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This enzyme is part of the innate immune system and attacks peptidoglycan by hydrolyzing the glycosidic bond between NAM and NAG sugars.
this antibiotic inhibits enzyme transpeptidase which interferes with cell wall sythesis
This antibiotic binds to the small RSU and inhibits protein synthesis
The antibiotic inhibits bacterial growth by binding to the 50s ribosomal subunit preventing protein synthesis
This broad spectrum drug binds to bacterial DNA gyrase; inhibits DNA replication
This kind of DNA carries one or more resistance genes in bacteria
This type of drug characteristic has the capacity to inhibit growth but not to cause microbial death
The ______ the therapeutic index, the better the drug as well as _____ selective toxicity
3 tests to determine MIC
- Dilution suseptibility test
- Disk Diffusion Test
- The E-Test
2 Targets for antifungal drug?
- Membrane sterols
- Chitin --> Chitin synthase
This antiviral is used to treat influenza A infection and acts by blocking penetration and uncoating
This antiviral acts by competative inhibition on viral DNA polymerase
This drug used for H1N1 is a neuraminidase inhibitor. It reliees flu symptoms faster
This drug is used to treat Malaria. It suppresses protozian reproduction
these 3 things could protect bacteria from drug administration into the body
blood clots, necrotic tissue, biofilms
3 Ways drug resistance occurs
- blocks entrance
- pump the drug out once it has enetered (efflux pumps)
- drug inactivation through chemical modification
What difference in membrane lipids do archae posses?
isoprenyl glycerol ether linkages
3 properties of a good drug?
- High therpeutic index
- target molecule is specific to pathogen
- Great toxic selectivity
- Broad range
- No resistance against drug
How can we determine the effectiveness of a drug?
- MIC test
- Minimal Inhibition Concentration
Why is drug administration methods a consideration for drug effectiveness?
It must be considered how the drug spreads through the body with regards to how fast it moves through the body, the half-life of the drug which may be dependant on the location of the pathogen infection. The drug stability must also be considered.
Characteristics of a BSL-1 pathogen?
Not known to cause disease in humans
Characteristics of BSL-2 pathogen?
Associated with human disease.
Characterstics of BSL-3 pathogen?
- potential aerosol tranmission
- disease may be serious or lethal
Characteristics of BSL-4 pathogen?
- high risk of life-threatening disease
- agents with unknown risk of tranmission
What is bacteriophage typing?
characterizing based on specificity of phage surface proteins for cell surface receptors.
a agar plate is inoculated to grow a thick lawn. The lawn is sectioned, and to each section a phage is added. The specific phages will kill bacteria causing plaques. The bacteria are them labeled and catagorized based on phage sensitivities.
Describe molecular genetics classification methods.
- the analysis of proteins and nucelic acids. Tests for routine clinical microorganisms. Quick results due to DNA hybridization.
- The benefit is it requires the presence of fewr microorganisms.
- Uses PCR
Amplifying (PCR) small RSU and then comparing the sequences with international databases. A hugh benefit - high conservation of 16s rRNA in bacteria.
What is MLST?
the sequencing and analyses of "house-keeping genes" in bacteria.
Describe Genomic fingerprinting?
Identifies pathogens. Compares DNA fragments by restriction endonuclease digestion.
Describe Plasmid fingerprinting.
Identifies isolates of the same or similar strains by plasmids. Cuts the plasmids into fragments with restriction endonucleases and seperates them by gel electrophoresis.
- direct agglutination is good for the diagnosis of certain diseases. It identifies quickly when cultures are not feasible
- Hemagglutination is used in blood typing, viral heagglutination and DIAGNOSIS of inlfuenza.
- The test is done in plate which constitutes many latex-coated wells.
- The wells bind to either antigens or antibodies.
- Complementary binfing will cause to blood to clot forming a positive test,.
A patient is thought to have a viremia. You know you should do viral aggultination. How will you go about it?
- Antigens from the virus are in the blood. The immune system should have also reacted if the infection is not too fresh.
- If the virus antigens are known and available, bind these to the wells, The blood should have antibodies so once added to the well they should neutalize the virus thus preventing clotting,.
How can we test for measals?
- Viral hemagluttination.
- Add the blood to the plates. If it contains the virus it should clott. If we add available measle antibodies, it should break up the clots.
Describe complement fixation
- the test is very sensitive, can detect very small amounts of antibodies from a suspect microorganism in blood serum.
- indicator cells are added ( sheep RBC coated with complement-fixing antibodies)
- if the immune complex is present (antigen+antibody) in serum, the it uses the complement, and thus the indicator cells are not lysed.
- If there is no infection, complement is not used up and the indicator cells are lysed.
Describe Western Blotting
- Gel electrophoresis of a protein followed by a transfer to a sheet for analysis of banding patterns.
- The Western Blot identifies presence and specific protein among different strains of microorganisms
- It also shows strain-specific antibodies in the event of an immune response
describe properties of an exotoxin
- toxic protein released by both types of proteins into the surrounding
- treatment is available
- very potent, can be lethal
- toxoids can provide immunity
- can be a super-antigen --over-stimulates the immune system causing excessive cytokines and organ failure
- no treatment available
- gram-negative bacteria
- a lipid-A molecule of the membrane release when cell dies
- causes fever, septic shock
What is the fundamental process of infection?
competition for resources with microflora
What is zoonoses?
A term that describes disease that is tranmitted from animal to human
A measure of virulence?
LD50! Measure the pathogen dose required to kill 50% of infected hosts.
the first line of defense (human host) against pathoghens?
intact skin and flushing systems
Properties of the skin that provide immunity?
- keratinocytes - skin sheds removing microorganisms that manage to attach
- slightly acidic (pH 5-6) due to skin oil
- high [NaCl]7subject to periodic drying
Immunal properties of mucous membranes?
- a coating; resists microbial penetration and traps microorganisms
- antimicrobial enzymes (3): lysozyme, lactoferrin and lactoperoxidase
Descibe cationic proteins
damage bacterial plasma membranes through electrostatic interations - formation of ionic pores in membrane altering membrane permeability
- proteins release by microflora
- proteins are toxic to other types of the same strain
Role of complement proteins?
- augments phagocytosis
- defends against infection by opsonization, activiated leukocytes, and lysis of bacteria
- they enhance antibody response and immunologic memory
- dispose waste
process of coating (tagging) bacteria for phagocytosis
This type of protein recruits phagocytes to the proteins site of activation and puctures bacterial cell membrane causing it to lyse. What protein is it?
A protein or glycoprotein release by one cell population that acts as a signalling molecule
5 functions of cytokines?
- promotes apoptosis
- stimulates cell differentiation
- attracts phagocytic cells and lymphocytes
- stimulate cell migration
- TNF- promotes inflammation, fever, induces apoptosis
- regulates growth and differentiation process in blood cells
What is the role of interferons?
- a regulatory cytokine
- a respons to viral infction
- acts to prevent viral repplication and assembly thus limiting viral infection
How do macrophages induce fever?
phagocytosis of bacteria releases cytokines. Endogenous pyrogens that are produced by the macrophages.
Whats so special about the fever trait?
- stimulates leukocytes
- enhances specific activity of the immune system
- enhances growth inhibition by decreasing available iron to the pathogen
what tissues are microbe free?
- brain tissue
- spinal tissue and fluid
how are accute-phase proteins developed and what role do they play in immunity?
- macrophage ingests bacteria and releases cytokines
- cytokines act on the liver causing it to produce acute phase proteins
- they bind to the bacteria and act by opsonization
This kind of cell is phagocytic, circulates in the blood, and migrates to the site of infection
This type of cell is present in mucous membranes, APC, elicits immune resonse from anive T and B cells and presents to T cells "activating it"
the role of APCs in immunity?
to activate wandering lymphocytes after phagocytosis
describe the process of inflammation
- injured cells release cytokines which increase permeability of blood capillaries
- selectins attract neutrophils to the site
- neutrophils activated when they encounter cytokines
- neutrophile moph to squeeze through capillaries and attack pathogen
Describe stage 1 pathogen (wolfe)
- A microbe that is present in animals but has not yet been found in humans under normal conditions
- - most malaria plasmodia
Describe what a stage 2 pathogen is (wolfe)
- A pathogen of animals that has under normal conditions been transmitted to humans but not between humans
- - anthrax, rabies, west nile
Describe level 3 pathogen (wolfe)
- A pathogen that can undergoe a few replication cycles from secondary tranmission to humans but occasional outbreaks from primary infection soon die out
- such as Ebola
describe level 4 pathogen (wolfe)
- A disease that exists in animals but can survive in human to human transmission without animal involvement
- such as cholera and influenza A
Describe a stage 5 pathogen (wolfe)
- A pathogen that is exclusive to humans
- such as falciparum malaria, small pox, HIV
Describe some characteristics of an acute disease
- easily tranmitted
- quickly leaves victim dead
- immune to re-infection
- dense population of humans is a factor
How has agriculture become problematic with regards to disease?
- It lead to a spike in human population and density
- spike in animal population and density (domestication)
- provided easy spreading
- farmers would come into closer contact with their animals
- the animals become sufficient conduits for pathogen transfer
Which diseases can be related to domestication of animals? (a problem of agriculture)
smallpox, TB and influenza
Describe a barrier to pathogen tranmission from stage 2-3.
- differences between animal and human behaviors that affect transmission
- obstacles include transmitting though different human tissues (as in BSE)
How can a pathogen tranfer from class 2-3? (wolfe)
- pathogen has adapted to transmit different or more efficient ways
- pathogen has evolved to infect an additional vector (thus increasing transmission)
What may be a reason from increasing emergence of infectious diseases between 1940 and 2004?
- resistant strains had evolved
- pathogens had recently entered the human population for the first time
- increases of agriculture
- increase of human population and density
- an increase of suceptability (through AIDS pandemic)
- improper use of antimicrobials in developed countries
- viruses have poor mutation error correction (especially RNA)
identification od bacterial strains based on suseptibility to specific phages
wisualization tech. using flourescently labelled antibodies to detect antigens
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