Term
| What are the sources and actions of histamine? |
|
Definition
Sources: mast cells, basophils, platelets
Actions: Vasodilation, increased vascular permiability and endothelial activation |
|
|
Term
| What are the sources and actions of prostaglandins? |
|
Definition
Sources: mast cells leukocytes
Actions: vasodilation, pain, fever |
|
|
Term
| What are the sources and actions of leukotrienes? |
|
Definition
Sources: mast cells, leukocytes
Actions: Increased vascular permeability, chemotaxis, leukocyte adhesion, leukocyte activation |
|
|
Term
| What are the sources and actions of TNF, IL-1, and IL-6? |
|
Definition
Sources: Macrophages, endothelial cells, mast cells
Actions:
Locally --> endothelial activation (expression of adhesion molecules)
Systemically --> Fever, metabolic abnormaities and hypotension |
|
|
Term
| What are the sources and actions of chemokines? |
|
Definition
Sources: leukocytes, activated macrophages
actions: chemotaxis, leukocyte activation |
|
|
Term
| What are the sources and mechanisms of action of platelet activating factor? |
|
Definition
Sources: leukocytes, mast cells
Actions: vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst |
|
|
Term
| What are the sources and mechanisms of action of complement proteins? |
|
Definition
Sources: plasma (produced by the liver)
Actions: leukocyte chemotaxis and activation, direct killing (membrane attack complex), vasodilation (via stimulation of mast cells, which contain histamine, prostaglandins, and leukotrienes) |
|
|
Term
| What are the sources and actions of Kinins? |
|
Definition
Source: plasma (produced by the liver)
Actions: increased vascular permeability, smooth muscle contraction, vasodilation, pain |
|
|
Term
| Which arachidonic acid metabolites (Eicosanoids) induce vasodilation? |
|
Definition
PGI2 (prostacyclin), PGE1, PGE2, PGD2 (made by mast cells)
PGI2 is also a potent inhibitor of platelet aggregation
PGD2 is also chemoattractant or neutrophils
PGE2 is hyperalgesic and can also be involved in fever (if suboptimal concentrations of bradykinin and histamine) |
|
|
Term
| Which arachidonic acid metabolites (Eicosanoids) induce vasoconstriction? |
|
Definition
Thromboxane A2, leukotrines C4, D4, E4
TxA2 is also a potent platelet aggregating agent |
|
|
Term
| Which arachidonic acid metabolites (Eicosanoids) induce increased vascular permeability? |
|
Definition
Leukotrines C4, D4, E4
p.s. these also induce vasoconstriction |
|
|
Term
| Which arachidonic acid metabolites (Eicosanoids) induce chemotaxis and leukocyte adhesion? |
|
Definition
| Leukotrine B4 and Hydroxyeicosatetraenoic acid (HETE) |
|
|
Term
| What leyukotrine does not contain cysteinyl? |
|
Definition
| Leukotrine B4, most prominent leukotrine in neutrophils, is also chemotactic for neuts (aggregation and adhesion to endothelium) and activates neuts (generation of ROS and release of lysosomal enzymes) |
|
|
Term
| What are CpG islands and what is their overall impact on DNA transcription? |
|
Definition
| 8-12 repeats of CG nucleotides located in the promotor region of genes. These regions are preferentially methylated (this physically prevents binding of RNA polymerase and INHIBITS gene transcription) |
|
|
Term
| Which of the histone proteins is not in the nucleosome? |
|
Definition
H1- linking protein that helps stabilize overall chromatin architecture.
Also the only histone protein that's not in a dimer |
|
|
Term
| What residues on histones are more commonly methylate and what is effect on gene transcription? |
|
Definition
Typically lysine and to a lesser extent arginine, methylation of these residues wraps the chromatin more tightly around the nucleosome resulting in inhibition of gene transcription
** can sometimes activate gene transcription depending on the residue that is methylated |
|
|
Term
| What are the components of the nucleosome? |
|
Definition
| DNA segments (147 BP), wrapped around a histone (comprised of 4 dimers, H2A, H2B, H3, H4) |
|
|
Term
| What enzyme acetylates histones and what is the effect on gene transcription? |
|
Definition
| Histone acetyltransferases (HAT) preferentially acetylate lysine residues which activate gene transcription |
|
|
Term
| What is the effect of histone deacetylases (HDACS) on gene transcription? |
|
Definition
| They deacetylate lysine residues on histones thereby inhibiting gene transcription. |
|
|
Term
| Which is more active, heterochromatin or euchromatin? |
|
Definition
| Euchromatin (ie. increased histone acetylation), more differentiated cells have to express more specific genes and therefore have more euchromatin and acetylated histones than pluripotent stem cells or cancer cells (which are more methylated) |
|
|
Term
| What is the average size of a micro RNA (miRNA) vs. a long noncoding RNA (lncRNA) |
|
Definition
| miRNA is on average 22 nucleotides, lncRNA is on average 200 nucleotides |
|
|
Term
| What is the effect of miRNA on gene transcription by what major mechanisms does it achieve this effect? |
|
Definition
| Major effect is inhibitory via cleavage of mRNA, steric hindrance that prevents ribosomes from binding and translating mRNA, and sequestration |
|
|
Term
| What enzyme allows primary miRNAs (Pri-miRNA) to be converted into precursor (Pre-miRNA) and where in the cell does this occur? |
|
Definition
| Pri-miRNA is converted into Pre-miRNA by a multi-protein complex called the microprocessor, which includes an enzyme (Drosha) and an RNA binding protein (DGCR8, aka Pasha). This occurs in the nucleus. |
|
|
Term
| How does pre-miRNA (precursor miRNA) get from the nucleus to the cytoplasm? |
|
Definition
|
|
Term
| What enzyme is responsible for converting pre-miRNA into mature miRNA in the cytoplasm? |
|
Definition
|
|
Term
| What are the components of the RNA induced silencing complex (RISC)? |
|
Definition
| guide strand of mature miRNA bound at the 5' end to transactivation response RNA binding protein (TRBP) + Argonaute 2 (Ago2) + protein kinase RNA activator (PACT) and other RNA binding proteins |
|
|
Term
| Other than size, how are long noncoding RNA (lncRNA) different from micro RNA (miRNA) |
|
Definition
| lncRNA can bind to DNA and RNA (miRNA just affect RNA) and can either activate or repress gene transcription (miRNA just suppress gene transcription by degrading or impairing translation of mRNA) |
|
|
Term
| Which phospholipids are more prevalent on the inner cell membrane leaflet in health? |
|
Definition
| Phosphatidylserine and phosphatidylethanolamine |
|
|
Term
| Which phospholipids are more prevalent in the outer leaflet of the cell membrane in health? |
|
Definition
| phosphatidylcholine and sphingomyeln |
|
|
Term
| What phospholipid is more prevalent in the outer leaflet of the cell membrane in cells undergoing apoptosis? |
|
Definition
|
|
Term
| What is the function of flippase? |
|
Definition
Maintain phospholipid asymmetry of the plasma membrane, flipping phosphatidylserine and phosphatidylethanolamine to the inner leaflet
flippase flips in |
|
|
Term
| What is the function of floppase? |
|
Definition
Keeps phosphatidylcholine and sphingomyelin on the outer leaflet of the plasma membrane
Floppase flops out |
|
|
Term
| What are the two major mechanisms for endocytosis? |
|
Definition
| Caveolae mediated (lipid rafts rich in cave-in protein that take in small molecules and some receptors e.g. folate) and receptor mediate (clatherin coated pits, can take in larger molecules) |
|
|
Term
| What is the difference between belt desmosomes/desmosomes and hemidesmosomes? |
|
Definition
| Belt desmosomes/desmosome attached cells to each other and major protein involved is cadherin vs. hemidesomosomes attach cells to basement membranes and major protein involved is integrin |
|
|
Term
| What is the major vasoacitve amine and what is its major action? |
|
Definition
| Histamine, causes vasodilation and increased vascular permeability |
|
|
Term
| What are the major arachidonic acid metabolites, what are their actions and what molecule antagonizes them? |
|
Definition
| Prostaglandins and leukotrines, involved in vascular reactions. leukocyte chemotaxis and activation. Antagonized by lipoxins (which is also an AA metabolite, generated by 12-lipoxgygenaase) |
|
|
Term
| Which cytokines are most important in acute inflammation and what are their major actions? |
|
Definition
| TNF, IL-1 and chemokines, mainly participate in leukocyte recruitment, migration, and activation. |
|
|
Term
| What are the three major functions of the complement pathway? |
|
Definition
Leukocyte chemotaxis (C3a, C5a and to a lesser extent C4a)
Opsonization and phagocytosis (C3b)
Cell killing (formation of MAC from multiple C9 molecules) |
|
|
Term
| What are the principle mediators of vasodilation in inflammatory reactions? |
|
Definition
| Histamine and prostaglandins |
|
|
Term
| What are the principle mediators of increased vascular permeability in inflammatory reactions? |
|
Definition
| Vasoactive amines (histamine, serotonin), complement proteins (C3a and C5a <-- via liberation of histamine from mast cells and other WBC), and leukotrienes C4, D4, E4 (i.e. cysteinyl containing leukotrienes) |
|
|
Term
| What are the principle mediators of increased vascular permeability in inflammatory reactions? |
|
Definition
| Vasoactive amines (histamine, serotonin), complement proteins (C3a and C5a <-- via liberation of histamine from mast cells and other WBC), and leukotrienes C4, D4, E4 (i.e. cysteinyl containing leukotrienes) |
|
|
Term
| What are the principle mediators of chemotaxis, leukocyte recruitment and activation in inflammation? |
|
Definition
| Cytokines (TNF, IL-1), chemokines, complement proteins (C3a, C5a) and leukotriene B4 |
|
|
Term
| What are the principle mediators of fever in inflammatory reactions? |
|
Definition
Cytokines (IL-1, TNF)
prostaglandins |
|
|
Term
| What are the principle mediators of fever in inflammatory reactions? |
|
Definition
Cytokines (IL-1, TNF)
prostaglandins |
|
|
Term
| what are the principle mediators of pain in inflammatory reactions? |
|
Definition
| Prostaglandins and bradykinin |
|
|
Term
| What are the principle mediators of tissue damage in inflammation? |
|
Definition
| Lysozomal enzymes from WBC, ROS |
|
|
Term
| What are the major cytokines that stimulate fever and what is their site of action? |
|
Definition
| TNF and IL-1 stimulate production of prostaglandins in the hypothalamus |
|
|
Term
| What are the major cytokines that stimulate fever and what is their site of action? |
|
Definition
| TNF and IL-1 stimulate production of prostaglandins in the hypothalamus |
|
|
Term
| What cytokine is most important for stimulating production of acute phase proteins by the liver? |
|
Definition
|
|
Term
|
Definition
| LC3 is a protein that is specific for the autophagosome and can be detected via immunohistochemistry |
|
|
Term
| How are enzymes produced in the RER directed to the appropriate region of the golgi for incorporation into the lysosome? |
|
Definition
| These enzymes are tagged with a mannose-6-phosphate which recognizes the M6-phosphate receptor in the golgi --> buds off to form the lysosome |
|
|
Term
| How are misfolded proteins directed to the proteasome? |
|
Definition
|
|
Term
| What type of cell surface receptor is most important in growth factor signaling? |
|
Definition
| Receptor tyrosine kinases |
|
|
Term
| What are the Ink4 inhibitors and what is their significance? |
|
Definition
| P16, P15, P18, P19 are the Ink4 inhibitors, they inhibit ONLY cyclin dependent kinase (ie. CDK) 4 and CDK6 which are necessary for progression of the cell from G1 --> S in the cell cycle. |
|
|
Term
| What are some cell changes associated with reversible cell injury (via light microscopy and EM)? |
|
Definition
Cell swelling and fatty change!
also plasma membrane blebbing, loss of microvilli, small amorphous densities in mitochondria, dilation of ER |
|
|
Term
| What are some cell changes associated with irreversible cell injury (light microscopy and EM)? |
|
Definition
| Nuclear changes: Karyolysis, pyknosis, karyorhexis! also increased cellular eosinophilia (H&E), large amorphous densities in mitochondria, cell and organelle rupture |
|
|
Term
| What cytokine is most important in deposition of connective tissue? |
|
Definition
|
|
Term
| What are the three components of virchow's triad of thrombosis? |
|
Definition
| Endothelial injury, altered blood flow, hypercoagulability (inherited disorder or secondary to environmental or disease factors i.e. bed rest, pregnancy, metastatic neoplasia etc.) |
|
|
Term
| What are the 3 major factors in the pathophysiology of septic shock? |
|
Definition
1. Inflammatory responses to microbial products (pathogen associated molecular patterns, PAMPs) --> activation of WBC, complement, coagulation (via factor 12)
2. Endothelial activation and injury: increased vascular permeability and increased production of vasodilators (NO, C5a/C3a, and platelet activating factor)
3. Procoagulant state (inflammatory cytokines increase production of tissue factor and decreased production of inhibitors to coagulation by endothelium (tissue factor pathway inhibitor, thrombomodulin, protein C) |
|
|
Term
| Leakage of what major mitochondrial protein contributes to development of apoptosis? |
|
Definition
| Cytochrome C (located between inner and outer mitochondrial membranes) --> activates caspases |
|
|
Term
| What organelle plays the biggest role in both apoptosis and necrosis? |
|
Definition
| Mitochondria (mitochondrial damage and dysfunction leads to decreased ATP and increased ROS --> cell membrane damage and necrosis VS. loss of survival signals (e.g. growth factors) and/or DNA damage --> leakage of mitochondrial proteins and apoptosis) |
|
|
Term
| how does increased intracellular calcium affect mitochondria? |
|
Definition
| Stimulates opening of mitochondria permeability transition pore --> depolarized the mitochondria and stops oxidative phosphorylation --> ATP depletion and cellular dysfunction |
|
|
Term
| What four types of enzymes can be activated by increased cytosolic calcium? |
|
Definition
| phospholipase and protease (membrane and cytoskeletal injury), endonuclease (nuclear damage), ATPase (further depletion of ATP) |
|
|
Term
| What are BH3 only proteins? |
|
Definition
e.g. BIM, BID
A type of BCL2 protein that senses DNA damage or decreased survival signals --> antagonizes antiapoptotis proteins (also BCL2 proteins) and activation of proapoptotis proteins (also BCL2p proteins) --> apoptosis |
|
|
Term
| What are the components of the apotosome? |
|
Definition
Cytochrome C + APAF-1 = apoptosome intrinsic/mitochondrial pathway: (apoptosome cleaves pro-caspase 9 -> active Caspase 9 then activates capsize 3 --> apoptosis)
Â
extrinsic/death receptor pathway: Caspase 8 |
|
|
Term
| What is the function of Smack and diablo? |
|
Definition
pro-apoptotic
Smack and Diablo are mitochondrial proteins that bind and neutralize inhibitors of apoptosis resulting in capsase activation and apoptosis) |
|
|
Term
| What type of mutations best follow mendalian modes of inheritance? |
|
Definition
point mutations
Silent (different codon, same amino acid)
nonsence (stop codon, premature termination at protein translation)
Missence (changed to a different amino acid --> conservative (biologically similar to wild type aa) vs. non-conservative (very different biochemical properties of new aa) |
|
|
Term
| How do frameshift mutations arise and what are the typical phenotypic results in end proteins? |
|
Definition
| insertion or deletion of nucleotides in anything other than multiples of 3 --> typically result in misfolded proteins --> ER stress and misfolded protein response |
|
|
Term
| What type of structures are most offend affected by autosomal dominant mutations? |
|
Definition
| receptors and structural proteins |
|
|
Term
| T/F- in the case of autosomal dominant mutations at least one of the parents must be affected |
|
Definition
| false- if the mutation is inherited then yes, a parent must be affected (because only one copy of the mutated allel is necessary for the mutated phenotype), BUT sporadic mutations can occur in cases where both parents or normal |
|
|
Term
| What is incomplete penetrance for genetic mutations? |
|
Definition
you have the mutation but are phenotypically normal
Autosomal dominant mutations often have incomplete penetrance due to the variable ability of the remaining normal allel to compensate for the mutated one |
|
|
Term
| What is variable expressivity for genetic mutations? |
|
Definition
anyone that has the mutation invariably develops the disease phenotype, but the degree to which you're affected is variable
Usually occurs in autosomal recessive because all diseased individuals are homozygous. The variability in expressivity is affected by epigenetics and other unknown factors. |
|
|
Term
| What is the #1 mendelian disorder? |
|
Definition
| Autosomal recessive mutations |
|
|
Term
| T/F in the case of autosomal recessive mutations, parents are always unaffected |
|
Definition
|
|
Term
| which chromosomal abnormalities are usually lethal (embryonic)? |
|
Definition
Monosomy (missing a chromosome)
Trisomy (1 additional chromosome, more common in cattle) |
|
|
Term
| What chromosomes are most likely to have mosaicism? |
|
Definition
|
|
Term
| What type of proteins are most offend affected by autosomal recessive mutations? |
|
Definition
|
|
Term
| what is the molecular tag to direct molecules to lysosomes? |
|
Definition
|
|
Term
| What three enzymes are most often implicated in cases of glycogen storage diseases? |
|
Definition
hexokinase (aka glucokinase)
phosphofructokinase (type VII)
Glucose-6-phosphatase (type 1) |
|
|
Term
| What are the purine nucleotides? |
|
Definition
|
|
Term
| What are the purine nucleotides? |
|
Definition
|
|
Term
| What are the pyrimidine nucleotides? |
|
Definition
| Thymine, cytosine, uracil (RNA) |
|
|
Term
| What amino acids help histones bind to DNA and why? |
|
Definition
| arginine and lysine, these are positively charged amino acids which can strongly bind to negatively charged DNA molecules |
|
|
Term
| What is a nondisjunction error in mitosis? |
|
Definition
| failure of chromosome pairs to separate during cell division -> results in one cell with both chromosomes and the other with neither. |
|
|
Term
|
Definition
| Two or more populations of cells with different chromosomal karyotype (number and appearance of chromosomes in a cell) in the same animal. <-- usually the result of mitotic errors in early development |
|
|
Term
| What are two examples of secreted pattern recognition receptors (PRRS)? |
|
Definition
Collectins (ex. mannose binding lectins and pulmonary surfactant)
Pentraxin (a pentamer, includes CRP which activates the classical pathway of complement)
*largely function to bind to microbial surfaces and activate complement |
|
|
Term
| What are two examples of transmembrane pattern recognition receptors? |
|
Definition
Toll-like receptors (TLRs)
C-type lectins
*mostly limited to macs, NK cells, and dendritic cells |
|
|
Term
| What are some examples of cytosolic pattern recognition receptors? |
|
Definition
retinoic acid-inducible gene (RIG)-1-like receptors (RLRs)
nucleotide-binding domain (NOD)
Leucine-rich repeat-containing receptors (NLRs)
**widely distributed, present in all nucleated cells |
|
|
Term
| Which cytokine is most important for recognizing intracellular pathogens (e.g viruses)? |
|
Definition
Type-1 interferon
** increased transcription of Type 1 IFN is mediated by signaling of a cytosolic PRRs (Retinoid acid-inducible gene-1-like receptor aka RLR) which detect abnormal RNA |
|
|
Term
| How do leucine-rich repeat-containing receptors (NLRs) regulate immunity and inflammation? |
|
Definition
Increased activation of a variety of nuclear transcription factors including: nuclear factor kappa B, interferon regulatory factor, and nuclear factor of activated T lymphocytes
Some are a component of the inflammasome- a multi protein complex that ultimately activates caspase-1 and ultimately cleaves and activates pro-inflammatory cytokines |
|
|
Term
| Which TLRs detect gram negative bacteria? |
|
Definition
| 4 (LPS), 5 (Flagellin, also present on Gram +) |
|
|
Term
| Which TLRs detect viral nucleic acids (i.e. intracellular molecules)? |
|
Definition
| TLR 3 (DNA), 7 (ssRNA), 8, 9 (DNA) |
|
|
Term
| What are the major PAMPS (ie. things that are detected by PRRs) associated with gram positive bacteria, gram negative bacteria, viruses, and fungi? |
|
Definition
Gram positive- peptidoglycan
Gram negative- LPS
viruses- double stranded RNA
fungi- alpha-glucans |
|
|
Term
| What is the universal signaling molecule for nuclear factor kappa B activation? |
|
Definition
| MyD88 (a receptor associated kinase that is associated with the cytoplasmic domain of all TLRS, IL-1 receptors and IL-18 receptors) |
|
|
Term
| What is the significance of B7 with regards to adaptive and innate immunity? |
|
Definition
B7 is a costimulatory ligand present on dendritic cells and necessary for them to activate naive T lymphocytes in the context of MHC antigen presentation.
B7 binds to the CD28 receptor on T lymphs. This occurs in the context of TLR mediated PAMP recognition |
|
|
Term
| What types of cells have MHC class I molecules vs. MHC class II molecules? |
|
Definition
MHC I - all nucleated cells
MHC II- mostly antigen presenting cells
** T cells can only recognize antigens in the context of MHC molecules (vs. B cell receptors (Ig) which can directly recognize antigen) |
|
|
Term
| What are the most common lymphocytes in the peripheral blood? |
|
Definition
T Lymphocytes
** most have alpha-beta TCR |
|
|
Term
| Which TLR doesn't have MYD88 adapter? |
|
Definition
|
|
Term
| Which TLRs are endosomal? |
|
Definition
|
|
Term
| What is the most important down streaming signaling for TLRs? |
|
Definition
|
|
Term
| Which two molecules make up AP-1? |
|
Definition
|
|
Term
| What nucleotides are involved in trinucleotide repeat mutations? |
|
Definition
Cytosine and Guanine
** usually occurs in the 5 prime untranslated regions or introns (resulting in gene silencing)
Gain of function mutations may if located in the exon (less common than gene silencing for trinucleotide repeat mutation, tends to affect protein conformations) |
|
|
Term
| If a gene exhibits paternal imprinting, what allel is silenced? |
|
Definition
Paternal allel (so maternal allel is expressed if the gene has paternal imprinting)
*** this occurs in the gamete prior to fertalization |
|
|
Term
| What signal molecule is essential for autophagy initiation? |
|
Definition
Beclin-1
*LC3 drives physical formation of the autophagosomal membrane |
|
|
Term
| What are the most potent inducers of pyroptosis? |
|
Definition
| Flagellin (induces cannonical NLRP3/caspase-1 pathway) LPS (non-cannonical, unknown cytosolic receptor/other caspase (11 in mice, 5 in people) pathway) |
|
|
Term
| What is the effect of inflammasome formation? |
|
Definition
activation of IL-1b (lymphocyte activation, pyrogen) and IL-18 (macrophage activation, INFgamma)
(pro IL-1b and IL-18 are transcribed via NF-kb pathway secondary to TLR recognition of PAMPS/DAMPS but need to be activated by Caspse-1 of the inflammasome) |
|
|
Term
| What structural protein is involved in inflammasome mediated activation secondary to detection of microbial DNA (and autoimmune reactions agains host DNA)? |
|
Definition
|
|
Term
| What is the executioner caspase for apoptosis? |
|
Definition
|
|
Term
|
Definition
Costimulatory molecules on antigen presenting cells (CD80/CD86)
** B7 proteins bind to receptors on T cells which either activate (CD28) or inhibit (CTLA4) that T cell |
|
|
Term
| What second signal molecule on T lymphocytes is activating vs. inhibitory? |
|
Definition
CD28 activates
CTLA4 inhibits |
|
|
Term
| T/F T cells cannot be activated in the absence of antigen presenting cells |
|
Definition
True- must be presented peptide AG via MHC as first activating signal
** then must have a second costimulatory signal (CD28) bind to B7 proteins (CD80/86) on the AG presenting cell |
|
|
Term
| What are the two costimulatory pathways that can activated B lymphocytes? |
|
Definition
1. CD21 (bind soluble complement proteins)
2. CD40 (binds to activated CD4+ T cells) <-- this is the most efficient was for B lymph activation |
|
|
Term
| What is the major cytokine that induces a TH1 response and what cytokines are produced by TH1 lymphs? |
|
Definition
INF-gamma (and also IL-12) induce TH1
INF-gamma is the major cytokine produced by TH1 lymphs
***major pathway against intracellular microbes, macrophages activation, IgG production |
|
|
Term
| What is the major cytokine that induces a TH2 response and what cytokines are produced by TH2 lymphs? |
|
Definition
IL-4 induces TH2 response
Major cytokines produced by TH2 lymphs: IL-4 (+ IL-5, IL-13)
** major pathway against helminth parasites, eosinophil and mast cell activation, IgE production |
|
|
Term
| What is the major cytokine that induces a TH17 response and what cytokines are produced by TH17 lymphs? |
|
Definition
IL-23, IL-6, IL-1 (+ TGF-beta) incude TH17 response
Major cytokines produced by TH17 lymphs: IL-17 (IL-22)
** extracellular microbes, recruits mixed inflammatory cells |
|
|
Term
| What is the master regulator transcription factor for TH1? |
|
Definition
|
|
Term
| What is the master regulator transcription factor for TH2? |
|
Definition
|
|
Term
| What is the master regulator transcription factor for TH17? |
|
Definition
|
|
Term
| What surface antigen is associated with Treg? |
|
Definition
|
|
Term
| What is the master regulator transcription factor associated with Treg? |
|
Definition
|
|
Term
| How do CD8+ lymphs kill cells? |
|
Definition
Perforin (transmembrane pore forming molecule)
Granzymes (serine proteases that cleave aspartate residues and activate caspase enzymes ---> apoptosis) |
|
|
Term
| What antibodies and cells are associated with Type 1 hypersensitivity reactions? |
|
Definition
| Associated with TH2 response, IgE and eosinophils |
|
|
Term
| What antibodies and cells are associated with Type 2 hypersensitivity reactions? |
|
Definition
| IgG and IgM bind to antigens on normal cells/ECM and induce phagocytosis and complement activation (e.g. IMHA, neonatal isoerythrolysis, transfusion rxn) |
|
|
Term
| What antibodies and cells are associated with Type 3 hypersensitivity reactions? |
|
Definition
| IgG and IgM --> ag/ab complexes deposit in tissues (esp. kidney, joint, and small vessel) causing inflammation |
|
|
Term
| What antibodies and cells are associated with Type IV hypersensitivity reactions? |
|
Definition
Mediated by activated T cells:
CD4+ (Th1(INF-gamma) and Th17(IL-1, IL-6))
CD8+ (directly kill ag bearing target cells, eg. host/transplanted tissue, virally infected cells, tumor cells) |
|
|
Term
| What is the major cytokine produced by Treg? |
|
Definition
TGF-b
**ANTI-INFLAMMATORY! also involved in wound repair and fibrosis ** <-- alternatively activated macs |
|
|
Term
| What are the major effectors of early vs. late stage type I hypersensitivity disorders (e.g. allergic reactions) |
|
Definition
Early phase- preformed mediators (histamine, enzymes, heparin, AA metabolites) --> vasodilation, increased vascular permeability, smooth muscle spasm
Late phase- cytokines/chemokines (TNF, IL-1, IL-4) --> enhance leukocyte recruitment (esp. EO) that amplify and sustain the inflammatory response in the absence of the offending antigen |
|
|
Term
| What are the granule contents of mast cells? |
|
Definition
| histamine, enzymes (neutral proteases, acid hydrolases), proteoglycans (heparin, chondroitin sulfate) |
|
|
Term
| What are the granule contents of platelets? |
|
Definition
dense granules: contain small molecules (e.g. serotonin, ADP)
Alpha granules: contain proteins, most important (eg. factor V, vWF, fibrinogen, VEGF, PDGF, matrix metaloproteases, TNF and other cytokines) |
|
|
Term
| What cells mediated central vs. peripheral tolerance? |
|
Definition
Antigen presenting cells mediated CENTRAL tolerance
Tregs mediate PERIPHERAL tolerance |
|
|
Term
RE neoplasia, which are reversible and which are irreversible:
initiation, promotion, progression |
|
Definition
Initiation (i.e. mutation) is IRREVERSIBLE
Promotion (something that enables the initiated cell to proliferate) is ALWAYS REVERSIBLE
Progression (accumulation of additional mutation (IRREVERSIBLE) and/or epigenetic dysregulation (REVERSIBLE) <-- BOTH |
|
|
Term
| What is a driver mutation with regards to neoplasia? |
|
Definition
Driver mutations are specific to the development and progression of a tumor
vs. passenger mutations- just the product of genomic instability and often doesn't contribute to the development of neoplasia |
|
|
Term
| What happens when a ligand binds to a receptor tryosine kinase? |
|
Definition
1) dimerization of the receptor
2) autophosphorylation of the kinase component |
|
|
Term
| T/F all non-receptor tyrosine kinases are proto-oncogenes |
|
Definition
| True (e.g. Jak, Src, Abl) |
|
|
Term
| What is the number one ligand for G protein coupled receptors? |
|
Definition
|
|
Term
| Which signaling pathway directly effects gene transcription without any signal transduction? |
|
Definition
|
|
Term
| What component of the notch signaling pathway induces affects gene transcription? |
|
Definition
|
|
Term
| In the Wnt-Frizzled pathway, what is the ligand and what is the receptor? |
|
Definition
Wnt is the ligand
Frizzled is the receptor
** beta-catinin is normally associated with the Frizzle receptor, when free it translocates to the nucleus and stimulates cell proliferation |
|
|
Term
| What TLRs are located intracellularly? |
|
Definition
|
|
Term
| What TLR recognizes double stranded RNA viruses? |
|
Definition
|
|
Term
| What TLRs recognize single stranded RNA viruses? |
|
Definition
|
|
Term
| What TLR recognizes LPS (i.e. gram negative bacteria)? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What TLR recognizes flagellin? |
|
Definition
|
|
Term
| What TLR recognizes gram positive bacteria? |
|
Definition
TLR1, TLR2, TLR6Â
Â
***Ligand for all is lipoprotein |
|
|
Term
| What TLR recognize fungi? |
|
Definition
|
|
Term
| What TLR recognize protozoa? |
|
Definition
|
|
Term
| What adapter protein does TLR 3 use? |
|
Definition
|
|
Term
| What are the INK4 inhibitors and what CDKs do they inhibit? |
|
Definition
p15, p16, p18, p19 are the INK4 inhibitors
selectively inhibit CDK4 and CDK6 (progression from G1 to S) |
|
|
Term
| T/F RB is hypophosphrylated (active) in quiescent cells |
|
Definition
True
** becomes phosphorylated (inactive) when cells progress through G1/S checkpoint |
|
|
Term
| What major biosynthetic pathway is vitamin C required for? |
|
Definition
| Hydroxylation of pro collagen (via activation of prolyl and lysyl hydroxylases) |
|
|
Term
| What vitamin is important for orderly differentiation of mucus secreting epithelium? |
|
Definition
|
|
Term
| What is the primary site for xenobiotic biotransforming enzymes? |
|
Definition
| Endoplasmic reticulum (microsomes) and cytoplasm |
|
|
Term
| In mature animals what tissue is most resistant to ionizing radiation? |
|
Definition
Brain
** ionizing radiation (e.g. X rays) causes DNA damage, so rapidly dividing tissue are most susceptible to injury |
|
|
Term
| Which enzyme is implicated in glycogen storage disease type III? |
|
Definition
| Glycogen debranching enzyme |
|
|
Term
| What is the effect of MLH1 mutations with regards to neoplasia? |
|
Definition
| MLH1 mutations causes DNA mismatch repair--> genomic instibility, mutator phenotype and tumor progression |
|
|
Term
| What enzyme deficiency is associated with mucopolysaccharidosis type 1? |
|
Definition
|
|
Term
| What coagulation factors are substrates of thrombin (factor 2)? |
|
Definition
Thrombin converts Factor 1 (fibrinogen) --> fibrin and activates Factor 13 to cross link the fibrin (clot stability)
Also activates factor 11 and cofactors 8 and 5 |
|
|
Term
| What enzyme cleaves fibrin during thrombolysis? |
|
Definition
|
|
Term
| What does platelet glycoprotein IIb-IIIa bind to? |
|
Definition
|
|
Term
| What condition is associated with deficiency in GpIIa-IIIb? |
|
Definition
| Glanzmann thrombasthenia (GpIIb-IIIa is a platelet glycoprotein that binds to fibrinogen and enhances PLT aggregation) |
|
|
Term
| What condition is associated with deficiency in GpIb? |
|
Definition
| Bernard-Soulier syndrome (GpIb is a platelet glycoprotein that binds to exposed von willebrand factor on subendothelial collagen) |
|
|
Term
| Which coagulation factor accelerates factor Xa production of thrombin (factor 2)? |
|
Definition
|
|
Term
| What signaling pathway is most important for physiologic cardiac muscle hypertrophy? |
|
Definition
| PI3 kinase/Akt (vs. G protein coupled receptors are more involved in pathologic cardiac hypertrophy) |
|
|
Term
| What are PPARs and where are they located? |
|
Definition
| Peroxisome proliferator activated receptors- these are nuclear hormone receptors that function as transcription factors to regulate energy homeostasis and glucose/FA metabolism |
|
|
Term
| Caveolae are most prevalent on which type of cell? |
|
Definition
|
|
Term
| How is scramblase different from flippase and floppase? |
|
Definition
Scramblase is ATP INDEPENDENT and moves phospholipids from inner to outer leaflets along concentration gradients
vs flippase ATP to move phosphatidylserine and phosphatidylethanolamin back inside against concentration gradient (highest concentration of these lips is inner mb)
vs. floppase, ATP to move phosphatidylinositol, sphingomyelin and cholesterol against concentration gradient to outer MB |
|
|
Term
| What mb phospholipid can bind to phagocyte receptors? |
|
Definition
| Phosphatidylserine (moves to the outer mb leaflet during apoptosis as a signal for phagocytosis) |
|
|
Term
| In naive mature B cells, what are the membrane-bound antigen receptors comprised of? |
|
Definition
|
|
Term
| What complement receptor is found on B lymphs? |
|
Definition
|
|
Term
| What receptor does TGF-alpha bind to? |
|
Definition
| EGF (epidermal growth factor receptor)- a receptor tyrosine kinase, stimulates proliferation of epithelial cells |
|
|
Term
| Which growth factor inhibits matrix metalloproteinase expression in wound healing? |
|
Definition
|
|
Term
What are the major functions of VEGF-A?
vs. VEGF-B/PIGF
vs. VEGF-C/D |
|
Definition
Vascular proliferation in response to injury and in tumors, and maintenance of endothelial health (esp. near fenestrated capillaries)
VEGF-B/PIGF- embryonic vessel development
VEGF-C/D- endothelial and lymphatic development |
|
|
Term
| What is the major signaling pathway for receptors that lack intrinsic tyrosine kinase activity? |
|
Definition
|
|
Term
| Where in the cell cycle does p53 induce cell cycle arrest? |
|
Definition
| G1 (Increased levels of p53 result in increased transcription of p21 --> inhibition of CDK4 --> inhibition of RB phosphorylation --> cell cycle arrest) |
|
|
Term
| T/F stem cell division is asymmetric |
|
Definition
|
|
Term
| What is a choristoma/heterotopia? |
|
Definition
Microscopically normal tissue/cells present in an abnormal location (eg. corneal dermoid)
vs. hamartoma- excessive focal overgrowth of mature cells/tissue native to the organ in which it occurs |
|
|
Term
| What transcription factors are associated with loss of e-cadherin expression in carcinomas undergoing epithelial to mesenchymal transition? |
|
Definition
|
|
Term
|
Definition
Apoptosis stimulated by loss of cellular adhesion
(often downregulated in metastatic tumor cells) |
|
|
Term
| What is the difference between a true hermaphrodite and a pseudohermaphrodite? |
|
Definition
True hermaphrotide = presence both both testicular and ovarian tissue
Pseudohermaphrodite = disagreement between phenotypic (i.e. external genitalia) and gonadal (testicular and ovarian tissue) sex |
|
|
Term
| What are the four major mechanisms for hepatic lipidosis? |
|
Definition
1. increased delivery of FA from gut or adipose
2. decreased beta oxidation of FA --> ketones
3. decreased synthesis of apoprotein
4. decreased synthesis of lipoprotein/decreased release of lipoprotein from hepatocytes |
|
|
Term
| T/F Epigenetic modifications are inherited |
|
Definition
True
Epigenetics are heritable chemical modifications of DNA or histones that do not alter the DNA sequence (e.g. DNA methylation, histone acetylation/methylation) |
|
|
Term
| What is linkage disequilibrium with regards to genetics? |
|
Definition
| Coinheritance of SNPs along with disease causing mutations due to physical proximaty of the SNP and the causative mutation |
|
|
Term
| Which cytokine mediates the catabolic effects of endotoxic shock? |
|
Definition
|
|
Term
| What type of collagen predominates in the basement membrane? |
|
Definition
|
|
Term
| In the arachidonic acid pathway what is the precursor of prostaglandin E2, prostaglandin I2, and thromboxane A2? |
|
Definition
|
|
Term
| How does C3a increase vascular permeability? |
|
Definition
| Induction of histamine release from mast cells |
|
|
Term
| How does vitamin K contribute to the activation of the vit k dependent coag factors? |
|
Definition
Vit k is necessary for conversion of glutamine acid residues to gamma-carboxygluyamic acid
** vit k dependent factors are 2, 7, 9, and 10 |
|
|
Term
| Increases in what type of adhesion molecule is associated with type 1 endothelial cell activation? |
|
Definition
|
|
Term
| What do Weibel-Palade bodies contain? |
|
Definition
|
|
Term
| What is the role of autoimmune regulator protein (AIRE)? |
|
Definition
| Deletion of self-reactive T lymphs in the thymus (Central T lymph tolerance!) |
|
|
Term
| What cell surface molecule allows NK cells to participate in antibody dependent cellular cytotoxicity? |
|
Definition
CD16 (receptor for Fc portion of IgG)
**CD56 is another surface receptor for NK cells, of unknown function |
|
|
Term
| What receptors activate NK mediated cytotoxicity? |
|
Definition
NKG2D - recognizes cell surface molecules associated with stress (eg. DNA damage, viral infection)
**IL-12 also actives NK mediated cytotoxicity |
|
|
Term
| How are self reactive T lymphs destroyed in the context of central tolerance? |
|
Definition
| Extrinsic (FAS-FASL) mediated apoptosis |
|
|
Term
| What is the function of the nucleolus? |
|
Definition
| Synthesis of ribosomal RNA |
|
|
Term
| What organelles are associated with hydraulic change/vacuolar degeneration? |
|
Definition
| The vacuoles represent pinched off segments of swollen endoplasmic reticulum |
|
|
Term
| How does protein misfolding and DNA damage contribute to cell injury? |
|
Definition
| Activation of proapoptotic proteins |
|
|
Term
| Which free radical is inactivated by superoxide dismutase? |
|
Definition
|
|
Term
| Which reactive oxygen species in inactivated by catalase? |
|
Definition
H2O2
- inactivated by catalase in peroxisome, inactivated by glutathione peroxidase in mitochondria and cytosol |
|
|
Term
| T/F Metaplasia arises from direct reprograming of tissue stem cells |
|
Definition
|
|
Term
| T/F Vitamin A deficiency OR excess is associated with epithelial metaplasia |
|
Definition
|
|
Term
| What gene family is most important in the reprograming of tissue stem cells that results in metaplasia? |
|
Definition
|
|
Term
| What is the function of PTEN? |
|
Definition
| INHIBITS cell growth (via inhibition of PI3K, which prevents activation of AKT transcription factor) |
|
|
Term
|
Definition
Extra-chromosomal, circularized fragments of amplified DNA
***often don't cause too much trouble because they are rapidly degraded once the cell enters mitosis, but they can form after mitosis secondary to DNA damage and then cause a problem *** |
|
|
Term
| What two patterns of gene amplification can be microscopically observed in chromosomes? |
|
Definition
1. Homogeneous staining region (the amplified gene is inserted into a new region of the chromosome, may be located far from where the proto-oncogene is typically located)
2. Double-minutes (circularized, extra-chromosomal fragments of amplified DNA) |
|
|
Term
| What are four mechanisms in which RB can be abrogated in cancer? |
|
Definition
Loss of RB function (both alleys)
Amplification of CDK4/cyclin D
Loss of CDK inhibitors (p16/ink4a)
Viral proteins that bind to and inhibit RB |
|
|
Term
| What are the two signal transduction pathways associated with G protein coupled receptors? |
|
Definition
| cAMP and protein kinase C |
|
|
Term
| What are the transcription factors for TGF-beta receptors? |
|
Definition
|
|
Term
| T/F the TGF-beta receptor is always a heterodimer |
|
Definition
True
**one side has the ligand binding site (type II) and the other side has the kinase activity (type I) |
|
|
Term
| Which Smad is a nuclear transport molecule? |
|
Definition
|
|
Term
| Which Smads are inhibitory? |
|
Definition
|
|
Term
| What is the role of Smurfs? |
|
Definition
| Smurfs are ubiquitinases that degrade Smads (which are the transcription factors associated with TGF-beta signaling) |
|
|
Term
| What are the bridging proteins associated with receptor tyrosine kinases? |
|
Definition
|
|
Term
| How is RAS associated with the inner cell membrane? |
|
Definition
| Via a Farnesyl membrane anchor |
|
|
Term
| What transcription factor increases cyclin transcription? |
|
Definition
E2F
**normally sequestered by hypophosphorylated RB** |
|
|
Term
| Which protein couples the intrinsic (mitochondrial) to extrinsic (death receptor) pathways of apoptosis? |
|
Definition
|
|
Term
| What lipoxygenase is pro-inflammatory and which is anti-inflammatory? |
|
Definition
5-lipoxygenase is pro-inflammatory (production of leukotrienes)
12-lipoxygenase is anti-inflammatory (production of lipoxins) |
|
|
Term
| What eicosanoids play a role in hemostasis? |
|
Definition
Prostacyclin (PGI2) is produced by endothelium and causes vasodilation and inhibition of PLT aggregation
Thromboxane A2 (TXA2) is produced by PLT and causes vasoconstriction and promotion of PLT aggregation |
|
|
Term
| Which prostaglandins are most widespread and play a role in inflammation? |
|
Definition
PGE2 (vasodilation, increased vascular permeability, fever)
PGD2 (neutrophil chemotaxis, hyperalgesia) <- from mast cells |
|
|
Term
| What enzyme produces bradykinin and what enzyme degrades it? |
|
Definition
Kallikrein makes bradykinin from kininogen
Kininase degrades bradykinin |
|
|
Term
| How does calcium interact with coagulation factors (and which factors are calcium dependent)? |
|
Definition
Calcium binds to gamma-carboxylated glutamic acid residues on factors 2, 7, 9, 10
** these are also the vitamin K dependent factors because production of gamma-carboxylated glutamic acid requires vitamin K |
|
|
Term
| Which coagulation factor is Hagemann factor? |
|
Definition
| Factor 12 (i.e. the beginning of the intrinsic coagulation cascade) |
|
|
Term
| What transcription factors are associated with hypertrophy? |
|
Definition
|
|
Term
| What genes are associated with induce pluripotent stem cells? |
|
Definition
OCT3/4
Sox2
KLF4
c-Myc
Nanog
LIN28 |
|
|
Term
| What free radical is produced by phagocyte oxidase? |
|
Definition
|
|
Term
| What does superoxide dismutase detoxify? What does it generate? |
|
Definition
| SOD detoxifies superoxide and generates hydrogen peroxide |
|
|
Term
| What ROS can act distant from the site of production? |
|
Definition
|
|
Term
| What reactive oxygen species is a byproduct of oxidative phosphorylation? |
|
Definition
|
|
Term
| What is the most reactive oxygen free radical? |
|
Definition
|
|
Term
| What integrins are expressed on monocytes? |
|
Definition
|
|
Term
| What integrins are expressed on neutrophils? |
|
Definition
|
|
Term
| What integrins are expressed on T lymphs? |
|
Definition
| All except MAC-1 (i.e. LFA1, VLA4, a4B7) |
|
|
Term
| What integrins are expressed on dendritic cells? |
|
Definition
|
|
Term
| What integrin ligands bind a4B7? |
|
Definition
MadCAM-1 (on gut/mucosal surfaces)
VAM-1 (also binds VLA4 on monos and T lymphs) |
|
|
Term
| What integrin binds LFA1? |
|
Definition
|
|
Term
| What is the respiratory burst? |
|
Definition
upregulation of NADPH oxidase by activated WBC
*** produces superoxide --> spontaneously dismutates to hydrogen peroxide (converted to hypochlorite by myeloperoxidase in PMN) |
|
|
Term
| Where does arachidonic acid come from? |
|
Definition
|
|
