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FSOM-Foundations
Exam 3
369
Medical
Graduate
10/23/2012

Additional Medical Flashcards

 


 

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Term
Sinusoidal vs Fenestrated
Definition
-Sinusoids: large pores that greatly increase the permeability of a membrane. No diaphragm to cover pore. Example in the liver.
-Fenestrae: small pores that allow for aqueous diffusion through a membrane. They do have a diaphragm. Example in the glomeruli.
Term
3 Overall categories of transport processes:
Definition
1) Passive transport
2) Active transport
3) Other transports including: transcellular and paracellular.
Term
Passive Transport:
Definition
1) Lipid diffusion: Many drugs are transported this way. Very important b/c cell membrane is the biggest barrier
2) Aqueous Diffusion:
a) Via structural pathway: filtration process in glomeruli
b) Via aquaporins: aquaporins only let in water. aquaglyceroporins let in water and glycerol
Term
Types of special transport processes
Definition
1) Primary Active transport: ATP-binding. Selective, cancer cells use them to pump out chemo
2) Secondary active: solute carriers. molecules hitchhike with other molecules to be transported against their gradient.
3) Facilitated diffusion: SLC transport w/no energy input, solutes flow w/their electrochemical gradients
Term
Two important primary active transporters:
Definition
-Multidrug resistance (MDR) and multidrug resistance protein (MRP1)
-important role in drug absorption, contribute to blood brain barrier
-cancer cells over express MRD and MRP1
Term
What is transcellular transport?
Definition
-moving drugs or solutes from one side of a membrane to the other side in polarized cells
-Example is glucose absorption from the GI
-Also
Term
What is transcytosis?
Definition
-Moving a vesicle from one side of the membrane to the other to release its content.
-Basically endocytosis and exocytosis
-Good for large stuff
Term
Absorption principles of drugs at physiological pH:
Definition
-acid drugs: absorption increases w/increasing pKa
-basic drugs: absorption increases w/decreasing pKa
Term
Ion trapping
Definition
-Drugs will accumulate in different compartments based on their pKa and pH difference across membranes
-Basic drugs will accumulate in acid conditions and visa versa
-Keep in mind that ionized stuff doesn't pass the membrane very well.
Term
Why are absorption and distribution important in in drug administration?
Definition
-Absorption: a drug must get into the systemic circulation and be at an adequate concentration at its receptor to have its effect. Rate of abs will determine time to max conc and peak affect.
-Distribution: all the fluids of the body are involved and all the proteins in those fluids. The influences of these fluids and proteins can affect a drug.
Term
Acronym affecting drug concentration profile:
Definition
ADME
A: absorption
D: distribution
M: metabolism
E: excretion
Term
3 Phases of oral drug administration:
Definition
1) Pharmaceutical: breaking down the dosage form and dissolving active ingredients
2) Pharmacokinetic: absorption, distribution, metabolism, extretion
3) Pharmacokinetic: drug-receptor, drug-drug interaction
Term
Three factors affecting oral absorption
Definition
-Direct interaction: physiological (gastric emptying), pH
-Inhibition of drug metab in the gut: some drugs have to he metabed in the gut and then the liver before getting in the blood
-Inhibition of transport process: grape fruit juice inhibits some transporters
Term
Role of Grape Fruit Juice
Definition
-GFJ may block the organic anion transporter polypeptides (OATP)
-GFJ can inhibit CYP3A4, a main metabolizing enzyme in the gut
-only affects low bioavailable drugs
Term
Effect of GFJ on OATP vs. CYP34A
Definition
Effect on OATP is reversible, effect on CYP34A is irreversible
Term
Disadvantages of oral drug administration
Definition
-Slow
-First pass effect
-not available if patient is unconscious
Term
Rectal administration
Definition
Advantages: 50% of blood bypasses the liver (first-pass effect), can be given if patient is unconscious
Disadvangates: absorption is erratic
Term
Definition of bioavailability:
Definition
relative amount of an administered drug dose that reaches the systemic circulation or site of action unchanged
Term
Intramuscular injection
Definition
-lipid soluble abs via simple diffusion
-lip insoluble abs via interendothelial loose junctions
-large molecules via transcytosis
Term
Types of parenteral drug routes
Definition
(Parenteral means not by mouth)
-IV, intramuscular, subcutaneous
Term
Intrathecal injection
Definition
-Into the subarachnoid space
-good for anything CNS
Term
Topical application
-2 types
Definition
-Sublingual and transdermal
-Transdermal: must be lipid soluble
Term
Pharmaceutical equivalence vs. bioequivalence
Definition
Pharm equivalence: same active ingredients, same strength, concentration, dosage form or route of admin
Bioequivalence: same rates and bioavailability of the active ingredient
Term
FDA criteria for a generic drug
Definition
1) Must be pharmaceutically equivalent
2) Must be 80-125% bioequivalent
3) Must have same effectiveness and safety profiles
Term
3 Steps of tissue distribution for a drug
Definition
-Initially depends on blood flow, more to areas of high blood flow
-Second phase to muscle, viscera, skin, and fat is much slower
-Final phase is based on drug affinity: lipid like will go into all organs and fat. Ionized will stay in the plasma and interstitial compartments
Term
Drugs binding to plasma proteins
Definition
-Albumin is the main drug binding protein, can act as a storage depot for drugs
-Bound drugs are inactive
-can be a problem in hypoalbuminemia
Term
Redistribution and storage of a drug
Definition
-Example is thiopental injected via IV to knock someone out
-Very lipid soluble, so it gets into the brain quick.
-It then redistributes as the [plasma] decreases and much of it ends up in fat. This can increase the half-life effect
Term
What did Paracelsus say?
Definition
All substances are poisons, The right dose differentiates a poison from a remedy.
Term
First law of pharmacokinetics
Definition
Amount in body=concentration*volume of distribution
Term
Clearance equation:
-essential definition
Definition
Clearance=(UxV)/P
U=conc in urine
V=urine production rate
P=conc in plasma
Must be irreversibly removed from plasma
Term
Second Law of pharmacokinetics
Definition
target (steady) concentration= (infusion rate)/(clearance rate)
Term
clearance vs. elimination rate
Definition
-clearance rate doesn't change
-elimination rate is constantly changing exponentially
Term
3 Simplifying assumptions for pharmacokinetic studies
Definition
1) 100% bioavailability
2) Instant distribution
3) Constant volume and elimination
Term
Three basic parameters of pharmacokinetics:
Definition
1) Volume of diet from Dose=Vol*Css
2) Infusion rate from I=Cl*Css
3) Half life: time to 50% of the drug left in body
Term
Elimination half life equation
Definition
C=Co*e^(-kt)
t1/2=.693/k
Term
Characteristics of the ideal therapeutic regimen
Definition
1) Maintain effective concentrations
2) Min. conc. variability - to avoid toxic and maintain therapeutic levels
3) Minimize total dose
Term
What is the pharmacodynamic lag?
Definition
-The time between drug infusion and the drug's effect.
-This discrepancy is called hysteresis
-Can be dealt with by having a biophase drug
Term
2 Routes of drug excretion:
Definition
Renal: primary route via urine, especially for low metabed drugs
Biliary: secondary route via fecal route
Term
Glomerular filtration of a drug
Definition
-Large pores allow water and drug to filter, but not RBC or proteins
Term
Barriers if filtration in the glomerulus
Definition
1) Fenestrated endothelium (60-100 nm)
2) Porous basement membrane
3) Podocytes with slits of 25-60 nm
Term
Tubular Secretion in drug excretion
Definition
-Occurs in the PCT
-Place of ionized drug excretion
-Drugs bound to proteins can be secreted if they dissociate
Term
Passive tubular reabsorption
Definition
-Occurs in the DCT
-bi-directional, but net is abs b/c of high conc in urine
-better for non-ionized and lipid drugs
Term
Drug excretion in bile
Definition
-Good for stuff that is >300 Da
-Drug filters with blood through sinusoids, drug gets absorbed and then secreted into bile ducts
-Simple diffusion into the Space of Disse
Term
Main transporter in bile excretion:
Definition
MDR3 is a flipase
-defects in the gene can lead to crystalized cholesterol
-defects lead to low phospholipids in the bile
Term
Enterohepatic cycle
Definition
-Drug gets metabolized in the liver into glucuronides
-If the glucuronide has MW>500 it ends up in bile
-It can then later get cleaved and reabsorbed in the gut
-Slow excretion of drugs
Term
Why do we have drug metabolizing enzymes?
Definition
1) to remove xenobiotics (foreign substances), metab enzymes have evolutionary advantage
2) Cometabolism: enzymes that break down drugs also breakdown naturally occurring agents.
Term
Main goals of drug metabolism
Definition
-Make the substance more polar so it can be excreted.
2 phases:
Phase I: Add an alluring functional group to make it more polar and act as a reactive center for phase II
Phase II: covalently conjugate the drug and make it even more polar
Term
What's the most common sequence of Phase I/II drug metabolism and what is involved?
-drug example
Definition
-Oxidize in PI and then glucuronidate in PII.
-CYP3A4 is the most common oxidase enzyme
-an example is midazolam
Term
How does cimetidine work?
Definition
-It was the wonder drug of the 80s
-It competitively inhibits histamine at H2 receptors
-It also inhibits a lot of CYPs
Term
Phase I rxns
Phase II rxns
Definition
Phase I: HOR: Hydrolysis, Oxidation, Reduction
Phase II: SAGGMeth: Sulfate, acetate, glucuronic acid, glutathione, methyl group
Term
Describe cytochrome P450.
Definition
-It contains heme
-It is a monooxygenase
-Crucial for oxidation in Phase I of drug metabolism
Term
How do CYPs work and what do they need?
Definition
-They integrate one O atom into the drug and one O atom is converted to water.
-A cosubstrate is required: NADPH cytochrome P450 reductase provides 2H+ and 2 electrons.
-End result is a drug with OH
Term
What is an important P450 independent oxidation?
-What part of this leads to metabolism disorders?
Definition
-Ethanol oxidation via alcohol dehydrogenase
-Chronic alcohol use leads to build up of NADH
Term
Acetaminophen
-what does it inhibit and what process makes it non-toxic?
Definition
-Inhibits cyclooxygenase
-sulfation occurs without a phase I reaction
Term
What's the most common phase II rxn?
-what is needed for the rxn and where are the enzymes?
-what class of drugs are deactivated this way?
Definition
Glucuronidation
-need glucuronyl transferase and UDP-glucuronic acid
-the enzymes are in smooth ER
-benzodiazepines and acetaminophen are deactivated this way
Term
What mechanism is extremely important for protecting against toxic metabolites?
Definition
-Glutathione via glutathione s-transferase (GST)
-They are transferred to evil toxic electrophiles
Term
How acetaminophen is metabolized:
Definition
-Can either be by glucuronidation or sulfation of phase II for non-toxic intermediates
-Metabolism by CYPs in phase I can lead to toxic intermediates
Term
What is the most common CYP polymorphism?
-what people does this involve?
-what drugs are important?
Definition
-CYP2D6
-Mutants are highest in caucasians
-duplications are highest in ethiopians and saudis
-metoprolol (beta blocker) & tricyclic antidepressants are inactivated by it, codeine/hydrocodone are converted to useful metabolites by CYP2D6.
Term
What is another important polymorphism that is not CYP2D6?
Definition
-CYP2Cs
-CYP2C19 is why some asians metabolize diazepam (valium) slowly. May also affect proton pump inhibitors (PPIs) like omeprazole.
-CYP2C9: important for caucasians, might affect clearance of warfarin
Term
How are slow acetylators affected?
Definition
-slow acetylators have less NAT, in 50% of white/black people
-have toxic effects of high isoniazid
Term
Why are CYP3A4 enzymes so common?
Definition
Shapes don't matter for them.
Term
How does ethanol use lead to acetaminophen toxicity?
Definition
-Ethanol stimulates CYP2E1 deactivation of tylenol, which leads to the toxic intermediate NAPQI
-Ethanol also decreases GSH, which cannot rescue from NAPQI
Term
Define a virus and what they need to do what they do.
Definition
-Metabolically inert obligate intracellular parasites
-They have a set of genes covered in a protein coat
-They invade and reprogram cells to produce large progeny
Term
4 properties to classify a virus
Definition
-Size
-Shape/symmetry
-Numbers/sizes of morphological units in the capsid
-presence of absence of a lipid protein envelope
Term
2 types of virus protein coats
Definition
-Icosahedral and helical
Term
Vocab: viral resistant, viral susceptibility, productive/abortive/latent infection
Definition
-resistant: no receptors for virus to bind
-susceptible: virus can enter and express/establish genome
-producitve: full viral cycle occurs and progeny are produced
-abortive: viral genes expressed, but no progeny. cell probably dies
-latent: viral genome is established and cell remains viable
Term
How genome is released for viruses with different nucleic acids
Definition
RNA is released into the cytoplasm and DNA is released into the nucleus
Term
example of ds DNA viruses
Definition
-Adenovirus/herpes virus
-early and late proteins are encoded that lead to replication
Term
example of ss +rna
Definition
-picornaviruses, poliovirus
-code for a polyprotein
-same sense as mRNA
Term
example of ss -RNA virus
Definition
-Influenza
-has to code for it's own polymerase
Term
example of retrovirus
Definition
-HIV
-has ss RNA and DNA
Term
What is the microbiome?
-What is it useful for?
Definition
-The microbes that make up our normal flora
-Outnumber cells 10:1
-Important for immunity, heart disease, obesity, and preventing infections?
Term
What's the general size of a bacteria?
Definition
1-2 μm
Term
Unique characteristic of bacterial membrane as compared to human membranes
-Unique characteristic of cell wall
Definition
-Does not contain any sterols
-Cell wall has peptidoglycan (also called murein)
Term
Structure of peptidoglycans and purpose
Definition
-Long polymers of N-acetylglucosamine (NAG) and N-actelymuramic acid (NAM)
-They are crosslinked due to penicillin binding proteins (PBP)
-Purpose: rigidity and prevention of osmotic lysis
Term
Gram positive bacteria
Definition
thicker walls, up to 20 peptidoglycan layers, also have teichoic acid (sticks out and functions as an adhesion)
Term
Gram negative bacteria
Definition
thinner walls, one layer of peptidoglycan
-also has two lipid bilayers with a periplasm in between
Term
Limitations of gram staining
Definition
-Mycobacteria (TB, leprosy) have G+ like cell wall and don't take up the dye
-Spirochetes are too small (need dark-field micro)
Term
Outer leaflet of outer membrane of G- bacteria and it's 3 parts
Definition
-Lipopolysaccharide (LPS)
1) Lipid A: most superficial layer, cause of toxic effects in humans
2) Core polysaccharide: attached to Lipid A w/7-9 sugars
3) O antigen: polysaccharide w/repeating sugars. Not all G- have it, ones that do can be targeted w/antibodies
Term
Importance of the LPS
Definition
-Extremely toxic, referred to as endotoxin
-Low concentration: causes fever, stimulates B cell and macrophages
-High Concentration: Septic shock, hypotension, circulatory collapse, death
-Acts by overstimulating cytokines
Term
General gram staining method
Definition
-Use crystal violet+iodine complexes, wash with alcohol
-Stain gram neg w/safranin
Term
Bacterial capsules: characteristics and functions
Definition
-Layers of organic polymers, highly hydrated
-Block phagocytosis
-Can be used for serotyping and making vaccines
Term
Capsular bacteria to remember
and relevant diseases
Definition
Streptococcus pneumoniae
Neisseria meningitidis
Haemophilus influenzae

-Can cause bacteremia and sepsis in patients w/out a spleen
-Meningitis
Term
Flagella
-What's it made of?
-What property do they exhibit?
Definition
-Flagella are long helical filaments made of a single protein: flagellin.
-It's connected to a flexible hook that is attached to the basal body (motor)
-They exhibit chemostaxis, moving towards an attractant through a series of runs (CCW) and tumbles (CW)
Term
3 Ways to serotype a bacteria
Definition
-H antigens on flagella
-K antigens on capsule
-O antigens on G- bacteria outer membrane
Term
Pili: structure, function, role in immunity
Definition
-Made of subunits of pilin
-Key in adhering to human tissue
-Have specificity for certain receptors
-antigenic variation to avoid detection
Term
Chromosome replication in bacteria
Definition
Begins at the oriC
-Can have multiple growing forks at one time
-need gyrase to unlink the loops
Term
Bacterial ribosome
Definition
A 70S unit made of 50S and 30S subunits
-They are a target for antibiotics
Term
What does the body try to keep away from bacteria?
-How does bacteria try to get it?
Definition
-Free iron necessary for bacteria growth
-Siderophores try to remove iron from the host
Term
Fermentation vs Respiration
Definition
Fermentation: organic compounds are e- donors, uses substrate level phosphorylation, no O2 needed, not very efficient, end product is acids and alcohol
Respiration: normal respiration stuff, e-transport chain, e-acceptor is O2 or NO3-
Term
How O2 can affect bacteria and classifications
Definition
-O2 can lead to H2O2 or superoxide anion (O2-), bacteria need either SOD or catalase to survive.
-Aerobe: needs O2, no ferm; anaerobe: killed by O2, ferm
-Faculative anaerobe: good w/O2 or ferm
-Indifferent: ferm regardless of O2
Term
Clinical ways to ID bacteria
Definition
1) Stain it
2) look at it
3) Use antibodies
4) PCR and compare
Term
What are the three different types of media for growing bacteria?
Definition
-Enrichment: encourages growth of certain organisms
-Selective: inhibit growth of certain organisms
-Differential: allows organisms to be distinguished from one another.
Term
What are obligate intracellular bacteria?
-examples
Definition
-Only grow inside of eukaryotic cells
-Rickettsia and chlamydia
-Must be grown on monolayers of cells
Term
Another name for bacterial growth and phases
Definition
-Also called planktonic growth
-Lag Phase: getting used to the new enviroment
-Exponential: rapidly dividing
-Stationary: growth slows b/c of nutrient exhaustion and accumulation of waste.
Term
Bacteriacidal vs bacteriostatic
Definition
bacteriocidal is the ability to kill bacteria
bacteriostatic prevents bacteria growth and division
Term
MIC and MBC
Definition
Minimum inhibitory concentration: least amount of antibiotic that kills
Minimum bactericidal concentration: min. amount of antibiotic that kills a predetermined portion of inoculum(99.9%)
MIC is more useful
Term
Two tests to determine bacteria susceptibility
-One test to determine strength of concentration
Definition
Dilution: bacteria grown in serial dilutions of antibiotic
Diffusion: paper disks are soaked with certain antibiotics and plates are grown
-E test tells concentration needed.
Term
3 forms of bacteria genetic exchange
Definition
-Transformation: naked dna is released and picked up
-Transduction: bacteriophages transfer dna
-Conjugation: info passed on through the sex pilus, classic example is the F-Plasmid
Term
Insertion sequence vs transposon
Definition
IS-small, moved by transposase
Transposon: larger, carry extra genes, some have IS elements at the end
Term
Special type of plasmid that transfers antibiotic resistance?
Definition
-R plasmid
Term
3 plasmids that are important for virulence:
Definition
Escherichia coli: enterotoxins
Shigella spp: type III secretion that leads to epithelial cell inv.
Clostridium tetani: tetanus toxin
Term
What's a bacteriophage? 2 types?
Definition
-A virus that attacks bacteria
1) Virulent phage: lyses bacteria due to many new virions (lytic infection)
2) Temperate phage: can have a lytic infection or a lysogenic infection. Lysogenic is where it stays with the bacteria as it grows and gets passed onto its progeny (then it is called a prophage). Can change the characteristics of the bacteria
Term
5 virulent determinants carried by a bacteriophage
Definition
-Corynebacterium diphtheriae: diptheria toxin
-Vibrio cholerae: cholera toxin
-Clostridium botulinumL botulinum toxin
-Escherichia coli: shig-like toxins
-Streptococcus pyrogenes: pyrogenic exotosins A and C
Term
What are the 3 aspects of an integron?
Definition
1) Needs a promoter
2) needs a recombination site
3) need integrase to get the gene cassette into the genome
Term
5 general targets of antibiotics
Definition
1) Cell wall
2) 50S/30S ribosome subunit
3) RNA polymerase
4) DNA replication
5) Metabolism
Term
Why can't the body eliminate HIV?
Definition
1) Latent infection
2) HIgh mutation rate
3) The fact that immune cells are attacked directly
Term
What cells does HIV affect?
Definition
-Macrophages and CD4 T-cells
Term
HIV life cycle
Definition
-Dock on cell and release RNA
-RNA is transcribed into DNA via reversetranscriptase
-DNA is integrated into host genome by integrase and camps out for however long
-Viral genes eventually become protein and is reassembled as a new virus
Term
What are some HIV accessory factors?
Definition
Tat: transcription regulator
Rev:regulates splicing
Nef:enhances viral infectivity, helps evade immune system
Vpr: allows infection of non-mitotitic cells
Term
What gene is key for HIV entry and a mutation of it can provide resistance to HIV?
Definition
CCR5 gene
Term
HAART treatment
Definition
Highly active anti-retroviral therapy
-very effective at keeping viral load down
-usually involves 2 nucleosides and a protease inhibitor
Term
What is a zoonosis?
Definition
A disease that is communicable to humans from animals
Term
What is an arbovirus and what are the 3 families?
-What's the genetic material?
Definition
-An arboviruses are "arthropod borne", ie mosquitos/ticks
-3 families: flavi(Yellow fever/west nile), toga(equine), bunya(mice)
-They are all RNA viruses
Term
SARS
Definition
Severe acute respiratory syndrome
-From civets (raccoons)
-Death rate 6%
-superinfectors
-New type of corona virus
Term
What do enteric viruses have in common
Definition
-They are naked, no lipid envelope
-They have stable capsids (so they can survive in stomach pH)
Term
Why does protein synthesis initially drop in cells infected with polio?
-How is PKR involved?
Definition
-They initially thought it was because the cell was trying to shut things down.
-PKR inhibits translation and is degraded by polio
-The virus shuts down translation, it cuts the poly-A cap and affects another protein associated with nutrient detection (the cell thinks it's starving)
Term
How does poliovirus get it's genetic info in a cell?
Definition
-When it binds it changes conformation and injects RNA into the cell
-The RNA is +sense and is a polyprotein
Term
Why would the poliovirus shut down translation?
Definition
-It uses a mechanism to translate independent of the cap so it hijacks the cell as it's own little factory.
Term
3 ways poliovirus avoids an immune response
Definition
1) Blocks translation so interferons can't be made
2) Hides the uncapped 5' rna end from the cell
3) Cleaves TATA binding protein so cell can't transcribe dan
Term
What are the major causes of human GI diseases?
Definition
-Rotovirus and Norovirus
Term
Rotovirus, unique characteristic
-how is it transmitted?
Definition
-Has dsRNA, doesn't need a polyprotein because it has 11 segments that code for it's proteins
-Brings it's own polymerase and translates dsRNA inside a capsid so that cell can't detect dsRNA
-Triple layer
-transmitted oral-fecal
Term
VP vs NSP
-example
Definition
VP=viral protein that is part of the structure of a virus
NSP=non structural protein that does stuff to prepare the virus
is. polymerase is structural in rotovirus, but not in poliovirus
Term
What causes diarrhea in rotovirus infections?
Definition
-NSP4 is released along side the virus and binds to cells triggering release of water
-Only known secreted viral toxin
Term
What is special about RSV?
Definition
It only has one serotype, yet the body can't create immunity against it.
-Stands for Respiratory Syncitial Virus
-If it's a syncitium, you know that it's fusigenic and has an envelope
Term
Parainfluenza
-typical diseases
Definition
-Similar to influenza, only has 4 serotypes so it doesn't reinfect very well
-Pneumonia, croup, bronchitis
Term
Parvovirus B19
Definition
-Fifths disease, slapped cheek
-Erythrovirus because it infects RBC precursors
-Most common cause of infectious miscarriage
Term
General characteristics of influenza virus
-types
Definition
-It's a coiled enveloped viruss (all coiled are enveloped)
-It's a - sense RNA
3 types: A,B,C. A is the most important, B is kind of important, C is irrelevant. Vaccines have A and B
Term
What's on the surface of influenza virus?
Definition
-Glycosylated proteins
-Hemagglutinin (HA)
-Neuraminidase (NA)
-17 types of H, 10 of N
-Only H1, H2, H3 affect humans
Term
How does influenza get into a cell and what are the following events?
Definition
-It binds via HA onto sialic acid on a cells surface and gets endocytosed.
-M2 is a key channel on the virus that allows protons to flow through
-This triggers HA(the loaded spring) to fuse the endosome membrane.
-This is why flu isn't enteric, pH is the trigger and the stomach would set it off.
Term
Why is influenza targeted to the respiratory tract?
Definition
-HA is cleaved by tryptase clara in the lungs and becomes an activated receptor.
Term
Influenza polymerase
Definition
Brings it's own RNA-dependent RNA Polymerase, two functions
1) Transcriptase: turns -rna-->+rna-->proteins
2) Replicase: -rna-->+rna-->-rna
Term
Influenza gene expression
Definition
-RNA is brought into the nucleus for splicing and capping
-Viral polymerase hijacks cellular polymerase in a process called cap snatching
Term
What causes seasonal flu?
Definition
Antigenic drift: point mutations in HA and NA
Term
What causes pandemic flu?
-How receptor tropism plays in
Definition
-Antigenic shift due to zoonosis
-co-infection of different serotypes can cause reassortment
-Tropism: all about sialic acid linkage. Humans have 2-6, birds have 2-3, pigs have both
Term
What is viremia?
Definition
Hepatic viruses get in the blood
Term
Hep A virus
-what kind of virus?similar to?
-another name?
-what type of genetics?
-when does it get ya?
-how is it passed?
Definition
-A picornavirus, HEV is very similar in all aspects but it's a hepevirus
-Infectious hepatitis
-naked +ssRNA, one serotype
-acute infection, no chronic carrier state
-worse if you are older
-fecal-oral
Term
Hepatitis B-What kind of virus? Another name?
-Transmitted?
-Who does it get?
-Genetics
Definition
-Hepadna virus, called serum hepatitis
-Transmitted by blood
-Worse for children, can be life long chronic disease
-dsDNA virus
Term
Unique aspect of HBV genetics
Definition
-Has a DNA genome
-Uses cellular DNA dependent RNA polymerase to make mRNA and cellular ribosome to make viral proteins
-Unique: has viral RNA dependent DNA polymerase to turn mRNA into DNA genome copy
-Reverse transcriptase does its job in the capsid
Term
What is the leading cause of cirrhosis world wide?
Definition
HBV
Term
Hepatitis D Type of virus? other name?
-Genetics
-Unique?
Definition
-A dependovirus, also called delta agent
-Requires infection by Hep B first, very serious
- -ssRNA, enveloped
-viroid/plant virus like & rna is catalytic
Term
Hepatits C
-vaccine?
-carrier state?
-type of virus?
Definition
-Used to be common in blood transfusions
-Most common blood borne infection in US
-No vaccine
-High chronic carrier state
-flavivirus
Term
What cancers are the following associated with:
HPV,EBV,HTLV,HBV/HCV, Human herpesvirus 8
Definition
HPV: cervical/genital carcinomas
EBV: Burkitt's lymphoma and nasopharyngeal carcinoma
HBV/HCV: hepatocellular carcinoma
Human herpesvirus 8: Kaposi's sarcoma, lymphoma
Term
How HPV leads to cancer:
Definition
Viral proteins induce cell proliferation:
-E6 degrades p53, also activates telomerase
-E7 binds to and inhibits RB
Term
How EBV leads to cancer
Definition
-Myc is translocated, overexpression of Myc leads to over proliferation
-Linked to Burkitt's Lymphoma and Hodgkin's Disease
Term
HHV-8 and cancer
Definition
-AIDS patients w/Kaposi's sarcoma
Term
HTLV and cancer
-Genetic route
-How does it lead to cancer
-Incubation
Definition
Human T-Cell Leukemia Virus
-RNA virus that is transcribed into DNA and inserted into the genome
-Can induce cell proliferation w/out producing virus
-Unrelated mutations can lead to T cell lymphoma
-Incubates 30 to 40 years
Term
Heb B and cancer
Definition
Hepadnavirus, reverse transcriptase is still important
Liver damage leads to immune response
-chronic infection/inflammation leads to cancer
Term
Hep C and cancer
-genetics
Definition
-Flavivirus family, rna that codes for own polymerase, single protein that is cleaved
-50% of infections are not cleared and can lead to liver cancer 20-30 years later
Term
Merkel Cell Cancer
Definition
-Rare & aggressive skin cancer
-Caused by a recently discovered virus Merkel cell polyomavirus (MCV) that is found integrated into the genome of tumor cells
Term
Example of clinical and true latency?
Definition
Clinical latency: HIV
True latency: Herpes
Term
Overall Human Herpes Virus facts
Definition
-There are 3 classes of Herpes, and there are 8 types of class I that affect humans.
-Of those 8 there are 3 subfamilies: α, β, γ
Term
Name the different herpes viruses in each subfamily
Definition
α-HSV-1, HSV-2, VZV
β-CMV, HHV-6, HHV-7
γ-EBV, KSHV
Term
HSV basics
-2 types
-transmission
-infection duration
Definition
-HSV-1 is above the waist, HSV-2 is below the waist
-transmitted via intimate contact
-infected for life
Term
Severe HSV +treatment
Definition
-Encephalitis
-Keratitis: most common cause of infectious blindness
-Both can be treated with acyclovir
-Neonatal herpes is also a problem
Term
Primary vs. secondary host
Definition
-Primary: virus infects and establishes latency, host is relatively unaffected by benign recurrence
-Secondary: virus causes fatal encephalitis
Term
Herepes structure
Definition
Membrane bound, large genome, tegument proteins, and capsid proteins
Term
Basic Herpes lifecycle
Definition
1) Virus infects mucosa epithelial cells
2) Enters nerve endings and transfers down to the soma
3) Deliver genes into genome, stays circular
4) Goes dormant, dna stays in nucleus
5) Stress or other stimulation reactivates down the same axons
6) Rebuilt in the nucleus, buds out of nucleus, goes through the golgi before exiting the cell
Term
Tegument proteins
Definition
-important in herpes virus
-surround the capsid
-proteins that help start mRNA transcription, ie VP16
-help the virus stay silent if in axon, VP16 gets left behind
-or gets things going if near the nucleus like in epithelial cells
Term
Sites of HSV latency
-what rna is expressed?
Definition
HSV-1 is in the trigeminal ganglion
HSV-2 is in the sacral ganglion
-only the LAT rna is expressed during latency
Term
VZV infectious cycle
Definition
-Enters through respiratory, goes through blood to liver, replicates then goes back into blood.
-Infects skin and causes pox, then travels through neurons to the dorsal root ganglion into a latent state
Term
CMV
-who has it? transmission?
Definition
Cytomegalovirus
-90-95% of adults have it, usually not a problem
-oral/respiratory transmission
-can infect infants
Term
Innate immunity
-characteristics
-types
Definition
-phagocytes(PMN,macrophage), mast cell, dendritic cells, NK, some proteins & anti-microbial peptides.
-Fast, general response. No memory, but passed on through evolution (ie against LPS), important for co-stimualation in adaptive immunity
Term
Adaptive Immunity
-characteristics
-types of cells
Definition
-Highly specific, delayed response, many effector responses, memory cells with long term survival.
-Includes T and B lymphocytes
Term
Primary and secondary immune responses:
Definition
-Due to memory B cells
-Secondary response is much quicker and larger than the primary response
Term
4 types of lymphocytes and their functions
Definition
1) B-Lymphocyte: make antibodies, APC, memory
2) T-Helper: activate macrophages, inflammation, activate other T-cells/B-cells
3) Cytotoxic T Lymphocyte (CTL): kill infected cells that express a microbial antigen
4) Natural Killer: kill infected cells, not antigen required
Term
Divisions of adaptive immunity:
Definition
Humoral: B cells, mediated by antibodies, good against extracellular pathogens
Cell-mediated: T-cells, mediated by cytokines, good against intracellular pathogens,
Term
4 Signs of inflammation
Definition
1) Rubor: redness
2) Calor: heat
3) Dolar: pain
4) Tumor: swelling
Term
5 steps of innate immune response
Definition
1) Resident cells recognize
2) Inflammatory response
3) Neutrophils travel through blood stream
4) Neutrophils travel through blood vessel into tissue
5) Neutrophils phagocytose and release more inflammatory
Term
How innate cells recognize pathogens?
-types of cells
-what recognizes them?
Definition
-Mast, dendritic, macrophages, NK
-Use toll-like receptors (TCRs)-molecules not on eukaryotic cells
-Recognize PAMPs (pathogen associated molecular pattern molecules) ie LPS
-Recognized by PRRs (pattern recognition receptors)
Term
Effects of inflammatory molecules:
Definition
1) Resident cells phagocytose
2) Recruit other cells via chemotaxis
3) trigger bone marrow to up production of innate cells
4) tell local blood vessels to express signals telling circulating cells where to stop.
Term
Cytokines-what is it?
-characteristics
-examples
Definition
-A small signaling molecule, many names, depends on what makes it
-Produced in response to infection, high potency, usually act locally, synergistic
-Interleukins, interferons, IL-2
Term
How does an NK know not to kill a healthy cell?
Definition
-NK co-express inhibitory and and activating receptors
-All cells express MHC so NK won't attack them
-If a virus inhibits MHC expression in a cell, then NK will kill that cell
Term
Chemokines
Definition
-Large family of small peptides
-Main function is recruiting leukocytes
-Can be highly specific for the type of cell they recruit
Term
What does IFN-γ do?
Definition
-Macrophages secrete IL-12 in response to ingested microbes
-NK pick up on the IL-12 and secrete IFN-γ
-IFN-γ tells macrophages to kill their intracellular microbes
Term
What does TNF and IL-1 do?
Definition
They upregulate adhesion molecules in endothelial cells for leukocyte recruiting
Term
Complement
Definition
-A bunch of proteins
-Many are proteolytic enzymes
-Activate innate cells, kill bacteria, make bacteria easier to phagocytize
Term
TCR vs B-Cell receptor
Definition
-TCR is always on the cell surface of T cells
-The B-Cell receptor is an antibody, it can be on the surface of the membrane or in secreted form (immunoglobin)
Term
Structure of an antibody
Definition
-2 Heavy Chains (IgH) and 2 light chains (IgL)
-Variable Region on the N-terminus varies in AA sequence
-
Term
What is responsible for the specificity of an antibody?
Definition
-IgH: within the variable region are 3 stretches of AA called the hyper variable regions or complementarity determining regions (CDR1, CDR2, CDR3). During development, the Variable, Diversity, and Joining segments are assembled randomly. The variable region is then spliced to the constant region.
-IgL: same process except there's only a V and J segment
Term
How many antibodies interact with a bacterial cell?
Definition
-Antigens have a variety of epitopes that interact with many different antibodies
Term
How many isotypes of Ab are there and how are they identified?
-2 fancy ones...
Definition
There are 5 classes
-They are identified by their heavy chain
-IgM and IgA can form polymers. IgM makes a pentemer and IgA makes a dimer
Term
Features of the TCR
Definition
-Similar to the immunoglobin antibody
-An α-chain similar to the light chain with V&J segments, and a β-chain similar to the heavy chain with V,J,&D segments
Term
Summary of the mechanisms of diversity for antibody receptors and TCRs
Definition
1) Combinatorial diversity: multiple copies of VDJ that can be combined in random orders 2) Junctional diversity: happens between the joints of VDJ. P region addition adds/deletes nucleotides causing frame shifts. N region diversification also adds nucleotides through TdT
Term
Isotype switching
Definition
-Keep the same antigen specificity, just change the effector
-Needs prior b-cell activation and t-cell help
-Only changes the constant region
Term
What is Somatic Hypermutation?
Definition
-Random mutations in the V regions of B-cells happen at a high rate to create Ab with higher Ag affinity
-Occurs in the germinal centers
-Important in the later stages of an immune response and in repeat responses.
Term
What happens to B-cells at some point eventually?
Definition
-They can become Plasma cells and secrete lots of Ab
-This happens by alternative splicing of mRNA that gets rid of the transmembrane domain.
Term
3 types of self recognition and the results for developing lymphocytes:
Definition
1) Positive selection: weak self recognition-->mature cell
2) Failure of Pos selection: can't recognize self--> dead
3) Negative selection: strong self recognition-->dead
Term
What is antigen presentation (generally)
Definition
-A TCR recognizes both the peptide being presented and the polymorphic residue on the MHC of the APC
Term
Class I MHC vs Class II
Definition
Class I: on all cells in the body except RBC, present to CD8, only one transmembrane domain, 3α and 1β, tighter peptide groove
Class II: only on certain immune cells, present to CD4, 2 transmembrane domains, 2α and 2β, looser peptide groove
Term
How MHC class I/II bind their receptors
Definition
Class I: CD8 interacts with α1,α2,α3
Class II: CD4 interacts with α1,β,β2
Term
What is the most polymorphic locus in the human genome?
Definition
-The genes encoding the MHC, also Human Leukocyte Antigens
-Class I has HLA-A, HLA-B, HLA-C
-Class II has HLA-DR, HLA-DP, HLA-DQ
-A person inherits 3 Class I and 3 Class II, and they are expressed co-dominantly
Term
What mechanisms are responsible for the variableness of the MHC?
Definition
-Polymorphism and polygeny together contribute
Term
What kind of cells have MHC class I/II?
Definition
-All cells have MHC class I, except RBC
-Most hematopoietic cells have class II (t-cell, b-cell, macrophage, dendritic cell) and thymic epithelium
-Makes sense b/c all cells can get infected and would need to be killed by CD8, whereas CD4 only need to recognize Ag from APC and activate other cells.
Term
Important aspects of peptide binding to MHC
Definition
-Many different peptides can bind to the same MHC
-MHC only binds one peptide at a time
-MHC can only bind peptides
-There is a slow off rate, so the peptide binds for a long time and allows enough time to be located by T-Cell
Term
Antigen presentation to naive t-cells vs. effector t-cells
Definition
-Naive T-cells: encounter antigen in secondary lymph organs, need antigen receptor and co-stimmulation. DC are best equipped to present to naive CD4
-Effector T-cells: encounter antigen out in the tissues, don't need co-stimmulation. DC, macrophage, b-cell, any virally affected cell can present
Term
Antigen capture in the spleen vs. lymph node
Definition
Spleen: captures Ag that enter blood
Lymph node: captures Ag that enters CT or epithelium
Term
How do DCs know where to go once capturing Ag?
Definition
-Activated DC express CCR7 a chemokine receptor that leads them to T-cell rich medulla in a lymph node
Term
Endogenous vs exogenous MHC expression
Definition
Endogenous: Class I MHC, peptide in cytosol and broken down in proteasome, gets transported into ER by TAP, then peptide gets associated with MHC and moved outside the cell
Exogenous: Class II MHC, Ag gets ingested into endosome, Ag gets broken down randomly by lysosomes, Ag associates with MHC class II and goes to the membrane
Term
What's it called when class I MHC presents exogenous Ag?
Definition
-Cross-presentation, this may be important in CD8 T-cell responses against viruses and tumor cells
Term
If MHC Class II are formed in the ER, how do they avoid mixing with MCD Class I and presenting endogenous Ag?
Definition
`-They are bound by the invariant chain (li) on the peptide groove.
-MHC class II li is moved to an endosome and degraded to CLIP
-CLIP is later removed by HLA-DM and allows class II to bind peptide
Term
What is MHC restriction?
Definition
T-cells only recognize Ag presented by self MHC
-They are trained in the thymus
Term
What is AIRE?
Definition
It is an important protein called autoimmune regulator
-Those deficient in AIRE have difficulty with negative selection
Term
Importance of the CD3 and ζ regions of a TCR
Definition
-The α and β chains form the core of the receptor, but only have a small cytoplasmic domain
-The other factors have larger cytoplasmic domains and help with the effector functions
Term
Importance of CR2 in B-cells
Definition
-Complement receptor 2 makes binding Ag more efficient (1000x more signal)
-There is also a small complement cascade
Term
Potential actions of activating B-cells
Definition
-Entry into cell cycle for clonal expansion
-Express more cytokine receptors
-Interact w/t-cells
-Start secreting IgM for humoral response
Term
T-B cell interactions in lymphoid tissue:
Definition
-T cells get activated by DC w/Ag
-B cells get activated by binding the same Ag
-B cells then migrate from the follicle to the t-zone and B/T cells further activate each other
-T cell gets MHC/coactivation, B Cell gets growth and differentiation signals, also CD40 ligand
Term
What is CD40 important for?
Definition
B-Cells: important for isotype switching, affinity maturation, secretion, and B cell memory
Term
What are Ag dependent and independent B-cells?
-Where do they reside?
Definition
-Follicular cells depend on Ag and are in the spleen/lymph nodes
-Marginal zone b cells are also in the spleen/lymph nodes but are independent of Ag
-B1 b-cells are in the peritoneal cavity and are also Ag independent.
-The Ag independent ones are good at recognizing polysaccharides and lipids
Term
6 Things Ab do
-What drives three of them?
Definition
1) neutralize microbes and toxins
2) Opsonization for phagocytes
3) Ab dependent cytotoxicity
4) Lyse microbes
5) phagocytize microbes w/complement fragments
6) inflammation
(4,5,6 are through complement activation)
Term
Isotypes of Ab and what they do:
Definition
Spell GAMED
IgG: most important, opsonization, activation of complement, cytotoxicity, neonatal immunity,
IgA: mucosal immunity, secreted in breast milk
IgM: first one made in humoral response, low affinity, BCR on naive b-cells
IgE: allergic response and parasites
IgD: or really important
Term
How can Ab neutralize pathogens?
Definition
-block microbe from binding to cells
-block infection of adjacent cell
-block binding of toxin to cell receptor
Term
What's the deal with Fc receptors?
Definition
-Ab will only bind to Fc Receptors on phagocytes if the Ab has bound Ag
-Same thing for cells that can kill specific targets
-Ab-Ag Fc allows for initiation of complement through C1q binding
-Opsonization is also mediated via FcR
-FcR also activates mast cells, basophils, and eosinophils
Term
3 Main steps of complement
Definition
1) Goal is to get C3 convertase via 3 different pathways: Classical, Lectin, Alternative
2) Cleave C3
3) Recruit inflammatory cells, opsonize pathogens, kill pathogens
Term
Main players in the complement pathway:
Definition
-The goal is to get C3 convertase to cleave C3
-C3b then plays a role in the cleavage of C5
-C5b then recruits the factors necessary to set up the MAC(membrane attack complex)
-C3a and C5a are also potent chemoattractants that recruit leukocytes
Term
What does IL-2 do?
Definition
-It's a growth factor that promotes T-cell proliferation
-CD4 cells secrete it and it acts in autocrine fashion
-CD8 cells aren't great at secreting it and need help from CD4
Term
What happens at the immune synapse?
-What is the ITAM?
Definition
-It's a synapse between the TcR/CD3 and MCH.
-the t-cell needs co-stimulation to activate
-TCR/CD3 recognizes the antigen
-CD3 has ITAM(immunotyrosine activating motiff)
-The ITAM has tyrosines that have down stream effects when phosphorylated
Term
How does ITAM get activated and what is the cascade?
Definition
-TCR has p56lck which is a tyrosine kinase
-p56lck phosphorylates ITAm-->ZAP70-->MAP kinase-->transcription factors for t-cell differentiation.
Term
What's the role of integrins in the immune synapse?
Definition
-They help promote strong APC-TCR interactions
Term
How does co-stimulation lead to t-cell differentiation?
Definition
-ie B7 binds CD28 and cytokines are released
-IL-12 leads to Th1 cells, IL-4 leads to Th2, IL-1/6 lead to Th17
Term
What does the immune synapse do for b-cells?
Definition
-CD40 stimulation tells B-cells to undergo isotype switching.
Term
Th1, Th2, Th17 functions
Definition
Th1: macrophage activation (via IFN-γ), opsonization
Th2: Histamine from mast cells, eosinophil activation
Th17: neutrophil response, anti-microbial peptides for epithelial cells
Term
What is CD62L?
Definition
-It's a ligand that keeps t-cells in the nodes. Once activated, T-cells down regulate CD62L and leave the node.
-It will then home to the area of inflammation
Term
What is a DTH?
-What is necessary to call it a DTH?
Definition
-Delayed type hypersensitivity
-Th1 cells home to a region of infection and cause swelling
-ie PPD test for Tb
-must have prior exposure to Ag
Term
How do CTL kill infected cells?
-2 ways
Definition
-Perforin mediated: perforin creates pores and granzymes are released that initiate apoptosis
-FasL-mediated: FasL on CTL interacts w/Fas on targeted cell to initiate apoptosis
Term
Immunologic tolerance definition:
-Central vs. Peripheral
Definition
-The inability to launch an Ab/T-cell response to a previously encountered antigen
-Central is for self-antigens in the lymphoid organs
-Peripheral is for self-antigens in the peripheral tissue
Term
How can B-cells escape negative selection?
Definition
-Through receptor editing
Term
What is anergy?
Definition
-Functionally inactive rather than just dead
Term
What 3 pathways lead to T-Cell inactivation in the periphery when presented with self antigen?
/3 related processes of peripheral tolerance
Definition
1) No co-stimulation
2) Negative (inhibitory) receptor
3) T-regulatory cell inhibits
-Result is anergic t-cell
-Clonal anergy, clonal deletion(via fas/apoptosis), and Reg via Tregs
Term
What's the significance of anergic t-cells and IL-2?
Definition
IL-2 is the main T cell growth factor, if there's enough it around (i.e. in an inflammatory response) it can re-activate the anergic t-cell, amounting to an autoimmune response
Term
How does the body get back to immune homeostasis after an immune response?
Definition
-When the Ag is cleared lymphocytes are triggered to apoptose.
-Inhibitory receptors are also used to shut things down.
Term
Autoimmune response vs autoimmune disease
Definition
-Autoimmune response is not that uncommon, probably going on all the time. T-cell/Ab response to self Ag
-Autoimmune disease: T-cell/Ab response to self Ag that leads to pathology (ie diabetes, MS)
Term
4 things that can encourage autoimmunity

3 things that come together for AI
Definition
-Age(later in life), sex(more in women), genetic factors(many are MHC related), infections
-Genes, environment, immune regulation
Term
Ways to promote autoimmunity:
Definition
1) Inappropriate co-stimulators: if an APC is forced to express B7 when presenting self-Ag AI can occur
2) Molecular mimicry: microbes that look like self Ag
3) Infection: epitope spreading
4) Defects in regulatory molecules
Term
Prophylactic Immune Tolerance used for:
How it works
Definition
-Good for treating AI diseases, organ transplants, & allergic diseases
-expose the person to a little bit of Ag, then a little more, etc
Term
3 ways that tumors can evade the immune system:
Definition
1) Don't produce tumor Ag
2) Mutation in MHC presenting genes
3) Produce inhibitory signals
Term
3 Ways to potentially vaccinate against tumors:
Definition
1) Use tumor Ag pulsed DC
2) Put cDNA plasmid for tumor Ag into DC
3) Put co-stiumulation stuff into a tumor cell
Term
3 forms of transplant (graft) rejection
Definition
1) Hyperacute: happens within minutes, due to pre-existing Ab, hemorrhage and thrombi
2) Acute: days to weeks, mostly CD8 cells
3) Chronic: 6-12 months, mostly CD4 cells, hallmark is graft arteriosclerosis and fibrosis of tissue
Term
Difficulties in bone marrow transplants:
Definition
-Even a slightly immuno competent person can reject it
-Donor/host must be matched at the MHC class I and II level
-The graft can reject the host
Term
How do we know that immunity can launch a response to tumors?
Definition
1) Tumors surrounded by lymphocytes have a better prognosis
2) tumor transplants are rejected by animals previously exposed to the tumor
3) immunodeficient individuals have increased risk of cancers
Term
Type I hypersensitivity
-Time frame/mediator
-Mechanism
Definition
-Happens within minutes and is IgE mediated
-Should be an IgG response, but a Th2 action causes class switching
-Fc Receptors on mast cells are activated, phosphorylating ITAMS, and resulting in histamine release, lipid mediators, and cytokines
Term
Type I hypersensitivity symptoms
Definition
-Vasodilation, smooth muscle contraction, tissue damage, inflammation, localizes swelling
Term
Type I hypersensitivity treatments
Definition
-Epi: broncho dilator, heart contraction
-Corticosteroids: suppress cytokines
-Na Cromlyn: for asthma, antagonizes IgE
-Anti-histamines: antagonists of histamine receptors
Term
Type II hypersensitivity:
-Mediator
-pathways involved
Definition
-Ag is on a specific tissue/cell type
-Mediated by IgG or IgM
-Damage from Fc/Complement: activation of cells, opsonization, interferes w/hormone signaling
Term
Type II hypersensitivity diseases:
Definition
Graves: autoimmune against thyroid
Myasthenia gravis: AI against muscle, Ab interfere at neuromuscular jxn, leads to muscle weakness
Acute Rheumatic fever: strep Ab attacks heart
Hemolytic disease of the fetus
Term
Type III hypersensitivity
-example
Definition
-A systemic response due to soluble Ab
-Similar mechanism to type II, Complement/Fc reactions
-examples include lupus, serum sickness, and post-strep glomerulonephritis
Term
Type IV Hypersensitivity
Definition
-T-Cell mediated, causes DTH
-Inflammation and tissue damage
-CD8 from viral cells, CD4 from autoimmune
-Poison ivy is an example
Term
What is a super antigen?
Definition
-Some bacterial toxins can bind directly to MHC class II and TCRs and can activate multiple t-cells at once
-They can activate 2-20% of t-cells on the first go
-Can lead to septic shock
Term
Immunodeficiency diseases caused by defects in lymphocytes:
Definition
-SCID: severe combined immunodeficiencies(defects in both T and B cells), x-linked
-DiGeorge syndrome: no thymus
Term
What is a selective B-cell maturation defect disease?
Definition
-X-linked agammaglobulinemia, due to a defect in Btk
Term
4 ways to treat congenital immunodeficiencies:
Definition
1) Enzyme replacement
2) Passive immunization: γ-globulin from healthy patients (for XLA)
3) bone marrow transplant (for SCID)
4) Gene therapy
Term
S. aureus
-Full name, metab type, G?
-How to ID
-Treatment
Definition
-Staphylococcus aureus; facultative anaerobe, G+
-Most virulent, causes staph toxic shock syndrome
-catalase/coagulase positive
-historically penicillin, can't really use methicillin either
-Vancomycin might be the only option
Term
Toxins of S. aureus
2 SA stop in at the spa to exfoliate for proper valentines love pore cleaning. Alf is there and clots up from too much protein on his A.
Definition
-TSST-1: Toxic shock syndrome toxin, superantigen (SA)
-Staph enterotoxins A-E, G-I: food poisoning, SA in GI, resistant to boiling
-Exfoliatin: scalding skin syndrome
-Alpha-toxin: a hemolysin, forms pores
-Panton-Valentine leukocidin(PVL): toxin associated w/MRSA
-Coagulase: forms clots
-Protein A: blocks IgG by binding to Fc
Term
Clinical problems from S. Aureus
Definition
1) Faruncle (boil) and Carbuncle (group of boils)
2) Joint/bone infections - most common cause is S. Aureus
3) TSS: high fever, vomiting, diarrehea, sore throat, rash, shock
4) Staph food poisoning: 2-5 hr after digesting food
5) scalded skin syndrome
6) Cellulitis:
7) Hospital acquired infections (Nosocomial infections)
8) endocarditis
Term
MRSA
-caused by a variant in what?
-what encodes it?
Definition
-Methicillin resistant staphylococcus aureus
>20% of hospital acquired
-PBP2: penicillin binding protein, different protein that penicillin can't bind
-encoded by the mecA gene
Term
Streptococci G?, catalase?
-3 types
Definition
-Gram+, catalase negative
-α-hemolytic: partial hemolysis, green tint, viridans strep & S. pneumoniae
-β-hemolytic: complete hemolysis, S. Pyogenes, S. agalactiae
-γ-hemolytic: no hemolysis, S. Bovis, many enterococci
Term
α-hemolytic bacteria
Definition
Viridans Streptococci: many species, normally in the mouth, dental caries, endocarditis
Streptococcus pneumoniae: respiratory tract infections
Term
Streptococcus pyogenes- general stuff
-Determinants of pathogenicity (5)
Definition
-Extracellular, purulent (lots of pus), GAS
-Streptolysin: O & S, form pores in cell membranes
-M-Protein: block phagocytosis
-Strep pyrogenic exotoxins (SPEs): scarlet fever rash, strep TSS, SuperAg
-Streptokinase: lyses clots
-C5a peptidase: prevents phagocyte recruitment
Term
Diseases related to S. Pyogenes (8)
Definition
-Strep pharyngitis-->ARF
-Scarlet fever (sandpaper rash)
-Strep TSS (usually no rash, no tampon)
-Impetigo: yellow crust on children
-Cellulitis, necrotizing fasciitis: infection in the muscles, life threatening
Term
JONES criteria
Definition
-Used to diagnose Acute Rheumatic Fever
-J: polyarthritis, O: carditis, N:nodules sub-q, E: erythema marginatum, S: sydenham chorea
-Must have two major, or 1 major and 2 minor
-Minor include: fever, joint pain, prolonged PR on EKG
Term
S. Agalactiae
Definition
-Important for pregnant women
-Lives in the vaginal tract and can be passed on to newborns
-Called group B strep (GBS)
Term
Weird thing about streptococcus Bovis
Definition
-They really aren't a big deal and they aren't enterococci
-But if you see it you have to worry about GI cancers
Term
Enterococci
-clinical significance
-Bacteria family
Definition
-Not really a big deal, but they do have Vancomycin resistance, so they can be a problem
-Formerly Group D strep, not hemolytic
Term
Bacillus-general info
-2 important ones
Definition
-Gram +, aerobic
-Anthracis: causes anthrax; Cereus: causes food poisoning
Term
Bacillus anthracis-growth
-Virulent factors
-3 forms of anthrax
-Prevention
Definition
-Grows in chains, forms spores, usually in herbivores
-A-B toxin: B is binding (forms pore), A is active, does the damage
-Cutaneous, Inhalation (this one'll kill ya), GI
-Vaccine available
Term
Listeria-important species
-General characteristics
-How it invades cells
-How it avoids vacuoles
-How it gets around
Definition
-Only one important one: Listeria Monocytogenes
-G+, Facultative intracellular, does well at refrigerative temps
-Internalin is an adhesion
-Uses Listeriolysin-O to avoid vacuoles
-Uses ActA to polymerize host actin and move around (comet tails)
Term
Diseases caused by listeria
Definition
-Meningitis
-Neonatal disease
Term
Corynebacteria, general info
-What does it cause?
-Determinants of pathogenicity
Definition
-Aerobic, G+ bacilli
-Very potent toxin, causes diphtheria
-DT(diptheria tooxin): heat labile, A-B toxin, inhibits protein synthesis(specifically in pharyngeal epithelium)
Term
What is a toxoid?
Definition
-A chemically treated toxin that loses it's toxicity, but retains immunogenicity and can be used as a vaccine.
Term
Clostridia
-general characteristics
-4 to know
Definition
-G+, anaerobic robs, spore forming
-Make some of the most potent toxins
-4 to be aware of: C. tetani, C. botulinum, C. perfringens, C. difficile
Term
C. tetani-spores?
-Determinants of pathogenicity
-How to ID
Definition
-Spores can remain viable for many years
-Tetanus toxin: A-B toxin, blocks release of pre-synaptic inhibitory NTs
-Lockjaw is first symptom
-Spores look like tennis rackets, most wounds have it, but most show toxin present to diagnose infection
Term
C. Botulinum-G, metab, shape, spores?
-Toxin
-Toxin effect
Definition
-G+, anaerobic, rod shaped, spore producing
-Make botulinum toxin, similar to tetanus, AB toxin
-blocks acetylcholine release-->flaccid muscles
Term
3 types of botulism
Definition
1) Food-borne: symmetric descending paralysis, death
2) Wound botulism: similar Sx as food-borne, no GI Sx, common in heroin injection
3) Infant botulism: infants are susceptible b/c they don't have normal flora yet
Term
C. Perfringens
C. Difficile
Definition
Clostridium Perfringens: food poisoning, gas gangrene
Clostridium Difficile: diarrhea w/antibiotic use
Term
Actinomycetes
-two medically important ones
Definition
-True bacteria, resemble fungi w/branching
-Nocardia and Actinomyces
Term
Nocardia spp-3 medically important types
-G?, shape, metab
-Pathogenicity
Definition
-N. Farcinica, N. asteroides, N. brasilliensis
-G+, bacilli, aerobic
-block phagocytosis, need cell-mediated response
Term
Clinical importance of Nocardia
Definition
-Seen in immunocompromised patients
-Pulmonary nocardiosis: subacute pneumonia w/nodules
-Transcutaneous inoculation: nasty foot
Term
Actinomyces Israelii, G?, Shape, spores?, metab
Definition
-G+ bacilli, no spores, anaerobic
-part of normal flora
-infected foci spread ignoring planes
-really only a problem with poor hygiene
Term
Enterobacteriaceae, G?, metab?
-Main types
-3 non floral
Definition
Large group of G- facultative anaerobes.
-Includes Escherichia coli, and much of the normal flora
non-floral: Salmonella, shigella, and yersinia
Term
E coli
-Most common cause of what?
-determinants of pathogenicity
Definition
-Part of the normal flora
-most common cause of traveler's diarrhea
-alpha-hemolysin, pili for bladder
Term
ETEC-full name
-cause of what?
-Pathogenicity toxins
-How they lead to diarrhea
Definition
-Enterotoxin E Coli
-Most common cause of travelers diarrhea
-Heat labile toxin (LT): AB toxin, stimulates adenylate cyclase
-Heat stable toxin (ST): stimulates guanylate cyclase
-Both AMP and GMP regulate ion channels
Term
EPEC-full name
-Unique pili
-Special secretion system
Definition
-Enteropathogenic E. Coli
-Pili is a bundle (BFP)
-Exhibits type III secretion system
Term
Type III secretion system
Definition
-Acts like a needle/syringe for putting toxins into cells
-Used in EPEC, P. Aeruginosa, Salmonella, shigella, bordetella, yersinia, and chlamydia.
-Secretes the Tir receptor, a receptor for intimin on EPEC for tighter binding.
Term
EHEC-full name
-toxin
-Disease, and treatment not to use
Definition
Enterohemorrhagic E Coli
-Also has type III secretion system
-Shiga-like toxin
-Can lead to HUS (hemolytic uremic syndrome)
-Antibiotics increases HUS
Term
Shigella spp.
Definition
-Cause dysentery (bloody/mucous diarrhea)
Term
Salmonella enterica-includes what?
-killed by what?
-metab/in or out of cells?
-secretion system causes what?
-unique from shigella how?
Definition
-Includes typhi (typhoid fever)
-Killed by acid in stomach, need large inoculum
-facultative intracellular
-type III secretion causes ruffling that takes in bacteria
-Unique from shigella in that it can get in the blood stream
Term
Yersinia spp.-diseases caused
-determinants of pathogenicity
Definition
-some cause diarrhea, Y. pestis causes plague
-Y pestis has: hms to be in the flea foregut, blocks flea blood meal, meal gets regurgitated into host, yersinia travels to and proliferates in lymph nodes
-forms bubo
Term
Pseudonomads- metab, G?, shape?
-most medically important:
-important skill of P. aeruginosa
-Diseases caused
Definition
-Aerobic G- rods
-P. aeruginosa: grow in moist environments
-Exhibit Quorum sensing: bacteria can sense their neighbors
-Opportunistic pathogen, causes hot tub folliculitis
Term
Legionella-metab, G?, shape?
-most medically important (causes what?, live where?)
-cool way it gets in cells, how it avoids destruction
-causes severe form of what?
Definition
-aerobic, G-, rods
-L. pneumophila: causes Legionairre's disease, live in water
-Has the cool coiling phagocytosis, blocks lysosomes, recruits ribosomes, uses type IV secretion
-causes severe form of pneumonia
Term
Vibrios, associated with?, G?, shape
-major species
Definition
-associated with sea water, G-, rod shaped
-Vibrio cholerae: causes cholera
-Vibrio vulnificus: sea water (if cut by a shell you become vulnerable)
Term
Helicobacter, G?, Shape?
-responsible for what human infections
-important species and pathogenicity factors
Definition
-G-, slender spiral
-responsible for most human infections
-Helicobactor pylori: urease that gets ammonia from urea to create an alkaline environment,
Term
Haemophilus-G?, shape?
-important species
Definition
-G-, coccobacilli
-H. Influenzae-->causes lots of respiratory related infections
Term
Bordetella-species that causes what?
-G?, shape?metab?
-Determinants of pathogenicity:
Definition
-Bordatella pertussis causes whooping cough
-tiny G- coccobacilli, strict anaerobe
-Many D of P: many adhesion factors for resp. epithelium, pertussis toxin (AB Toxin)
Term
Brucella

Francisella
Definition
Small, aerobic, gram- coccobacillus
-mostly affects animals
-can cause long term fever, chills, malaise
Francisella tularensis are small facultative, G+, coccobacilli, that are similar to Brucella, classically from rabbits
-site of inoculation gets ulcerated
Term
Pasteurella
Definition
Small coccobacilli, G-
-usually from dog/cat bites
Term
Neisseria, G?, Shape?
-Two to remember
Definition
G+, diplococci
-N. Meningitidis: causes meningitis
-N. gonorrhoeae: STI
Term
General info about Gram Negative Anaerobes
Definition
-A lot of them are part of the normal flora
-They are opportunistic pathogens
Term
Rickettsiaceae-type,G?, shape?
-4 important species
Definition
-Obligate intracellular, G- coccobacilli
-Transmitted by insects
-Ricketsia rickettsii: RMSF from ticks
-Coxiella burnetii: cause of Q fever (no rash), from sheep
-Ehrilichia chaffeenses/Anaplasma phagocytophilum: both from ticks
Term
Bartonella spp
-Two medically important types
Definition
-Not obligate, formerly under Rickettsiaceae.
-B. henselae and B. quintana: both cause angiomatosis
Term
Chlamydia
Definition
-Obligate intracellular organism
-Complicated life cycle: elementary body (EB, EC and metabolically inactive), reticulate body (RB).
-C. trachomatis is the STI
Term
Mycoplasma
Definition
Not obligate intracellular, but similar to chlamydia
-has plasma membranes with sterols obtained from eukaryotes, no cell walls,
-Cling to bronchial epithelium, common cause of CA pneumonia
Term
Borrelia
Definition
Spirochetes that cause Lyme disease
Term
Treponema
Definition
Spirochete that causes syphilis
Term
Leptospira
Definition
Spirochetes that mostly affects animals, transmitted to humans by animal urine
-Has a Primary phase that clears up and then a secondary phase that shows up a few days later
Term
General info about mycobacteria
Definition
-Gram +, but don't stain, cell wall is mostly lipids
-Grow slowly, cause chronic disease
Term
M. Tuberculosis
-important to split into 3 parts
Definition
-Facultative intracellular, strict aerobe
-Pretty much only infects humans
-Most common cause of infectious death
-Historically called Consumption
-3 parts: exposure, infection, disease
Term
How Tb survives to be passed on
Definition
-Can live in airborne droplets for hours
-Lives in a phagosome and blocks fusion with a lysosome
-Eventually spreads to lymph nodes and the rest of the body (starting the infection phase).
Term
Tb disease phase
Definition
-Primary infection gets cleared by most adults
-In 10% of patients reactivation occurs and starts the disease phase
Term
Two types of Tb/symptoms of classic Tb
Definition
Symptoms: fever, weight-loss, night sweats
1) Pulmonary: bloody cough, cavities in lung
2) Extrapulmonary: can occur in lots of other organs, mostly in HIV patients
Term
Treatment of Tb
Definition
-Latent phase: treat with isoniazid for 9 months
-Disease phase: treated with multiple drugs (isoniazid and rifampin)
-mutiple-drug-resistant (MDR) Tb is out there...
Term
Mycobacterium leprae
Definition
-Causes leprosy, very slow replication, obligate intracellular pathogen
-2 forms:
Tb leprosy: intense cell-mediated response, few bacteria, Th1 response.
Lepromatous leprosy: no cellular immune response, lots of bacteria, Th2 response
Term
3 Classes of parasites that infect humans:
Definition
1) Protozoa (single-celled eukaryotes)-multiply in hosts
2) Helminths (multicellular worms)-multiply outside hosts
3) Arthropods (arachnids/insects)
Term
4 Protozoa that infect GI
Definition
Amoebas, Ciliates, Flagellates, Sporozoans
Term
Amoeba life cycle
Definition
1) Cyst passed in stool
2) Ingested
3) Excystation (escape from cyst)
4) Trophozoite (grow, in the colon)
5) Encysts (be enclosed in a cyst, colon)
Rinse and repeat.
Term
Amebiasis
Definition
-cysts are infective
-rare finding is megacolon
-diagnosed by looking for cysts in stool
-fecal-oral transmission
Term
Flagellates
Definition
-Giardiasis (Beaver Fever)
-Similar life cycle to amoeba
-cysts survive in water
-bloating, gas, chronic diarrhea
-looks back at you
-fecal-oral transmission
Term
Primary Amoebic Meningoencephalitis
Definition
-Caused by amoeba found in soil and fresh water
-Happens during summer months
-Leads to death in one week
-Motile amoeba found in CSF
-passed on via contaminated water
Term
African Sleeping Sickness
-What carries it?
-How does the pathogen avoid the immune system?
Definition
-Caused by the flagellate trypanosoma bucei
-Transmitted from the tsetse fly (inject anti-coagulant, vasodilator, and analgesic
-Really high parasite level in blood
-Avoids immune system by changing it's coat via antigenic variation
Term
What are the 3 stages of Whooping Cough?
Definition
1) Incubation (2 weeks)
2) Cararrhal stage: mild coughing; very infectious
3) Paroxysmal stage: explosive cough
Term
What's the main difference between fungal and mammalian eukaryotic cells?
Definition
-Mammalian: cholesterol
-Fungi: ergosterol, cell wall with chitin and glycans
Term
What are the key fungal virulent factors?
Definition
1) Thermotolerance-only a few fungi can survive in warm temperatures
2) Exoenzymes- liberate nutrients, break through barriers, destroy Ab
3) Cell wall components-resist macrophages, adhesion to epithelia
Term
Scenarios that promote fungal disease (6)
Definition
-Immunosuppressed
-Antibiotic use
-warm/wet environment
-malnourished
-old/young
-catheters/hardware
Term
General targets of anti-fungal drugs
Definition
-membrane disruption, ergosterol synthesis, nucleic acid synthesis, glucan synthesis, microtubules
Term
Common anti-fungal drugs:
Definition
1) Amphotericin B (membrane disruption at ergosterol)
2) Azoles (inhibits sterol synthesis, toxic to humans)
3) 5-FC (nucleic acid analogue inhibiting synthesis/repair)
4) Capsofungin (impair cell wall through 1,3 beta-glucan)
5) Griseofulvin (microtubule synthesis inhibitor concentrating in skin/nails, good at low dose)
Term
5 Categories of Mycoses
Definition
1) Superficial
2) Cutaneous
3) Sub-cutaneous
4) Systemic
5) Opportunistic
Term
Superficial Mycoses:
Definition
-Pityriasis versicolor: very common, skin pigmentation is affected
Term
Cutaneous Mycoses
Definition
-Trichophyton, microsporum, epidermophyton floccosum
-All the Tinea (ringworm), tinea pedis is athletes foot.
Term
Subcutaneous Mycoses
Definition
Sporotrichosis: rose gardener disease
-moves along lymphatics
Term
Systemic Mycoses-where found?
4 main diseases
Definition
-Nitrogen rich soil and bird droppings
-Coccidioidomycosis: beavers, pulmonary infections
-Histoplasmosis: Tb-like infection, OH/MS river valleys
-Blastomycosis: pulmonary, fungus ball, skin lesions common
-Paracoccidioidomycosis: pulmonary, mostly in males
Term
Opportunistic Mycoses
Definition
-Candidiasis: thrush, Germ Tube Test
-Cryptococcosis: from pigeon feces, pulmonary, classic HIV disease from back in the da
-Aspergillosis: asthma-like symptoms, can cause hypersensitivity rxns
-Mucormycosis: poorly controlled diabetes is a risk factor
-Pneumocystosis: PCP, might be a protozoa
Term
What causes malaria?
-4 types
Definition
-A protozoa: Plasmodium spp
-P. falciparum: worst one
-P. vivax-latent
-P. ovale-latent
-P. malariae-chronic
Term
Life cycle of malaria
Definition
-Injected via bloodmeal
-Sporozites infect Kupffer cells and mature to merozoites
-Merozoites infect and proliferate in RBCs
Term
Symptoms of malaria
Definition
-Hypoglycemia, lactic acidosis, hyponatremia
-Massive hemolysis-Blackwater fecer (P. falciparum only)
-CNS injury (P. falciparum only as well)
-Splenomegaly, liver dysfunction
-Lots of organ issues b/c abnormal RBCs cause clotting
Term
Take home for malaria treatments:
Definition
Use a combination
most end in "quine"
Term
Toxoplasmosis
-2 stages
Definition
-From cat feces
-Vacuole form is fragile, cyst form is tough and invisible to the immune system
-Lots of people are infected (50% WW, 25% US), causes behavior changes
-Also a teratogen
Term
Chagas disease-caused by what?
-cycle
-symptoms
Definition
-Trypanosoma a protozoa
-Blood meal, abdomen engorgement, poop on the skin
-symptoms: fever, anorexia, periorbital edema, cardiomyopathy, megacolon
Term
Leishmaniasis-vector?infects?
-symptoms
Definition
-Sandfies are the vector, only infects macrophages
-visceral: parasites in macrophages of reticuloendothelial system
-cutaneous: sore w/outer indurated edges and necrotic center
-crazy face from immune consequences
Term
Trichomoniasis-protozoa name
-disease properties
Definition
-Caused by trichomonas vaginalis
-Venereal
-Causes: vaginitis, prostatitis, urethritis
Term
3 Types of helminths
Definition
1) Platyhelminths - flatworms trematodes(flukes) and cestodes (tapeworms)
2) Nematodes - roundworms
3) Annelids - segmented roundworms (leeches)
Term
General info about trematodes
Definition
-Also called flukes
-2 suckers, leaf shaped
-hermaphrodites
-causes schistosomiasis
Term
Schistosomiasis
Definition
-Caused by flukes
-Absorb Ab, main problem is from eggs
-Acute properties: cercarial dermatitis; Katayama fever from egg Ag, significant mortality
-Chronic properties: granulomas, Th1 immune response, GI/urinary Sx, pulmonary fibrosis
Term
Mechanisms of drug resistance for bacteria
Definition
1) Decreased uptake
2) Inactivation
3) Decreased affinity for drug target
4) Metabolite that competes with drug
5) Decreased intracellular activation
6) Increased expression of target?
Term
Diphyllobothriasis-category of parasite
Definition
-Cestode-fish tapeworm infection
-largest human tapeworm, 25 meters
Term
1) Taeniasis saginata

2) Taeniasis solium
Definition
1) Beef tapeworm, can't penetrate gut wall
2) Pork tapeworm, can penetrate gut wall and get into other organs. Infection of eggs leads to cysticercosis, can cause cysts in the brain
Term
Intestinal roundworms (4)
Definition
-Pinworm: female goes out at night, most common helminth, scotch tape test.
-Whipworm: rectal prolapse
-Large Roundworm: unique infection b/c larvae must mature in the lung, can be knocked narcotics
-Hookworm: multiple forms of larvae, use up calories, digest blood
Term
Filariasis
Definition
Filarial worms cause elephantiasis, calabar swelling, and river blindness
-They are nematodes in the blood, lymph and SubQ
Term
1) Bancroftian Filariasis
2) Malayan Filariasis
Definition
1) In blood from mosquito, block up lymph
2) In blood, obstruction more in limbs
-Both cause elephantiasis
Term
Loa Loa
Definition
-Adult worms move through subQ tissue
-Can be in the sclera of the eye
-causes Calabar swellings, might not be too noticeable
Term
River Blindness
Definition
-It's not the worms that cause the disease, it's the bacteria on the worms
-The bacteria have LPS and cause inflammation
Term
Trichinosis
Definition
-Caused by trichinella
-Form cysts on meat
Term
Larva migrans
-2 types
Definition
Visceral: From cats and dogs, transmitted orally, larvae become encapsulated in organs
Cutaneous: cat/dog hookworm, from direct skin penetration, can see beneath skin
Term
Hot to calculate k for drug half life
Definition
k=Clearance/Volume Dist
k=Cl/Vd
Term
B7 co-stimulation
Definition
-B7 is on B cells, binds CD28 on T-cell and activates t-cell.
-Once activated T-cell expresses CTLA-7 and when CTLA-7 interacts with B7 the T Cell is shut down, part of turning off the immune response
Term
Acute vs. Chronic inflammation
Definition
-Acute: occurs in minutes, lasts days, PMNs
-Chronic: Monocytes, lasts weeks to years
Term
What is exudate?
Definition
-The endothelium becomes very permeable and protein and fluid accumulate in the ECF
Term
Where are the preformed vasoactive materials stored?
-What stimulates release?
Definition
-Histamines are the material
-Stored in mast cells, basophils, and platelets
-C3a, C5a, and IgE stimulate release from mast/basophils
-Lots of stuff for platelets: ADP, PAF, collagen, thrombin, IgG
Term
What does NO do?
Where is it made?
Definition
-It's a vasodilator produced in macrophages
-It can also kill microbes
Term
What are the main transcription factors that are activated with TLR activity and what do they lead to?
Definition
-AP-1 and NFkB lead to more inflammatory cytokines
Term
What are P-Bodies?
Definition
-Molecules that rearrange on endothelial cells to slow down circulating PMNs.
-They rearrange in response to histamine and thrombin
Term
What leukocytes/endothelium do in inflammation
Definition
1) Roll, Sialyl-Lewis X receptors on PMNs interact with E/P-selectin on endo
2) Adhesion, Integrins on PMNs interact w/ICAM/VCAM on endo
3) Transmigration via PECAM
Term
What is the respiratory burst?
-And how does it facilitate killing bacteria?
Definition
-When PMNs phagocytose bacteria they increase O2 consumption
-They recruit MPO for making ROS
- O2- and H2O2 both kill stuff and facilitate other rxns
Term
What are two main rxns in PMNs for killing bacteria?
Definition
-Myeloperoxidase (a halide radical) is the main mechanism for killing extracellular bacteria inside a neutrophil phagosome
-The Fenton rxn, iron from the bacteria are used to reduce more H2O2
Term
How do macrophages kill bacteria?
Definition
With NO radicals
Term
What does CCL-2 do?
Definition
It recruits monocytes in chronic inflammation
Term
Big effect on vasculature from chronic inflammation
Definition
-Atherosclerosis
Term
Subsets of macrophages:
Definition
M1: Kill and clear pathogens, secrete more chemokines for inflammation
M2: anti-inflammatory and wound repair/fibrosis
Term
What makes up a granuloma?
Definition
-Monocytes/macrophages
-MCP1 recruits them and creates a ring
Term
Repair following inflammation
-mediated by what?
Definition
-Replacing dead cells with healthy cells
-May result in deposition of collagen and scarring if CT scaffolding is lost
-Mediated by macrophages that secrete VEGF and TGF-ß (stimulates fibroblasts)
Term
Growth factors to know
Definition
-EGF: epidermal GF, mitogenic for epithelial cells, hepatocytes, and fibroblasts
-HGF: hepatocyte GF, mitogenic for epithelial cells
-PDGF: platelet derived GF, for smooth muscle, fibroblasts, and endothelial cells
-FGF: fibroblast GF, same as PDGF
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