Infection & Immunity 2
Prokaryote (Monera):
• Cells that do not contain a nucleus
• Typically, very small, single-celled, & relatively simple in gross morphology
• First proposed by E. Chatton in 1937
Bacteria is everywhere
• Terrestrial
• Subterranean (up to 2 km) - More in sub- soil as such a large mass, but in low density
• Atmosphere
• Aquatic (including deep sea)
• Low & high temperature (from below -10 ○C to 130 ○C)
• High salt (up to saturated salt (4M))
• High & low pH (from 0 to 14)
• Heavy metals, toxins, etc.
• High radioactivity
• Free living individuals
• Community living populations
• Symbiotic relationships
Bacteria use sugars (simple and complex), organic acids, lipids, wide range of hydrocarbons, element cycling (e.g.,
fix nitrogen). Trillions of cells in the human body.
The Study of Infectious Diseases
• Microbiology
• Epidemiology • Physiology
• Microbial physiology
• Anatomy • Cell Biology
• Genetics
• Genomics • Immunology
• Evolution
History - Microbiology: a Fairly Young Discipline of Biology.
Antonie van Leeuwenhoek (1632 - 1723). Discovered existence of single cell microbes
• Developed one of the first microscopes
Louis Pasteur (1822 - 1895)
• French chemist - Founder of medical microbiology
• Fermentation sometimes led to formation of alcohol (wine) & sometimes to acetic acid (vinegar).
Alcohol is produced by yeasts (cf. “Pasteur effect”). Acetic acid is the result of bacterial
contamination
• Showed that boiled media that were exposed to air but not dust did not contaminate
• Further proof that bacteria did not appear spontaneously (cf. heat treatment “Pasteurisation”)
, Robert Koch (1843 - 1910)
• German physician - Founder of the scientific method of microbiology
• Discovered that anthrax was a transmissible disease - “chain of infection”
concept
• Developed the use of solid media (gelatin, later agar) to grow individual
colonies of bacteria. First pure culture (Mycobacterium tuberculosis). 1905
Nobel Prize in Physiology or Medicine for the identification of M. tuberculosis
Kock’s Postulates - Published 1884
• Four criteria to establish a causative link between a microbe & a disease
• However, some bacteria are very difficult to detect/isolate. Today: detection
by PCR. May not have an animal host (e.g. HIV/AIDS)
Some Fundamental Concepts
Infection vs. Disease Not all infections result in disease
• Infection: invasion of body tissue by a • Would we regard commensal bacteria as infecting?
(pathogenic) microbe • Asymptomatic infection
• Disease : a departure from health • e.g., ~10% population carries Neisseria meningitidis
Pathology - ‘damage’ or changes caused by a disease
Fundamental Concepts of Infectious Disease
Acquisition
• Infectious disease; agent must come from somewhere
• Direct host to host: airborne, STI, vectors
• From an animal host; zoonosis
• Environment: food, water, e.g. via injuries or ingestion
• Opportunistic: e.g., skin bacteria, commensal turned pathogen
• Nosocomial: hospital acquired
Adherence/Colonisation
• Most large host sites have clearance mechanisms
• Mucus, gut movement, blood, urine
• Bacteria have to overcome these/attach themselves
Multiplication
• Usually inoculum is small
• Infectious dose
• Pathogen replication often coincides with pathology &/or stimulates host response
Transmission
• Directly to new host
• Reservoir
• To environmental niche. e.g. Vibrio cholera is a marine organism
,Molecular Pathogenesis
• Identification of genes involved in pathogenesis - very difficult to define
“Molecular Koch’s Postulates” - Published 1988. Criteria to establish a causative link between a gene & a
disease.
1. The pathogenic property (& gene) under investigation should be found (only) in the pathogenic
members of a genus or species
2. Inactivation of the suspected virulence trait gene(s) should reduce pathogenicity in a suitable animal
model of disease
3. Replacing the mutated gene(s) should restore pathogenicity
Genes that fulfil these criteria are also known as virulence factors
Problems
• Some bacteria are very difficult to manipulate genetically
• May not have an animal host
• How do you quantify virulence or pathogenicity?
— LD50 (infectious dose required to kill half of the test animals, lethal dose)?
— Bacterial counts in different tissues?
— Morbidity vs. mortality of the test animals?
• Is a gene that contributes to general fitness of a bacterium a virulence gene?
, Bacterial Cells Structures
Cell shape and size
Bacteria are small - 0.2 - 0.5 mm - Nanobacteria
Average size = 1 - 10 mm wide by 2 - 500 mm long
The Surface is Important
• Bacterial exterior or surface is typically complex
• Complexity due to important functions
• Protects against chemical & biological threats
• Location of many metabolic functions
• Mediates attachment to surfaces – adherence/colonisation
• Wall-associated proteins
Gram Stain
Staining method for identification
of bacteria.
Get red or pink cells for gram-
negative or purple for Gram-
positive.
Gram-positive - purple
Thick hard cell wall that encloses he plasmic membrane. Double lipid bilayer.
Gram-Negative – red or pink
Extra outer lipid membrane.
Prokaryote (Monera):
• Cells that do not contain a nucleus
• Typically, very small, single-celled, & relatively simple in gross morphology
• First proposed by E. Chatton in 1937
Bacteria is everywhere
• Terrestrial
• Subterranean (up to 2 km) - More in sub- soil as such a large mass, but in low density
• Atmosphere
• Aquatic (including deep sea)
• Low & high temperature (from below -10 ○C to 130 ○C)
• High salt (up to saturated salt (4M))
• High & low pH (from 0 to 14)
• Heavy metals, toxins, etc.
• High radioactivity
• Free living individuals
• Community living populations
• Symbiotic relationships
Bacteria use sugars (simple and complex), organic acids, lipids, wide range of hydrocarbons, element cycling (e.g.,
fix nitrogen). Trillions of cells in the human body.
The Study of Infectious Diseases
• Microbiology
• Epidemiology • Physiology
• Microbial physiology
• Anatomy • Cell Biology
• Genetics
• Genomics • Immunology
• Evolution
History - Microbiology: a Fairly Young Discipline of Biology.
Antonie van Leeuwenhoek (1632 - 1723). Discovered existence of single cell microbes
• Developed one of the first microscopes
Louis Pasteur (1822 - 1895)
• French chemist - Founder of medical microbiology
• Fermentation sometimes led to formation of alcohol (wine) & sometimes to acetic acid (vinegar).
Alcohol is produced by yeasts (cf. “Pasteur effect”). Acetic acid is the result of bacterial
contamination
• Showed that boiled media that were exposed to air but not dust did not contaminate
• Further proof that bacteria did not appear spontaneously (cf. heat treatment “Pasteurisation”)
, Robert Koch (1843 - 1910)
• German physician - Founder of the scientific method of microbiology
• Discovered that anthrax was a transmissible disease - “chain of infection”
concept
• Developed the use of solid media (gelatin, later agar) to grow individual
colonies of bacteria. First pure culture (Mycobacterium tuberculosis). 1905
Nobel Prize in Physiology or Medicine for the identification of M. tuberculosis
Kock’s Postulates - Published 1884
• Four criteria to establish a causative link between a microbe & a disease
• However, some bacteria are very difficult to detect/isolate. Today: detection
by PCR. May not have an animal host (e.g. HIV/AIDS)
Some Fundamental Concepts
Infection vs. Disease Not all infections result in disease
• Infection: invasion of body tissue by a • Would we regard commensal bacteria as infecting?
(pathogenic) microbe • Asymptomatic infection
• Disease : a departure from health • e.g., ~10% population carries Neisseria meningitidis
Pathology - ‘damage’ or changes caused by a disease
Fundamental Concepts of Infectious Disease
Acquisition
• Infectious disease; agent must come from somewhere
• Direct host to host: airborne, STI, vectors
• From an animal host; zoonosis
• Environment: food, water, e.g. via injuries or ingestion
• Opportunistic: e.g., skin bacteria, commensal turned pathogen
• Nosocomial: hospital acquired
Adherence/Colonisation
• Most large host sites have clearance mechanisms
• Mucus, gut movement, blood, urine
• Bacteria have to overcome these/attach themselves
Multiplication
• Usually inoculum is small
• Infectious dose
• Pathogen replication often coincides with pathology &/or stimulates host response
Transmission
• Directly to new host
• Reservoir
• To environmental niche. e.g. Vibrio cholera is a marine organism
,Molecular Pathogenesis
• Identification of genes involved in pathogenesis - very difficult to define
“Molecular Koch’s Postulates” - Published 1988. Criteria to establish a causative link between a gene & a
disease.
1. The pathogenic property (& gene) under investigation should be found (only) in the pathogenic
members of a genus or species
2. Inactivation of the suspected virulence trait gene(s) should reduce pathogenicity in a suitable animal
model of disease
3. Replacing the mutated gene(s) should restore pathogenicity
Genes that fulfil these criteria are also known as virulence factors
Problems
• Some bacteria are very difficult to manipulate genetically
• May not have an animal host
• How do you quantify virulence or pathogenicity?
— LD50 (infectious dose required to kill half of the test animals, lethal dose)?
— Bacterial counts in different tissues?
— Morbidity vs. mortality of the test animals?
• Is a gene that contributes to general fitness of a bacterium a virulence gene?
, Bacterial Cells Structures
Cell shape and size
Bacteria are small - 0.2 - 0.5 mm - Nanobacteria
Average size = 1 - 10 mm wide by 2 - 500 mm long
The Surface is Important
• Bacterial exterior or surface is typically complex
• Complexity due to important functions
• Protects against chemical & biological threats
• Location of many metabolic functions
• Mediates attachment to surfaces – adherence/colonisation
• Wall-associated proteins
Gram Stain
Staining method for identification
of bacteria.
Get red or pink cells for gram-
negative or purple for Gram-
positive.
Gram-positive - purple
Thick hard cell wall that encloses he plasmic membrane. Double lipid bilayer.
Gram-Negative – red or pink
Extra outer lipid membrane.
