Midterm Flashcards
type IV hypersensitivity reactions
carried out by T helper cells (THI) causes CD8 T cells to target some drugs and macrophages to activate inflammatory response
alveolar ventilation
equal to (tidal volume- anatomical dead space) x frequency of breathing
-anatomical dead space = tidal volume x frequency of breathing
biological parameters
kept within a certain limit around the set point, such as temperature, ionic concentrations, osmotic pressure, etc.
steady state
describes whether rates of movement are equal
equilibrium in a two compartment model
balance between two compartments with no net transfer of energy or substances between the two
steady state in a two compartment model
reflects a constant rate of change between two compartments, even if it requires an input of energy. No net change over time
lipid rafts
association of sphingolipids and cholesterol with caveolin, a scaffolding protein
acts as platform for signal transduction
large molecule transport across the plasma membrane
ex: hormones, growth factors, transferrin, neurotransmitters
1. phagocytosis
2. endocytosis
- pinocytosis
- receptor mediated
3. exocytosis
- constitutive
- regulated
Nernst Equation
Ex= 61.5/z log [x]out/[x]in
voltage clamp electrophysiology
-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
Gaq signaling
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
tyrosine kinase receptor signaling
-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
fast inactivation of voltage-gated channels
-conformational change of the channel causes it to be “plugged”, no longer able to conduct ions
- applies to voltage-gated potassium and sodium channels
PNS
characterized by short postganglionic axons and long preganglionic axons
Layers of immune system
involves 3 layers of defense
-surface barriers
-innate immune system
-adaptive immune system
basic mechanisms of the innate immune system
-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
what happens when NK cell conditions are met
cytotoxic granules are secreted to kill virally infected cells, and cytokines are also released
T cell positive and negative selection
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
immune checkpoints
-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
Provenge
cancer vaccine
-autologous vaccine (cells come from patient)
-uses ex-vivo expansion and activation of dendritic cells
pressure changes during respiration
-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
negative feedback
involves deviation from the set point, and the control of a biological effector to return to this set point
positive feedback
involves a deviation from the set point that causes a biological effector to further increase this deviation
equilibrium
describes whether amounts are equal
fluid mosaic model of the plasma membrane
- 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
small molecule transport across the plasma membrane
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
nernst equation information
-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
ohms law
V=IR
experimenters are controlling the voltage, and measuring the resistance from the cell membrane, allowing the calculation of current
resting membrane potential
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
Na/K pump
exchanges 3 Na+ for 2 K+ using ATP in order to maintain concentration gradients of sodium and potassium
basics of G-protein coupled receptor signaling
- 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
Gas and Gai/o signaling
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
cAMP
second messenger that activates PKA
PKA
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
steroid hormone receptor signaling
-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
ion channels involved in the action potential
-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
Hodgkin and Huxley-Giant Squid axon
-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
the autonomic nervous system
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
SNS
characterized by long postganglionic axons and short preganglionic axons
PNS- one notable exception
- 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
surface barriers
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
innate immune system
second layer, fast but nonspecific immune response
-specific (pattern recognition)
- natural
-immediate
-no memory
-limited diversity
adaptive immune system
after the innate response, specific countermeasures to a pathogen are produced, but more slowly
-specific (antigen-mediated)
-acquired (experiential)
-long-lasting
-memory
-very diverse
DAMPS
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)
PAMPs
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)
NK cell activation
activated by type I interferons, which are increased in virus-infected cells
-interferons also upregulate expression of ligands that activate NK cells
NK cell inhibitory expression
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
T cells
-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
antibodies
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
Type I hypersensitivity reactions
IgE mediated, allergens or drugs form immunogenic peptides
type II hypersensitivity reactions
IgM or IgG trigger complement mediated phagocytosis of host cells seen as foreign
type III hypersensitivity reactions
large proteins or monoclonal antibodies form complexes with IgG
hallmarks of cancer
-self sufficiency in growth signals
-insensitivity to anti-growth signals
- evading programmed cell death
-limitless replicative potential
-sustained angiogenesis
-tissue invasion and metastasis
CAR-T cells
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
GP96-Ig
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
hypoxia and angiogenesis
-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
FVC and FEV1
-measured by spirometry
FEV1
amount of air that can be expelled from the lungs in the first second of exhalation
FEV1/FVC ratio
-good measure of lung function
-may change due to several factors, including strength of chest muscles, airway resistance, lung compliance, and age
compliance and airflow
-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
obstructive lung disease
-conditions like COPD
-exhalation is difficult, and air remains in the lungs
-results in poor airflow
restrictive lung disease
-conditions like asthma
-inhalation is difficult, the lungs are not being fully inflated
-also results in poor airflow
alveolar surface tension and pulmonary surfactant
-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
reversal potential of an ion
membrane potential value at which there is no net flux
what is nernst equation used for
used to calculate the potential of an ion (charge z) across a membrane
Effect of IP3
Causes calcium release from ER
Effect of DAG
Activates protein kinase C (PKC)
