions of gram NEGATIVE (neisseria meningitidis) pili attach to the
receptor on nasopharyngeal surface and retract to allow adhesion.
eg) cell wall proteins MSCRAMMs bind to matrix proteins in gram POSITIVE (staphylococcus aureus)
lipoteichoic acids mediate initial attachment where MSCRAMMs mediate stronger attachment via interaction
with ECM fibronectin
What are the host defences against bacteria and how do pathogens evade them?
Host defences = skin barrier, antimicrobial secretions (lysosome, lactoferrin, sIgA), lack of iron, complement,
phagocytes, antibodies.
→ Masking & hiding = immune defenses cannot see invaders as non self as microbes hide beneath a barrier
via a capsule (streptococcus pneumoniae) which is immunogenic, preventing exposed antigens from being
recognised by Ab & stops complement being deposited. No capsule easily phagocytosed OR TB invades
macrophages where immune cells wont recognise
→ Host mimicking = appear as self where protein A of staphylococcus aureus binds to antibody Fc region
causing inhibition of complement, phagocytosis where the cell is now covered in layer of host proteins OR
MSCRAMMs bind to ECM which also allows coverage of cell in host protein OR binding of serum factor H to
sialic acid capsule of neisseria meningitidis & M protein of streptococcus pyogenes to evade complement
killing. Normally fH binds to our cells to degrade C3b from targeting.
→ Destruction of phagocyte = bacillus anthracis produces toxin in phagolysosome that kills phagocyte OR
detoxify phagocyte via ROI or prevent its fusion (tb) OR complement proteolysis by destroying chemotaxins
(pyogenes) via proteases or blockage of 5a receptors via secretion of CHIPS (aureus)
→ Mis-information = antigenic variation where antigen on bacteria mutate to a state that isn't recognised by the
Ab produced for them OR outer membrane blebs releasing LPS & membrane proteins that act as immune
decoys which confuses host defences allowing them to stay just out of reach
, How do pathogens acquire nutrients to grow?
Bacteria need iron to grow as it is a cofactor for essential enzymes. Iron restriction via Lactoferrin in secretions,
Transferrin in blood, Functional in enzymes - Hb, Stored as ferritin in cells.
Pathogens acquire iron → Siderophores (small iron chelators that find & bind), Specific binding proteins (for
transferrin), Increasing available iron (haemolysin, protease activities), Adapting to high iron niche of
phagosomes, Evolving enzymes that use other co- factors like Mn
Chronic Inflammation & Carcinogenesis
Peptide ulcer disease → a breaking in lining of stomach/SI where HCl & pepsin are present causing Upper
abdominal pain, Belching, Vomiting, Weight loss, Bleeding
1. To explain how Helicobacter pylori can persist and cause chronic inflammation leading to disease
They have flagellum & motility; they allow them to swim fast towards the mucus layer. Helical shape allows
penetration of mucus. Use urease to produce ammonia that neutralizes acid causing mucus to ‘de-gel’. It
attaches to gastric epithelium via Lewis b carb receptor with BabA adhesion allowing colonisation in the gut.
Immune evasion → H.pylori is gram -ve and secretes LPS that is poorly recognized by TLR4 resulting in low
cytokine production. Flagellin is poorly recognised by TLR5, also low in cytokine. It produces vacuolating toxin
A that inhibits phagosomal maturation, T B cell proliferation, iNOS generator & induces apoptosis of
macrophage. It is coated with plasminogen & cholesterol allowing host mimicry
Chronic inflammation → Infection of stomach pyloric antrum results in lack of somatostatin produced thus no
inhibition of acid production from parietal cells and gastrin from G cells. This acid leaks into duodenum causing
inflammation leading to duodenal ulcer & acid hypersecretion (peptic ulcer) // infection of corpus causes loss of
parietal cell function thus loss of acid secretion where intestinal like cells grow in stomach leading to
inflammation. This can result in gastric ulcer via acid hyposecretion (gastric cancer)
2. To explain how Helicobacter pylori infection can elicit mutations and cause cancer
CagA is an oncogenic protein that is phosphorylated in the gastric cell where CagA-P stimulates apoptosis,
barrier disruption, cytokine production, cell proliferation, ROS release thus stimulating oncogenic pathways.
This occurs via type 4 secretion allowing cagA to inject into the host cell which can lead to gastric cancer
