Lecture 1

• Global burden of Disease-how important are infections
• Normally about >500,000 people are born and ~500,000 die in the UK every year. Deaths increased from 530,841 (2019) to 607,922 (2020)
• In 2020: COVID 19 (12.1%), Dementia and Alzheimer's (11.5%), Ischemic heart disease (9.2%), Cerebral vascular disease (4.9%), Lung cancers (4.7%)
• van Leewenhoek, 'animalicules'


  1676
• Jenner, Immunisation and Vaccination


  1796
• Pasteur, IDs are living organisms?

  1861
• Koch, rules to demonstrate 'cause and effect'

  1884
• Ivanovski, identified viruses


  1892
• Fleming, discovery of penicillin

  1929
• Miasma theory


  'charged air combined with organic decomposition from the earth' produced gases or miasms
• Blood generation theory


  Spontaneous generation in the blood / blood fermentation
• Germ Theory


  Infection was caused by a living organism, a contagium vivum
• Tipping the Swan necked flasks / bottles!
• Infectious diseases on the tree of life

  • Bacteria
  • Fungi
  • Protists
  • Helminths
  • Prions
  • Viruses
• What about parasites?
• A place for viruses on the tree of life
• A higher level classification of all living organisms
• Protists and helminths are often termed parasites and medically are often grouped together
• There isn't room for some infectious diseases on the tree of life
• Microbes are often grouped by how they affect their host

  • Parasites: benefit at the expense of the host
  • Pathogens: cause a disease in the host
  • Commensals: no effect on the host
  • Mutualists: benefit the host
• Classifying and comparing Infectious Diseases

  • Organisms or particle size
  • Genome size organisation
  • Replication / Reproduce / Spread
  • Immunity
  • Extracellular/Intracellular
• Viruses


  'Nucleic acid wrapped in a protein coat', Require a host cell for replication and 'energy production', Extracellular form is a 'virion', Most widespread of all pathogens, Receptors (e.g. CCR5 for HIV)
• Classification of viruses is based on: Envelope, Nucleic Acid
• Viral receptors and co-receptors on the host
• Immunity to viruses


  • Intracellular phase: Interferon, NK cells via loss of MHC, Cytotoxic T cells via MHC peptide recognition
  • Extracellular phase: Antibodies block entry to cells
• More from Dr Roberts on viruses
• Bacteria


  Unicellular organisms, Focus on disease causing bacteria, Fully independent existence, Genome and machinery necessary for survival, Prokaryotes, Extracellular or intracellular
• Bacterial cell wall types

  • Gram +ive
  • Acid fast
  • Gram -ive
• Medically important bacteria


  • Gut diseases: Escherichia coli, Campylobacter and Salmonella
  • Skin diseases: Staphylococcus aureus, Cutibacterium acnes
  • Respiratory disease: Staphylococcus aureus, Pseudomonas aeruginosa
• Immunity to bacteria


  • Extracellular bacteria: Phagocytes, Antibody, Complement
  • Intracellular bacteria: Cytotoxic T cells kill host infected cells and activate macrophages, Helper T cells activate macrophages (IFN) to kill bacteria by MHC recognition
• Fungi


  Eukaryotic, Unicellular, Single cells-yeasts, Branching filaments (hyphae)- molds, Dimorphic, Extracellular / Intracellular
• Fungal diseases


  • Yeast: Candida albicans, commensal but can overgrow in mouth, vagina following prolonged antibiotic treatment
  • Mold: Aspergillus fumigatus, lung infection in the immunocompromised
• Fungal immunity is similar to bacteria
• Protists


  Major group of eukaryotic organisms, Widely distributed in nature, Wide variety of morphologies, Wide variety of life cycles, Significant debate on Classification: Animal-like, plant-like, fungus-like, Sequencing, Parasitic life style, Diseases they cause
• Organisation and taxonomy is continuously evolving!!
• Protist diseases - Visceral (gut) infections

  • Amebiasis / Dysentery: Entamaeba histolytica
  • Giardiasis / Dysentery: Giardia intestinalis
  • Cryptosporidium/ diarrhoea: Cryptosporidium parvum
  • Toxoplasmosis: Toxoplasma gondii
• Protist diseases - Blood and tissue infections

  • Malaria: Plasmodium
  • Leishimaniasis: Leishmania tropica or L. mexicana
  • Trypanosomiasis (African sleeping sickness): T. brucei gambiense, T. brucei rhodesiense
  • Chagas Disease: T. cruzi
• Protist life cycles


  • Cyst
  • Trophozoite
• Plasmodium-a complex life cycle
• Diseases are extremely chronic, Only partial immunity