Mechanisms of Disease 1 HC17: Host versus invader

HC17: Host versus invader

Commensals, colonization and normal host defense

Sterile versus non-sterile areas:

A host has both sterile and non-sterile areas:

  • Nonsterile areas
    • Skin
    • Elementary tract
    • Alimentary tract
  • Sterile areas → no bacteria are present
    • The "inside"
    • Stomach
    • Deep respiratory tract
    • Urinary tract

The human body has 1014-15 bacteria and 1013 body cells. Most bacteria reside in the intestines.

Commensals:

Commensals are normally present in every person. The skin only contains gram-positive bacteria because they have a thick peptidoglycan layer, which makes them resistant against a dry environment. This doesn't necessarily cause symptoms → commensals are harmless unless the immune system is impaired.

Colonization:

Humans have colonization resistance → bacteria are present on skin and mucosae to protect against adherence by other microorganisms.

Normal host defense:

The human body has different measures to achieve sterility:

  • Physical
    • Barriers: skin and mucosae
    • Airways: ciliar activity, mucus, coughing
    • Urinary tract: voiding, antimicrobial factors
  • Chemical
    • Gastric acid → kills bacteria
    • Enzymes
      • Lysozyme in tears
  • Immunological

Exposure versus infection

Infection:

An infection is a structural or functional change caused by a micro-organism or its components or products. This includes the host response such as inflammation.

The microorganism staphylococcus aureus is carried by 1/3 of all humans in the nose. This, however, isn't an infection → nothing has changed. It only is a carrier. Something only becomes an infection once something has changed, for example:

  • Pain
  • Redness
  • Puss
  • Fever

Fever can have many causes, but more often than not it is caused by infection. The body temperature is regulated in the hypothalamus:

  1. Signals come from bacteria
  2. Lipopolic saccharides interact with Toll-like receptors on the macrophages → triggers the production of cytokines
  3. The interleukins attach to the epithelial cell and give signals → prostaglandins go to specialized cells which sets certain mechanisms in action:
    • Vasoconstriction → containing body warmth
    • Shivering → making body warmth
    • Brown adipose tissue → ATP → making body warmth

Exposure:

There are many forms of exposure:

  • Oral
  • Trauma/operation
  • Needle injury, blood, catheters
  • Artrhopod
  • Penetration of skin by the micro-organism itself
  • Ascending infection
  • Contact
  • Inhalation, aspiration

Exposure to micro-organisms leads to:

  • Colonization
    • No symptoms
    • Commensal or primary pathogens on skin or mucosae
    • Transiently or permanently
    • Competition for food and adhesion sites
  • Infection
    • Often, but not always
    • Symptoms and/or signs

Natural course of infection

There are 2 groups of pathogens which can cause infections:

  • Primary pathogens: no host defense disorder needed to become ill
  • Opportunistic pathogens: host defense disorder needed to become ill
    • The weaker microorganisms

Infection can be acquired endogenously or exogenously:

  • Endogenous
    • Commensals: "friendly" microorganisms every human has
      • Skin
        • Staphylococcus epidermidis
          1. Gram-positive
      • Throat
        • Streptococci
          1. Gram-positive
        • Neisseria species
          1. Gram-negative
        • Candida albicans
          1. A yeast
      • Bowel
        • Escherichia coli
          1. Gram-negative
        • Bacteroides fragilis
          1. Gram-negative
        • Clostridium species
          1. Gram-positive
    • Colonization: virulent microorganisms
      • Staphylococcus aureus
      • Streptococcus pyogenes
      • Streptococcus pneumoniae
        • Gram-positive
        • Decapsulated
      • Neisseria meningitidis
        • Decapsulated
      • Haemophilus influenzae
        • Gram-negative
        • Decapsulated
  • Exogenous
    • Other person
    • Zoonosis
    • Vectors
    • Environment

Staphylococci

Catheter infection:

A patient with acute myeloid leukemia starts chemotherapy. Chemotherapy wipes away all the bone marrow cells → there's a period of 3-4 weeks where there aren't any granulocytes → granulocytopenia. The following happens:

  • Day 20: still granulocytopenia + central venous line to give medication
  • Day 21: fever
    • Blood cultures are obtained
    • Prescription of antibiotics → vancomycin and gentamicin
  • Day 22: positive blood cultures
    • Gram-positive cocci in groups → staphylococci

The diagnosis is an intravenous catheter infection.

Different staphylococci:

The name of a staphylococcus is very important:

  • Staphylococci epidermidis
    • Commensal → present in everyone
    • Opportunist
    • Risk factors are required to cause problems:
      • Granulocytopenia
      • Foreign body
        • For example adhesion to catheters/prosthesis
  • Staphylococci aureus
    • 30% are carrier
      • Mainly in the nose
    • Primary pathogen
    • No risk factors required, but there is an increased risk in case of:
      • Granulocytopenia
      • Foreign body (biofilm)
      • Intravenous drug use

Diagnostics:

The difference between cocci is firstly made with the catalase test, and with more tests subsequently:

  • Positive catalase test → staphylococcus
    • Positive coagulase test → s. aureus
    • Negative coagulase test → s. epidermidis
  • Negative catalase test → streptococcus
    • Positive hemolysin test → a-hemolytical or b-hemolytical
      • S. pneumoniae is an example of an a-hemolytical bacteria
      • S. pyogenes is an example of a b-hemolytical bacteria
    • Negative hemolysin test → indifferent streptococci

Re-exposure:

Re-exposure from a bacteria can lead to 2 things:

  • Protective immunity → no disease
  • Infectious disease
    • The protective immunity isn't strong enough

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