Lecture 1 - General Principles of microbiology, Pathogenesis of Infectious Diseases Flashcards
Immunology
Study of our protection from foreign macromolecules / invading organisms & our responses to them
What does the first name represent in the written name of this pathogen ?
Listeria monocytogenes
Genus
What does the second name represent in the written name of this pathogen ?
Listeria monocytogenes
Species
What are microorganisms ?
- Organisms invisible to the naked eye (viruses, bacteria, fungi, some parasites)
- Majority harmless, many useful
- Very small proportion produce harmful effects in animals / plants
How big are we talking ?
Small, MICROSCOPIC → 1-2 microns (1 mm = 1 000 microns)
What is a virus ?
NON LIVING but require a living cell to grow / multiply
Tend to be simplest, but most dangerous !!!
- Made up of nucleic acids (either RNA or DNA, NEVER BOTH) + capsid (protein shell present in some cases)
- Enter cells & divert synthetic processes towards their own replication to make more viruses → Can potentially kill host cell
- Do so by attaching, injecting nucleic acid (penetration), highjack synthetic processes
Other bacteria (e.g. chlamydia) more complex than viruses, but still only grow / multiply in living cells
What are bacteria ?
Prokaryotes - UNICELLULAR
- Rigid cell wall with cytoplasm (keeps things in place)
- Genetic material organized in a circular chromosome
- No separate nucleus (known as a nucleoid)
- Both DNA & RNA
Replicate by binary fission – Gets twice its size, pinches off to divide
Mycoplasma → Do not have rigid cell wall (more fragile), grow on non-living media
What are eukaryotes ?
- Unicellular & multicellular animals, plants
- Contain membrane-bound structures [ organelles ]
- Genetic material organized in nucleus
Resident Flora
- Microbes that are always present, stay with us
- Relatively fixed type microorganisms regularly found in given area at certain age
- Most acquired throughout first years since our birth (picked up via vaginal birth - C section babies swabbed with flora from mother’s vagina)
What is the resident flora of the GI tract ?
Anaerobes & coliform organisms
What is the resident flora of the skin ?
Coagulase negative staphylococci
Transient Flora
- Found in a specific location for a given period of time (hours, days, weeks, months)
- Often as a result of displaced resident flora, injury / trauma, human behavior
What is the clinical importance of normal flora ?
- Protects person from infection by invasive organisms (to some extent)
- Normal flora is controlled by various host defences, which may result in infections caused by organisms that are not normally pathogenic in case of deficiency
- Disturbances in ecology & balance of normal flora may be produced by antibiotic therapy (basis of antibiotic induced diarrhea)
- Presence of normal flora in cultures may confuse the interpretation of lab results
Healthy, active gut flora participates in metabolism of host
- Certain microorganisms synthesize vitamin K
- Disturbances may cause secondary nutritional deficiencies
Regulates pH balance in female reproductive system
What are other ways microorganisms are useful to us ?
- Biotechnology
- Spoilage of foods
- Bioremediation
- Functional foods
What are places where there should NOT be any bacteria ?
- Brain / CNS
- Circulatory system
- Respiratory system
- Eyes
- Open wounds
Normal bacteria function as a ________________ ecosystem, with _______________ species at a site, with ________________________________ predominating
balanced, multiple, NO SINGLE ORGANISM
T / F : Organisms invade the body outside their normal territory
False, organisms do NOT invade the body outside their normal territory
Infection with bacteria occurs when :
A single species becomes predominate at a site at which there is normally many species
OR
When a single organism invades a body site that is normally sterile
The outcome of infection is determined by :
- The bacterial pathogenicity factors &
- The host response to those aggressive bacterial mechanisms [ host defences ]
Bacteraemia vs Septicaemia
Bacteraemia : Presence of bacteria in the blood
Septicaemia : If bacteria able to grow / divide in the blood
What protects us from the bad guys ?
Mechanical barriers
- Skin
- Saliva
- Mucous
- Tears
- Hairs, etc
Other helpers include :
- Antibodies
- Complement
- Immune cells (T-cells, NK cells, macrophages)
- Immune system (cell mediated; humoural)
Skin
- Most important mechanical barrier to the invasion of deep tissues by bacteria
- Innate component of immune system
- Colonized by large # organisms that do not usu. gain access to deeper subcutaneous tissues
- However, these may initiate an infectious process if a break in skin barrier occurs, allowing them to gain access to deeper layers
Adherence
Bacteria must be able to adhere to the host in order to initiate infectious process
- Ligands (usu small molecules) – Present on surface of bacteria & are able to bind to specific receptors on mammalian cell surface
Phagocytosis
Some cells (macrophages & blood neutrophils / polymorphonuclear cells) capable of ingestingbacteria + killing them
- Process depends on ability of phagocytic cells to attach to + form a vacuole around bacteria
- Some bacteria (eg. streptococcus pneumoniae) surround themselves with a polysaccharide capsule
– Protective coat that prevents engulfment by phagocytic cell
Opsonization – Host response can be production of antibodies to the capsule, which will bind / alter capsule surface to permit phagocytosis
Antibodies to Bacteria
- Antibodies can be formed by host against bacteria
- May function as an opsonin (phagocytosis) OR may kill organisms directly
Complement
Complex system of plasma proteins working together to resist bacterial infection
- Can kill some bacteria
- Functions on its own or works to enhance immune response
Cell Mediated Immunity
Vital defence of immune cells against bacteria
e.g. Mycobacterium tuberculosis & Legionella species killed by activated macrophages
What is the host defence against exotoxins ?
Antibodies
Metastatic Spread
Bacteria may become distributed around the body from a single focus of infection through the bloodstream (bacteraemia / septicemia)
When this occurs → Can then cause clinical symptoms / first sign of infection at a location distant from original infection / point of entry
Compromised Patients
Some patients may be deficient in some of the antimicrobial defences the body has → Thereby leading to infection
- May be due to a disease process (eg. Leukemia may give rise to a deficiency in phagocytosis)
- May be due to medical / surgical procedures & administration of medication (eg. Administration of immunosuppressive drugs to transplant patients may depress their immune system to the point where it is no longer effective as a defence)
Some host defence mechanisms are more important than others in prevention of certain infections, so it is possible to predict which infection will occur in which patient
- Vital in managing infections
What is a compromised patient at risk for ?
Phagocytic cells (eg. leukopenia) → Staphylococcus aureus, Streptococcus aureus, Streptococcus pneumoniae
Antibody mediated immunity / HUMORAL → Streptococcus pneumoniae, viral infections
Cell mediated immunity (incl. AIDS) → Tuberculosis, Legionella, AIDS-related infections
Microbial (infectious) diseases are a result of …
Interaction between microorganisms (adhering, penetrating, multiplying) & the host organism
Infection
Penetration of a microorganism (or a part of it capable of multiplication) into a host organism
Disease – Producing apparent changes / clinical manifestations
NO disease – Producing inapparent changes / infections (challenging w/ no obvious symptoms)
Colonisation
Establishment & multiplication of a microorganism in/on the body without producing ANY change (apparent nor inapparent)
- Must adhere + overcome / avoid detection from immune system
eg. Colonisation of the skin with micrococci
Contamination
Deposition of microorganisms without multiplication
- Bacteria doesn’t do much work yet, just deposited
eg. Contamination of sterile dressings by falling dust containing bacteria
eg. Contamination of drinking water with sewage)
What defines a clinical infection ?
AKA microbial disease
Occurs when changes result in functional damage to the infected host. Such changes occur when the balance between host and microorganisms is disturbed :
- Large VS Small # of microbes
- Increased VS Attenuated virulence
- Susceptible VS Resistant host
Clinical vs Sub-Clinical vs NO Infection
Clinical Infection → Disease ( easy to recognize )
Sub-clinical Infection → Inapparent / asymptomatic ( hard to diagnose since pathogens not at a high enough level that we can detect easily )
No Infection → OK
Microorganisms capable of producing clinical or subclinical infection are classified based on :
- Pathogenicity
- Virulence
- Opportunistic
What is pathogenicity ?
The ability of a microorganism to produce disease
Able = pathogen
Not = not
What is virulence ?
Relative capacity of a microorganism, within a group, to cause damage resulting in disease
- Degree of pathogenicity
More virulence = Better ability to cause disease (faster / more symptoms)
Less = Can cause disease but less fatal
What are opportunistic pathogens ?
Microorganisms that rarely cause disease in healthy humans, but often do so in humans whose defense mechanisms have been compromised (eg. by burns, injuries, etc)
- If bacteria goes where not supposed to → Even good bacteria can cause issues here
- Compromised immune system → Even good bacteria may cause issues
When pathogenic microorganisms enter the body, 2 opposing forces are set into action :
Microorganism – Strives to invade tissues, live & multiply (1)
Host – Strives to block the invasion of microorganisms + destroy them, tries to prevent 1 (2)
The capacity of a microorganism to initiate an infection & produce disease is dependent upon :
- Transmissibility
- Pathogenicity [ Invasiveness & Toxigenicity ]
Transmissibility
Transfer of an effective challenge amount of pathogen from a source to a host
Routes of Entry
- Inhalation (MOST common way we come in contact)
- Ingestion (2nd most)
- Break in protective barrier
- Direct deposit
Invasiveness
Microorganisms overcome their host’s immediate defence mechanisms through their ability to :
- Adhere to + persist on body surfaces
- Protect themselves against bactericidal substances present in body fluids
- Avoid ingestion + destruction by phagocytes
Means by which bacteria adhere to, evade the defence mechanisms – invade the host :
Surface structures (pili, fimbriae) – Adhere to specific receptors present on body cell surfaces
Capsules – Usu polysaccharides, protect the microorganisms against leucocytes
- Enzymes – Although not toxic per se, may contribute towards the virulence of the pathogen that elaborates them
eg. Coagulase : Enzyme accelerating the clotting of plasma; the clot formed around the focus of infection constitutes a barrier against leukocytes and body fluids
eg. Hyaluronidase : Enzyme which hydrolyses the polymerized hyaluronic acid; the latter is part of the intercellular ground substance of mesodermal tissue. Hyaluronidases, also known as “spreading factors” help bacteria by liquefying the viscous polymer and facilitating the spread of fluids carrying the bacteria.
Toxigenicity
Ability of bacteria to produce toxic substances that damage host tissues or upset systems vital to the host
Exotoxins
Proteins made inside + excreted / pushed out by living bacterial cells
- Host must be ALIVE
- Have specific affinities for host systems, bind to specific cells (eg. diphtheria exotoxin & cardiac muscle + nervous tissue; botulinum exotoxin & nervous tissue)
- Active in very small concentrations, very potent
eg. Botulinum neurotoxin, one of most toxic substances can kill a man in 0.0001 mg dose - Thermolabile (Sensitive to heat)
Can exert their effects in areas distant from where they were originally synthesized
Endotoxins
Toxic substances associated structurally with the bacterial cell (not secreted) & liberated only when the cell wall disintegrates
- Less specific + less potent than exotoxins, BUT may produce marked clinical effects such as pyrexia (fever), malaise, & vasomotor disturbances such as septic shock
- Thermostable (Resistant to heat)
- HUGE problem if released
