BMS2052 Notes - WEEKS 1-6 PDF

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WEEKS 1-6...

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BMS2052 NOTES WEEK 1: HOST PATHOGEN INTERACTIONS Learning objectives • • • • • • •

Describe the general types of microorganisms. Explain the role of the normal microbiota of the human body. Describe why it is important to study infectious diseases in context of all disease. Explain the basic principles of how pathogens cause disease. Demonstrate how to determine the causative agent of an infectious disease. Explain the MIMs model of the human body in relation to infection Explain how infectious diseases are transmitted.

Contribution of Microbes Represents most of Earth’s biomass -

Essential to life and ecosystems Recycle carbon and nutirents, then used by plants and animals Degrade organic matter, degrade of detoxify pollutants

Types of microorganisms Acellular -

Viruses: non living particle of protein and nucleic acid, can only replicate in a living cell.

Cellular: -

Prokaryotes: bacteria and archaea Eukaryotes: fungi, protozoa, helminths

The Microbe to Human relationship Microbes exist in a symbiotic relationship with the human host. Symbiosis- close and stable biological interaction with another organism Symbiont- small organism Host- larger organism Most of the cells in your body are not your own -

Microbial cells utnumber body cells by 10x Host cell : microbes = 1 :10 1013 human cells: 1014 microbes

Microbiota = the total microbial population of a given site or habitat (eg body = human microbiota) Microbiome = the genetic content of the microbiota Human Microbiome Project - cataloguing the human microbiome (aka human metagenome)

Human Microbiota Comprise bacteria, archaea, viruses and eukaryotic microbes. Microbes reside in all areas of the body that are exposed to the external environment. -

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Skin, nails, hair, eyes, genitalia, URT, mouth, GIT, lower sections f urogenital tract In a healthy human host, the internal tissues are normally free of microorganisms (eg. brain, heart, blood, kidneys, liver) and the normal microbiota of resident and transient microorganisms (primarily bacteria) colonise the surface tissues. Normal microbiota considered beneficial. The composition of microbes varies with location- determined by pH, temp, oxygen, water, nutrients. Colonisers acquired rapidly after birth 24-48h old. Normal microbiota is continuously changing throughout life.

Microbiota Play an important role in health and disease Some examples: -

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Use bidirectional communication with the gut-brain axis between microbiota, enteric nervous system and CNS to modulate metabolism and GIT homeostasis, appetite, stress and anxiety, memory. Via the gut-brain axis, there is stimulation of the host immune response to maintain normal development and maturation of immune function. Offer a much wider range of metabolic process than human cells so can increase extraction of energy and nutrient from food (eg. breakdown of undigested carbohydrates and synthesising vitamins). Provide a physical barrier protecting from exogenous pathogens by competing for nutrients occupying space and producing antimicrobial substances.

Microbiota and disease Dysbiosis of the normal microbiota → infection (entry to body and growth) → disease (host damage as a result of infection and manifests as signs and symptoms) Pathogen- microbe that can cause disease Host to pathogen interaction is detrimental to the host. -

Pathogenesis- the process whereby an organism causes disease Eg. pathogen colonises the gut mucosal surface causing an inflammatory response- cellular and tissue damage. Treatment of an infectious disease can affect the microbiota, such as treatment with antibiotics displace the ratios of species of normal microbiota.

Relationships between microbes and their human hosts 3 categories of symbiosis that are relevant to human hosts 1. Mutualism 2. Commensalism 3. Parasitism Mutualism -

Two independent organisms living together to their mutual benefit. Example- bacteria in the colon o Further breakdown of undigested carbohydrates- additional nutrients to host o Protection of colonisations and infection from potential pathogens o Stimulation of the immune response o Breakdown of waste products o Bacteria benefit by assured food supply and sheltered environment o Escherichia coli- production of vitamin K and some B vitamins

Commensalism -

A symbiotic relationship in which one participant benefits and the other is unharmed. Normal microbiota has the benefit of being present and grow as a community but they neither benefit nor harm the human host. Normal microbiota are often described as residents or commensals where they are existing without disease. Example- oral microbiota o Existing in the mouth and benefit from the food source of sugars o No advantage to human and in the health, there is no harm

Parasitism -

Where one organism (microbe) benefits at the expense of the other (host) Ranges from slight harm to death Traditionally, parasites were considered as the protozoal and helminths microbes which can become pathogens and cause disease It is now accepted to view host- pathogen interactions as parasitic as the benefit is to the parasite (pathogen) o Microparasites- viral, bacterial, protozoal, fungal pathogens o Macroparasites- helminth pathogens

The Normal Microbiota In health- Usually comprised of commensals and mutualistics In disease- caused by some of the normal microbiota as endogenous pathogens which are mostly opportunistic pathogens -

Considered as a parasitic relationship when pathogen damages the host to cause infection and disease.

Microbiota at various body sites

Skin Mechanically strong barrier to infection. Inhospitable environment -

Slightly acidic pH High concentration of NaCl Many areas low in moisture

Microbiota vary with -

Moisture level- moist and dry Amount of oxygen- aerobic on epidemernis, microaerohphilic in deeper regions (eg hair follicles)

Inhibitory substances -

Eg. lysozyme, antimicrobial peptides

Normal microbiota includes both resident and transient micoroganisms. -

Staphylococcus spp, Proprionibacterium acnes, Streptococcus spp., Micrococcus spp. Candida spp., etc. Major inhabitant = Staphylococcus epidermidis (up to 90% of resident aerobes)

Nails: Trapped dust under nails contains mostly fungi (Aspergillus, Penicillium, Cladosporium, Mucor)

Mouth Complex habitat 500-600 different bacteria including anaerobes Archea in gingival crevices - anaerobes Entry point for other bacteria to colonise URT Saliva and food particles are potential sources of microbial nutrients -

Saliva contains antibacterial substances such as lysozyme.

Respiratory tract Upper respiratory tract (URT) -

Nose Nasal cavity and naso pharynx Throat: oropharynx and larynx Many species as part of normal microbiota Similar to organisms in oral cavity

Lower respiratory tract -

Trachea, primary bronchi, 2ndary … until alveoli for gas exchange

Nose Normal microbiota found just inside the nostrils at the nares Nasal mucus contains lysozyme Most common bacteria found in the nose are Staphylococcus spp. -

Staphylococcus epidermidis and Staphylococcus aureus (a potential pathogen) predominate (in 10-40% adult noses)

Also aerobic corynebacteria ("diphtheroids") Small numbers of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can also be found in the nasopharynx (upper throat).

Lower Respiratory Tract Trachea, bronchi, bronchioles and alveoli (lungs) do not normally have microbiota Microorganisms removed by: -

Continuous stream of mucus produced by goblet cells onto respiratory surface which has ciliated epithelial cells Microbes trapped in mucus. Cilia beat to move the mucus upwards mouth (moving mucus carpet) mucocilary escalator Phagocytic action of alveolar macrophages mop up any LRT organism

Therefore LRT Normally also free of invading pathogens

Gastrointestinal tract

Stomach Hostile environment for bacteria -

acidic pH (2.0) “barrier” to entry to intestinal tract Microbial load - 102-103 per ml of gastric fluid (may be less than 10 viable bacterial cells per ml)

Gastric mucosa -

acid-tolerant Lactobacillus spp. and Streptococcus spp. Helicobacter pylori found in half the human population (gastric ulcers)

Small intestine As distance from stomach increases -

pH increases bacterial/microbial numbers increase

Small intestine (SI) -

Duodenum lightly colonised to low levels (...