Colonisation and invasion of the host

• Describe how epithelia act as a physical barrier from pathogens

  Stratified epithelia consists of multiple layers of epithelial cells, which are held together by tight junctions. This makes it very difficult for pathogens to squeeze through. As well as this, mucous membrane provide an additional physical barrier.
• Describe how the skin is adapted to limit the risk of pathogen invasion

  The skin has a physical barrier in the form of stratified squamous epithelia, which is below layers of dead and keratinised cells. These cells are difficult to digest and therefore not favourable for infection by pathogens. The outside of the body exhibits a low temperature (less than 37 degrees C). Constant cell turnover means that pathogens are shed off and antibacterial secretions, such as lysozymes and acids, decrease the pH.
• Describe immune action in the skin

  Langerhan cells are a type of dendritic cell where their dendrites extend up into the skin and sample bacterial antigens to present to the Skin Associated Lymphoid Tissue (SALT). CD8 T-helper cells are found in the epidermis and CD4 T-helper cells can be found in dermis, alongside NK cells and eosinophils.
• How do pathogens penetrate the skin?

  Pathogens can colonise natural openings, such as hair follicles, sebaceous glands and sweat glands. These include Propionibacterium acnes, which causes acne. They can also penetrate the skin through insect bites, animal bites and abrasion, wounds and burns, such as Staphylococci and streptococci.
• Describe how mucosal surfaces prevent pathogen invasion

  Mucosal epithelial cells have a rapid cell turnover and are attached to one another via tight junctions and desmosomes, which prevents pathogens from invading underlying tissue. Mucosal surfaces contain goblet cells, which secrete mucus, a glycoprotein matrix that acts as a physical barrier and contains secretory IgA and antibacterial proteins (lactoferris and lactoperoxidase). M cells are part of the MALT and present antigens to underlying mucosal associate lymphoid cells.
• What is the MALT?

  This is the mucosal associated lymphoid tissue, which is a collection of lymphoid cells distributed throughout the mucosa of the GI, respiratory and GU tracts. It includes T and B cells, dendritic cells, neutrophils and macrophages.
• Describe the action of Paneth cells

  These are found in the small intestine only and they secrete antimicrobial proteins and peptides including crypitidins and other defensins such as lysozymes and phospholipases.
• How do pathogens adapt to evade the muco-ciliary escalator?

  Pathogens, such as Neisseria meningitidis, can adhere to the respiratory epithelium which prevents them from being displaced by the cilia. They can also produce toxins that inactivate the cilia, such as Haemophilus influenzae.
• Describe the pathogen defences of the eyes

  Blinking washes away dirt and pathogens and tears contain anti microbial agents such as lysozymes, lactoferrin and sIgA.
• Describe the defences from pathogen invasion in the GI tract

  Mouth: saliva contains lactoferrin and lysozymes

  Stomach: low pH, proteolytic enzymes such as trypsin

  Small intestine: bile salts act as a detergent and kill microbes and rapid peristalsis prevents adhesion of microbes

  Large intestine: abundant resident microbiota and mucus

  Peyers patches: lymphoid follicles associated with the GALT
• Describe the defences against pathogen invasion in the urinogenital tract

  Bladder: flushing action of sterile urine and low pH

  Vagina: resident microbiota (lacto bacilli produce low pH)

  Cervical plug acts as a physical barrier.
• Describe how microbes colonise mucosal surfaces

  • May lack surface proteins that bind to mucins
  • They can move through mucin or into spaces between mucin strands, e.g., facilitated by flagella
  • Produce mucinases (usually a hyaluronidase) that catalyses the hydrolysis of mucopolysaccharides.
  • Target M cells
  • Exploit neutral pH of the mucosa, e.g., Helicobacter pylori in the stomach
• Describe sIgA proteases

  SIgA molecules can bind to bacterial antigens and interact with mucins. Proteases cleave the IgA molecule at the hinge region, which inhibits its actions. Usually these proteases are specific for sIgA1.
• How microbes resist antibacterial peptides?

  • LPS in gram -ve bacteria and capsular polysaccharide layer creates physical barrier to antibacterial peptides
  • Peptidases
  • Cytoplasmic proteins counteract defensin permeabilisation, which protects the cells ion balance.
  • Iron acquisition mechanisms to counteract lactoferrin, e.g., siderophores.
• How do microbes resist low pH?

  They can produce urease, which converts urea to ammonia and therefore increases local pH, e.g., helicobacter pylori. They also posses H+ pumps that pump H+ ions out of the cell.
• Describe how microbes adhere to host cell surfaces

  Adhesins are bacterial components that mediate the interactions between bacterium and the host cells surface. Adhesins engage with specific host cell receptors, which allows bacteria to engage with specific cells to target a specific niche. They can also corrupt host cells by co-opting underlying signalling pathways and establish persistent infections. A bacterium may possess a single adhesin or several distinct adhesins. Other surface molecules can aid in adhesion, such as lipoteichoic acids.
• What are pilli and fimbriae?

  These are rod-shaped macromolecular structures from chains of polymerised subunits of protein called pillin. The tip usually contains adhesin, which allows the, to attach the host cell receptor.
• What is the trigger mechanism?

  This is when bacteria inject effectors through a type III secretory system. These effectors cause massive cytoskeleton changes that trigger bacterial internalisation.
• What is the zipper mechanism?

  This is when bacteria express surface proteins that bind to eukaryotic surface receptors (invasins). These trigger a cascade of signals that lead to the formation of a vacuole that engulfs the bacterium.
• Pescribe how the body's microbiota acts as a barrier from pathogen invasion

  Microbes exclude potential pathogens via colonisation resistance.

  Microbiota form biofilms that act as a physical barrier preventing the adhesion of pathogens to epithelia. They can alter the physiochemical environment to make it unfavourable to pathogens, such as lacto bacilli in the vagina, which produce acid to lower the pH. They also utilise available nutrients within a site, which means that potential pathogens have to compete for these resources.