
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:
- Signals come from bacteria
- Lipopolic saccharides interact with Toll-like receptors on the macrophages → triggers the production of cytokines
- 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
- Gram-positive
- Staphylococcus epidermidis
- Throat
- Streptococci
- Gram-positive
- Neisseria species
- Gram-negative
- Candida albicans
- A yeast
- Streptococci
- Bowel
- Escherichia coli
- Gram-negative
- Bacteroides fragilis
- Gram-negative
- Clostridium species
- Gram-positive
- Escherichia coli
- Skin
- Colonization: virulent microorganisms
- Staphylococcus aureus
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Gram-positive
- Decapsulated
- Neisseria meningitidis
- Decapsulated
- Haemophilus influenzae
- Gram-negative
- Decapsulated
- Commensals: "friendly" microorganisms every human has
- 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
- 30% are carrier
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
- Positive hemolysin test → a-hemolytical or b-hemolytical
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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Mechanisms of Disease 1 2020/2021 UL
- Mechanisms of Disease 1 HC1: Introduction to G2MD1
- Mechanisms of Disease 1 HC2: Introduction to the immune system
- Mechanisms of Disease 1 HC3: Innate and adaptive immune responses & key cytokines
- Mechanisms of Disease 1 HC4: Pathology of normal immune response
- Mechanisms of Disease 1 HC5: B- and T-cell generation and diversity
- Mechanisms of Disease 1 HC6: Mechanisms of adaptive immunity
- Mechanisms of Disease 1 HC7: Effector mechanisms of antibodies
- Mechanisms of Disease 1 HC8: B-cell development and antibodies
- Mechanisms of Disease 1 HC9: Tissue injury and repair
- Mechanisms of Disease 1 HC10: Repair mechanism
- Mechanisms of Disease 1 HC11: Pathology of inflammatory reactions
- Mechanisms of Disease 1 HC12: Introduction to infectious diseases
- Mechanisms of Disease 1 HC13: Bacteria
- Mechanisms of Disease 1 HC14: Viruses
- Mechanisms of Disease 1 HC15: Fungi and parasites
- Mechanisms of Disease 1 HC16: Invaders
- Mechanisms of Disease 1 HC17: Host versus invader
- Mechanisms of Disease 1 HC18: Immune deficiencies and infection risk
- Mechanisms of Disease 1 HC19: Pathology of infectious diseases
- Mechanisms of Disease 1 HC20: Diagnostics of infectious diseases
- Mechanisms of Disease 1 HC21: Essential microorganisms
- Mechanisms of Disease 1 HC extra: Mycobacterial infections (tuberculosis)
- Mechanisms of Disease 1 HC22: Antimicrobial therapy
- Mechanisms of Disease 1 HC23: Principles of antibiotic pharmacotherapy
- Mechanisms of Disease 1 HC24: Introduction MOOC
- Mechanisms of Disease 1 HC25: Epidemiology
- Mechanisms of Disease 1 HC26: Prevention and control
- Mechanisms of Disease 1 HC extra: COVID-19
- Mechanisms of Disease 1 HC27: Mechanisms of hypersensitivity reactions
- Mechanisms of disease 1 HC28: Pathology of allergy
- Mechanisms of Disease 1 HC29: Asthma
- Mechanisms of Disease 1 HC30: Pathology of autoimmunity
- Mechanisms of Disease 1 HC31: HLA and autoimmunity
- Mechanisms of Disease 1 HC32: Vasculitis
- Mechanisms of Disease 1 HC33: Systemic Lupus Erythematosus
- Mechanisms of Disease 1 HC35: Infections and autoimmunity
- Mechanisms of Disease 1 HC36: Immune cells in rheumatoid arthritis
- Mechanisms of Disease 1 HC37+38: Pharmacology: immunosuppression
- Mechanisms of Disease 1 HC39: Pathology of transplantation

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Mechanisms of Disease 1 2020/2021 UL
Deze bundel bevat aantekeningen van alle hoorcolleges van het blok Mechanisms of Disease 1 van de studie Geneeskunde aan de Universiteit Leiden, collegejaar 2020/2021.
This bundle contains notes of all lectures from the module Mechanisms of Disease 1, Medicine, Leiden
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