Glossary of Block V, Week II

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What is DNA primary, secondary and tertiary structure?
primary - sequence of bases
secondary - base pairing/alpha helix
tertiary - supercoiling
In what direction is nucleotide polarity?
5' to 3'
Describe variations in the helical structure of DNA.
different types of helices:
A form, B form, Z form etc.
There can also be triple and qaudraplex helices.
What type of labels would you use in direct DNA detection?
Radioactive enzyme labels
Give two examples of labels used in indirect DNA detection.
Biotin (binds to protein A)
Antigen (binds to antibodies)
Where are Restriction Fragment Length Polymorphisms (RFLPs)used?
In DNA fingerprinting
What determines the location of the origin of replication (ori)?
The RNA primer is always the determinant of the ori.
What are the functions of the following enzymes>
1. Primase
2. Helicase
3. DNA Polymerase
4. Topoisomerase
5. Exonuclease
6. Ligase
1. facilitates binding of RNA primer to DNA strand
2. Unwinds DNA helix
3. polymerization of new DNA strand
4. Removes supercoils (unwinds)
5. Removes RNA primers
6. Links Okazaki Fragments
Does DNA replication occur unidirectionally or bidirectionally?
What is rolling circle replication and what is unique about it?
What is the final result?
DNA replicates in a circle (ie. in a plasmid).

Unique in that there is only one replication fork.

The final result is a double stranded, linear DNA that can be cut and packed (viruses), or a new plasmid can be made.
Where is coupled transcription-translation observed?
In bacteria
What type of mutation does UV radiation produce?
pyrimidine (thymine) dimers
What is the Ames test?
A test for mutagenesis. Bacteria is spread on an Agar plate, the chemical in question is placed in the center of the plate. There is no histidine on the plate, and the bacteria can only grow in histidine. Therefore, if growth is random we know the chemical is not a carcinogen. If growth is concentrated (especially around the center of the plate) we know the chemical is a mutagen.
How are Thymine dimers replaced?
photolyase cut the T-T bond
Describe base excision repair.
DNA glycosylases scan for damage

Once damage is found they bend DNA at the site of the lesion.

glycosylase removes the lesion, Purinic enzyme (APE) removes the damaged base. Other enzymes replace it adding the correct base.
What are the four steps of excision repair?
1. Nick
2. 3'-5' exonuclease excises damaged area
3. 5'-3' polymerase replaces with correct sequence
4. Ligase seals the nicks
What is the key thing that allows mismatch repair to accurately occur?
methylated strands (old ones) are identified: other strand is nicked, then excision repair occurs.
Describe SOS (error prone) repair
the SOS error prone polymerase will stop replication at the mutation (ie. T-T dimer).
In order to keep replicating it incorporates anything (misincorporation). The mutation is "overcome" and replication continues as before.
What are the following associated with?
Rec A, Rec BCD
Genetic recombination.
Define hyperplasia
an increase in the number of cells in an organ or tissue (may or may not be accompanied w/an increase in volume)
Give an example of how hormonal stimulation causes hyperplasia.
During puberty: estrogen leading to breast epithelial cell proliferation
Give an example of how increased functional demand can result in hyperplasia.
At high altitudes an increase in erythrocytes is observed
Give an example of how persistant cell injury can result in hyperplasia.
corns and calluses are a result of persistant cell injury
Define hypertrophy
an increase in cell size, which results in an increase in the size of an organ
What causes the increase in cell size during hypertrophy?
the synthesis of more structural components causes the increase in cell size. (An increase in function usually goes along with this)
Give an example of physiologic hypertrophy
The influence of hormones causes this. for example: in males during puberty muscles undergo hypertrophy.
Give an example of hypertrophy due to increased functional demand.
Increased muscle size and strength during exercise.

(LVH due to hypertension, increase in smooth ER in liver due to increased use of the P450 system, uterine growth during pregnancy)
Define atrophy
shrinkage in cell size

(caused by loss of cell substance and accompanied by diminished function)
In atrophy does the cell # stay the same?
What are 6 causes of atrophy?
1. decreased workload
2. loss of innervation
3. diminished blood supply
4. inadequate nutrition
5. loss of endocrine stimulation
6. aging
define metaplasia
the conversion of one differentiated cell to type to another.
What is the most common type of metaplasia, and, in general, is metaplasia reversible?
most common type is columnar to squamous conversion.
Yes, metaplasia is reversible
Give two examples of metaplasia
1. alteration of respiratory tract due to smoking
2. alteration of esophageal lining due to GERD.
Why is metaplasia considered a two edged sword?
because by converting to squamous cells you add protection to the organism under irritation: but you lose the columnar cell which functioned in secretion.
Define dysplasia
the disordered growth and maturation of cellular components of a tissue.
In dysplasia, describe the changes to the following:
1. size and shape
2. nuclei
3. epithelial cells
1. from uniformed to varied
2. enlarged, irregular and hyperchromatic nuclei
3. disordered arrangement
Where does dysplasia most commonly occur?
in squamous epithelium (skin, bronchus, cervix)
1. Is dysplasia reversible?
2. Why is dysplasia a serious concern?
1. yes, dysplasia cen regress
2. dysplasia is a concern because it shares many features with cancer and is considered a precursor lesion for cancer development.
What is a common pathological process that provides a "marker" of dead cells. (hint - there are two kinds: dystrophic and metastatic)
pathologic calcification
Which type of calcification is found in nonviable or dying tissues? It is also seen in necrotic areas.
Dystrophic calcification
Why does dystrophic calcification occur in necrotic areas?
dystrophic calcification occurs when necrotic cells or cellular debris is not cleaned up by leukocytes (via phagocytosis).
Give three examples of where dystrophic calcification is found. (limit to the cardiovascular system)
atherosclerotic plaque
aged heart valves
necrotic areas following an MI
What is a Psammoma body?
A single necrotic cell becomes a seed crystal for further mineral deposits. More layers accumulate that make the molecule look like a grain of sand. This is known as a psammoma body.
describe the pathogenesis of dystrophic calcification. (2 steps)
1. Initiation:

extracellular - occurs in membrane bound vesicles that are derived from degenerating or dying cells.

intracellular - calcium is accumulated in the mitochondria of dead or dying cells.

2. Propagation of crystal formation:
depends on concentration of calcium and phosphates in ECF, mineral inhibitors and collagen.
Name two proteins that are involved in propagation of dystrophic calcification.
1. osteopontin - Ca++ binding phosphoprotien, binds to hydroxyapetite, also used in normal bone formation.

2. Collagen - enhances crystal growth
1. When does metastatic calcification occur?

2. Give some examples of some causes.
1. metastatic calcification occurs in normal tissues when there is hypercalcemia.

2. causes range from hyperparathyroidism (and hyperthyroidism) to vitamin D intoxication to some cancers.
Give an example of how dystrophic calcification can be a cause of organ dysfunction.
(ie. where do you see it when it causes organ dysfunction)
- calcific valvular disease
- blockage of electrical signal in heart
- atherosclerosis
Where is metastatic calcification typically seen?
typically seen in the interstitial tissues of the blood vessels, kidneys, lungs and gastric mucosa.
Does metastatic calcification cause organ dysfunction?
No, it generally does not cause dysfunction unless the calcification is massive.
describe heterophagy
(and it's relationship to reacting to surrounding cell injury)
heterophagy - uptake of extracellular materials via endocytosis (phago- or pino- cytosis). heterophagy is often seen in neutrophils and macrophages when they digest irreversibly injured cells and associated debris.
what is autophagy and where/when is it observed?
autophagy is the highly specific "digestion" of intracellular contents. The cell forms an autophagolysosome.

It is observed in injured cells and cells undergoing atrophy.
Describe the induction of smooth ER in hepatocytes. Why does it occur?
the induction of ER is an adaptive response to accommodate increased liver function (this boosts the P450 system). The result is increased tolerance to drugs metabolized by that system (ie. barbituate abuse results in anesthesia and analgesic resistance).
What mitochondrial changes occur during cell atrophy and hypertrophy? Is this of diagnostic significance?
increase in number with cell hypertrophy; decrease in number with cell atrophy. Seldom of diagnostic significance.
Are cytoskeletal abnormalities of diagnostic significance?
not really, only a few are significant
What is a mallory body and why is it significant?
a mallory body is an eosinophilic intracytoplasmic inclusion mainly made up of prekeratin. Mallory bodies are characteristic of liver disease.
microtubule associated proteins and neurofilaments found in the brain are called __________ and are characteristic of Alzheimer's disease.
Neurofibrillary tangles
what are the three mechanisms that result in accumulation of various substances in the cell?
1. normal endogenous (fatty change in liver)
2. abnormal endogenous (storage diseases)
3. abnormal exogenous
What kinds of lipids can accumulate inside of cells?
all major types of lipids can accumulate in cells (TAGs, Phospholipids, Cholesterol)
What is steatosis and where is it most commonly seen?
steatosis is fatty change (abnormal accumulations of triglycerides within parenchymal cells). Usually seen in liver, but also seen in heart, muscle, kidney.
In what four pathologic processes are accumulations of cholesterol and cholesterol esters seen in?
1. Atherosclerosis
2. Xanthomas
3. Inflammation and Necrosis
4. Cholesterolosis
What are Xanthomas?
intracellular accumulations of cholesterol-laden macrophages.
Clusters of these are found in the subepithelial connective tissue of the skin producing masses known as xanthomas.
What is cholesterolosis?
accumulations of cholesterol-laden macrophages in the lamina propria of the gall bladder.
1. Fatty ingrowth refers to an accumulation of lipids within ____________.
2. Where is this most often observed and is it of concern?
1. stromal connective tissue
2. Seen most often in heart and pancreas. Not of concern, causes no adverse affects on cardiac or pancreatic function.
1. Where in the body is protein accumulation very likely?
2. What symptom is caused by this?
3. Mechanism?
1. the kidney.
2. intracellular protien accumulation is seen in diseases that have proteinuria.
3. protiens must leak across the glomerular filter, then they are pinocytosed by the proximal tubule.
1. What are Russel bodies?
2. How are they made?
1. Russel bodies are accumulations of immunoglobulins in plasma cells.
2. When the ER of a plasma cell is synthesizing immunoglobulins it may become distended and produce large, homogenous, eosinophilic inclusions (Russel bodies).
1. When would you see an accumulation of glycogen?
2. What would it look like histologically?
3. In what classic disease do you see glycogen deposited in the kidney, liver cells, heart muscle and pancreatic beta cells?
1. seen in patients with disorders in glucose or glycogen metabolism (ie. glycogen storage diseases).
2. glycogen masses look like clear vacuoles within the cytoplasm.
3. diabetes mellitus results in glycogen deposits in the kidney, liver, heart and pancreas.
what is the most common exogenous cellular pigment and what can excessive accumulation result in?
Carbon (coal dust) is the most common exogenous cellular pigment. accumulation results in black lung and lymph node tissue. In coal miners a fibroblastic reaction or emphysema is seen, resulting in coal miners pneumoconiosis.
What is the endogenous pigment that is associated with wear and tear and aging?
Lipofuscin granules are a sign of aging due to oxidative damage.
Where would lipofuscin granules be most prominent?
in the liver and heart of aging patients, or in patients with severe malnutrition.
how and where is melanin formed?
melanin is formed when tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes.
What is hemosiderin and what is it most commonly a marker of?
hemosiderin is a hemoglobin-derived pigment in which iron is stored in cells. It is golden-yellow to brown, and can be a marker of acute and chronic tissue damage via hemorrhage.
What are some other causes of hemosiderin accumulation?
impaired utilization of iron, hemolytic anemias, transfusions, increased absorption of dietary iron.
Where is bilirubin accumulation most commonly found (2) and what would it look like histologically?
most commonly found in liver and kidneys
histologically appears as mucoid, green-brown to black, amorphous, globular
What would a hyaline change look like histologically?
you would see cells with a homogenous, glassy, pink appearance.
Why is hyaline change important?
in long-standing hypertension and diabetes, the walls of arterioles become hyalinized resulting in pathologic processes ( the kidneys).
What is the heredity of Cystic Fibrosis?
Which population is it most common in?
autosomal recessive
most common in caucasian population.
what percentage of whites are heterozygous carriers for CF?
25% (1 in 2,500 live births)
What are the two organs most effected by CF?
Lungs (Chronic PUlmonary Disease)
Pancreas (Deficient exocrine pancreatic function)
What is the genetic explanation behind CF?
Mutation in chromosome 7, the CFTR gene. The CFTR regulates secretion of Cl- by epithelial cells. If you mutate CFTR, the Cl- channel is damaged. No Cl- can exit the cell now - water cannot follow Cl-, the result is a viscous mucous.
What are the 3 different mutation in the CFTR that lead to CF?
1. failure of CFTR synthesis
2. failure of CFTR transport to the plasma membrane
3. failure of ATP binding to the CFTR
what occurs in many CF paitents at birth?
meconium ileus (due to failure of pancreatic enzymes to process intestinal contents - results in increased viscosity of contents).
Describe the early lung pathology of a CF patient.
increased mucous secretions
hypertrophy of mucous glands
mucous plugging of bronchioles
clear secretions
Describe the intermediate lung pathology of the CF patient
prone to lung infections (pseudomonas)
repeated bouts of nectrotizing pseudomonas pneumonia
inflammation and necrosis
Describe the late lung pathology of the CF patient
hyper inflated lungs, cyanosis, clubbing
scarring and hyperinflation may lead to pneumomthorax or emphysema
chronic lung disease overworks heart, resulting in cor pulmonale (RVH, pulmonary HTN, edema, hemorrhage)
What are the pancreatic complications of CF?
mucous blockage of the (exocrine)pancreatic ducts leads to necrosis of the pancreatic secreting cells.
What are the early pancreatic changes in the CF patient?
- duct ectasia (dilated ducts), results in necrosis of exocrine pancreas.
- causes loss of digestive enzymes.
- fat atrophy
What are the late changes of the pancreas in the CF patient?
Inflammation and necrosis leads to collagen deposition and fibrous and fatty tissue. (endocrine pancreas is preserved until late in the disease).
What influence does CF have on:
1. the appendix
2. male reproductive tract
3. Liver
1. fills with secretions (due to lack of pancreatic enzymes), leads to a mucocele.
2. vas deferens becomes plugged - leads to scarring, fibrosis and sterility.
3. blockage of bile ducts. most liver changes due to heart failure and HTN.
What are 3 factors that affect aging?
1. genetic factors
2. Diet
3. Social Conditions
What are the 2 major theories of aging?
1. Clock Theory
2. Acccumulated Damage Theory
What is the Hayflick number and what aging theory is it related to?
The Hayflick # is the number of times a cell can divide before it undergoes senescence. (~60, on average)
Explain the clock theory related to telomere shortening and incomplete replication of chromosome ends.
Telomeres (DNA sequences that "CAP" the chromosome) are formed by telomerase. They function to ensure complete replication at the chromosome ends and protect the chromosome end from degradation. W/o telomerase the chromosome shortens with each division and the cell has a limited lifespan. This will cause the cell to quickly reach senescence.
What are the telomerase levels in germ cells, stem cells and somatic tissues?
Telomerase is high in Germ cells, low in stem cells and absent in somatic tissues.
What is the possible connection between telomerase and tumors?
in an immortal cell telomerase is reactivated and the telomeres are not shortened. Telomere elongation is an essential step in formation of some tumors.
Explain the clock theory related to "clock genes"
this theory postulates that genetically set clocks are involved in controlling the rate and timing of aging.

p53 is included in this theory, as it has been shown to produce a shorter lifespan and aging (but fewer tumors)
Explain (in general)the ROS theory.
accumulated damage of lipids, protiens and nucleic acid by ROS shortens lifespan. This theory thinks that accumulated environmental and metabolic damage causes aging.
How is caloric intake related to lifespan?
Caloric restriction extends the lifespan because there is less oxidative stress. Seen in POWs.
What is the defect in Werner's syndrome and what is the result of this defect?
the defect is in DNA helicase. Causes no DNA replication, repair (or other functions that require DNA unwinding) resulting in accelerated aging.
What is a bacteriophage?
a virus that has "invaded" a bacteria. They cannot survive on their own (must live in host cell)
What are the 5 stages in the bacteriophage lytic cycle?
1. Attachment
2. Injection
3. Replication/Synthesis
4. Assembly
5. Release/lysis (death of host)
What is a "temperate" bacteriophage?
a bacteriophage that can undergo either the lytic or the lysogenic cycle depending on the conditions
What are the 4 steps in the bacteriophage lysogenic cycle?
1. Attachment
2. Injection
3. Insertion of DNA into host chromosome
4. Expression of phage genes
V. cholerae, when combined with this phage, produces this gene product which causes?
V. cholerae, when combined with CTX phage, produces the cholerae toxin which causes cholera.
E. coli, when combined with this phage, produces this gene product which causes?
E. coli, when combined with the lambda phage, produces a shigalike toxin which causes hemorrhagic diarrhea.
Clostridium boltulinum, when combined with this phage, produces this gene product which causes?
Clostridium botulinum, when combined with the clostridial phage, produces the botulinum toxin which causes botulism.
Corynebacterium diptheriae, when, combined with this phage, produces this gene product which causes?
C. diptheriae, when combined with the corynephage beta, produces the diptheria toxin which causes diptheria.
S. pyogenes, when combined with this phage, produces this gene product which causes?
S. pyogenes, when combined with the T12 phage, produces the erythrogenic toxin which causes scarlet fever.
regarding specimens, define:
1. direct
2. indirect
3. site w/normal flora
1. a direct specimen is from normally sterile tissue (blood, liver)
2. an indirect specimen is a specimen that started out sterile but got contaminated by passing through a site with normal flora (urine)
3. pharynx, colon
What are 3 characteristics you can use to identify bacteria in the lab?
1. Cultural characteristics
2. Biochemical characteristics
3. Toxin production
What are 5 ways you can see an antigen/antibody reaction in the lab?
1. Precipitation
2. Agglutination (either Ab or Ag is fixed to a larger molecule which precipitates)
3. Neutralization
4. Compliment fixation
5. fluorescent labeling methods
What are 3 Nucleic Acid techniques that are used in the lab to identify bacteria?
1. DNA probes (target one bacterial DNA)
2. PCR
3. Ribotyping
What organisms are often resistant to disinfection procedures?
endospores and viruses
Sterilization for the most part eliminates all forms of life. What occasionally remains?
endotoxins and prions
How hot does an autoclave get to sterilize? Time frame?
121 degrees C (15-30 min)
Give some examples of gas sterilization.
ethylene oxide, formaldehyde
used for plastics
Describe "Cold Sterilization"
Irradiation, can be ionizing or UV. used for plastics and heats-sensitive metals.
What is important in filtration sterilization? What is this technique used for?
Pore size is important.
used for heat-sensitive liquids.
1. Which organisms have the most resistance to germicidal chemicals?
2. Which have the least resistance?
1. prions, then bacterial endospores
2. enveloped or medium sized viruses (Herpes simplex, HepB, HIV). Then it is vegitative bacteria (Pseudomonas, Staph, Salmonella).
Which two bacteria are obligate intracellular?
What bacteria has no cell wall?
Which bacteria have a cell wall and are spiral shaped? (3)
1. Treponema
2. Leptospira
3. Borrelia
Name a Gram (+), Catalase (+) Cocci
Name a Gram (+), Catalase (-) Cocci
Name the bacteria:
Gram (+)
Spore Forming
Name the bacteria:
Gram (+)
Spore forming
Name the bacteria:
Gram (+)
Not spore forming
stains w/acid fast stain
Name the bacteria: (2)
Gram (+)
Not spore forming
Does NOT stain W/acid fast
Name the gram (-) bacteria that has a Cocci shape.
Name the bacteria:
Gram (-)
Which Gram (-) bacteria do not grow well on SBA, are aerobic and are bacilli? (2)
Is Vibrio Oxidase (+) or (-)?
does it ferment glucose?
Oxidase (+)
Yes it ferments glucose
Name the Oxidase (+) Gram (-) bacteria that do not ferment lactose. (4)
Is Escherichia Oxidase (+) or (-)? Does it ferment lactose?
Oxidase (-)
Yes it ferments lactose
What is the other gram (-) oxidase (-) bacteria that ferments lactose?
Which bacteria do not ferment lactose?
Are they oxidase (+) or (-)?
They are oxidase (+) and gram (-)
What are the five causes of infectious disease?
1. Bacteria
2. Viruses
3. Fungi
4. Parasites
5. Arthropods (ie. lice)
1. Parasitism
2. Commensalism
3. Symbiotic
4. Host
5. Infection
1. One organism derives benefit at the other organism's expense
2. one organism derives benefit without benefiting or harming the other organism
3. mutually bebeficial
4. Organism in which a parasite lives
5. Growth of microorganisms within a host
1. Endemic
2. Epidemic
3. Zoonosis
4. LD50
5. ID50
1. a disease remains at a constant (low) level within a population
2. Sudden increase in disease level
3. disease transmitted from animals to man
4. number of organisms when used as an inoculant will kill 50% of a test population
5. nuber of organisms when used as an inoculant will infect 50% Of a test population
1. Incubation period
2. Latent period
3. Horizontal transmission
4. Vertical transmission
1. time between infection and disease.
2. time between infection and infectiousness
3. transmission to other individuals
4. transmission to offspring
What are the four classifications of hosts in regard to infections?
1. Susceptible
2. infected but latent
3. infected but infectious
4. recovered and immune
What is the difference between a classic (obligate) and an opportunistic pathogen?
classical pathogens cause disease upon entering the human body: opportunistic infections only cause disease under appropriate circumstances.
1. Virulence
2. Virulence factor
3. Pathogenicity island
1. capacity of a microorganism to cause disease
2. a genetic factor that is required to cause disease
3. a region of DNA that encodes for functions required for virulence.
Define pathogen
a potential to cause harm to a host
What are Koch's 4 Postulates?
1. presence of a microorganism should correlate with the occurance of a specific disease.
2. microorganism must be cultivated in pure culture from the diseased animal.
3. isolated species must induce the same symptoms when inoculated back into host
4. microorganism must be able to be reisolated from host.
Function of Koch's postulates?
Used to classify microorganisms as infectious agents
What are the 6 steps in microbial pathogenesis?
1. Encounter
2. Attachment to host cells
3. Invasion
4. Cell and tissue damage
5. Evasion of cell defenses
6. Shedding from the body
What are the 5 common symptoms seen in the host response to infection? (aka. flu-like symptoms)
1. Fever
2. Anorexia
3. Lethargy
4. Myalgia
5. Metabolism changes
What are the two general metabolism changes seen in the host response to infection?
1. Switch to glycogen metabolism, followed by catabolism to fuel gluconeogenesis.
2. Reduction in plasma iron and zinc. (via increasing levels of transferrin)
Why is the skin considered a "microbial desert?" (3)
1. it is impermeable to most infectious agents
2. Low pH and lack of water provide a poor environment for most bacteria
3. Direct inhibition of growth by lactic and fatty acids present in sweat and sebaceous secretions.
So how to microbes overcome the skin defenses? (4)
1. find a lesion
2. find a new route of entry
3. learn to grow on skin
4. find a new mechanism of transmission (ie. arthropod transmission)
How do mucous membrane function in antimicrobial action? (3)
1. mucous acts as a direct barrier to attachment
2. Ciliary action, coughing and sneezing help remove bacteria
3. Tears, saliva and urine have a flushing action on bacteria.
What is the microbial response to mucus?
They respond with adhesins
1. Capsules
2. Pili
3. Fimbrae
Which antimicrobial agents are found in the following body secretions?
1. Gastric juice
2. tears, nasal secretions, saliva
3. semen
4. breast milk
1. acid
2. lysozyme
3. spermine and zinc
4. lactoperoxidase
What is the microbial response to:
1. lysozymes?
2. acid?
3. antibodies?
4. toxins surrounding them?
1. direct inactivation by extracellular proteases
2. neutralization of acid (ie. urease production of H. pylori)
3. Develop capsules
4. transport into cell and inactivate (ie. Salmonella, after taking in defensins, uses the breakdown products for food)
How do normal, commensal flora suppress growth of pathogenic bacteria?
1. Occupy "niches"
2. compete for nutrients
3. produce inhibitory substances, such as acids and bacteriocidins.
What is a bacteriocidin?
a compound produced by bacteria that can inhibit the growth of other bacteria.
Where are normal flora numbers low in the body? Why is this significant?
flora numbers are low in the respiratory and urinary tract. This results in frequent infections by pathogenic microorganisms.
What are the two functions of complement as it relates to bacteriocide?
1. Can result in the direct lysis of cells
2. Produces an acute inflammatory response by working with phagocytic cells.
1. Where would the "a" part of compliment be found in an acute infection?
2. Where would the "b" part of compliment be found in an acute infection?
1. as chemokines in the system - the a portion is an ALARM that helps to trigger the inflammatory response.
2. "b" would be found bound to bacteria.
Which pathway of compliment is used most often in an acute infection?
The alternative pathway
What are 4 microbial responses to compliment that make them resistant?
1. Extracellular proteases
2. Capsule
3. Extended lipopolysaccharides
4. Shortened lipopolysaccharides
* Without LPS compliment doesn't work. LPS can be too short or too long and it will not function.
1. What is another name for polymorphonuclear cells (PMN's)
2. Function
1. Neutrophils
2. 1st line of defense agains microbes. They move into tissues via diapedesis in response to compliment components and cytokines.
What is the function of macrophages in infection?
They function as antigen presenting cells (APCs) in cell-mediated immunity.
They respond more slowly than neutrophils.
What are some microbial responses to phagocytosis?
1. Kill the phagocytes
2. Use capsules so you don't get phagocytosed
3. Escape from the phagosome
4. Block fusion with lysosomes
5. Live in phagolysosome
What are two advantages of attachment (adhesion)
enhanced toxicity
Increased resistance to antimicrobial agents
What is the role of adherence in disease
1. Adherence is essential for initiation of disease
2. Adherence allows tissue tropism (specificity)
3. Adherence is the first step in cellular or tissue invasion to gain access to deep tissues
What are three ways to block adherence?
1. Receptor analogs
2. anti-receptor antibodies
3. lectins
What do adhesins target in order for them to work?
ECM proteins and cell adhesion proteins. (glycoprotiens and glycolipids)
Give an example of a bridge molecule that would be used in bacterial binding to the host cell.
What are the two types of pili used in adhesion?
1. Type IV bundle (forming)pili
2. Curli
Besides pili, what other structure do bacteria use in adhesion?
Once adhesion has occured, what are the advantages of a bacteria moving into deeper tissues? (3)
1. escape host defenses
2. less competition
3. dissemination
What are the two basic routes of invasion?
1. Transcellular (through host cells)
2. Pericellular (around host cells)
What are the 3 host responses that are initiated by bacteria and result in host cell death?
1. Inflammation
2. Immune Response
3. Compliment and Coagulation Cascade
Define endotoxin. What is the most common endotoxin?
an endotoxin is intrinsic (part of) the bacteria. LPS (in Gram - bacteria) is the most common endotoxin
1. Define exotoxin.
2. What are the 4 types?
1. exotoxin is secreted by the bacteria into the environment
1. A-B toxins
2. Membrane disrupting
3. Superantigens
4. Hydrolytic enzymes
What 2 types of A-B toxins are there and what is the difference between the two?
Simple - One A and one B subunit
Complex - One A and multiple B subunits
What are the functions of the A and B subunits?
A subunit - has toxin activity
B subunit - has specificity and translocation functions
What must the A subunit have in order to function?
ADP ribosylation activity
What happens after an A-B exotoxin is endocytosed?
Acification of the vacuole helps in the translocation, which stimulates structural changes in both subunits, which facilitates entry of the A subunit
Does the A-B toxin need to be endocytosed by the host cell?
No, the A subunit can sometimes cross the cytosolic membrane so endocytosis is not necessary.
Give examples of 2 hydrolytic enzymes used by membrane disrupting cytotoxins.
1. hyaluronidases
2. proteases
3. DNAases
What is the effect of DNAases?
They reduce the viscosity in pus and aid the spread of bacteria.
How do superantigens work?
They target MHC class II molecules and T cell receptors.
Describe polyclonal T-cell activation and its results
Superantigens take part in the polyclonal activation of T cells.

This results in overstimulation of the immune system.

The immune system overproduces IL-2 and TNF-a: the end result is shock.
What is a toxoid and how is it useful?
A toxoid is a toxin molecule lacking the toxic activity but capable of stimulating an immune response. This allows exotoxins to be neutralized and used as vaccines.
Rheumatic heart disease is an autoimmune disease provoked by bacteria. What causes this and how does it happen?
Rheumatic fever is caused by Streptococcus pyogenes. S. pyogenes has lingering effects, and antibodies and T cells are stimulated by this. These antibodies and T-cells cross react with heart tissue, and this leads to an immune response directed against heart tissue.
What effects does sepsis have on:
1. HR
2. Temp
3. RR
4. WBC
1. elevated (>90 bpm)
2. very low or very high (< 36 deg. or >38 deg)
3. fast (>20 bpm)
4. very high (>12,000), very low (<4000), or lots of bands (>10%)
What 5 symptoms are associated with severe sepsis?
1. hypotension
2. lactic acidosis
3. oliguria
4. confusion
5. hepatic dysfunction
How is septic shock defined as far as symptoms go?
sepsis with hypotension despite fluid resuscitation.
Define refractory septic shock.
non-responsive septic shock that lasts for more than 1 hr.
Define: Systemic Inflammatory Response Syndrome
response to a wide variety of clinical insults that may be noninfectious in etiology. (ie. burns, pancreatitis)
What is the mortality rate of a patient in septic shock?
What are some risk factors for sepsis? (6)
1. Factors that weaken/breach host defenses
2. hospitalization, duration of hospital stay
3. operative procedures
4. indwelling catheters
5. indwelling IV devices
6. underlying chronic conditions
What are TLRs and what do they do?
TLRs - Toll Like Receptors. They bind to PAMPs and thereby trigger the inflammatory response
Where in gram (-) bacteria is the endotoxin found?
It is found in the outer leaflet.
Techoic acids are chains of repeated ______________.
what are three ways of cellular activation by endotoxin?
1. upregulation of cytokine expression by neutrophils and macrophages.
2. activation of compliment
3. upregulation of the adhesive capacity of neutrophils and endothelial cells
How does endotoxin activate compliment?
via activation of CD 14
How is LPS inactivated? (via which molecule)
1. bacterial/permeability increasing protein (BPI) is released after LPS stimulates the neutrophils.
2. BPI binds and neutralizes free LPS
1. What are the proinflammatory mediators in sepsis?
2. What are the modulating mediators in sepsis?
3. What is the anti-inflammatory mediator in sepsis?
1. TNF-a, IL-1, IL-8, IFN-gamma
2. IL-6, IL-12
3. TGF-b
Which molecules have been shown to induce sepsis in models?
TNF-a and IL-1
IL-1 is such a key mediatior in sepsis because it leads to the activation of?
1. cytokine release by immune cells
2. compliment
3. coagulation cascade
Why is administering antibiotics during septic shock questionable?
It is thought that they kill bacteria releasing more endotoxin making the sepsis worse.
what is the purpose of gene regulation?
- gives bacteria resources to change genome if needed. they can:
- make products when and where they are needed
- make products in the amounts needed
1. what is an operon
2. what is a regulon
1. single transcriptional unit (genes transcribed from a single promoter)
2. set of several operons that share a common control mechanism
what four things must an operon contain?
1. promoter
2. operator
3. gene
4. terminator
what are the two targets of prokaryotic gene regulation?
in regards to regulation: what is cis and what is trans?
cis - generally a sequence, must be located on the same DNA as the gene
trans - generally a diffusible protein or RNA molecule, need not be located on same DNA as the gene
a promoter sequence would be what type of regulation? (in relation to cis and trans)
(+) and (-) control:
which one?
when protien is bound to DNA or RNA, expression is turned OFF
(-) control: control by turning off
(+) and (-) control:
which one?
when protein is bound to DNA or RNA, expression is turned ON
(+) control: control by turning on
Where is the sigma subunit found and what role does it play in initiation of transcription?
the sigma subunit of RNA polymerase is the portion that binds to the DNA promoter sequence
termination of transcription is often dependant on a protein called _______?
give an example of rho independent termination?
RNA forms a hairpin loop, thereby stopping tanscription
give an example of rho dependent termination
rho binds to the ribosome core and kicks the ribosome off the sequence
what is the principle of transcriptional control?
to regulate the amount of mRNA produced from genes
Repressor control is also known as _______________ control.
describe the events of repressor control
a repressor protien binds to the operator and interferes with RNA polymerase - this inhibits transcription
describe the events of repressor inactivation
a cofactor binds to the repressor protien releasing it from the operator - this allows transcription
describe the events of an operator "null" mutation
the operator sequence is mutated so the repressor protien can't bind - transcription is always on
describe a "super operator" mutation in the lac operon
the operator sequence is mutated so the repressor protien binds even when lactose is present - transcription is always off
describe a repressor "null" mutation
repressor protien is mutated so it cannot bind to the operator sequence - transcription is always on
describe a "super repressor" mutation in the lac operon
mutated repressor protien can't bind to cofactor (lactose) - transcription is always off
describe trp operon repression
the repressor binds to the operator only when the cofactor (trp) is present, inhibiting transcription of genes needed to synthesize additional trp.
what happens to the trp operon when trp is absent?
transcription proceeds; new trp is synthesized
in the lac operon the genes are always ___, in the trp operon the genes are always ___.
lac operon - always off
trp operon - always on
what is the role of an activator protien?
an activator protien binds to a DNA sequence (binding site) and HELPS RNA Polymerase begin transcription
describe positive regulation in the lac operon
the activator is produced turning genes on.
what is attenuation?
a type of regulation in which the rate of translation (aa incorporation) controls the rate of transcription (mRNA)
regarding attenuation:
what happens to transcription and translation when the aa concentration is low?
transcription increases
translation slows
regarding attenuation:
what happens to transcription and translation when the aa levels are high?
transcription slows
translation increases
describe attenuation in the trp operon when trp levels are low
protien stalls
mRNA continues
describe attenuation in the trp operon when trp levels are high
protien continues
mRNA stops
which allows for more specific regulation, attenuation or (+) or (-) regulation?
attenuation allows for more regulation(like a dimmer).
((+) or (-) regulation: like an on-off switch)
what is important about the difference in sigma subunits?
different sigma subunits are promoters for different functions (for example, one sigma subunit promotes a housekeeping gene, where another promotes a heat shock protien). switching these subunits helps the prokaryote adapt to changing environmental situations
describe promoter inversion
sequence: geneA-promoter-geneB
the promoter can flip and change the direction of transcription to express the other gene
describe gene inversion
sequence: geneA-STOP-geneB
the above sequence can be flipped allowing gene B to be expressed.
what is the name of the enzyme that flips the genes?
invertase (aka. recombinase)
describe the general mechanism of inversion
- invertase "loops" DNA and brings ends together
- ends are cut and spliced to opposite end
- results in an inverted segment
give an example of gene inversion
- Salmonella flagella types (switch causes 2 infection waves)
describe (in general) gene cassettes
an expression site contains a gene that can be switched for other genes depending on the needs of the organism
where would we see gene cassettes being used?
in antigen variation - the result often is relapsing fevers due to the constant switching of the gene cassette
describe ineficcient termination
termination of a gene is controlled by an inefficient terminator upstream sequence (not by the promoter). Termination is not complete allowing a portion of the gene to be completely expressed
what is a major advantage of inefficient termination?
the cell can make protiens in a certain ratio
describe antitermination
gene transcription induced by inhibiting termination
give an example of antitermination
lambda N protien - masks terminator allowing transcription to continue.
the termination codon always begins with what letter?
what is the start codon?
what is the Shine/Delgarno sequence?
the ribosome binding site - once the ribosome binds here translation begins

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