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week 5 Flashcards

1
Q

clinical manifestations of an allergic reaction:

A

anaphylaxis
urticaria
angioedema
dermatitis
respiratory allergy

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2
Q

treatment considerations for an allergic reaction:

A

preparation for anaphylaxis (epi pen)
food diaries
trial avoidance of potential triggers
antihistamines
nasal steroids
allergy shots (immunotherapy)

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2
Q

treatment considerations for an allergic reaction:

A

preparation for anaphylaxis (epi pen)
food diaries
trial avoidance of potential triggers
antihistamines
nasal steroids
allergy shots (immunotherapy)

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3
Q

describe the appearance of hives:

A

edematous wheals that blanch with pressure

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4
Q

key treatment for hives:

A

remove offending agent

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5
Q

types of allergy testing:

A

RAST serum testing (IgE antibodies)
skin allergy testing

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6
Q

what is angioedema?

A

a diffuse, non-pitting tense swelling of the dermis and the subcutaneous tissue

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7
Q

what medications are angioedema reactions associated with?

A

ACE-inhibitors and NSAIDs

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8
Q

what is Celiac disease?

A

a food insensitivity

an immune reaction to gluten (protein in wheat, barley, and rye)
sx: diarrhea, bloating, gas, fatigue
Tx: remove gluten from diet

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9
Q

what is drug provocation testing?

A

-administer a medication to a patient in a graduated manner under close observation
-appropriate for patients who are UNLIKELY to be allergic (e.g. “penicillin allergies”)

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10
Q

features common among all signal transduction/intracellular signaling pathways:

A
  1. extracellular stimulus (i.e hormone, neurotransmitter, growth factor)
  2. receptor on cell membrane
  3. intracellular cell signaling pathway
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11
Q

what are the types of intercellular signals?

A

autocrine: itself (e.g. T lymphocytes with cytokines)
paracrine: nearby cells (e.g. neuromuscular junction)
endocrine: hormones released into blood stream and stimulates distant locations (e.g. insulin)
juxtacrine: signal binds to neighboring cell receptor, two cells need to be connected (e.g. notch receptor)

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12
Q

basic features of the receptor ligand mediated interactions and signal transduction:

A
  1. specificity
  2. amplification
  3. modularity
  4. sensitization and termination
  5. integration
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13
Q

describe ligand-receptor specificity:

A

binding of ligand to receptor is mediated by NON-COVALENT interactions

binding brings about a conformational change that alters the activity of the receptor

typically high affinity/specific interaction but the same ligand may bind other isoforms of the receptor or an entirely different receptor with different affinities

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14
Q

how does amplification occur?

A

enzyme/kinase reactions

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15
Q

what are enzyme/kinase cascades?

A
  1. enzymes arranged in a hierarchy in which one enzyme activates many molecules of a second enzyme; amplifications of several orders of magnitude within seconds
  2. 2nd messengers
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16
Q

what is a second messenger?

A

intracellular molecule generated in response to extracellular stimuli (1st messenger) that exerts an effect on signaling proteins/enzymes

examples: cAMP, cGMP, phospholipids, calcium

present at low concentration in unstimulated cells, rapidly increase during ligand binding (this increase is TRANSIENT)

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17
Q

describe modularity in terms of ligand binding?

A

protein receptors = multiple domains that recognize specific binding partners (via domains and motifs)

ensures specific interactions

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17
Q

describe modularity in terms of ligand binding?

A

protein receptors = multiple domains that recognize specific binding partners (via domains and motifs)

ensures specific interactions

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18
Q

which amino acids do protein kinases phosphorylate?

A

serine, threonine, and tyrosine

-OH groups
-binding is determined by the AA sequences (domains) surrounding these amino acids

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19
Q

what is the role of phosphatase?

A

removes phosphate from phosphorylated serine, threonine, or tyrosine

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20
Q

results of phosphorylation:

A

-alters interactions with other proteins (e.g. act as docking sites)
-oxygen can H bond with the phosphate, these negative charges can repel Asp or Glu, affecting enzyme conformation and activity
-regulation (phosphatase, reverse)

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20
Q

results of phosphorylation:

A

-alters interactions with other proteins (e.g. act as docking sites)
-oxygen can H bond with the phosphate, these negative charges can repel Asp or Glu, affecting enzyme conformation and activity
-regulation (phosphatase, reverse)

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21
Q

what is receptor desenstization?

A

receptor signaling is terminated by interacting proteins when the signal is present continuously - uncoupled from the signaling cascade via a protein

receptor down regulated

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22
what is the fate of a desensitized receptor?
receptor internalization/endosome --> lysosome
23
what is enzyme integration/ "cross talk"?
utilization of the same pathways and enzymes by numerous receptors instead of having their own pathways "integration of the response", "unified response" converse with each other at several levels e.g. growth factor receptor (EGF receptor) and epinephrine on a beta adrenergic receptor
24
describe why micelles are formed:
-forms in a solution of amphipathic molecules that have a larger, more polar head than tail -head cross section is greater than fatty acid chain (wedged shaped) -ONE TAIL? e.g. fatty acids, sodium dodecyl sulfate -driven by concentration
25
describe why vesicles are formed:
-small bilayers fuse into a spherical vesicle -concentration dependent manner -central aqueous cavity discloses dissolved molecules
26
what is the clinical importance of vesicles?
useful as artificial carriers of molecules (i.e. drugs)
27
describe bilayer formation:
-forms when lipids with polar head groups are MORE THAN ONE LIPID TAIL -cross section: heads are equal to that of side chain -e.g. phospholipids, sphingolipids -hydrophilic heads interact with water, FA tails are packed inside
28
what is an example of a membrane that is mostly lipid?
myelin sheath aids in signal conduction
29
name examples of membranes with more protein than lipid composition:
-plasma membranes of bacteria -membranes of mitochondria and chloroplasts
30
what is membrane fluidity determined by?
FA composition melting point
31
characteristics of FLUID membranes:
-shorter and more unsaturated FA chains -less interactions of the side chains --> more fluidity
32
association of fluidity and melting temperature:
more double bonds (unsaturation) - melting temp decreases increasing length of FA tails - melting temp increases
33
at higher temps, cells need ____________.
more long, saturated FAs
34
at lower temperatures, cells need ________.
shorter, more unsaturated FAs
35
explain the fluid mosaic model:
lipids form a VISCOUS, 2 dimensional solvent in which proteins are inserted and integrated either more or less deeply proteins can be embedded in or associated with the membrane
36
characteristics of membrane fusion:
-membranes fuse together w/o exposing the lipids to aqueous environment -can be spontaneous or protein mediated e.g. budding of vesicles from Golgi, exo/endocytosis, viral infection, fusion of endosome to lysosome, fusion of sperm and egg, cell division cytokinesis etc.
37
what are the different types of membrane embedded proteins:
-receptors -channels, gates, pumps -enzymes
38
what are peripheral membrane proteins?
-associate with the polar heads of the membrane -relatively loose association -IONIC interactions -disrupted via high salt or change in pH
39
what are purified peripheral membrane proteins?
no longer associated with the lipids
40
what are amphitropic proteins?
-can be conditionally attached to the membrane via COVALENT interaction with lipids or carbs that are attached to the lipids -allows for biological regulation: attachment vs detachment from lipids -REVERSIBLE attachment
41
what are integral membrane proteins?
-span entire membrane -asymmetry like the membrane (different domains in different compartments) -tightly associated with the membrane -hydrophobic stretches interact with hydrophobic membrane regions -can be removed by detergents -purified int. membrane proteins still have phospholipids associated with them
42
monotropic vs polytropic intergral membrane proteins:
monotropic: only reacts with one side, do not span the full membrane polytropic: span the full membrane
43
type I IMP:
single transmembrane helix N terminus is outside "don't talk to aNy1 outside"
44
type II IMP:
single transmembrane helix N terminus inside
45
type III IMP:
multiple transmembrane helices in a single polypeptide
46
type IV IMP:
transmembrane domains of several different polypeptides assemble to form a channel through the membrane
47
type V IMP:
held to the bilayer via covalently linked proteins
48
type VI IMPs:
have both transmembrane helices and lipid anchors
49
what is a hydropathy plot
-used to predict transmembrane domains -increased hydropathy index -- more hydrophobic -- transmembrane component
50
what are the types of passive diffusion?
-simple diffusion via bilayer -ion channel -facilitated
51
what are the types of active diffusion?
primary (ATP) secondary (coupled to another gradient)
52
what is the exergonic process of solute movement across a membrane driven by?
driven by increase in entropy going from ordered to disordered (more microstates, less constraint) energetically favorable
53
net movement of solute across a membrane is proportional to ______ but the ______ is the same in both directions.
concentration difference, rate
54
what x2 factors does membrane potential depend on?
1. asymmetric distribution of ions across the membrane 2. selective ion channels in the plasma membrane
55
ion channel structure:
4-5 transmembrane helices with polar core polar side chains point inwards, towards the pore hydrophobic side chains point out towards membrane
56
properties of ion channels:
cation and anion selective ion selective (e.g. pore loop family: selectivity filter)
57
example of pore loop filter:
K+ channels
58
describe the steps of K+ channel selectivity:
1. large water filled vestibule allows for K+ hydration 2. helix dipole stabilizes K+ 3. backbone carbonyl oxygens form a cage that fits K+ precisely, replaces waters of hydration spheres
59
what is an aquaporin?
H2O channel allows water movement down its gradient provides for a rapid movement
60
what are the 3 amino acids that are associated with aquaporin pores?
Arg: electrostatic repulsion Asn: dipole reorientation His: size restriction
61
clinical significance of aquaporins:
roles in urine production and water retention in kidneys e.g. vasopressin (APQ2-antidiuretic hormone) APQ2 cells in renal collecting duct promotes increased reabsorption of water, allows for concentration of urine defect=decreased water permeability in proximal tubule, increased urine output (polyuria), decreased urine concentrating ability
62
explain facilitated diffusion:
uses a membrane spanning protein - induces a conformational change down concentration gradient does not require energy for larger molecules such as sugars and AAs
63
the kinetics of facilitated diffusion are similar to ______.
an enzyme catalyzed reaction Kt = concentration at which substrate uptake is half maximal Tmax = transporter-catalyzed uptake is at maximal transport rate (saturated)
64
overview of secondary active transporters:
1. ion moving down its electrochemical gradient 2. solute moving from an area of low to high concentration (harnessing energy)
65
what are the types of primary active transporters?
1. P-ATPase -phosphorylation -ion transport 2. F-ATPase -coupling factor -H+ transport coupled to ATP hydrolysis/synthesis -F0/F1 components 3. V-ATPase -vacuolar -H+ transport coupled to ATP hydrolysis -V0/V1 components 4. ABC transporters (ATP binding cassette) -bind and hydrolyze ATP -for sugars, AAs, ions, peptides, proteins, hydrophobic compounds (e.g. cholesterol, drugs)
66
equations for facilitated diffusion kinetics:
67
describe transport rate for simple diffusion:
linear growth growth directly proportional to concentration gradient
68
describe the steps of Na+/K+ ATPase:
P-ATPase (dependent on phosphorylation) 1. transporter binds 3 Na+ from inside the cell 2. phosphorylation favors P-ENZ2 3. transporter releases 3 Na+ and binds 2 K+ from the outside 4. de-phosphorylation favors ENZ1 5. transporter releases 2 K+ to the inside 6. transporter resets
69
describe F-ATPase structure:
2 distinct multisubunits 1) hydrophobic F0 portion embedded in membrane 2) hydrophilic F1 portion protrudes into aqueous space
70
example of F-ATPase -H+/ATPase:
inner mitochondrial membrane in animals protons move down their concentration gradient (proton-motive force) drives ATP synthesis
71
V-ATPase/H+-ATPase purpose:
vacuolar - ATPase how cells internalize extracellular material, ligands, and plasma membrane proteins and lipids by endocytosis proton transport coupled to ATP hydrolysis via rotary mechanism e.g pumps protons into lysosomes (acidifies them), activates degradative enzymes
72
describe the structure of a V-ATPase:
V1 peripheral domain - hydrolyzes ATP V0 intergral domain - proton transport
73
describe the structure of an ABD transporter:
transmembrane domains span the membrane nucleotide binding domains (NBD)
74
what are the steps of ABC transporters:
1. substrate binding 2. nucleotide binding domain (NBD) dimerization 3. rotation of 90 degrees 4. ATP hydrolysis 5. Pi released first, followed by ADP
75
what type of transporter is a cystic fibrosis transmembrane conductance regulator (CFTR)?
ABC transporter Cl- (and also HCO3-) channel NBD dimerization opens Cl- channel depends on cAMP, PKA, and ATP (all 3 needed)
76
steps for CFTR channel opening/closing:
1. regulatory domain phosphorylated by PKA (cAMP stimulates PKA), allows ATP to bind (CLOSED) 2. ATP binds, allowing for NBD domain dimerization, opening of channel (OPEN) 3. hydrolysis of ATP and dephosphorylation (CLOSED)
77
what mutation in CFTR leads to cystic fibrosis?
mutation of Phe508 in the NBD1 domain
78
how is CFTR different from typical ABC transporters?
1. has a regulatory domain 2. acts as an ion channel, not a typical transporter
79
what type of transporter is GLUT-1?
-passive/facilitated
80
function of GLUT1 and location:
found in erythrocytes, galactose, and mannose function: transports glucose across blood brain barrier substrate: glucose, galactose, and mannose
81
GLUT 1 deficiency:
GLUT 1 deficiency syndrome (GLUT1DS) -deprivation of brain glucose -early onset encephalopathy -early onset seizures -delay in development
82
what type of transporter is Cu2+/ATPase?
primary active transporter
83
location and function of Cu2+/ATPase:
location: plasma membrane and cytoplasmic vesicles substrate: Cu2+ function: Cu absorption from the intestine and excretion in the liver
84
disease in Cu2+ - ATPase:
Wilson's Disease excessive deposition of copper in the liver and brain hepatic failure, acute hepatitis, progressive chronic liver disease
85
what type of transporter is the Neutral Amino Acid transporter (solute carrier family (SLC)?
secondary active transport
86
location and function of neutral amino acid transporter:
location: apical brush border of small intestine and kidney proximal tubules substrates: 10 essential AA (leucine, isoleucine, valine, methionine, phenylalanine, tryptophan, threonine, and histidine) function: AA transport
87
disordered neutral AA transporter:
Hartnup disorder: failure to thrive, photosensitivity, intermittent ataxia, nystagmus and tremor, pellagra (low niacin) like skin changes on face, neck, forearms, and dorsal aspects of hands and legs
88
what is hypersensitivity?
inappropriate or excessive immune response to exogenous and endogenous (self) antigen against self - autoimmunity
89
general characteristics of hypersensitivity diseases:
1. involved adaptive immunity 2. classified based on the hypersensitivity reaction/the immune effector response 3. developments often have a genetic disposition 4. clinical presentation depends on mechanism 5. imbalance between effector function and control/limiting mechanisms 6. mechanisms of tissue injury are the same as defenses against pathogens -therapy: negate effector molecule, suppress activation and function of immune response
90
phases of hypersensitivity:
sensitization - generates effector T cell, 1 previous exposure effector phase - re-exposure to same antigen leading to effector function/tissue injury ** can remain sensitized in the absence of re-exposure due to memory
91
what are the hypersensitivity class types?
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POM (6 decks)

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