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Human and Pathophysiology > Midterm > Flashcards

Midterm Flashcards

1
Q

type IV hypersensitivity reactions

A

carried out by T helper cells (THI) causes CD8 T cells to target some drugs and macrophages to activate inflammatory response

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2
Q

alveolar ventilation

A

equal to (tidal volume- anatomical dead space) x frequency of breathing

-anatomical dead space = tidal volume x frequency of breathing

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3
Q

biological parameters

A

kept within a certain limit around the set point, such as temperature, ionic concentrations, osmotic pressure, etc.

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4
Q

steady state

A

describes whether rates of movement are equal

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5
Q

equilibrium in a two compartment model

A

balance between two compartments with no net transfer of energy or substances between the two

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6
Q

steady state in a two compartment model

A

reflects a constant rate of change between two compartments, even if it requires an input of energy. No net change over time

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7
Q

lipid rafts

A

association of sphingolipids and cholesterol with caveolin, a scaffolding protein
acts as platform for signal transduction

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8
Q

large molecule transport across the plasma membrane

A

ex: hormones, growth factors, transferrin, neurotransmitters
1. phagocytosis
2. endocytosis
- pinocytosis
- receptor mediated
3. exocytosis
- constitutive
- regulated

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9
Q

Nernst Equation

A

Ex= 61.5/z log [x]out/[x]in

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10
Q

voltage clamp electrophysiology

A

-used to study current from ion channels
- one or two electrodes are placed into a cell, and current is injected to prevent the cell membrane potential from changing
-by adjusting the amount of current injected to keep the membrane potential constant, you know exactly how much current is flowing through the membrane

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11
Q

Gaq signaling

A

activation of the Gq pathway results in the hydrolysis of phosphoinositide 4,5- biphosphate (PIP2) by phospholipase C (PLC) into diaclyglycerol (DAG)and inositol triphosphate (IP3)

-phosphoinositides are regenerated throughout this process

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12
Q

tyrosine kinase receptor signaling

A

-agonist binds one receptor subunit, allowing for dimerization with another ligand bound subunit
- cytosolic domains of the receptor undergo autophosphorylation
- receptor now acts as a kinase, turning on intracellular enzymes or transcription factors

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13
Q

fast inactivation of voltage-gated channels

A

-conformational change of the channel causes it to be “plugged”, no longer able to conduct ions
- applies to voltage-gated potassium and sodium channels

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14
Q

PNS

A

characterized by short postganglionic axons and long preganglionic axons

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15
Q

Layers of immune system

A

involves 3 layers of defense
-surface barriers
-innate immune system
-adaptive immune system

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16
Q

basic mechanisms of the innate immune system

A

-certain patterns exist on pathogens that allow them to be identified and targeted, but this is still a nonspecific response
-phagocytic cells, including neutrophils, macrophages, eosinophils, and dendritic cells, engulf pathogens to dispose of them
-viruses are inside of healthy cells are are not engulfed by phagocytic cells
-NK cells cause cell death in this case

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17
Q

what happens when NK cell conditions are met

A

cytotoxic granules are secreted to kill virally infected cells, and cytokines are also released

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18
Q

T cell positive and negative selection

A

T cells must be able to recognize self antigens presented by MHC on thymus cells (positive selection) but not too strongly (negative selection)
- “death by neglect” refers to T cells that die during positive selection because they fail to interact with MHC/self-antigen at all

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19
Q

immune checkpoints

A

-can act to suppress T cell activation, necessary to maintain homeostasis and turn off immune response when there is no threat
-CTLA-4 on T cell binds B7 on APC to block costimulation
-PD-1 on lymphocytes interacts with PD-L1 or PD-L2 on myeloid/epithelial cells in a negative feedback loop, terminating inflammation

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20
Q

Provenge

A

cancer vaccine
-autologous vaccine (cells come from patient)
-uses ex-vivo expansion and activation of dendritic cells

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21
Q

pressure changes during respiration

A

-inspiration: diaphragm and external intercostal muscles contract which expands thoracic cavity
-expanded thoracic cavity means pleural pressure decreases/transpulmonary pressure is increased
-increased transpulmonary pressure means lungs inflate
-expanded lungs mean pressure inside alveoli is negative/subatmospheric
-gas flows from outside the body to inside the lungs (from higher pressure to lower pressure)
-exhalation: diaphragm relaxes , thoracic cavity shrinks
-pleural pressure increases/transpulmonary pressure decreases
-lungs deflate
-pressure in alveoli > atmospheric pressure
-gas flows from lungs to outside the body (fick’s law)
-cycle repeats

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22
Q

negative feedback

A

involves deviation from the set point, and the control of a biological effector to return to this set point

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23
Q

positive feedback

A

involves a deviation from the set point that causes a biological effector to further increase this deviation

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24
Q

equilibrium

A

describes whether amounts are equal

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25
Q

fluid mosaic model of the plasma membrane

A
  • integral proteins or peripheral proteins are capable of moving in the phospholipid bilayer
  • the phospholipid bilayer refers to the organization of several amphipathic phospholipid molecules, which have a polar head group and a fatty acid tail
  • unique lipids may have unique functions: phosphoinositides are involved in signal transduction and cholesterol increases membrane stiffness
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26
Q

small molecule transport across the plasma membrane

A

ex: gases, lipid-soluble molecules, sugars, amino acids, ions
1. diffusion- dependent on Fick’s law (J=DA(C1-C2)/ change in x

carrier mediated: fast but saturatable
1. passive transport
2. active transport

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27
Q

nernst equation information

A

-ion flow is dependent on concentration gradient
-relates this concentration to energy (voltage)
-equilibrium or reversal potential
-ion flow can be positive or negative depending on the charge of the ion and direction of flow
- positive ion efflux is positive current, positive ion influx is negative current
- if the nernst potential is equal to the cell’s membrane potential, there is no net current
- know how to relate membrane potential and an ion’s reversal potential to direction of current

28
Q

ohms law

A

V=IR
experimenters are controlling the voltage, and measuring the resistance from the cell membrane, allowing the calculation of current

29
Q

resting membrane potential

A

if we use the nernst equation for every ion channel in the cell, the sum of these current will be zero if the cell is at resting membrane potential
-the cell membrane is considered negative to its surrounding environment
-controlled by multiple factors but one major contributor is the Na/K pump

30
Q

Na/K pump

A

exchanges 3 Na+ for 2 K+ using ATP in order to maintain concentration gradients of sodium and potassium

31
Q

basics of G-protein coupled receptor signaling

A
  • GPCRs are associated with heterotrimeric G proteins, with alpha, beta, and gamma subunits
  • the alpha subunit is GDP, freeing the subunits to engage in signaling
  • in this process, Ga is bound to GTP, and the beta/gamma subunits remain closely associated
  • G beta/gamma is also capable of signaling
  • eventually, Ga hydrolyzes GTP to GDP and the heterotrimeric complex forms again
  • signaling stops when the GPCR is phosphorylated by GRKs, which facilitates beta-arrestin2 recruitment and receptor internalization
  • enter endosomes, wheter they may be brought back to the cell surface (active) or degraded in lysosomes
32
Q

Gas and Gai/o signaling

A

Gas and Gai/o proteins couple to adenylyl cyclase, the enzyme responsible for producing cyclic AMP
- stimulatory G proteins increase AC function, inhibitory G proteins decrease it

33
Q

cAMP

A

second messenger that activates PKA

34
Q

PKA

A

tetrameric protein kinase (2 catalytic and 2 regulatory subunits)
-cAMP binding to regulatory subunits frees catalytic subunits to engage in enzymatic processes
-has many downstream effectors including ion channels and transcription factors

35
Q

steroid hormone receptor signaling

A

-receptor may be cytosolic
-ligand binding causes translocation to the nucleus
- receptor ligand complex is able to bind to DNA and act as a transcription factor

36
Q

ion channels involved in the action potential

A

-largely driven by voltage gated sodium and potassium channels
-once a voltage threshold is reached, sodium channels open to cause the “spike” of the AP
- terminates because sodium channels inactivate quickly

37
Q

Hodgkin and Huxley-Giant Squid axon

A

-characterized the ap of the giant squid axon
- understand the graph
- below -50 mV, both channels are inactivated
- beyond -25 mV the current voltage relationship is linear
- in between the current voltage relationship is nonlinear

38
Q

the autonomic nervous system

A

generally, neurons extend from the spinal cord to ganglia, and another neuron originating from the ganglia will innervate effector organs
-primary neurotransmitter involved is acetylcholine

39
Q

SNS

A

characterized by long postganglionic axons and short preganglionic axons

40
Q

PNS- one notable exception

A
  • another important signaling pathway- nitric oxide production and guanylyl cyclase are related to smooth muscle contraction and relaxation
    -works by controlling the amount of calcium in the cytosol
    -referred to as noradrenergic noncholinergic action
41
Q

surface barriers

A

skin and membrane secretions
- physical barrier in the skin
- chemical barriers provided by antimicrobial secretions in the lung
- commensal bacteria are harmless, but make it harder for pathogens to harm us

42
Q

innate immune system

A

second layer, fast but nonspecific immune response
-specific (pattern recognition)
- natural
-immediate
-no memory
-limited diversity

43
Q

adaptive immune system

A

after the innate response, specific countermeasures to a pathogen are produced, but more slowly
-specific (antigen-mediated)
-acquired (experiential)
-long-lasting
-memory
-very diverse

44
Q

DAMPS

A

damage associated molecular patterns
-biomolecules that can initiate a noninfectious inflammatory response
-nuclear or cytosolic proteins released from the cell following tissue injury
-DNA, RNA, purine metabolites (ATP, Adenosine, nono/polysaccharides)

45
Q

PAMPs

A

pathogen associated molecular patterns
-activate innate immune responses by identifying nonself molecules
-recognized by TLRs and other pattern recognition receptors
-bacterial LPS, endotoxins, dsRNA, unmethylated CpG motifs
-triggers activation of signaling cascades in immune cells (I.e. interferons)

46
Q

NK cell activation

A

activated by type I interferons, which are increased in virus-infected cells
-interferons also upregulate expression of ligands that activate NK cells

47
Q

NK cell inhibitory expression

A

NK cells express inhibitory receptors on their surface to prevent self-cytotoxicity
-bind MHC class I
-virally infected cells downregulate MHC class I
-also express Fc receptors, which engage in antibody dependent cell cytotoxicity

48
Q

T cells

A

-involved in adaptive immunity by recognition of specific antigen sequences
-CD4 T cells are activated by antigen presenting MHC II molecules
-3 signal theory of T cell activation

49
Q

antibodies

A

IgM: dominant class of antibody secreted during a primary immune response
IgD: found in plasma (small amounts) and on the surface of some naive B cells
IgG: major antibody produced in response to secondary antigen encounters (adaptive immunity)
IgA: secretory immunoglobulin
IgE: allergic reactions and anti-parasitic immunity

50
Q

Type I hypersensitivity reactions

A

IgE mediated, allergens or drugs form immunogenic peptides

51
Q

type II hypersensitivity reactions

A

IgM or IgG trigger complement mediated phagocytosis of host cells seen as foreign

52
Q

type III hypersensitivity reactions

A

large proteins or monoclonal antibodies form complexes with IgG

53
Q

hallmarks of cancer

A

-self sufficiency in growth signals
-insensitivity to anti-growth signals
- evading programmed cell death
-limitless replicative potential
-sustained angiogenesis
-tissue invasion and metastasis

54
Q

CAR-T cells

A

chimeric antigen receptor T cells
-modification of individual’s own T cells to target tumors
-modified portion is derived from monoclonal antibodies
-capable of vinding tumors without MHC, which is very important because tumors tend to limit MHC expression as.a means of immune evasion
-tend to be ineffective against solid tumors

all CAR-T cells contain ScFv antigen binding region and intracellular CD3-zeta chain
- 2nd and 3rd gen CAR-T cells introduce costimulatory domains
-4th gen additionally incorporate cytokines

55
Q

GP96-Ig

A

cancer vaccine
-GP96 is a heat shock protein
-if an infected cell dies, proteins and peptides from the virus will exit the cell bound to GP96 (acts as chaperone)
-GP96 will then bind receptors on APCs, allowing for cross presentation of antigens to T cells

56
Q

hypoxia and angiogenesis

A

-tumors rapidly outpace available oxygen supply, leading to hypoxia
-as a result, tumors increase VEGF expression, a potent angiogenic factor
-HIF-1a becomes stabilized under hypoxic conditions
-dimerizes with HIF-1b to promote glycolysis and angiogenesis
- in normoxic conditions, proline hydroxylation of HIF-1a leads to ubiquitination and degradation
-hypoxia also prevents T cell penetrance of tumors and causes accumulation of adenosine

57
Q

FVC and FEV1

A

-measured by spirometry

58
Q

FEV1

A

amount of air that can be expelled from the lungs in the first second of exhalation

59
Q

FEV1/FVC ratio

A

-good measure of lung function
-may change due to several factors, including strength of chest muscles, airway resistance, lung compliance, and age

60
Q

compliance and airflow

A

-a metric that affects how much work is required for ventilation
-essentially the ability of the lungs to accommodate stretching
-high compliance makes it more difficult to exhale, reducing airflow
-conversely, increasing lung compliance makes it harder to inhale, causing similar deficit in airflow

61
Q

obstructive lung disease

A

-conditions like COPD
-exhalation is difficult, and air remains in the lungs
-results in poor airflow

62
Q

restrictive lung disease

A

-conditions like asthma
-inhalation is difficult, the lungs are not being fully inflated
-also results in poor airflow

63
Q

alveolar surface tension and pulmonary surfactant

A

-in healthy individuals, increases alveolar stability at low lung volumes
-without it, alveoli would collapse after expiration
-this effect is achieved by decreasing alveolar surface tension
-also associated with an increase in lung compliance

64
Q

reversal potential of an ion

A

membrane potential value at which there is no net flux

65
Q

what is nernst equation used for

A

used to calculate the potential of an ion (charge z) across a membrane

66
Q

Effect of IP3

A

Causes calcium release from ER

67
Q

Effect of DAG

A

Activates protein kinase C (PKC)

Human and Pathophysiology (2 decks)

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