Week 2 Flashcards

Question

Why would IgA NOT be a part of complement fixation?

Answer 1

* It is found in the mucosa, whereas complement proteins are floating around in the blood

Answer 2

* Are found on innate immune cells (macrophages, neutrophils, NK cells) * Fc receptors recognize and bind the constant region of the antibody (with antigen bound)

Answer 3

* IgG * IgA * IgE

Answer 4

* phacocytosis by macrophages * killing by natural killer cells

Answer 5

* degranulation of eosinophils * degranulation of mast cells

Answer 6

* B-cell hybridoma technology * Inject a pathogen into an animal --\> polyclonal response * Isolate the specific B-cell clone that you want * Fuse the B-cell clone with a myeloma cell --\> "an immortal B-cell" with a single specificity = monoclonal antibody

Answer 7

* The V-regions are from a mouse * The rest of the antibody is from a human

Answer 8

* The hypervariable regions are from a mouse * The rest is from a human

Answer 9

* The whole antibody is human but is produced in a mouse * You alter mice antibody genes to produce human antibody genes * This is the least immunogenic of the monoclonal antibodies, but it has ethical considerations

Answer 10

* Used for DETECTION of antibodies and antigens in the blood * Coat the antigen onto some sort of sticky surface * Direct and indirect ELISA

Answer 11

* Coat antigen onto a sticky surface * An antibody specific to your antigen of interest is tagged with an enzyme * Incubate antibody with antigen-coated surface * Add enzyme's substrate * If there is a color change --\> your antibody is detecting the antigen it binds to. * The more the color change, the more antibody (and antigen) is present in that sample.

Answer 12

* Coat sticky surface with antigen/sample of patient's blood * Add a primary monoclonal antibody specific to antigen of interest that you're testing for * Add a secondary POLYCLONAL antibody that binds to the primary monoclonal antibody. The secondary antibody is the one tagged with an enzyme * Several of these secondary antibodies will bind to the primary enzyme, which increases the sensitivity of the test (more likely to get a positive test if the antigen is present).

Answer 13

* A form of indirect ELISA * Coat sticky surface with a monoclonal antibody * Add the sample * If antigen is present, it will bind monoclonal antibody * Use a primary monoclonal antibody that will bind antigen a second time * Use secondary polyclonal antibody with the enzyme * This increases sensitivity AND specificity over standard direct ELISA

Answer 14

* HIV detection * Viral antigens themselves * Antibodies produced from HIV infection * ELISA has high sensitivity and is used for initial screening for HIV. Diagnosis is confirmed using RT-PCR, which is more specific.

Answer 15

* Sandwich ELISA * gp120 is considered the "capture antibody" * The antigen being measured here is the patient's antibodies against HIV viral protein

Answer 16

* Main purposes is to detect changes or particular subsets of cells in the blood (i.e. allows you to count things) * Main application: you can't see what kind of leukocytes are present under a microscope. This method allows you to figure that out.

Answer 17

* Use flourophore molecules that have Ab conjugated to them. * The antibodies are specific for proteins on the surface of immune cells. * So Ab-flourophore1 binds to type 1 immune cells. Ab-flourophore2 binds to type 2 immune cells. * Then you send the cell-Ab-flourophore through a detector that spits out results onto a dot plot that you can read to see which immune cells and how many are present.

Answer 18

1. X-linked agammaglobulinemia * This is a disease where you don't produce B-cells * You use flow cytometry to check and can see that basically there are no B-cells in patient's blood 2. CD4 T-cell count in HIV * Used to monitor their T-cell count

Answer 19

* It has a diversity gene segment * There is only 1 heavy chain locus but 2 light chain loci

Answer 20

* Used by B-cells and T-cells to produce receptors with a wide array of specificity * This is basically DNA splicing

Answer 21

1. V and J segments are selected at random and recombined first. This is the ONLY recombination event for light chains

Answer 22

1. First recombination is to join a D segment to a J segment 2. Second recombination combes DJ segment to a V segment

Answer 23

* The light chain undergoes only 1 recombination event (VJ) * The heavy chain undergoes 2 recombination events (DJ then VDJ) * The light chain has no D region

Answer 24

recombinases (RAG enzymes)

Answer 25

* recombination signal sequences (RSS) in the DNA flanking V,D, and J segments

Answer 26

* The DNA that is cleaved out during somatic recombination of BCRs

Answer 27

* The area that is joined together to form the recombined VJ segment

Answer 28

* The process by which broken strands of DNA are rejoined during somatic recombination * This rejoining is done by DNA repair enzymes, NOT RAG enzymes

Answer 29

junctional diversity

Answer 30

* The process by which random nucleotides are added between V-J regions (in the light chain) and D-J/V-DJ regions in the heavy chain * A major source of BCR diversity in antigen binding site specificity

Answer 31

* The enzyme that adds the nucleotides in junctional diversity process

Answer 32

* Immature B-cell is the stage when the heavy chain and light chains have paired up * This is when you have a functional BCR that can be trafficked to the cell surface * B-cells remain immature as long as they're in the bone marrow

Answer 33

* early pro-B cells * Heavy chain DJ rearrangement has occurred

Answer 34

* stromal cells (in the bone marrow)

Answer 35

* Junctional diversity can add nucleotides in such a way that the reading frame of the entire gene is shifted * This frequently results in nonproductive rearrangements * B-cells that have one nonproductive rearrangement can try again on the other chromosome. If both fail, that B-cell dies. * About half of developing B-cells die at the pro-B cell stage (due to nonproductive DJ rearrangement)

Answer 36

* heavy chain rearrangement has occurred successfully (DJ and VDJ rearrangements)

Answer 37

* A pro-B cell must have undergone heavy chain rearrangement to form VDJ segment AND * A **surrogate light chain (SLC)** must be made to pair up with the heavy chain while the real light chain is being recombined

Answer 38

* Expression of only one of two copies of a gene (present on separate chromosomes) is allelic exclusion

Answer 39

* When a functional heavy chain is made and a surrogate light chain pairs with it, you have a pre-B cell. * At this stage, RAG enzymes are turned off to prevent any further rearrangement of the heavy chain on the other chromosome. That is allelic exclusion * This ALSO happens for the light chain

Answer 40

* Heavy chain only has 1 locus. Failure at one chromosome gives only one other chance (on the other chromosome). * Light chain has 2 different loci. If rearrangement is nonproductive at light chain locus #1, then the cell keeps trying. * If there are multiple failures, the next locus is tried. * \*\*The light chain can try multiple times at a locus, but the heavy chain only tries once\*\*

Answer 41

* Heavy chain allelic exclusion occurs so that heavy chain rearrangement is turned off after a functional heavy chain is made. This ensures only one type of BCR is made. * Light chain allelic exclusion occurs after a fully functional BCR is made. This ensures that each B-cell only expresses one type of BCR. * Together, allelic exclusion at the heavy-chain and then light-chain Ig loci ensures expression and secretion of Igs of a single antigen-specificity in individual B cells.

Answer 42

1. Heavy chain expression inside the B-cell --\> pairing of SLC (and progression to pre-B cell stage). No pairing --\> death. 2. Light chain expression inside the B-cell --\> functional B-cell receptor (and progression to immature B-cell stage).

Answer 43

* The process of making sure B-cells do not attack self * This all occurs in the bone marrow as part of B-cell development

Answer 44

* First it's given a chance to rearrange the light chain - this is called "B cell editing" * If that doesn't work, it undergoes apoptosis * These B-cells that are strongly reactive are ones that recognize multivalent self molecules

Answer 45

* It is modified to be unreactive but then is still sent to the periphery * An unresponsive B-cell in the periphery is called **anergic**

Answer 46

* It is sent to the periphery

Answer 47

* One way is that B-cells can escape central tolerance * B-cells sometimes don't encounter all possible self molecules inside the bone marrow (like insulin). When it is sent to the periphery, it can encounter them and react towards them.

Answer 48

* Self-specific B cells that do not encounter self-antigen in the bone marrow are called ignorant. * These can encounter self antigen outside the bone marrow and be reactive

Answer 49

* Anergic B cells * Ignorant B-cells

Answer 50

* Concentration of drug * Affinity of receptor (Kd)

Answer 51

* The number of receptors * The intrinsic efficacy of the drug-receptor complex

Answer 52

* Strength of stimulus * Tissue sensitivity

Answer 53

* Can determine by knowing concentration of the drug and the Kd

Answer 54

* Can help you determine the total number of receptors that are occupied (which is important in knowing the stimulus)

Answer 55

* The drug concentration needed in order to have 50% of receptors occupied

Answer 56

* Ec50 = Concentration of drug required to generate a half maximal response * Ed50 = dose of drug required to generate a half maximal response * \*\*These two things are different. Dose is what is taken. Concentration is at the site of action.

Answer 57

* A measure of the drug's potency * Lower Ec50 = higher potency

Answer 58

* When Ec50 is reached before Kd * You get a half maximal response before you occupy 50% of receptors

Answer 59

* The tissue is very sensitive * The intrinsic efficacy of drug-receptor complex is high * You have lots of receptors

Answer 60

* Affinity of receptor (Kd) * Total number of receptors * Intrinsic efficacy * Sensitivity

Answer 61

* Intrinsic efficacy * sensitivity * receptor number * NOT Kd

Answer 62

1. surmountable 2. insurmountable 3. physiologic antagonism

Answer 63

* Two different receptors that cause two different responses can antagonize each other

Answer 64

1. hypertrophy 2. hyperplasia 3. atrophy 4. metaplasia 5. intracellular accumulation of metabolic products

Answer 65

* definition: cells get bigger * Can be physiologic (ex: workout out) or pathologic (ex: heart gets bigger in response to hypertension)

Answer 66

* cells get bigger AND there is more of them * example of pathologic process: warts from HPV are the result of too much epidermis

Answer 67

* definition: cells shrink and you have fewer of them * example: 80 year old brain is smaller than a 23 year old brain

Answer 68

* definition: a change in cell types * ex: heartburn causes acid to come out of stomach and into distal esophagus. This acid does not just damage the esophageal cells, it turns them from squamous epithelium to columnar epithelium.

Answer 69

* Biochemical changes happen first * Changes visible in light microscopy and organ level lag behind this

Answer 70

1. accumulation of water (hydropic changes) 2. accumulation of lipid (steatosis) 3. Glycogen 4. Protein 5. Pigments

Answer 71

* hydropic changes (accumulation of water) * Cell injury often disrupts glycolysis, Krebs, and ETS --\> ion balance gets fucked up --\> water inside the cell * You'll see clear vacuoles

Answer 72

* Genetic disorders * alcoholic liver injury * obesity * diabetes * toxins

Answer 73

* Lysosomal storage disease * See an accumulation of glycolipids --\> appearance of lipid inclusions * Primarily affects heart, kidney, and blood vessels

Answer 74

* Clear vacuoles in cytoplasm

Answer 75

* Glycogen storage disorder * Diabetes

Answer 76

* Resorption * Excess synthesis of protein * Defects in folding (usually genetic) * Aggregation of abnormal proteins

Answer 77

* Normal state: liver secretes anti-trypsin to inhibit trypsin, which is an enzyme that breaks down protein. Anti-trypsin prevents trypsin from degrading elastic layers of the lung. * Pathology: A mutation in anti-trypsin results in accumulation of non-functional (improperly folded) anti-trypsin in the liver. And you lose lung function b/c trypsin is breaking down lung layers. * The anti-trypsin accumulations are seen as big pink globules in the liver.

Answer 78

* accumulation of protein (amyloid proteins)

Answer 79

* Caused by a malignant plasma cell, which results in the accumulation of protein in the cell * specifically, the protein is a build up of light chains

Answer 80

* Bright luminescence on a congo red stain

Answer 81

* Hemosiderin * Lipofuscin * Melanin * Exogenous substances

Answer 82

* It is a byproduct of hemoglobin breakdown * Externally it appears as bruising * Under light microscope it appears as brown pigment

Answer 83

* Caused by normal wear and tear - i.e. this is a physiologic change, NOT pathologic * Reddish hue to it

Answer 84

* Coal Miner's lung * Example of exonenous substance building up and causing cellular injury

Answer 85

* Necrosis is characterized by inflammation; apoptosis is not * Necrosis shows hydropic changes; apoptosis shows cell shrinkage * Necrosis shows autolysis and leakage of intracellular contents; apoptosis shows nuclear fragments and blebbing)

Answer 86

* Cytosol: cell swelling (hydropic change), eosinophilia * Eosinophilia is a very pink stain of the cells. This is b/c transcription shuts down, and RNA stains blue. But protein stains pink and is more durable than RNA. * Nucleus: karyolysis (chromatin fades), pyknosis (nucleus shrinks), karyorhexis (nucleus fragments)

Answer 87

1. coagulative necrosis 2. liquefactive necrosis 3. Caseous necrosis 4. Gangrenous necrosis 5. Fibrinoid necrosis 6. Fat necrosis

Answer 88

* "Death in place" * Characterized by ghosts of cells - no nucleus, but the cell architecture remains

Answer 89

* Ischemia * Heart attack

Answer 90

* Cells are intact but missing nuclei

Answer 91

* The tissue dies and then disintegrates, so you just see a void of tissue

Answer 92

* \*\*Stroke * Abscess (dead tissue is replaced by pus = neutrophils)

Answer 93

* Tissue takes on a cheese-like appearance * Dead cells persist but then are surrounded by inflammatory cells

Answer 94

* Tuberculosis

Answer 95

* Central area of dead tissue walled off by inflammatory cells

Answer 96

* Tissue dies and then is accompanied by bacterial infection

Answer 97

* Diabetes

Answer 98

* An accumulation of fibrin in?around the arteriole * Only seen in 1 particular setting: vasculitis

Answer 99

* This is necrosis specifically of adipose tissue * Most commonly caused by pancreatic injury --\> leakage of digestive enzymes

Answer 100

* After a heart attack, the damaged tissue begins remodeling * The tissue is much weaker during this time and can result in rupture * Often occurs 5-9 days after the heart attack during remodeling phase

Answer 101

1. Eaten up by macrophages and neutrophils 2. Scarring 3. Calcifications

Answer 102

* NADPH oxidase disorder

Answer 103

* Cannot generate reactive oxygen species in phagolysosomes

Answer 104

* catalase positive organisms * Because they can break down hydrogen peroxide * Results in recurrent fungal infections

Answer 105

* Measures the ability of phagocytes to generate reactive oxygen species * ROS reduce NBT --\> purple color in the neutrophils (normal lab finding) * People with CGD can't reduce NBT, so their neutrophils don't turn purple/blue

Answer 106

* Defect in gp91 protein, a component of NADPH oxidase * Shows X-linked pattern of inheritance

Answer 107

* Membrane-bound * Alpha chain and beta chain * Variable region and constant region

Answer 108

* VJ recombination happens as somatic recombination * Primary transcript is made, then extra J regions are spliced * There is a single C-region

Answer 109

* There are 2 somatic recombinations: DJ followed by VDJ * There are 2 clusters of D-J-C regions from which recombination can occur. It's random as to whether somatic recombination occurs in cluster 1 or cluster 2.

Answer 110

* The C-regions that can be used for somatic recombination in TCRs are almost identical * In BCRs, there are many different types of C-regions that can be spliced with VJ (light chain) or VDJ (heavy chain). This variability of C-regions is responsible for antibody class (IgG, IgM, etc.) * In TCRs, there is basically only one constant chain available for the alpha chain and essentially only one for the beta chain, so there are not different "classes" of TCRs.

Answer 111

* RAG enzymes

Answer 112

* Results in SCID * A complete inability to produce an adaptive immune response (have no functional B or T-cells)

Answer 113

* Results in Omenn Syndrome * B-cells are usually more affected than T-cells

Answer 114

* The multiplicity of V-alpha regions

Answer 115

* junctional diversity

Answer 116

* These are heterodimers that associate with the TCR * They are needed in order for TCR to get to cell surface * They have Tyrosine-based Activation Motifs (ITAMs) on their intracellular portions, which are crucial in cell signaling

Answer 117

* These are homodimers that associate with the TCR * They have ITAM residues that are important for cell signaling

Answer 118

* peptide fragments on MHC molecules * NOT free antigen

Answer 119

* My T-cells will only recognize peptide fragments on MY MHC molecules * i.e. My T-cells would not recognize peptide fragment displayed on MHC molecules of another person

Answer 120

* Peptides are presented on MHC1 molecules * Antigens are derived from within the cell * CD8 T-cells recognize these

Answer 121

* Peptides are presented on MHC2 molecules * Antigens are derived from outside the cell * CD4 T-cells recognize these

Answer 122

* One heavy chain - the alpha chain. The alpha chain can vary between different MHC molecules * One Beta-microglobulin. There is no variation in this molecule. The exact same B-microglobulin complexes with every MHC1 molecule.

Answer 123

* An alpha chain and a beta chain * Both chains have variable sequences

Answer 124

* TCR binds both the peptide fragment and the MHC molecule * CDRs 1 and 2 of the TCR bind the MHC molecule * CDR 3 of the TCR binds the peptide fragment

Answer 125

* Intracellular antigens * Proteasome chews up antigen to generate peptide fragments * Fragments transported to endoplasmic reticulum by TAP * Binding to MHC1 occurs in ER with the help of Tapasin, ERp57, and Calreticulin * After peptide binds MHC1, they are trafficked to cell surface

Answer 126

* Transports antigen peptide fragments from cytosol to ER lumen, where they can bind to MHC1 * Problems with TAP --\> Bare lymphocyte syndrome

Answer 127

* Caused by dysfunctional TAP protein * Can't get peptide fragments into ER lumen --\> can't get peptide fragments onto MHC1 --\> lymphocytes don't have MHC1 on cell surface * Results in high susceptibility to viral infection (recall MHC1 is the main pathway of chewing up viral antigens)

Answer 128

* Proteins that aid in the process of getting peptide fragment bound to MHC1 in the ER lumen

Answer 129

* Antigen is taken up via endocytosis from extracellular space * Antigens are chewed up in phagolysosome * MHC2 molecules bind peptides in phagolysosome

Answer 130

* Recall MHC1 molecules bind their peptide fragments in ER lumen * MHC2 molecules make a stop in the lumen as they are being trafficked to the golgi to bud off as vesicles that will fuse with phagolysosome * **Invariant chain** is a peptide that binds MHC2 molecules while MHC2 is in ER

Answer 131

* Once MHC2 molecules get into their vesicles, the invariant chain is digested, leaving a very small molecule - CLIP - bound in the MHC2 groove * HLA-DM removes CLIP once MHC2 vesicle fuses with phagolysosome. This results in peptide fragment being able to bind MHC2

Answer 132

* These are found on the T-cells * Mature T-cells express either CD4 or CD8 * They bind to MHC molecule at different sites than the TCR binds * They're referred to as co-receptors

Answer 133

* All nucleated cells * Thus they can be killed by cotytoxic T-cells during a viral immune response

Answer 134

* Dendritic cells, B-cells, macrophages, thymic epithelial cells * MHC2 molecules are responsible for presenting extracellular pathogens, so MHC2 molecules must only be present on cells that are responsible for presenting these pathogens to T-cells

Answer 135

1. **Polygeny** - in each individual there are multiple genes that encode for class I heavy chains and class II alpha and beta chains 2. **Polymorphism** - for each MHC gene there are many different variants within the population

Answer 136

* HLA locus

Answer 137

* Mismatches in MHC expression b/w donor and recipient

Answer 138

* MHC1 genes are on the right * A,B, and C are the only regions involved in the presentation of antigens * These are the genes that encode the alpha chain of MHC1 (The B-microglobulin is not encoded by MHC locus) * MHC2 genes are on the left * There are 5 clusters. Within each cluster is an alpha chain and beta chain region. * Only DP, DQ, and DR regions are involved in antigen presentation

Answer 139

* Humans differ in the number of DR Beta regions they express * i.e. Like other MHC2 clusters, DR has a single alpha chain region * But unlike the other MHC2 clusters, the DR region has variability in how many beta chain regions there are.

Answer 140

* Within a single individual, there can only be 2 different variations of HLA A (and that is only if the individual is heterozygous) * But within the population, there are many different variations of MHC molecules expressed

Answer 141

* The regions that bind the TCR * The regions that bind the peptide

Answer 142

1. It's the basis of MHC restriction * My T-cells can only recognize my MHC markers because my MHC markers are often genetically different than someone else's MHC markers. In order to find a transplant match, you need to find people with matching MHCs. 2. It dictates the type of peptide each MHC molecule can bind * Individuals who are heterozygous at more MHC loci are better able to respond to a variety of pathogens

Answer 143

* Allows individuals to bind a variety of pathogens * Allows populations to bind peptides from a variety of continually changing pathogens

Answer 144

1. "Interallelic conversion" - i.e. regular meiotic recombination 2. "Gene conversion" - i.e. also done during meiosis. Just involves adjacent MHC genes on the same chromosome switching places. Same result as interallelic conversion.

Answer 145

* The particular combination of MHC alleles that a person expresses * A single individual can express 2 different haplotypes if they are heterozygous * There are thousands of different MHC haplotypes within the population

Answer 146

* T-cells from an individual of one HLA type can recognize and respond to (i.e. attack) MHC molecules expressed by an individual * In order for transplants to be successful, the two individuals must be of the same HLA type

Answer 147

* denoting, relating to, or involving tissues or cells that are genetically dissimilar and hence immunologically incompatible, although from individuals of the same species.

Answer 148

* Host recipient T-cells attack the transplanted tissue * Occurs when HLA types between donor and recipient are not compatible.

Answer 149

* Occurs when T-cells from the donor attack host tissues * Occurs during bone marrow transplants (whereas host vs. graft disease is usually an organ transplant) * Mature T-lcells from the donor must be completely eradicated before a bone marrow transplant. If they are not, then some of these mature T-cells from the donor will recognize recipient tissue as foreign and attack.

Answer 150

* A very small portion of T-cells can recognize foreign MHC and attack that cell * This is in contrast to MHC restriction, which is still true. The MAJORITY of T-cells can only recognize self MHC. * Alloreactivity is the driver of transplant rejections

Answer 151

* Thoracolumbar region of the spine

Answer 152

* Craniosacral regions of the spine

Answer 153

* Parasympathetic: connections are located very close to target organs. (preganglionic neurons are very long) * Sympathetic: connections are located very close to spine (preganglionic neurons are very short)

Answer 154

* Sweat glands * Adrenal gland * Blood vessels

Answer 155

* Sympathetic is usually felt as systemic effects. This is because adrenal gland releases NE into bloodstream. * Parasympathetic is usually more discrete to particular organ

Answer 156

* Always acetylcholine (for both sympathetic and parasympathetic)

Answer 157

* acetylcholine

Answer 158

* epinephrine/norepinephrine * \*\*Except for sweat glands, which uses acetylcholine for sympathetic response * \*\*Adrenal gland does not have a postganglionic receptor. It releases NE directly into bloodstream

Answer 159

* Nicotinic * Voltage-gated ion channel * Increases calcium or sodium * Muscarinic * GPCR * Increases calcium OR * Decreases cAMP/Increases K+

Answer 160

* Adrenergic receptors * Alpha * Beta

Answer 161

* Only under sympathetic control * Epinephrine binds alpha1 receptor in SMOOTH muscle, which increases calcium * Causes Increased smooth muscle contraction --\> vasoconstriction * Epinephrine binds beta2 receptor in SKELETAL muscle, which decreases cAMP and decreases calcium * Causes vasodilation in skeletal muscle

Answer 162

* Only innervated by sympathetic nervous system * Preganglionic receptor is cholinergic nicotinic, which acetylcholine binds * There is no postganglionic receptor. * When Ach binds, NE is released into bloodstream.

Answer 163

* There is only sympathetic innervation here * \*\*But this is an exception, which is that acetylcholine is the primary NT for sweat glands. In all other sympathetic situations, it's epinephrine. * Ach binds muscarinic receptor * Causes increased sweat production

Answer 164

* Parasympathetic * Ach binds muscarinic receptor in two different places: SA/AV nods and cardiac myocytes * SA/AV nodes --\> decreased rate of contraction * Cardiac myocytes --\> Decreases force of contraction * Sympathetic * NE binds B-adrenergic receptor in two different places: SA/AV nodes and cardiac myocytes * SA/AV nodes --\> Increases HR * Cardiac myocytes --\> Increases force of contraction

Answer 165

1. Rate of contraction is dictated by receptors on SA/AV nodes (pacemaker node), while force of contraction is dictated by receptors directly on cardiac myocytes 2. Normally we say calcium increases smooth muscle contraction and cAMP causes relaxation. But that only applies to SMOOTH MUSCLE. Cardiac muscle is not smooth muscle. In the heart, cAMP does result in increased force and increased rates of contraction. Inhibition of cAMP by parasympathetic muscarinic receptors decreases force and rate of contraction.

Answer 166

* Sympathetic --\> bronchoconstriction and increased secretions. Results from increased calcium. * Parasympathetic --\> bronchodilation and decreased secretions

Answer 167

* Parasympathetic --\> more peeing. Results from sphincter muscle relaxation but contraction of detrusor muscle * Sympathetic --\> less peeing. Results from sphincter muscle contraction but relaxation of detrusor muscle.

Answer 168

* Sympathetic --\> pupil dilation * NE causes CONTRACTION of circular muscles (=miosis) * Parasympathetic --\> pupil constriction * Ach causes CONTRACTION of radial muscles (=mydriasis)

Answer 169

* Degrades acetylcholine in the synapse

Answer 170

* M1, M3, M5 --\> calcium results in excitatory signal * M2, M4 --\> lower cAMP and increase K+ --\> inhibitory

Answer 171

* Neuronal (found at ganglia of all receptors, both sympathetic and parasympathetic, making these clinically useless drug targets) * Muscular - found at neuromuscular junction

Answer 172

* In the heart * Acetylcholine binds this and it inhibits cAMP and leads to a potassium efflux --\> hyperpolarization. * This hyperpolarization means that any further stimulation will not have an affect, which is why this is an inhibitory response.

Answer 173

* Binds muscarinic and nicotinic receptors * Is positively charged so cannot cross the blood-brain barrier * Therapeutic use: Used locally to prep for eye surgery * Causes pupillary constriction by making circular muscles contract * Therapeutic effect: pupillary constriction * Toxic effects: decreased HR, decreased force of contraction. Bronchoconstriction.

Answer 174

* There is no parasympathetic stimulation of blood vessels * BUT there are M3 receptors in blood vessels, which Ach binds * Results in increased calcium --\> nitric oxide synthesis, which diffuses out to the smooth muscle and causes relaxation --\> **vasodilation** * \*\*\*Normally we think of calcium causing smooth muscle contraction, but this is different.

Answer 175

* Inhibit degradation of acetylcholine in the synapse * Result in amplification of Ach

Answer 176

* Edrophonium * Pyridostigmine * Physostigmine * Donezapil

Answer 177

* Is a competitive inhibitor of acetylcholinesterase, does not form covalent intermediate

Answer 178

* This is a carbamate * Forms a covalent intermediate in acetylcholinesterase binding pocket that is slowly reversible * Used to treat Myasthenia Gravis

Answer 179

* Also a carbamate, forms a covalent intermediate with acetylcholinesterase binding pocket * Used to treat overdose of muscarinic antagonist (i.e. atropine)

Answer 180

* Does not form a covalent intermediate, but it lasts so long b/c the drug's half life is extremely long * Used to treat Alzheimer's

Answer 181

* Many of these are poisonous * Diisopropyl flourophosphate = insecticide * Sarin = nerve gas * These can all cross the blood-brain barrier * Toxicity: DUMBBELS

Answer 182

* Mnemonic for toxicity that results from acetylcholinesterase inhibition (too much acetylcholine amplification) * D = diarrhea * U = urination * M = miosis (pupillary constriction) * B = bradycardia (slow HR) * B = bronchorrhea (too much secretions) * E = emesis (vomiting) * L = lachrymation (tears/crying) * S = salivation * \*\*These are all results of overstimulation of parasympathetic nervous system\*\*

Answer 183

* Pralidoxime * Acts as an antidote for the irreversible inhibitors * Mechanism: reverses inhibition of acetylcholinesterase * Therapeutic use: antidote for pesticide or nerve gas poisoning * Therapeutic effect: reverses DUMBBELS * Toxic effects: At very high doses, can itself inhibit acetylcholine

Answer 184

* Acts as an antidote for the irreversible inhibitors * Mechanism: reverses inhibition of acetylcholinesterase * Therapeutic use: antidote for pesticide or nerve gas poisoning * Therapeutic effect: reverses DUMBBELS * Toxic effects: At very high doses, can itself inhibit acetylcholine

Answer 185

* This is BOTOX * Mechanism: Inhibits the release of Acetylcholine * Therapeutic use: reduces wrinkles * Therapeutic effect: local muscle paralysis * Toxic effects (due to escape from injection site): Neuromuscular weakness, respiratory depression

Answer 186

* BCR signaling occurs via Ig-alpha and Ig-beta * TCR signaling occurs via CD3 and TCR zeta ITAMS

Answer 187

* Nicotinic cholinergic * This is one place acetylcholine stimulates sympathetic response

Answer 188

* Muscarinic cholinergic * This is the second place acetylcholine stimulates sympathetic response

Answer 189

* Adrenal gland (nicotinic cholinergic receptor) * Sweat glands (muscarinic cholinergic receptor)

Week 2 Flashcards

(221 cards)