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Terms in this set (518)

- Histamine, an important inflammatory signaling molecule, is stored in the granules (vesicles) of mast cells, found in connective tissue
- Histamine released at sites of damage triggers nearby blood vessels to dilate and become more permeable
- Activated macrophages and neutrophils discharge cytokines, signaling molecules that enhance an immune response, in order to promote blood flow to the site of injury or infection
- Increase in local blood supply causes the redness and increased skin temperature
- Blood engorged capillaries leak fluid into neighboring tissues, causing swelling
- Activated complement proteins promote further release of histamine, attracting more phagocytic cells that enter injured tisses and carry out additional phagocytosis (enhanced blood flow to the site helps deliver antimicrobial peptides--the result is an accumulation of pus, a fluid rich in white blood cells, dead pathogens, and cell debris from damaged tissue)
- Sever tissue damage or infection may lead to a system response that causes injured or infected cells to secrete molecules that stimulate the release of addition neutrophils from the bone marrow
- In a severe infection, such as meningitis or appendicitis, the number of white blood cells in the blood may increase several fold within a few horus
- Fever: Substances released by activated macrophages cause the body's thermostat to reset to a higher temperature (elevated body temperature may enhance phagocytosis and speed up chemical reactions)
- Septic shock: Overwhelming systemic inflammatory response characterized by high fever, low blood pressure, and poor blood flow through capillaries (usually occurs in the very old or very young)
- Each person makes more than 1 million different B cell antigen receptors (only about 20,000 protein-coding genes in the human genome)
- Capacity to generate diversity is built into the structure of Ig genes
- A receptor light chain is encoded by three gene segments: a V segment, a joining (J) segment, and a C segment
- The V and J segments together encode the V region of the receptor chain, while the C segment encodes the constant region
- The light chain gene contains a single C segment, 40 different V segments, and 5 different J segments
- These alternative copies of the V and J segments are arranged within the gene in a series
- The pieces can be combined in 200 different ways
- Early in B cell development, an enzyme complex called recombinase links one light-chain V gene segment to one J gene segment
- This recombination event eliminates the long stretch of DNA between the segments, forming a single exon that is part V and part J
- There is only an intron between the J and C DNA segments, no further DNA rearrangement is required
- Instead, the J and C segments of the RNA transcript will be joined when splicing removes the intervening RNA
- Recombinase acts randomly, linking any one of the 40 V gene segments to any one of the 5 J gene segments
- Heavy chain genes undergo a similar rearrangement
- In any given cell, only one allele of a light-chain gene and one allele of a heavy-chain gene are rearranged (the rearrangements are permanent and are passed on to the daughter cells when the lymphocyte divides)
- After both the light and heavy chain genes have rearranged, antigen receptors can be synthesized
- Each pair of randomly rearranged heavy and light chains results in a different antigen-binding site
- For the total population of B cells in a human body, the number of such combinations is 3.5 x 10^6
- Mutations during VJ recombination add additional variation
- Generally, B cell activation by an antigen is aided by cytokines secreted from helper T cells that have encountered the same antigen
- Stimulated by both an antigen and cytokines, the B cell proliferates and differentiates into memory B cells and plasma cells
- Macrophage or dendritic cell can present fragments from a wide variety of protein antigens, whereas a B cell presents only the antigen to which it specifically binds
- When an antigen first binds to receptors on the surface of a B cell, the cell takes in a few foreign molecules by receptor-mediated endocytosis
- The class II MHC protein of the B cell then presents an antigen fragment to a helper T cell (this direct cell-to-cell contact is usually critical to B cell activation
- An activated B cell gives rise to thousands of identical plasma cells (these cells stop expressing a membrane bound antigen receptor and begin secreting approximately 2,000 antibodies every second of the cells 4 to 5 day life span)
- Most antigens recognized by B cells contain multiple epitopes so exposure to a single antigen normal activates a variety of B cells, with different plasma cells producing antibodies directed against different epitopes on the common antigen

1) After an antigen-presenting cell engulfs and degrades a pathogen, it displays an antigen fragment complexed with a class II MHC molecule. A helper T cell that recognizes the complex is activated with the aid of cytokines secreted from the antigen presenting cell
2) When a B cell with receptors for the same epitope internalizes the antigen, it displays an antigen fragment on the cell surface in a complex with a class II MHC molecule. An activated helper T cell bearing receptors specific for the displayed fragment binds to the B cell. This interaction, with the aid of cytokines from the T cell, activates the B cell
3) The activated B cell proliferates and differentiates into memory B cells and antibody-secreting plasma cells. The secreted antibodies are specific for the same antigen that initiated the response
- Doesn't actually kill pathogens, but by binding to antigens, they mark pathogens in various ways for inactivation or destruction
- Simplest activity is neutralization: antibodies bind to viral proteins in order to prevent infection of a host cell (neutralizing the virus)
- Similarly antibodies sometimes bind to toxins released in body fluids, preventing the toxins from entering body cells
- Opsonization: antibodies bound to antigens on bacteria present a readily recognized structure for macrophages or neutrophils (When antibodies facilitate phagocytosis they also help fine-tune the humoral immune response (this positive feed back between innate and adaptive immunity contributes to a coordinated, effective response to infection)
- Because each antibody has two antigen-binding sites, antibodies sometimes also facilitate phagocytosis by linking bacteral cells, virus particles, or other foreign substances into aggregates
- Antibodies sometimes work together with the proteins of the complement system to dispose of pathogens
- Binding of a complement protein to an antigen-antibody complex on a foreign cell (or an enveloped virus) triggers a cascade in which each protein of the complement system activates the next protein
- Ultimately, activated complement proteins generate a membrane attack complex that forms a pore in the membrane of the foreign cells that cause it to swell and lyse
- There is a mechanisms by which they can bring about death of infected body cells: when a virus uses a cell's biosynthetic machinery to produce viral proteins, these viral products can appear on the cell surface (if antibodies specific for epitopes on these viral proteins bind to the exposed proteins, the presence of the bound antibody at the cell surface can recruit a natural killer cell which releases proteins that cause the infected cell to undergo apoptosis)
Energy Investment
1) Hexokinase transfers a phosphate group from ATP to glucose, making it more chemically reactive. The charge on the phosphate also traps the sugar in the cell
2) Glucose 6-phosphate is converted to its isomer, fructose 6-phosphate by phosphogluco-isomerase
3) Phosphofructokinase transfers a phosphate group from ATP to the opposite end of the sugar, investing a second molecule of ATP. This is a key step for regulation of glycolysis
4) Fructose 1,6-bisphosphate is cleaved by aldolase into two different three-carbon sugars (isomers: Dihydroxyacetone phosphate and Glyceraldehyde 3-phosphate). The energy payoff phase occurs after glucose is split into two three-carbon sugars so the coefficient 2 precedes all molecules in this phase
Energy Payoff
5) Isomerase catalyzes the reversible conversion between the two isomers. This reaction never reaches equilibrium; Glyceraldehyde 3-phosphate is used as the substrate of the next reaction as fast as it forms
6) Triose phosphate dehydrogenase catalyzes two sequential reactions. First the sugar is oxidized by the transfer of electrons to NAD+, forming NADH. Second, the energy released from this this exergonic redox reaction is used to attach a phosphate group to the oxidized substrate, making a product of very high potential energy
7) The phosphate group added in the previous step is transferred to ADP (substrate level phosphorylation) in an exergonic reaction. The carbonyl group of a sugar has been oxidized to the carboxyl group of an organ acid (3-phosphoglycerate)
8) Phosphoglyceromutase relocates the remaining phosphate group
9) Enolase causes a double bond to form in the substrate by extracting a water molecule, yielding phosphoenolpyruvate (PEP), a compound with a very high potential energy, 2H2O leave here
10) The phosphate group is transferred from PEP to ADP by Pyruvate kinase (a second example of substrate level phosphorylation) forming pyruvate
- First molecule of the electron transport chain in complex I is transferred from NADH to flavoprotein (prosthetic group called flavin mononucleotide (FMN))
- Flavoprotein returns to oxidized state as it passes electrons to an iron-sulfur protein which then passes the electrons to a compound called ubiquinone (Q) (electron carrier that is a small hydrophobic molecule and is the only member of the electron transport chain that isn't a protein and is individually mobile within the membrane rather residing in a complex)
- Most remaining electron carriers between ubiquinone and oxygen are proteins called cytochromes (prosthetic group, heme, has an iron atom that accepts and donates electrons)
Last cytochrome of the chain, cyt a3, passes its electrons to oxygen
- Each oxygen atom also picks up a pair of hydrogen ions to form water
- FADH2 adds its 2 electrons to the chain from within complex II at a lower energy level
- The electron transport chain provides about 1/3 less energy for ATP synthesis when the electron donor is FADH2 rather than NADH
- Electron transport chain makes no ATP
- Establishing the H+ gradient is a major function, the chain converts energy using the exergonic flow of electrons from NADH and FADH2 to pump H+ across the membrane (form the mitochondrial matrix into the intermembrane space)
- H+ has a tendency to move back across the membrane, diffusing down its gradient and ATP synthase are the only sites that gives a route through the membrane for H+
- Certain members of the electron transport chain accept and release protons along with electrons
1) A photon of light strikes a pigment molecule in a light harvesting complex of PS II, boosting one of its electrons to a higher energy level. As this electron falls back to its groundstate, an electron in a nearby pigment molecule is simultaneously raised to an excited state. The process continues, with the energy being relayed to other pigment molecules until it reaches the P680 pair of chlorophyll a molecules in the PS II reaction-center complex. It excites an electron in this pair of chlorophylls to a higher energy state
2) This electron is transferred from the excited P680 to the primary electron acceptor. We can refer to the resulting form of P680, missing an electron, as P680+
3) An enzyme catalyzes the splitting of a water molecule into two electrons, two hydrogen ions, and an oxygen atom. The electrons are supplied one by one to the P680+ pair, each electron replacing one transferred to the primary electron acceptor. (P680+ is the strongest biological oxidizing agent known; its electron "hole" must be filled. This greatly facilitates the transfer of electrons from the split water molecule) The H+ are released into the thylakoid lumen. The oxygen atom generated by the splitting of another water molecule, forming O2
4) Each photoexcited electron passes from the primary electron acceptor of PS II or PS I via an electron transport chain. The electron transport chain between PS II and PS I is made up of the electron carrier plstoquinone (Pq), a cytochrome complex, and a protein called plastocyanin (Pc)
5) The exergonic "fall" of electrons to a lower energy level provides energy for the synthesis of ATP. As electrons pass through the cytochrome complex, H+ are pumped into the thylakoid lumen, contributing to the proton gradient that is subsequently used in chemiosmosis
6) Meanwhile, light energy has been transferred via light-harvesting complex pigments to the PS I reaction-center complex, exciting an electron of the P700 pair of chlorophyll a molecules located there. The photoexcited electron was then transferred to PS I's primary electron acceptor, creating an electron "hole" in the P700 called P700+. P700+ can now act as an electron acceptor, accepting an electron that reaches the bottom of the electron transport chain from PS II
7) Photoexcited electrons are passed in a series of redox reactions from the primary electron transport chain of PS I down a second electron transport chain through the protein ferredoxin (Fd) (this chain does not create a proton gradient and thus does not produce ATP)
8)The enzyme NADP+ reductase catalyzes the transfer of electrons from Fd to NADP+. Two electrons are required for its reduction to NADPH. This molecule is at a higher energy level than water, and its electrons are more readily available for the reactions of the Calvin cycle than were those of water. This process also removes an H+ from the stroma
1) When the membrane of the axon is at the resting potential, most voltage-gated sodium channels are close. Some potassium channels are open, but most voltage-gated potassium channels are closed
2) When a stimulus depolarizes the membrane, some gated sodium channels open, allowing more Na+ to diffuse into the cell. The Na+ inflow causes further depolarization, which opens still more gated sodium channels, allowing even more Na+ to diffuse into the cell
3) Once the threshold is crossed, the positive-feedback cycle rapidly brings the membrane potential close to ENa. This stage of the action potential is called the rising phase
4) Two events prevent the membrane potential from actually reaching ENa. Voltage-gated sodium channels inactivate soon after opening, halting Na+ inflow, and most voltage-gated potassium channels open, causing a rapid outflow of K+. Both evens quickly bring the membrane potential back toward EK. This stage is called the falling phase
5) In the final phase of an action potential, called the undershoot, the membrane's permeabiltiy to K+ is higher than at rest, so the membrane potential is closer to Ek than it is at the resting potential. The gated potassium channels eventually close and the membrane potential returns to the resting potential
- The sodium channels remain inactivated during the falling phase and early part of the undershoot and as a reuslt if a second depolarizaing stimulus occurs during this period, it will be ubalbe to trigger an action potential the downtime whe a second action potential can not be initiated is called the refractory period, interval sets a limit on the maximum frequiency at which action potentials can be generated