Recommended Reading for Lec 2 Flashcards
Notes on reading
Eradicating Infectious Disease - Viruses
Frontiers in Immunology
Small pox and Rinderpest only two diseases to be completely eradicated - both viral
Polio is 99% eradicated - 1% remains in India, Pakistan and Africa
Viruses are obligate intracellular pathogens (needing to live and reproduce inside a host cell) so are easier to target than other pathogens as their transmission to host cells can be interrupted by immunisation
Smallpox was more easily eradicated as it had no animal reservoir or latent phase
Polio is harder to eradicate as it is a live oral vaccine (so can revert back to pathogenic form) and can be sub clinical
Some viruses are impossible to eradicate, such as Herpes simplex, Herpes zoster (they reside latent in neurons - reactivation of disease spreads virus) and Influenza A (antigens constantly changing as a result of antigenic shift and drift). Other viruses like this include Hep C and HIV
Antigenic shift is responsible for the cross-species transmission of HIV and H1N1 (apes and pigs respectively)
Eradicating Infectious Disease - Bacteria
Frontiers in Immunology
Bacteria are harder to eradicate because most are NOT obligate intracellular pathogens.
Most bacteria are opportunistic pathogens: members of the normal flora that only cause disease if the host is immunodeficient or they access a normally sterile area.(e.g. Staph Aureus)
Pseudomonas aeruginosa and Bacillus anthracis (spores) can survive in the environment
Bacteria often have animal reservoirs (e.g. Ecoli 0157 in cattle)
Therefore, the nature of the bacteria–host relationship is a significant barrier to eradication of most bacterial infections
However, Chlamydia trachomatis could be a candidate for eradication due to having undergone genome reduction, turning it into an obligate intracellular pathogen, with no capacity for free living and no animal reservoirs
Eradicating Infectious Disease - should we?
Frontiers in Immunology
Eradicating some infections can be dangerous or cause unforeseen effects. Examples of this include:
- pseudomembranous colitis caused by C. difficile after treatment with broad-spectrum antibiotics
- over colonisation/infection of Staph Aureus after immunisation against Strep Pneumoniae (suggesting the two bacteria may be in competition with each other)
- increased incidence of gastro-esophogeal reflux disease, Barrett’s esophagus, and esophageal adeno-carcinoma after treatment for H. pylori. Treatment also causes increased grehlin secretion (hunger hormone) so H. pylori mediates the downregulation of grehlin (and treatment is therefore implicated in increased levels of obesity and metabolic syndrome)
- in mice, infection with Salmonella typhiniurium has life long effects on host immune regulation, even after the infection is eradicated
Microbe-host interactions are more complicated than previously thought and it is too simplistic to con- sider the eradication of microbial disease entirely beneficial
Infectious diseases that cannot be eradicated can usually be controlled to some extent, be it through the use of antimicrobial chemotherapy, vaccinations, or behavioral changes. A major barrier to such control is inadequate healthcare provision in developing countries, who bear the brunt of most infectious disease.
Allergic disease and the Hygiene Hypothesis
Perspectives in Public Health
In medicine, the hygiene hypothesis states a lack of early childhood exposure to infectious agents, symbiotic microorganisms (such as the gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system.
1989 - first proposed that rise of allergic disease may have something to do with reduced microbial exposure
The Delphi technique is a qualitative research method that relies on the judgement of individuals presumed to be knowledgeable and expert at what they do
The Old Friends (OF) Mechanism was proposed by Rook in 2003 and argues that the vital microbial exposures are not colds, measles and other childhood infections (the crowd infections), but rather microbes already present during primate evolution and in hunter-gatherer times when the human immune system was evolving.38–40 OF microbes include environmental species which inhabit indoor and outdoor environments, and the largely non-harmful commensal microbes acquired from the skin, gut and respiratory tract of other humans
major changes in water, sanitation and hygiene had occurred by 1920, it is difficult to ascribe the massive changes in the asthma prevalence from 1960 onwards to these changes
it is now clear that the most important times for OF exposure are early in development, during pregnancy, delivery, and the first few days or months of infancy
There is good evidence that contact with microbial diversity from the natural environment is crucial. Numerous studies now show that exposure to farm environments during the first 2–3years of life protects against allergic disorders
increasingly, the answer appears to be that the optimal composition of the microbiota is maintained by diet, which needs to be diverse, and contain fibre (polysaccharides digested by the microbiota rather than the human host), and polyphenols found in plant products. A diet deficient in fibre can lead to progressive extinctions of important groups of organisms, which are cumulative and increasingly difficult to reverse in subsequent generations. Polyphenols and also fish oils also appear to modulate the composition of the microbiota
Targeted hygiene is essential for public health and does not generally negatively affect the OF mechanism
The Human Microbiome Project
Nature Reviews, Microbiology 2009
The Human Microbiome Project
In recent years, there has been a growing appreciation of the extent of the commensal microbial populations in humans. Collectively, these populations have been termed ‘the human microbiome’, originally by Joshua Lederberg, and also the ‘human microbiota’. Owing to advances in DNA sequencing technologies and improvements in bioinformatics, it has become possible to characterize the great diversity in the human microbiota. In 2007, the US National Institutes of Health (NIH) launched the Human Microbiome Project as one of its major roadmap initiatives, earmarking ~US$140 million for its completion108. This major scientific endeavour has the following aims: • to determine whether individuals share a core human microbiome;
• to understand whether changes in the human microbiome can be correlated with changes in human health;
• to develop the technological tools to support these goals;
• to address the ethical, legal and social implications of human microbiome research.
One value of the Human Microbiome Project is that it can help us to ascertain how much the microbiota have been changing. Work is now ongoing, and the European Union and other countries are committed to similar projects, all working under the umbrella of the International Human Microbiome Consortium
Firmicutes, bacteroidetes, Actinobacteria and Proteobacteria dominate human mucosal and cutaneous habitats, which suggests that strong selective forces have limited diversity over at least hundreds of thousands of years of co-evolution. Despite this stereotypical assembly process, each individual in a single mammalian species, including Homo sapiens, has a virtually unique microbiota
What is a pathogen?
Nature Reviews, Microbiology 200(
• Pathogens are generally clonal
.
• Pathogens induce host responses. They usually cannot do their deeds without a trace.
- Infection with a pathogen can sometimes cause disease, which is a function of the interaction between the pathogen and the specific host, as determined by a matrix of host, microbial and environment circumstances.
- The gene pool of the host includes the genes of its resident microorganisms, which may be why many members of the microbiota are selected for by the host: to prevent colonization by pathogens instead.
More on H. pylori
Nature Reviews, Microbiology 2009
Gastric T cell and b cell populations also differ in H. pylori-positive and H. pylori- negative hosts. This might be expected, as the H. pylori-negative stomach has a diminished presence of the cellular elements of the immune system and reduced cytokine traffic, whereas the H. pylori-positive stomach has a rich population of immune cells. The enhanced T cell populations
in H. pylori-positive hosts include greater proportions of particular T cell subsets, including cells expressing forkhead box pro- tein P3 (FOXP3), which regulate immune functions. The stomachs of H. pylori-negative hosts have much lower numbers of these cells, which have systemic, as well as local, activities. several epidemiological studies show that H. pylori-positive individuals (especially individuals carrying cag-positive strains) have lower risks of childhood asthma, allergic rhinitis and skin allergies than those without H. pylori. The rise in childhood asthma and related disorders has occurred while H. pylori has been disappearing; the loss of gastric T cell populations and their systemic effects could provide a mechanism for these allergic diseases
Human - Microbe Interactions
Harley, Prescott, Klein’s Microbiology p.734-741
The normal human microbiota function not as pathogens but as symbionts that are among the host’s first line of defence against infectious agents
Bifidobactera represent approx 90% total intestinal bacteria in breast-fed infants - suggests that human milk may act as a selective medium for non-pathogenic bacteria
Switching to cow’s milk or solid food (mostly polysaccharide) appears to re-sult in the loss of bifidobacteria predominance, as Enterobacte-riaceae,
enterococci, bacteroides, lactobaccili, and clostridia increase in number
Gnotobiotic organisms are more susceptible to pathogens
The number of microorganisms necessary to infect a germfree animal and produce a diseased state is much smaller. Conversely, germfree animals are almost completely resistant to the intestinal protozoan Enta-moeba histolytica that causes amebic dysentery. This resistance results from the absence of the bacteria that
E. histolytica uses as a food source
Commensalism - an association between two organisms in which one benefits and the other derives neither benefit nor harm
Mutualism - Mutualism or interspecific cooperation is the way two organisms of different species exist in a relationship in which each individual fitness benefits from the activity of the other
Parasitism - In evolutionary biology, parasitism is a relationship between species, where one organism, the parasite, lives on or in another organism, the host, causing it some harm, and is adapted structurally to this way of life
^^ The above may be ecto- or endosymbiotic
Skin
Human - Microbe Interactions
Harley, Prescott, Klein’s Microbiology p.734-741
Internal tissues (CSF, blood, brain, muscles) are normally free of microbes
Surface tissues (mucous membranes, skin) colonised with microbes - 10(to the 12) on average human
Skin is a mechanically strong barrier to microbial invasion. Few microorganisms can penetrate the skin because its outer layer consists of thick, closely packed cells called keratinocytes
Continuous shedding of the outer epithelial cells removes many microorganisms adhering to the skin surface
The skin surface or epidermis is not a favorable environment for microbial colonization: in addition to a slightly acidic pH, a high concentration of sodium chloride, and a lack of moisture in many areas, certain inhibitory substances (bactericidaland/or bacteriostatic) on the skin help control microbial colonization.
E.g. the sweat glands release lysozyme (muramidase), an enzyme that lyses Staphylococcus epidermidis and other gram-positive bacteria by hydrolyzing the (1→4) glycosidic bond connecting N-acetylmuramic acid and N acetylglucosamine in the bacterial cell wall peptidoglycan. Sweat glands also produce antimicrobial peptides called
cathelicidins (Latin catharticus, to purge, and cida,
to kill) that help protectagainst infectious agents by forming pores in bacterial plasma membranes
E.g. The oil glands secrete complex lipids that may be partially de-graded by the enzymes from certain gram-positive bacteria (e.g. Propionibacterium acnes). These bacteria can change the secreted lipids to unsaturated fatty acids such as oleic acid that have strong antimicrobial activity against gram-negative bacteria and some fungi. Some of these fatty acids are volatile and may be associated with a strong odor. Therefore many deodorants containantibacterial substances that act selectively against gram-positivebacteria to reduce the production of volatile unsaturated fattyacids and body odor
See paper for diagram of human microbiota page 737
