Midterm #2 Flashcards

Question

From lecture, what are some of the things that happen during apoptosis?

Answer 1

1. The cell tends to detach from whatever it is normally attached to. 2. The mitochondria become permeable, releasing their contents into the cytosol. 3. The nucleus breaks down, releasing its contents. Nucleases break apart both the cellular and viral nucleic acids. 4. Phospholipids in the plasma membrane tend to evert, so that the outside of the cell now has unusual phospholipids on the outside. 5. The plasma membrane become permeable and the influx of fluid gives the cell its blebbed appearance.

Answer 2

* antibodies of the type IgG and IgM * antibody binds to its antigen on a microbe * Fc region of the antibody binds to an Fc receptor on a neutrophil or macrophage * Phagocytosis

Answer 3

* Phagocytosis by itself may not be enough to kill the microbes engulfed * Ex: TB: lysosomes are prevented from fusing with the phagosome

Answer 4

* more of the killing factors are synthesized, and the lysosomes are more likely to fuse with the phagosome * more potent mix is released into the phagolysosome.

Answer 5

* can be activated via antibodies bound to microbes * either IgG or IgM, especially the pentameric form

Answer 6

B Good! Helper T cells are CD4+, which means that bind to antigen displayed on MHC II molecules.

Answer 7

* have an Fc receptor for IgE * IgE binds to the cuticle of a helminth * Fc receptor on an eosinophil can bind to the Fc region on the IgE

Answer 8

* found especially under epithelia * large secretion vesicles filled with paracrine secretions like histamine * mast cells have Fc receptors for IgE * multivalent antigen appears again, it causes the the Fc receptors to cluster * receptors phosphorylate each other * tyrosine kinase * exocytosis of the vesicles and synthesis of prostaglandins and leukotrienes

Answer 9

* IgA is joined into dimers with a J-chain * binds to the basal surface of the intestinal or respiratory epithelium * engulfed by the cell, transported to the luminal membrane, and released into the lumen * dimeric IgA binds to bacteria or viruses * prevent their binding to the epithelium * cause agglutination * class of lymphocytes found within the epithelium itself * largely T cells * majority of the CD8+ variety * respond to some of the more common microbes in the lumen

Answer 10

* secretions such as saliva * antibacterial enzyme, lysozyme * antimicrobial peptides such as defensins * IgA * dimeric form binds to the inner surface of epithelial cells * engulfed by the cell by endocytosis * moves in a vesicle across the cell and is released into the lumen by exocytosis * IgA prevents binding and causes agglutination, swept away by mucous/body * epithelium also has lymphocytes embedded in it * special population that respond mainly to a restricted set of antigens typically found in the lumen of the GI tract and respiratory airways * Most are CD8+ T cells that kill infected cells

Answer 11

* phagocytosis by neutrophils or macrophages is its most likely fate * most effect opsonin is antibody in the form of IgG (or IgM) * Agglutination by these antibodies helps phagocytosis * Complement System * innate, IgG, especially IgM pentamer * opsonin C3b, MAC * C3a and C5a peptides serve as inflammatory paracrines * helminth worms, eosinophils become involved, especially if IgE is made * TH2 helper T cells * Eosinophils have vessicles with basic and toxic proteins * myeloperoxidase, oxygen radical story * Mast cells also release inflammatory paracrines

Answer 12

* slow the spread of the infection with IFN-alpha and IFN-beta * induce in nearby cells an "anti-viral state" * synthesis of certain proteins that slow viral replication and slow down cell growth and division * ultimate solution is apoptosis * caused by natural killer cells of the innnate system and cytotoxic T cells of the specific immune system * Macrophages then engulf the remains *

Answer 13

* "activation" of macrophages by **TH1 helper** T cells is the next step * recognizes the macrophage due to antigen displayed on an MHC II molecule * helper T cell releases** IFN-gamma** * increases the fusion of lysosomes with the phagosome and increases synthesis of oxygen radicals and other killing mechanisms * Cytokines are also released that cause inflammation and recruit further cells * wall off the pathogen through the formation of a **granuloma**.

Answer 14

The virus first binds to and infects cells of the upper airways: * macrophages phagocytize virus and release cytokines such as TNF-alpha, etc. * natural killer cells slow the infection * cytotoxic T cells (CTL) cause virally infected cells to undergo apoptosis * IgG promotes phagocytosis of any viruses entering the interstitial fluid * IgA is transfered to the lumen of the airways in order to bind to the viruses and prevent them from attaching to the epithelial cells

Answer 15

* person with a compromised immune system, it can lead to **bacterial pneumonia** * lung tissue fluid filled at autopsy * edema, neutrophils and other white blood cells fill the delicate alveoli

Answer 16

* Influenza A has two important surface molecules * **hemagglutinin**: binds to the surface of cells in the body, following which the cell takes up the virus and become infected * **neuraminidase**: enzyme that cleaves the molecule on the host cell that binds hemagglutinin. Hemagglutinin attachment must be broken for the new viruses to be free to move on and infect other cells.

Answer 17

* 16 different hemagglutinin types and 9 different neuraminidase * Antibodies against one type not effective against another type

Answer 18

* Bird Virus * Affect human: H1N1, H1N2 and H3N2 * H5N1 not normally infect humans * but when does, deadly * H7N9 also deadly * doesn't move from person to person well

Answer 19

* small variation, which creates a new strain * hemagglutinin and/or neuraminidase molecules acquire **point mutations** * This is why flu appear regularly * Requires a new vaccine * Create **epidemics** of flus

Answer 20

* Causes **pandemics ** * a new **subtype** is created * Flu A: genome is encoded in eight separate segments of RNA * **two different subtypes of influenza A infect the same individual**, it is possible for new viruses to wind up with segments of RNA from both sources * Usually pig/bird with double infection * antigenic shift occur in H5N1 or H7N9 to make human-human easy, cause a deadly pandemic * Influenza B cannot undergo antigenic shift

Answer 21

* three subtypes that the WHO feels are most important for the year * This years: protects against an influenza A H3N2 virus from 2012, the H1N1 virus that emerged in 2009 to cause a pandemic, and an influenza B virus * Intranasal flu vaccine: attenuated, live viruses, which usually work by causing mucosal immunity * Antivirals against influenza A * **neuraminidase inhibitors** * Oseltamivir (Tamiflu) is taken orally

Answer 22

* "Bird Flu" * 2010, for example, WHO identified 40 cases of H5N1, of which 50% were fatal * H7N9 is fairly similar * H1N1 subtype known as "swine flu" * When leads to hospitalization, significant portion of people die * Dangerous forms that can move deep into lungs and cause** viral pneumonia** *

Answer 23

* Bacterial: virus infects the upper airways * secondarily cause bacteria to move into lungs * fluid and neutrophils in aveoli * Viral: directly infect epithelium lining aveoli * fluid and cells accumulate in interstital space * necrosis

Answer 24

* H5N1 causes considerable release of **TNF-alpha** * cytokine storm * **Septic Shock** (sepsis: bacteria and toxins, septicemia: only bacteria) * endothelial permability increase, not enough blood profusion to tissues * **Disseminated Intravascular Coagulation (DIC)** * clotting factors and platelets depleated * organ failure due to clots * TNF-alpha and IL-1, make clots form * **Acute Respiratory Distress Syndrome (ARDS)** * epithelial inflammation out of hand * dyspnea and tachypnea * once develop, mortality 50%

Answer 25

The antigenic shift/drift has not taken place yet. Cannot create vaccine for an unknown virus

Answer 26

* Hep A: acute disorder * liver cells infected and macrophage/neutrophils cannot get at them * IFN-alpha and IFN-beta are released by virally infected cells * Induce an anti-viral state * Number of processes that lead to release of interferons. * Toll-Like Receptor and cytosolic protein that responds to RNA * NKC cause apoptosis of the infected cells * In one to two weeks, make antibodies, igM and IgG * cytotoxic T cell: causes the flu like symptoms * Hep B and C: immune system not good enough to clear out, * Chronic * treated with IFN-alpha * Increases the MHC1 molecules on cell surface

Answer 27

* dendritic cells phagocytosis some of virus * TH1 helper cells * lots of antigen and strong stimulation by antigen * Bind MHC II of macrophage * IFN-gamma * greater fusion of the lysosomes with phagosomes, phagocyte oxidase, and the release of cytokines that cause inflammation and recruit further macrophages. * If not work, additional macrophages, leading to a granuloma * Bacteria walled off but still tissue damage because helper T cells strongly stimulate the killing mechanisms and promote strong local inflammation * Granuloma can come back as secondary TB

Answer 28

* Taken by dendritic cells to lymph node * Become vegitative and start dividing * **Capsules** inhibit phagocytosis * causes hemorrhagic **lymphadenitis**, enter blood in large numbers * Toxins released by bacteria, **systemic inflammatory response** * Release oxygen radicals and TNF-alpha and IL-1

Answer 29

* Enters through mucous membrane or break in skin * macrophages and dendritic cells infected * virus **suppresses type I interferon** and divides rapidly * hypotension and shock * macrophages synthesis tissue factor and d dimer becomes present in blood * After three or four days, platlets are low, and bleeding, * **hemorrhagic fevers**

Answer 30

Natural Killer Cells

Answer 31

* On day 10 hematocrit is elevated * Dehydration concentrates the blood * Collapsed inferior vena cava * Dehydrated, hypovolemia * Edema in intestinal walls * Increased permeability of endothelial * High C-Reactive protein * Lots of TNF-alpha and IL-1 * Day 14 or 15 * More WBC and CRP * Less viral RNA and less diarrhea * Secondary bacterial infection from crossing compromised intestinal mucosa * Elevated lactate shows signs of septic shock, mitochondria not recieving enough oxygen * Epistaxis (nose bleeding) because of thrombocytopenia from platelets in endothelial * D-dimer levels show fibrin being formed throughout body, DIC * Increased breathing to offset lactic acidosis

Answer 32

* Type I hypersensitivity * Immediate hypersensitivity * Allergies

Answer 33

* Antigen called allergen * Inappropriate formation of TH2 cells * Small antigens with little inflamation * Steer towards IgE formation * Binds Fc receptors on mast cells * Within an hour * Secretion of mast cell vesicles * histamine * Release eicosanoids * Leukotriene C4 (anti-eicosanoid and LT drugs) * Begins in about 2-4 hours * Cytokine secretion from mast cells * Notable, TNF-alpha * Recruits more WBC (TH2, eosinophils) * Eosinophils release their toxic proteins * Long-term chronic inflammation * Treat with glucocorticoids (corticosteriods) *

Answer 34

* systemic response to an allergen * can lead to shock * uticaria in skin * mucosal irritation leading to vomiting and diarrhea * airways swell making it hard to breathe * penicillin=hapten (reponse after binding to protein in body) * Epinephrine to raise blood pressure and relax airways

Answer 35

* Involves Tcells and activated macrophages * Second introduction of antigen produces a larger response * macrophages producing damage * Contact dermatitis (hapten) * Langerhans in epidermid carry to lymph node

Answer 36

* B-Cells making antibodies * myasthenia gravis, antibodies bind to and inactivate acetylcholine receptors on skeletal muscle * IgG or IgM *

Answer 37

Antibodies bind platelets and lead to destruction

Answer 38

* B-cells secrete antibody that binds to a protein * Stimulating antibody bind to TSH receptor * Release thyroid hormone * Goiter

Answer 39

* antibodies produced to act on a pathogen * streptococci cross-react with molecules in the body * Damage to heart muscle and valves

Answer 40

* **complexes of the antibody and antigen** * young women * makes antibodies against a number of molecules in the nucleus * Complexes of the antibody and antigen form and cause damage as they are deposited in tissues * glomerulus of the kidney * skin and joints * sun exposure leading to rash

Answer 41

* T cells release cytokines that can cause inflammation directly or activate macrophages * **Inflammation** is a central feature of these disorders and fits the chronic type pattern * blocking TNF-alpha is an effective treatment *

Answer 42

* additional self-antigens become involved in the response * as attacked, more self antigens exposed, to which the immune system might respond

Answer 43

enzymes, growth factors, oxygen radicals, NO

Answer 44

* immune system attacks the synovial membrane * synovial inflammation and destruction of joint * early, bilateral stiffness * nodules on bony areas where lots of movement * synovial membrane inflammed * **hyperplasia** and creates finger like extensions * angiogenesis leading to abnormal structure, **pannus** * destroys the joint * pannus may extend over destroyed joint, leading to **ankylosis**

Answer 45

TNF-alpha or IL-1

Answer 46

TNF-alpha or IL-1 from macrophages enters the blood and stimulates release of acute phase proteins such as C-reactive protein. This is often associated with increased inflammation in the body.

Answer 47

* immune system responds to proteins in the myelin sheath of nerve cells * demylenation (especially visual pathways) * double vision, weakness, paralysis and various other neurological symptoms, interspersed with periods of remission *

Answer 48

* insulin secreting cells attacked * TH1 helper T cells and cytotoxic T cells are largely responsible * Perhaps some autoantibodies

Answer 49

* **electrical potential difference **between the inside of the cell and the surrounding extracellular fluid * especially important in muscle and nerve cells * **changes in their membrane potentials** are used to code and transmit information.

Answer 50

* net separation of charge between the two locations * measured in units of volts

Answer 51

* typical neuron, this is about –70 millivolts * minus sign indicates that the inside of the cell is negative * **very small number** of negative and positive ions need to be separated by the membrane *

Answer 52

The concentration gradient * The electrical potential difference * **Total energy change** for the movement of an ion across the membrane is the the **sum** of the energy change due to the **concentration gradient** and the energy change due to **electrical potential difference** * May act in same or opposite directions *

Answer 53

* Depolarization: membrane potential to become **less negative** * Hyperpolarization: become **more negative**

Answer 54

* hydrophobic layer creates a barrier * Exception like NO and CO2 and nonpolar substance (hormones and fatty acids) *

Answer 55

* multiple subunits form a pore * Each subunit consists of multiple transmembrane domains * Aquoporins and ion channels * Factors affecting rate of flow through an open ion channel * membrane potential * concentration gradient * Note that ions moving through an open ion channel affect the membrane potential.

Answer 56

* Selectivity * which ion allowed to travel through channel * Gating * open or closed

Answer 57

* open all the time * some K+ and Cl- * Ca++ and and Na+ are never ungated

Answer 58

* open/close in response to membrane potential * Key in generation of electrical signals in nerve, muscle, and cardiac cells * **voltage-gated Na+ channel**

Answer 59

* opened when regulatory molecules bind * neurotransmitter receptors are ligand gated channels * example is the **nicotinic acetylcholine receptor** * neuromuscular junction on skeletal muscle cells, and also at synapses in autonomic ganglia

Answer 60

* Afferent neurons (sensory neurons) * skin, touch and pressure * auditory and vestibular *

Answer 61

* Normally gated by temperature * Some ligands can open them * capsaicin for heat * menthol for cool

Answer 62

* carrier protein with specific binding site for molecule * **Glucose Transporter** * **Glucose Uptake** * **specific binding site** for glucose * **Concentration gradien**t determines rate of uptake * **Does not require ATP** * Control transport by controlled number of transport proteins in the membrane * Low insulin, few glucose transporters * High insulin, more glucose transporters

Answer 63

* two substances are required to bind in order for transport to occur * Free energy driving the transport is the **sum of the free energies for transport of both substances** * If it is in the same direction, it is called **cotransport** * If it is in the opposite direction it is called **countertransport**

Answer 64

* sodium-glucose cotransporter * carbobhydrate gradient will fluctulate * always steep gradient favoring Na+ into the cell * because of the sodium-potassium pump * Na+ gradient can move glucose against it's concentration gradient

Answer 65

* facilitated diffusion and coupled transport show **saturation** * **transport maximum (Vmax)** * every transporter is bound by substance * transport rate cannot increase

Answer 66

* energy for transport is derived from ATP hydrolysis * move molecules in one direction regardless of the concentration gradient * **Na+/K+-ATPase**, or sodium-potassium pump * moves three Na+ ions out of the cell and two K+ ions into the cell * Consumes about a third of ATP at rest * **Ca++-ATPases** and the **H+/K+-ATPase**. * keeps the Ca++ concentration low in the cytosol * Stomach acid secretion *

Answer 67

* that depend upon ATP binding for transport * **ATP-Binding Cassette** * two nucleotide binding domains that bind ATP * Ex: **multidrug resistance protein (MDR1)** * pump a wide variety of nonpolar drugs and toxins out of cells * resistance to chemotherapy in cancer cells * Ex: **CFTR** * forms a **Cl- channel** that is expressed on the apical plasma membrane of many epithelial cells. * Defective in cystic fibrosis * decreased secretion * ion channel that is **regulated by both phosphorylation and ATP binding** * bacterial toxins causing unregulated activity can lead to diarrhea

Answer 68

* Nonpolar sidechains face outward * Polar peptide bonds face inward

Answer 69

* 24 transmembrane domains * 4 clusters of 6 TMD * Each group of 4 is a homologous domain * Clustered to form a channel in the middle

Answer 70

* Very selective for Na

Answer 71

* gate opens in response to regulatory molecules that specifically bind to either the inside or outside * gate is controlled by a **voltage sensor**, which responds to the level of the **membrane potential**. * **several voltage sensors** must respond before the gate opens * **inactivation gate** limits the period of time the channel remains open

Answer 72

* Each homologous domain has one transmembrane domain **a positively charged amino acid** is found at **every third position**, giving a **total of four to eight positive charges per transmembrane domain**. * Voltage sensors * Deoplarize, voltage sensor move towards outside and gate opens

Answer 73

* Glucose across the apical membrane by sodium-glucose cotransporter * Na+ gradient is established by the **Na+/K+-ATPase** * located on basolateral membrane * Facilitated diffusion of glucose into the ECF is a **passive** process * **glucose transporter**

Answer 74

* Expand ECF * requires getting Na+ absorbed into the body, since the amount of Na+ in the ECF is the major determinant of ECF volume * glucose included to speed uptake of Na+

Answer 75

* solutes are moved across the epithelium, which then draw water into the lumen by **osmosis** * rate-limiting and regulated step in intestinal secretion is the movement of Cl- ions across the apical plasma membrane * Cl- is transported into the epithelial cell by a cotransporter expressed on the basolateral membrane * Na+ gradient, established by the Na+/K+-ATPase * Cl- down concentration gradient via Cl- channel CFTR

Answer 76

* member of the ATP-binding cassette (ABC) protein family * ATP binding is used to open an ion channel * **regulatory domain** that is phosphorylated by **protein kinase A (PKA)**, also known as **cAMP-dependent kinase** * **alpha subunit of the G-protein** to activate the enzyme **adenylyl cyclase** * Adenylyl cyclase produces the **second messenger cAMP** which activates PKA to phosphorylate CFTR * **cholera** toxin chemically modifies the alpha subunit of the G-protein so that it cannot inactivate

Answer 77

* connected to their target cells via **synapses** * A **neurotransmitter** crossing the small space in the synapse only travels about 20 nanometers

Answer 78

* **norepinephrine **is a neurotransmitter * acts as a hormone when released from the **adrenal medulla**

Answer 79

* neurotransmitters bind to receptors that are **ligand-gated** **ion channels** * closes channel, changed membrane potential * Neuronal signaling less than a second * Paracrine/Endocrine signaling minutes to hours

Answer 80

* intracellular signaling molecules * especially true for receptors coupled to trimeric G-proteins * **G-protein coupled receptors **or **GPCR**s * example is the enzyme adenylyl cyclase * uses ATP as a substrate to synthesize the second messenger **cyclic AMP** (**cAMP**) * **small** and **diffusible** * **amplify **a signal * Ex: each active adenylyl cyclase is capable of generating many molecules of cAMP.

Answer 81

* 2nd messanger because cellular concentrations are kept very low * **exocytosis of secretory vesicles** * **regulation of contraction** * One source of Ca++ is from the ECF * ER, or the sarcoplasmic reticulum in muscle cells * Ca++ released by second messanger **inositol triphosphate (IP3)** * binds to ligand-gated Ca++ channels * signal is rapidly terminated by **Ca++-ATPases** * transport Ca++ out of the cytosol

Answer 82

* Ca++ regulates cellular processes by binding to Ca++-binding proteins * Ca++-binding protein that regulates skeletal muscle contraction is called **troponin** * Ca++-binding protein found in all cells is the protein **calmodulin** * Ca++/calmodulin does not perform a cellular process itself, rather it works by binding and activating other protein * protein kinases

Answer 83

* Ligands: * peptide hormones, neurotransmitters, and odor molecules * seven transmembrane domains * many GPCRs have been identified in the human genome * known as orphan receptors, because their ligands have not been identified.

Answer 84

* GPCR associate with trimeric G-proteins * alpha, beta, and gamma subunits * Exchange GDP for GTP at alpha * Dissociates into alpha and beta-gamma * Alpha diffuse along membrane and activate enzymes to make second messangers * Beta-Gamma diffuse along membrane and activate ion channels * Inactive by alpha-subunit intrinsic GTPase activity * With GDP, can reassociate with the beta-gamma complex * **Cholera toxin** causes a chemical modification that prevents GTP hydrolysis and leads to unregulated signaling

Answer 85

* catalyzes the formation of the second messenger cyclic AMP (cAMP) * generate many molecules of **cAMP** * amplify the signal * bind to and activate **protein kinase A** * PKA then phosphorylates target proteins in the cell * cAMP is rapidly broken down by **phosphodiesterases** * Cholera toxin * destroys GTPase activity of G-alpha * persistant adenylyl cyclase activity * continuous cAMP * continuous activation PKA * Continuous phosphorylation of CFTR

Answer 86

* cleaves PIP2 * generate two second messengers, **IP3** and **diacylglycerol (DAG)** * IP3 (water soluable) binds and open ligand-gated Ca++ channel * DAG (lipid soluable) activates protein kinase C (PKC)

Answer 87

* G-protein Receptor Kinase (GRK) * Phosphorylates on GPCR * Beta-arrestin binds and prevents trimeric G-protien from associating * BA targets GPCR for endocytosis * receptor downregulation

Answer 88

* regulatory molecule binds and brings two receptor molecules together to form a dimer * phosphorylate each other * activates JAK, allowing it to phosphorylate the receptor * phosphotyrosine residues on the receptor proteins are binding sites for STAT proteins * Signal Transducer and Activator of Transcription * considered latent transcription factors * phosphorylated by JAK * Dimerize * binds to specific sequences in the DNA * Inactivation occurs when phosphatases remove phosphate groups from various proteins in the signaling pathway

Answer 89

* turn down the immune response * cytokine receptor blocker derived from a monoclonal antiis used to prevent transplant rejection * * binds to the IL-2 receptor. * cytokine receptor blocker derived from a monoclonal antibody * ruxolitinib * inhibit the kinase activity of JAK * treat a myeoloproliferative disorder * Tofacitinib * JAK inhibitor * treatment of rheumatoid arthritis

Answer 90

* molecules stimulating proliferation are growth factors * many growth factors signal through receptor tyrosine kinases * Examples: * **Vascular-endothelial growth factor** (VEGF) * promotes new blood vessel growth * maintenance of endothelial cells in filtration membrane of kidney * **Neurotrophins** * promote the survival and differentiation of neurons. * **Insulin-like growth factor-1 (IGF-1)** * produced in response to growth hormone * responsible for the majority of its growth-promoting effects.

Answer 91

* ligand binding causes receptor dimerization * receptor autophosphorylation: receptors phosphorylate each other * phosphotyrosine binding site for adaptor protein * adaptor protein bound to a guanine-nucleotide exchange factor (GEF protein) * GEF activates Ras, small monomeric G-binding protein * GTP replaces GDP * cascade of protein kinases * phosphorylation of transcripition factors * Ras control cell proliferation * other monomeric G-proteins involved in * Cell shape through effects on cytoskeleton * involved in membrane trafficking through exocytosis and endocytosis

Answer 92

* GTP is hydrolyzed to GDP * monomeric G-proteins like Ras are GTPases * GTPase activity of Ras increased by GTPase activating protein or **GAP protein**

Answer 93

* Mutant genes for proteins in these growth regulatory pathways are called **oncogenes** * normal cells to cancer cells * **proto-oncogene** is used to refer to the normal, unmutated form of the gene * activating mutations of Ras in one third of tumors

Answer 94

* ligand-activated transcription factors that bind nonpolar regulatory molecules *

Answer 95

* steroid hormones * thyroid hormones * retinoic acid * vitamin D3 * fatty acids * phospholipids.

Answer 96

physiological function and endogenous natural ligand are not known

Answer 97

* involved in metabolic regulation * Fibrates (which bind to the receptor PPAR-alpha) are a class of drugs used to treat dyslipidemia in order to lower the risk of cardiovascular disease * Thiazolidinediones (TZDs; which bind to the receptor PPAR-gamma) are used to promote insulin sensitivity in the treatment of type 2 diabetes mellitus

Answer 98

* Three important domains * transcriptional regulation domain * DNA binding domain * ligand binding domain.

Answer 99

* No ligand, inhibitory molecule binds the ligand binding domain * Ligand bind--\> conformational change * inhibitory molecule disscociates * Nuclear receptor binds DNA * Corregulator associates * group protiens that regulate gene transcription * Genes that are regulated by nuclear receptors contain particular DNA sequences (**response elements**) in their promoters, where the nuclear receptor binds *

Answer 100

* One particular receptor may associate with different groups of coregulators in different cell types * either enhance or inhibit transcription * differential recruitment underlies the action of drugs known as **receptor modulators** * Ex: **selective estrogen receptor modulator (SERM)** known as **raloxifene** * estrogen receptor agonist in bone tissue, but estrogen receptor antagonist in breast and uterine tissue.

Answer 101

* Neurotransmitter * Paracrine * relax smooth muscles in blood vessels * Synthesis: * nitric oxide synthase(NOS) is activated * enzyme acts on an amino acid (L-arginine) to create nitric oxide * Three forms NOS * phagocytes, neurons, and endothelial cells of blood vessels * NO diffuses to and activates a guanylyl cyclase * soluable, cytosolic GC * Guanylyl cyclase converts GTP to cyclic GMP * cGMP acts as a second messanger

Answer 102

* **Nitroglycerin** is converted to nitric oxide in the blood, which is why it dilates of blood vessels serving the heart. * **Sildenafil **(Viagra®) block a form of phosphodiestase found in the penis * cGMP not broken down * more cGMP means more blood

Answer 103

* skeletal muscles, which move the bones * somatic * and the viscera, which are all other organs * autonomic

Answer 104

* The cell body of the **preganglionic neuron** is in the central nervous system * the cell body of the **postganglionic neuron** ia found outside the central nervous system in an **autonomic ganglion**

Answer 105

* parasympathetic * preganglionic neurons in this case are in the brainstem or in the sacral spinal cord * long, projecting to autonomic ganglia close to the visceral organ * sympathetic: * preganglionic neurons are in the thoracic and lumbar spinal cord * axons tend to be short, with most autonomic ganglia lying close to the spinal cord

Answer 106

* Speed heart rate * preganglionic neurons are found in the **lateral horns** of the **first five thoracic segments** (approximately) * axons of these neurons then project to the **sympathetic ganglion chain** (mainly in this case the **inferior cervical ganglion**) lying just outside the vertebral column * in the ganglion the preganglionic neurons form synapses with the **postganglionic neurons** * axons of the postganglionic neurons then project out of the ganglion and approach the heart along the large blood vessels connected to the heart * spread over the surface of the heart before penetrating into the heart muscle tissue.

Answer 107

* Slows heart rate down * the cell bodies of the **preganglionic neurons** are in the **brainstem** (medulla) * axons project out via the **vagus nerve** * **next to the heart,** on the superior surface, are the cell bodies of the **postganglionic neurons** * postganglionic axons are short, and project a short distance to the special cardiac muscle fibers near the top of the heart that control the heart rate. *

Answer 108

* Dialates * cell bodies of the sympathetic p**reganglionic neurons** again are in the **lateral horns** of the **upper thoracic segments**, but project mainly to the **superior cervical ganglion** of the sympathetic chain ganglia. * In the ganglion are the cell bodies of the **postganglionic neurons**, and their axons then project up to the head and then through the superior orbital fissure and into the eye.

Answer 109

* Constricts * cell bodies of the parasympathetic **preganglionic neurons** are in the **brainstem** (midbrain) and their axons project out in the oculomotor nerve, which passes through the superior orbital fissure. * On the other side of the fissure is the **ciliary ganglion**, which contains the cell bodies of the **postganglionic** neurons. Axons from these neurons then proceed to the iris.

Answer 110

lateral horn

Answer 111

sympathetic ganglion

Answer 112

sympathetic chain ganglion

Answer 113

* inhaled antigen binds to IgE bound to mast cells * release of inflammatory paracrines * histamine, certain arachidonic acid derivatives, and cytokines * Immediately * blood flow increases * vessels become more permeable * glands begins secreting fluid * Several hours later * influx into the tissues of neutrophils * eosinophils * basophils * lymphocytes. * Treatments include: * oral antihistamines * intranasal corticosteriods * leukotriene inhibitors * if symptoms are severe, oral corticosteroids.

Answer 114

excessive and abnormal IgE response

Answer 115

* when ingested antigens move through the blood and lodge in the skin * producing red, itchy swellings called “hives” * respond to antihistamines * Genuine food allergies are also atopic * Urticaria is one possible result

Answer 116

* Severe food allergies * systemic release of histamine

Answer 117

* does not respond to antihistamines * treated with glucocorticoids * typical patient is a child with a tendency towards atopy

Answer 118

* Not atopic * In response to chemicals from the environment, such as cosmetics, drugs or organic solvents * Small molecules promote a cellular immune response against the skin after the small molecules bind to surface proteins on epidermal cells * cellular immune response is slower than a one involving IgE * rashes occur hours to days following the contact of the skin with the sensitizing agent * delayed * hay fever and other atopic allergies occur quickly * need an initial sensitizing exposure

Answer 119

* immature lymphocytes are deleted if they encounter antigen early * clonal selection * become tolerant to their antigen if they are steadily exposed to high concentrations * ex: self antigens * requires at least some stimulation of the innate immune response

Answer 120

* SLE * antibodies * Type I DM * T Cells

Answer 121

* antibodies * bind to and inactivate the acetylcholine receptors on skeletal muscle * The complexes are taken in by endocytosis and degraded, thereby reducing the total number of receptors on the muscle * weak and fatigued muscle * The complexes are taken in by endocytosis and degraded, thereby reducing the total number of receptors on the muscle

Answer 122

* B-cells secrete antibody that binds to a protein * stimulates the TSH receptor * excess secretion of thyroid hormone * goiter * exophthalmos * weight loss and various other problems associated with high utilization of energy

Answer 123

* antibodies produced against a pathogen, in this case streptococci, cross-react with molecules in the body. * Damage to the heart muscle and valves * antibodies that are formed in response to molecules in the bacterial cell wall.

Answer 124

* antibodies against a number of molecules, especially proteins associated with double stranded DNA * Complexes of the antibody and antigen form and cause damage as they are deposited in tissues * glomerulus of the kidney * attacks multiple organs * joints * connective tissue structures such as the skin * skin to sun readily damages the affected cells * erythematous rash

Answer 125

* immune system responds to proteins in the myelin sheath of neurons * Scattered islands (plaques) of demyelination occur in the central nervous system * eventually replaced by plaques of hardened tissues, which can be observed through magnetic resonance imaging (MRI) * "sclerosis" refers to "hardening" * At first, symptoms are often mild * relapsing-remiting-disorder * progressive phase, in which there is increasing neuronal loss * 3% chance each year of converting to the progressive phase

Answer 126

* immune system attacks the synovial membrane * synovial inflammation and destruction of the structure of joints * Both antibodies and T cells appear to be involved * joint becomes inflamed, it undergoes hyperplasia and throws up finger like extensions * extensive angiogenesis * growing, abnormal, wound repair structure is called a pannus * destruction of the adjacent bone and cartilage * pannus entirely across the destroyed joint leads to ankylosis

Answer 127

* prominent effects in the vertebral column * “Spondylitis” refers to inflammation of the vertebra * Ankylosis” refers to stiffening or fixation of a joint due to a disease process * pain and stiffness in the spine and buttocks * bony protuberances from the bodies of the vertebrae, and eventually this leads to complete fusion of the vertebrae * Certain variations of HLA antigens (MHC molecules) are very common in many patients * NSAIDs, immunosuppresives methotrexate and glucocorticoids, and blockers of TNF-alpha

Answer 128

* blocks voltage-gated Na+ channel * Japanese puffer fish, Fugu * binds with high affinity and specificity to block the pore of the voltage gated Na+ channel found in the neurons and muscle cells *

Answer 129

* lidocaine * blocking the opening of the voltage-gated Na+ channel * lower affinity for the channel * much higher concentration is needed to effectively block the channel * block nerve impulses along the axons of afferent neurons carrying pain information

Answer 130

* mutations in the protein CFTR * ABC protein * Cl- (chloride) channel * protein plays a key role in epithelial secretion * transport of Na+ and Cl- into the lumen; water then follows by osmosis * Flow of Cl- across the apical membrane through the CFTR channel is the rate-limiting and regulated step in this process * mucus in the airways does not get sufficiently hydrated * difficult to clear and causes clogs in the airways and degeneration * environment that is conducive to the development of serious infections * Treat with antibiotics * autosomal recessive genetic disorder * protein does not get transported from the rough endoplasmic reticulum (rER) to the apical plasma membrane * digested via mechanisms in the rER designed to remove defective protein * Drugs: CFTR correctors * correct for this trafficking defect and restore expression of the protein on the apical plasma membrane * Another type of mutation results in mutant proteins that are expressed on the cell surface, but that function poorly * Ivacaftor (trade name Kalydeco) * CFTR potentiator, that is, it prolongs the amount of time that the channel stays open

Answer 131

* important type of G-protein coupled receptors * endogenous agonists (active chemical in the body that binds the receptor) are the catecholamines, norepinephrine and epinephrine * Norepinephrine is the neurotransmitter released by sympathetic postganglionic neurons at their targets

Answer 132

* alpha and beta * alpha-1 receptors causing constriction of blood vessels * beta-1 receptors in the heart that stimulate increased heart rate and force of contraction, * beta 2 receptors that cause dilation of the airways

Answer 133

* refers to the tightness with which a ligand binds to a receptor * dissociation constant, Kd * low Kd is indicative of a high affinity

Answer 134

* refers to the range of effects of ligand binding on receptor activity * and thus, biological response * partial agonist * do not produce the maximal biological response * antagonists * drugs that bind the receptor and prevent activation * inverse agonists * Drugs that inhibit basal activity

Answer 135

* ligand-gated ion channels * rapid depolarization of the post-synaptic cell in response to acetylcholine * postganglionic neurons at the synapses in autonomic ganglia and on skeletal muscle cells in the neuromuscular junction. * Myasthenia gravis * muscle weakness because the somatic efferent neuron has difficulty activating skeletal muscle fibers

Answer 136

* G-protein coupled receptors * act over a longer time course because more steps are involved before ion channels are opened or closed * slow synaptic transmission * found on the targets of parasympathetic postganglionic neurons, for instance the smooth muscle fibers of the circular muscles in the iris * muscarinic antagonist to the eye in order to paralyze the circular muscles and prevent constriction of the pupil

Answer 137

* stimulated by growth hormone releasing hormone (GHRH) * peptide hormone that binds to a GPCR on GH-releasing cells in the anterior pituitary

Answer 138

* by excess GH secretion (hypersecretion) * usually due to a tumor in the anterior pituitary * contain a mutation in the G-alpha subunit * lacks GTPase activity * levels of cAMP * stimulates GH hypersecretion

Answer 139

* chemically modifies the alpha subunit of the G-protein * block its GTPase activity * G-alpha remains active * continually stimulating adenylyl cyclase * to produce increased cAMP * stimulates protein kinase A, which phosphorylates CFTR, the chloride channel involved in intestinal secretion * greatly increases flow of Cl- through CFTR * increasing intestinal secretion

Answer 140

* failure in the development of the immune system * various genetic mutations * X-linked gene coding for a subunit of the IL-2 receptor * required for the development of B and T cells * mutation in the gene coding for a JAK protein (JAK3 * treated with a bone marrow transplant * bubble boy

Answer 141

* mutation in a GAP protein * prolonged Ras activity leading to the development of **neurofibromas** * benign tumors that are derived from **Schwann cells** *

Answer 142

* 18-20% of breast cancers are caused by overexpression of the receptor tyrosine kinase HER2 * Treatments: * Monoclonal antibody drugs that bind to receptors * Small molecules that are tyrosine kinase inhibitors * trastuzumab (marketed as Herceptin) * monoclonal antibody that binds to the extracellular domain of the receptor * preventing receptor dimerization * promoting receptor down-regulation * Lapatinib (trade name: Tykerb) * blocks growth factor signaling by preventing receptor phosphorylation * targets epidermal growth factor receptors

Midterm #2 Flashcards

(172 cards)