Bacteria and disease Flashcards
Do are humans colonised with microorganisms?
From birth
Are microorganisms considered to be benign or malignant?
Benign
Why are microorganism considered benign?
Few contribute to health and fewer pose direct threats to health
What do microorganism normally associate with in humans?
Human body tissue
Do most microorganism cause diseases?
No
What are the few diseases caused by microorganisms?
- Viruses (Influenze, Lassa fever, AIDS)
- Bacteria (Diptheria, TB, anthrax)
- Fungi (Candidiasis)
- Protozoa (Malaria, sleeping sickness)
Define microbial pathogenicity:
The biochemical mechanisms whereby microorganisms cause diseases
Do have an equal or unequal probability of causing infections and disease?
Unequal
Define infection:
Successful persistence or multiplication of a pathogen on or within the host
Define disease:
An interaction which causes significant overt damage to the host
Define pathogenicity:
The way in which a microorganisms causes disease
Define virulence:
Relative term e.g. one pathogen vs another
Do different microorganisms have the same or different pathogenic potentials (virulence)?
Different
What are examples of low virulence?
Common cold, salmonella food poisoning, candidiasis, Pneumocystis crania pneumonia
What are examples of high virulence?
Malaria, anthrax, plague and Lassa fever
What factors affect the severity of a microorganism disease?
- Host
- Immunological status
- Physiological status
- Genetic makeup
- Route of infection (inhalation, skin, ingestion)
- Dose (high, low)
What can an infectious dose/lethal dose graph measure?
Virulence
How do you find the virulence from an infectious dose/lethal dose graph?
Look at quantity when 50% infected
On an infectious dose/lethal dose graph does a lose dose mean in terms of virulence?
High virulence
What is the infectious dose of Bacillus anthracis?
10,000
What is the infectious dose of Vibrio cholerae?
10^6
What is the infectious dose of Salmonella enterica?
10^9
What is the infectious dose of Campylobacter jejuni?
800
What is the infectious dose of Francisella tularensis?
10
What is the infectious dose of Mycobacterium tuberculosis?
50
What is the route of infection of Mycobacterium tuberculosis?
Inhalation
What is the route of infection of Francisella tularensis?
Insect bite
What is the route of infection of Campylobacter jejuni?
Ingested in food
What is the route of infection of Salmonella enterica?
Ingested in food
What is the route of infection of Vibrio cholerae?
Ingested in water
What is the route of infection of Bacillus anthracis?
Inhalation
How does a pathogen need to do in order to cause a disease?
- Colonise host tissues
- Grow within host tissue
- Avoid host defence mechanisms
- Cause damage to the host
How do pathogens damage the host?
Via 2 principal mechanisms
- Produce effectors which damage host tissue
- Evoke profound immune responses which cause damage
What are exotoxins?
Toxins as effectors
What do neurotoxins cause?
Paralysis
What do enterotoxins cause?
Sickness and diarrhoea
What do cytotoxins cause?
Cell death
What toxin does Diphtheria produce?
Diphtheria toxin
What toxin does Anthrax produce?
Anthrax toxin
What toxin does Cholera produce?
Cholera toxin
What toxin does Gangrene produce?
Alpha toxin
What toxin does Tetanus produce?
Tetanus toxin
What are the types of mode of actions of toxins?
- AB toxins
- Cytolytic toxins
What is the mode of action of AB toxins?
- B portion binds to cell and facilitates translocation
- A portion which possesses catalytic activity
What is the mode of action of cytolytic toxins?
Damage cytoplasmic membrane
What are endotoxin?
Pryogen
What is another name for endotoxin?
LPS
What do endotoxins causes?
Production of cytokines from immune cells upon binding to cell surface receptors
What are the two immune systems?
- Innate immunity
- Adaptive immunity
What is innate immunity?
- Non-specific
- General
- Immediate response
- No immunological memory
What is the adaptive immunity?
- Specific to antigen
- Lag time from exposure to response
- Immunological memory after exposure
What is involved in a humoral innate immunity?
- Complement
- Enzymes
- Cytokines
What is involved in cellular innate immunity?
Phagocytes
Natural killer cells
Patter recognition receptors
What is involved in humoral adaptive immunity?
Antibodies
Cytokines
What is involved in cellular adaptive immunity?
T cells
B cells
What cells are derived from bone marrow stem cells?
- Myeloid precursor
- Lymphoid precursor
What cells are derived from myeloid precursors?
Monocytes
Neutrophil
Mast cells
What cells are derived from monocyte?
Dendritic cells
Macrophages
What cell is derived from lymphoid precursor by thymus maturation?
T cell
What cell is derived from lymphoid precursor by bone marrow maturation?
B cells
What cell is derived from B cells?
Plasma cells
What does PAMP stand for/
Pathogen associated molecular patter
What does PRR stand for
Pattern recognition receptor
Describe an antibodies?
Made of 4 polypeptide chains with variable and constant regions
What immunity is antibodies involved in?
Adaptive immunity
What are the different classes of antibodies?
- IgM
- IgG
- IgE
- IgD
- IgA
What do antibodies recognises?
Foreign antigens on cell surface of pathogens
What is specificity in terms of immune response?
Immune cells have surface reports that interact with individual antigens
What is memory in terms of immune response?
- First antigen induces multiplication of antigen-reactive cells
- More of exposure to same antigen = faster and strong immune response
What is the result of an immune response?
antigen preexposure triggers a much stronger secondary response
What are T cells required for?
Protection against intracellular pathogens
Why are antibodies required?
Protection against toxins and extracellular bacteria
What does introduction of pathogen antigen cause?
Weak primary response but after second antigen exposure the secondary response is much stronger
What is key of vaccinations?
To introduce a non active toxin or an attenuated strain
What are the two types of T cells?
- T helper cell
- T cytotoxic cell
Is CD4 T helper cell or T cytotoxic cell?
T helper cell
Is CD8 T helper cell or T cytotoxic cell?
T cytotoxic cell
What complex does CD4 form?
Tri-molecular complex
How do CD4 cells work?
- Presents forge in antigen to macrophage
- Causes release of cytokines, TNF-a, GM-C5F, IFN-y
- Cytokine release
- Increases phagocytosis of all pathogens; inflammation
How do CD8 cells work?
Binds to antigen on target cell
Release of granules
Cell death by apoptosis
What are different types of vaccines?
- Toxoid vaccines
- Live, attenuated vaccines
- Inactivated vaccines
- Subunit vaccines
- Conjugate vaccines
- DNA vaccines
- Recombinant vector vaccines
What is the toxin vaccine?
Toxin which have been inactivated by heat or by from aldehyde which cross links the protein side chain
What is the live, attenuated vaccine?
Contains live strain of microorganisms
What is the subunit vaccine?
RNA encoding spike protein delivered in a lipid molecule
What is an inactivated vaccine?
Contains an inactive strain of whole microorganism or bacteria
What is the conjugated vaccine?
Works against the o antigen polysaccharide
What is the DNA vaccine?
Inject DNA and host cell replicated and makes antigen in situ
How many antigens can a subunit vaccine contain?
1 to 20 or more antigen
How do you make a subunit vaccine simply?
Pathogen can be grown and then use chemicals to break it apart and gather important antigens
Antigen molecules from the pathogen can be used using recombinant DNA technology
What is foreign DNA uses tagged with to facilitate purification of recombinant antigen?
Gene encoding a tag
How do conjugate vaccines work?
- Pneumococcal polysaccharide linked to diphtheria taxied binds to B cell with anti-polysaccharide antibody
- Conjugate antigen is taken in and digested by the B cell
- Polysaccharides cannot be presented to the Th2 cells by B cells. Peptides from the toxoid are efficiently presented by the B cell to the Th2 cells
- Interaction with the toxoid peptide presented by the B cell activates the Th2 cell
- Activated Th2 cell makes cytokines that drive the B cell to make plasma cells
- Plasma cells make antibodies to pneumococcal polysaccharide. The antibodies bind to the capsule and neutralise or opsonise the pathogen
What is the problem with live attenuated vaccines?
Identifying which genes to knockout if no obvious virulence factors
How do we knockout genes?
By homologous recombination
How do we knockout genes by homologous recombination?
- Gene X disrupted by slotting another gene
- Gene X cloned in to plasmid
- Introduce a middle antibiotic resistance cassette
- Take out interrupted gene and introduce bacteria
