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cell bio UTSW 2010

celllular biology course at the university of texas southwestern school of med

acidophilic low pH: proteins (eosin) pink.
basophilic low pH: nucleic acids (phosphates), sulfates (e.g. glycosaminoglycans), [hematoxylin] blue. high pH: protein, nucleic acids, sulfates.
PAS periodic acid-Schiff, stains carbohydrates
outer layer of mesothelium + its connective tissue serosa
connective tissue without containing an outer layer of mesothelium adventitia
loose layer of connective tissue & serosa on the basal side of the mucosa lamina propria
contrast paraffin-embedding vs. plastic-embedding paraffin = shrinkage, wash-out of extracellular matrix ("halo" can help identify cells). plastic = can cut thinner slices, greater tissue integrity.
fixative process that retains or washes out RBCs immersion fixation = blood remains. perfusion fixation = better tissue integrity, but blood is washed away.
"working" cells in an organ parenchyma
supportive connective tissue + vessels in an organ stroma
tissue layers of the mucosal tube (in to out) mucosa (epithelium + lamina propria), submucosa (dense connective tissue), muscle, serosa/adventitia
molecules preferentially located in outer leaflet sphingomyelin, phosphatidylcholine, (glycolipids, sphingolipids), GPI-modified proteins. NOTE: lumen of ER resembles extracellular leaflet.
molecules preferentially located in inner leaflet lipids w/terminal amine (e.g. phosphatidylserine, phosphatidylethnanolamine; (-) charged), acylated/prenylated proteins
component of lipid domains sphingomyelin/glycosphingolipids, cholesterol, acylated or GPI-anchored proteins. Form due to phase properties of lipids.
lipid-anchoring of proteins modified by glycosylphosphatidylinositol (GPI), fatty acylation, or prenylation
list 6 types of membrane proteins 1. ion pumps, 2. channels, 3. receptors, 4. transducers (couple extracellular ligand to intracellular enzyme), 5. surface membrane enzymes, 6. structural proteins that organize the bilayer
freeze fracture tissue coated w/carbon & platinum. cytoplasmic side = P face. extracellular side = E face.
mechanism for formation of membrane invaginations selective expansion of inner part of membrane bilayer only. --> tubules
Hh signaling in cilia 1 GLI & SUFU -> cilia tip via intraflagellar transport protein (IFT). 2 GLI = inactivated & transported back to soma. 3 when Hh binds PTCH1, SMO inserted in membrane -> cilia. 4 SMO + SUFU block GLI inactivation. 5 acivated GLI -> soma -> gene expression.
cilia detection of fluid flow PC1/PC2 (polycystin 1/2) = stretch-activated Ca++ channel -> AP1-dpdt gene transcription. IFT is required for insertion of PC1/PC2 in ciliary membrane. IFT mutation -> polycystic kidney disease.
lateral mobility of membrane elements 10^-8 to 10^-11 cm/sec
types of membrane proteins x structure Integral (need detergents to remove), Lipid-Anchored (detergents), Peripheral (easily rinsed off w/salt or acid)
role of cholesterol in membranes organizes (e.g. organizes caveolae w/glycosphingolipids), specifies organelle membranes in high concentrations
microvilli structure maintained by: actin filaments
honeycomb structure in ER caused by: HMG Co-A Reductase overexpression
cells that have abundant rough vs. smooth ER rough = secretory cells (e.g. pancreatic acinar cells). smooth = cells for steroid production or detoxification.
types of secretory vesicles all originate in TGN. constitutive = hard to see in EM (do not accumulate). Regulated = stored in cytoplasm until triggered release. shape determined by contents.
lipid bilayer synthesis @ outer layer of ER on template. P'lipids inserted in cytoplasmic side. Flippases (TM proteins) move specific lipids to opposite side. Scramblases flip phospholipids to opposite leaf (symmetric growth). Flippases fail in apoptosis = immune recognition.
synthesis of integral membrane proteins 1)Ribosome starts translation, 2)SRP binds signal sequence(SS) & stops translation, 4)Ribosome docks @ ER, 5)Peptide elongates→ translocator[ATP] until stop-transfer sequence, 6)SS cleaved, 7)Glycosylation in lumen, 8)Chaperones in lumen fold protein[ATP]
synthesis of secreted protein protein completely secreted into ER lumen. signal sequence cleaved
Effects of protein misfolding in ER integral membrane proteins are taken to the cytoplasm for deglycosylation, ubiquitylation, degradation (e.g. CFTR).
posttranslational modifications made in Golgi sulfation, fatty acylation, phosphorylation, carbohydrate chains
Signal Recognition Particle binds signal sequence in nascent protein, halts translation, takes ribosome to rough ER & docks @ high affinity SRP receptor, ribosome binds translocator, SRP & receptor dissociate. nascent protein -> translocator via channel in large ribosomal subunit.
Glycosylation in the ER (O-glycosylation & N-glycosylation) oligosaccharide transfered from ER lipid to Asparagine in nascent protein (N). glycosylation determines how protein folds. glycosylation determines if immune system can tell if "self" or not.
stop transfer sequence stops translation, hydrophobic sequence -> carboxy terminal outside, n-terminal inside
protein folding in ER 1st glycosylation = 3 glucoses -> initiates folding. chaperones in ER (e.g. connexin) detects sugar as sign of improper folding -> binds & helps to refold -> glucosidase cleaves glucose = correctly folded.
incorrect folding in the ER glucosyl transferase detects sugar modifications in incorrectly folded protein -> refolds. unfixable proteins -> chaperones guide to translocator -> sugars cleaved in cytoplasm -> Ubiquitination & proteasome degradation.
functions of golgi cisternae addition & trimming of carb chains, sulfation, fatty acylation, phosphorylation. each cisterna specialized. mannose sugars removed @ cis. membrane domains in TGN via cholesterol & glycosphingolipids @ low pH.
golgi retrieval of resident ER proteins KDEL receptor in lumen of golgi, 4 aa's attached to ER resident proteins, returns proteins to ER
Rab (specificity) from TGN, Rab binds to forming vesicles (GTP-dpdt), transported to target membrane. specific receptor binds specific Rab.
SNAREs (specificity) mediate fusion of vesicles w/membrane. v-SNARE (synaptobrevin) docks 2 matching t-SNARE (syntaxin & Snap25 in neurons). hydrolyze Rab GTP --> Rab leaves vesicle & is recycled.
tetanus toxin cleaves synaptobrevin (v-snare)
botulinus toxins die from respiratory paralysis. toxin cleaves Snap25 t-SNARE (e.g. Botox). lasts 3-4 months.
3 major pathways delivering material to early endosomes endocytosis, phagocytosis, autophagy
lysosome maturation M6P-modified proteins -> vesicle in trans golgi (=primary lysosome). when material to be degraded is added = mature lysosome. when material is not degraded, lysosome = residual body.
lysosomal storage vs. transport diseases storage diseases = undigested substrates accumulate in lysosomes. transport diseases = digested substrates (small molecules) accumulate in lysosome.
mitochondrial membrane specializations outer = porins (<10kDa pass). inner = high [cardiolipin], oxidative phosphorylation molecules.
mitochondria containing few cristae specialized for lipid metabolism, Calcium storage
types of mitochondrial disease 1. Mt genomic mutation, 2. defective protein delivery to Mt, 3. defective protein fxn in Mt, 4. Mt + genomic mutations. Usually affect high energy tissues (muscle, heart, brain). Mt Myopathy -> "parking lot" inclusions.
peroxisome fxn 1. oxidative enzymes break down organic substrates -> H2O2. 2. catalases break down FA's: FA + O2 -> acetyl CoA + H2O2 ->H2O + O2.
lysosome hydrolases! Nuclease, Protease, Glycosidase, Lipase, Phosphatase, Sulfatase, Phospholipase. low pH (5) = H pumped in (ATP-dpdt).
recycled break-down products transferred out of lysosomes: specific transporters for: aa's, simple sugars. Probably carrier proteins for: cholesterol, FA's
macro-autophagy vs. chaperone-assisted autophagy macroautophagy = membrane forms around defective organelles. Chaperone-assisted autophagy = chaperones guide proteins to their destruction in lysosome via LAMP-2A receptor. both = lysosomal enzymes delivered to autophagaosome -> autophagolysosome.
autophagic vacuole can refer to either autophagosome or autophagolysosome (indistinguishable w/out IHC)
I-Cell Disease inability to digest lysosomal contents. M6P receptor defect.
Tay-Sachs disease no hexosaminidase A = defective lysosomal enzyme -> protein build-up. Storage Disease.
Niemann-Pick disease no sphingomyelinase = defective lysosomal enzyme -> protein build-up. Storage disease.
Infantile Sialic Acid Storage Disorder disfunctional lysosomal carrier protein -> sialic acids build up in lysosomes. Transport Disease.
peroxisome production self-replication
Zellweger Syndrome defective enzyme that imports proteins into peroxisome. -> abnormal liver, cystic kidneys, NO MUSCLE TONE, craniofacial abnormalities. mortality @ 6 months old.
lipid droplets found in ALL cells. characteristic associated proteins including lipases. production = from discrete regions of ER
Chanarin-Dorfman Syndrome ABHD5 mutation(normally breaks down TAGs in lipid droplets). -> ichthyosis, myopathy, hepatosplenomegaly, vacuolated granulocytes
types of endocytosis 1. phagocytosis, 2. receptor-mediated endocytosis, 3. caveolae-mediated endocytosis (LDL endocytosis via receptor) (targets = trancytosis, ER, or endosomes). viruses & toxins use all 3 pathways.
phagocytosis & fate of phagocytosed material for > 1 million MW particles. opsonized, continuous contact required -> zippering effect. actin & myosin -> invagination & internalization. vesicle -> lysosome + ROS's kill microbe.
fates of LDL R, EGF R, transferrin, IgG R LDL R: R recycled, ligand degraded (separation x pH). EGF R: both degraded. transferrin: both recycled. IgGR: R recycled, ligand = transcytosis.
clathrin-coated pits no good for cell debris/bacteria. adaptin links triskelion to grouped receptors (grouped by clathrin or AP2 binding di-leucine, NPXY, or YXX-Phi motifs). rapid uncoating by HSP's after endocytosis. vesicle pH -> 5.5 after endocytosis.
clathrin AP2 (4 peptides) + triskelion (3 radiating arms, 2 peptides). AP2 attaches clathrin to membrane. either clathrin forms on pre-shaped membranes OR clathrin motor drives vesicle formation.
budding in ER, Golgi different AP2 + coatamers instead of clathrin.
clathrin-coated pit vesicle pinch-off pinchase (dynamin)
caveolin small (<180 aa's), dimer, loop inserts b/tw 2 P-lipid layers of membrane, self-assembles into 10 nm filaments (homoheptamer), alpha helix mediates self assembly. filaments criss-cross internal caveolar membrane.
types of caveolar pits I: don't move. when endocytosed -> endosomes via microtubule highways. II: move around on membrane. when endocytosed -> wait just below cell membrane. concentrate Ca & folate. III: stretch deep into cell (instigated x prions or shishigei toxin)
caveolae detergent-resistant, cholesterol & glycosphingolipids, caveolin, pinchase machinery unknown
Nuclear Pore complexes ~3000 in a nucleus, composed of Nups (~30 types, ~500 in #). pass water & small molecules. viruses collect @ cytoplasmic filamentous moiety. basket structure on nucleoplasm side. pore= 60 nm diameter outside, 40 nm inside.
Nuclear lamina composed of intermediate filaments, b/tw nuclear envelope & heterochromatin. provides shape + scaffolding for chromatin. disassembly for mitosis.
nuclear speckles pre-mRNA splicing factor assembly & modification centers.
cajal bodies dynamic pre-mRNA splicing factors. associated w/fibrillarin & COILIN.
PML bodies nuclear "promyelocytic leukemia" particles. made of PML, SUMO1, & transcription factors. involved in post-translational modifications & regulation of transcription. targeted by viruses.
nucleolus rRNA synthesis site, associated w/fibrillarin.
intranucleolar domains F (fibrous) = ribosomal genes transcribing large amounts of rRNA. G (granular) = ribosomes assembled, densely packed ribosomes. FC = 5 chromosomes including rRNA genes + RNAPolI + txn factors.
Hutchinson-Guilford Progeria mutated A-type lamins (laminopathy). other laminopathies include muscular dystrophy & cardiomyopathy. "MAY lead to increased cell turnover & telomere shortening" --Wright
Nuclear Signals nuclear localization signals (NLS's: classical mono/bipartite + nonclassical), vs. Nuclear Export Signals (NES's: Leucine-rich)
protein import into nucleus protein w/NLS binds Kap-alpha which binds Kap-beta1 -> enters nucleoporin. inside nucleus Ran binds GTP (via GEF) -> Ran binds Kap-beta1 -> protein freed.
protein export from nucleus protein w/NES binds CRM1 + Ran-GTP -> passes through nucleoporin. Ran GAP hydrolyzes GTP -> protein is freed.
mRNA export from nucleus mRNA uses different chaperones than protein does to exit through NPC. globular mRNA is unwound -> linear as it passes through NPC
Leukemia & Nups Nup98 = gene translocation -> causative in multiple types of leukemia. transport disrupted = interrupted gene expression
viral interruption of nuclear transport viral M-protein inhibits host mRNA export. NS1 protein from influenza virus binds nucleoporins & "takes over the machinery."
chromatin DNA + structural proteins. hetero = condensed, darkly staining w/basic dyes, predominant in metabolically inactive lymphocytes & sperm. Eu = lightly stained, most transcribed, in metabolically active neurons, liver, etc.
Spinal Muscular Dystrophy due to reduced levels of SMN, or mutated SMN
Promyelocytic Leukemia cause = PML bodies disassemble. treat w/ retinoic acid.
nucleostemin binds p53 tumor suppressor, regulates cell cycle and differentiation [CANCER].
disorders of cell loss AIDS (loss of certain lymphocytes) , Alzheimer's, Parkinson's, Aplastic Anemia, Myocardial Infarction
Disorders of cell accumulaiton cancer, lupus, glomerulonephritis, virus
cell stages G1 & G2 = RNA & proteins made, S = DNA, RNA, proteins made. G1 -> S -> G2 -> M - -> G0 or G1
malfunction of cell division checkpoints -> mitotic catastrophe (failure to arrest prior to mitosis). Can lead to aberrant chromosome segregation, cell death, or aneuploidy -> cancer
apoptosis TNF, TGF-beta instigate (external). oncogenes (myc), tumor suppressors (p53), nutrient deprivation, mitotic catastrophe (internal). chromatin condensation, Mt releases CytC, caspases activated, DNA ladders
antiapoptotic factors growth factors, hormones, Bcl-2 regulators
microfilaments 6 nm diam, 2 actins entwined. stress fiber= contractile bundle of opposite polarized fibers. cell cortex = gel-like network. Tight parallel bundle = bundle w/same polarity fibers. Myosins walk along. lamellipodia & filopodia @ leading edge of moving cell.
intermediate filaments 8-10 nm diam, strong. keratin ECs (type I acidic, type II basic), vimentin-like (vimentin = fibroblasts & mesenchyme, desmin = muscles, GFAP = glial), neurofilaments neuronal, lamins nucleus. associated w/cancer. also in microvilli & stereocilia.
microtubules 24 nm diam, alpha/beta tubulin, 13-mer spiral. MAP's. singlet = cilia core. doublet = cilia axoneme. triplet = basal body/centriole.
desmosomes attached to intermediate filaments w/cadherin
Epidermolysis Bullosa Simplex mutated keratins
cilia 9+2 in cilia/flagella: 9 doublets/2 singlets, Dyneins associated w/MT's move cilia. 9+0 in primary cilia, immotile sensory organ (olfactory cells)
centrosome 2 centrioles (microtubule organizing center) + gamma tubulin halo where microtubules grow from.
kinesin Kinesins walks along MT's anterogradely. head = walks (ATP-dpdt), rod, tail = binds carried molecule. Dynein walks in opposite direction (retrograde)
Nocodazole disrupts microtubules (ends intracellular trafficking)
MT's & mitosis spindle formation (metaphase). chromosomal segregation (karyokinesis)
Colchicine disrupts MT's. No mitotic spindle can form. -> multiple satellite nuclei.
Vincristine destabilizes MT's -> prevents mitosis -> apoptosis
Taxol stabilizes MT's -> prevents mitosis -> apoptosis
Tau protein MAP -> neurofibrillary tangles in Alzheimer's
Situs Inversus reversal or randomized organ locations. associated w/flagellar dynein-related protein malfunction.
Syndromic male sterility due to MT dysfunction in flagellum
Cystic Diseases of Kidney (CDK) monogenic diseases. primary cilia, basal bodies, or centrosomes disrupted. CDK gene disruption may also -> retinal degradation or anosmia
microfilaments in focal adhesions extracellular matrix protein binds alpha/beta integrins (TM) which bind alpha actinin which binds vinculin & ACTIN microfilaments
microfilaments in cell migration actin polymerizes @ + end -> protrusion. contraction @ trailing edge = via Myosin II + dissociation. dissociated actins move to the leading edge.
Cytochalasin!!! disrupts microfilaments, prevents cytokinesis
Phallotoxins fungal, bind & stabilize F-actin
Latrunculin A :) from red sea sponge, disrupts microfilament organization
viruses that alter actin motility listeria, shigella = toxin. vaccinia viruses = motility used for infection.
Usher Syndrome mutation of unconventional myosins -> sonsorineural hearing loss or retinitis pigmentosa.
Epidermolysis Bullosa Simplex mutated keratins (blistering)
hematocrit 44% of blood volume. RBC's. 1-2% = reticulocytes.
RBCs live 4 months, destroyed in spleen. 2 million made/sec. 7-8 micron diam, 1 micron thick.
Leukocytes 1% of blood volume. Buffy Coat.
Platelets live <14 days. 2-3 microns diam. 2-400K per cubic mm blood.
Fluid Phase ~55% of blood volume. plasma = w/anticoagulants (contains fibrinogen). serum = clotted RBC's (no fibrinogen)
composition of WBCs neutrophils 55-60%. eosinophils 4-5%. basophils <0.5%. monocytes 3-8%. lymphocytes 30% (80% T, 15% B, 5% natural killer = large granular lymphocytes). granulocytes only live a few days.
WBC diam's granulocytes 10-12 microns. monocytes 20 microns. lymphocytes 8-10 microns (small) or 12-18 microns (medium & large).
Thrombocytopenia <50K platelets. -> bleeding out. autoimmune disease.
WBC fxn's neutro: microbial infection. eosino: parasites/allergy. baso: allergy/anaphylactic shock. mono: clean up after infection -> macrophages. lympho: pathogen immunity.
RBC shape spectrin + protein 4.1 impt't for horizontal shape. ankyrin + band 3 impt't for thickness shape.
RBC disorders anisocytosis <6 or >9 microns diam. poikilocytosis (sphero- due to ankyrin/spectrin/band4 mutation; ellipto- due to spectrin/band4.1 mutation). hypochromic = low Fe. anemic = low hematocrit (low Hb/cell or fewer cells).
contents of primary azurophilic granules acid hydrolase, myeloperoxidase, lysozyme, elastase, bacteria permeability proteins
neutrophil fxn selectin (ECs) binds neutrophils-> margination. chemokines up affinity for ICAM (ECs)-> adhesion. mast cells release histamine & heparin-> loosen EC jxn's. release granules w/gelatinase -> diapthesis & extravasation. ->phagosomes w/ROS's. die -> pus.
eosinophil function specific granules contain basic/cationic enzymes that form pores in parasites for ROS's to enter.
basophil fxn specific granules = venule & bronchiolar constriction, capillary & arteriolar dilation. overall -> edema. also contain chemoattractants for other granulocytes.
monocyte fxn phagocytic, differentiate into macrophages
thrombocytopenia autoimmune or drug hypersensitiity. prolonged bleeding <50K/cubic mm or hemorrhage when <10K/cubic mm blood.
epithelial cell fxn sensation, protection, secretion, absorption, transport, excretion
basement membrane interface b/tw epithelium & connective tissue. contains proteoglycans, glycoproteins, laminin, & collagens. akin to external lamina of muscle cells. basal lamina = type IV collagen, laminin, proteoglycan.
basolateral epithelium often interdigitate. separated from apical domain via tight jxns (zonula occludens).
tripartite jxn zonula occludens (tight jxns; occludin & claudin), zonula adherens (actin network), desmosomes (intermediate filaments, cadherins = cell-to-cell). from apical to basal.
Zot (zona occludens toxin) 2nd cholera toxin, opens tight jxns -> diarrhea. Zot + insulin = insulin absorbed in intestine. Zot + dye = dye gets past BBB. human protein Zonulin = similar.
signaling injury in bronchial epithelial cells erB2 ligand (heregulin) apical cannot pass tight jxns unless injury. When injury, passes & binds erbB2
fascia adherens @ border of cardiac muscle cells
actin staining light microscopy v. poor staining w/H&E = white area
prickles caused by intermediate filaments remaining when cytoplasm shrinks (artifact). connect to desmosomes
helicobacter pylori method of invasion disrupts tight junctions
focal adhesion extracellular integrins connecting w/intracellular actins
gap jxns connexons in tube-shape. contant gap b/tw cells, <1000 MW passes. tumors lack. can close. = "nexus" junction
ribosome size ~20-25 nm diam.
Charcot-Marie-Tooth disease type I: demyelinating syndrome of gap jxns b/tw layers of myelin sheath. Type II: kinesin mutation of axonal transport. distal weakness, muscle wasting, absent reflexes (stork leg).
EC classification simple/stratified/pseudostratified layers, shape of superficial cell layer squamous, columnar, cuboidal, surface specialized. transitional epithelium = bladder.
endo vs. mesothelium endo lines vessels, meso lines body cavities & organs (e.g. peritoneum)
exo- vs. endocrine glands terminal web @ apical side contracts. endocrine gland = completely sealed off + secretes from basal. exocrine gland maintains connection to outside world + secretes from apical.
types of secretion merocrine = secretory vesicles (e.g. pancreatic acinar cells), apocrine = pieces of cell pinched off (e.g. mammary glands). Holocrine = whole cells are shed (e.g. sperm, sebaceous glands). Cytocrine = secrete directly into adjacent cells
gland characterization endo/exocrine, simple vs. branched duct, uni/multicellular, alveolar (huge lumen) vs. acinar (grape-like) gland, serous vs. mucous vs. both secretion
examples of squamous, cuboidal, & columnar epithelium squamous = mesentery, kidney tubules = cuboidal, intestinal = columnar, male urethra = stratified columnar!, trachea = pseudostratified ciliated, bladder = transitional epithelium.
examples of types of glands intestinal submucosa (secretes HCO3-) = simple branched tubular, pancreas = compound acinar serous, mammary = compound alveolar apocrine, trachea = pseudostratified mucous submandibular = serous & mucous.
metaplasia normal EC type changes in reponse to pathological conditions (e.g. smoking). cells have normal properties, but abnormal shape.
connective tissue fixed cells fibroblasts, macrophages, mast cells, adipocytes
connective tissue: wandering cells granulocytes, agranulocytes, plasma cells
connective tissue: extracellular structures collagen, reticular fibers, elastic fibers, ground
6 fxn's of connective tissue 1 connect (tendons), 2 protect/divide/ensheathe/separate/lubricate, 3 support/give shape (facial features, organs), 4 storage (fat), 5 regulate diffusion & slow infection, 6 organize housekeeping/defense/repair (wounds)
collagen >40 genes -> 25-30 different types. triple helix -> fibrils -> fibers -> bundles. synthesized as tropocollagen then released to auto-polymerize extracellularly.
elastin fibrillin tube w/elastin inside. elastin has unusual aa's -> branching. resting state = random coil. tension = elongated protein. blood vessels = elastin laminae/lamellae. vocal cords, trachea, ligaments, lung, dermis.
Marfan's Syndrome firillin mutated -> ocular, musculoskeletal, cardiovascular (aortic aneurysms). TGF-beta signaling disrupted.
chronic sun exposure fibrillin microfibrils remodel -> wrinkles
white adipose 15% men, 22% women body weight. 90-95% TAG's. produce adipokines (leptin, TNF-alpha, prostaglandins, sex hormones, glucocorticoids)
brown adipose heat generation
ground substance "filler" b/tw collagen & cells. cushions, lubricates. poorly stained. proteoglycans + glycoproteins. forms networks to block bacteria & bind + charged molecules (hydrogel speeds electrolyte transport).
proteoglycans glycosaminoglycan core (GAG) = repeated disaccharide chain (e.g - charged chondroitin sulfate, dermatan sulfate, HA). - charge = resists compression. HA not attached to core protein, viscous in joints. net-formation blocks bacteria. binds growth factors.
glycoproteins sugar-decorated protein dominated by protein portion
wandering cells macrophages, histiocytes ingest errant melanin, tattoo dye. precursor cell in bone marrow -> promonocytes -> monocytes -> macrophages (tissue). in liver = Kupffer cells.
plasma cells derive from precursor lymphocytes. single "cart wheel" nucleus. major job = secretion w/no granules. make Ab's = extensive rough ER.
mast cells immediately beneath epithelial surface, early defense against parasites; allergic reactions; regulate microvascular blood flow. IgE Ab's bind R -> heparin, histamine, proteoglycans released. derived from same progenitor as basophils.
fibroblasts from embryonic mesenchymal cells, produce provide invasion path in tumorigenesis (integrin-dpdt). long stretched out nuclei visible in collagenous areas. bind fibronectin via integrins.
define the various --mysiums epimysium = around whole muscle (large vessels & nerves). peri = around fascicles (small vessels & nerves). endo = around myofibers (capillaries & nerve endings).
define fascicles & the myo--'s myofilament = actin & myosin. myofibril = many myofilaments. myofiber = single multinucleate cell. fascicle = grouped fibers in a muscle
fxn of different sarcomere divisions A-band = thick+thin filaments. H-band = thick only. I-band = thin only + z-line. M-line: anchors thick filaments. Z-line: anchors thin filaments.
molecular components of the sarcomere thick filaments= myosin, thin= actin + tropomyosin + nebulin (-> thin fil. length). Titin = from M to Z-line, prevents overextension. alpha actinin= connects actin to integrins to ECM. Desmin= strxrl support (int. filament). tropomodulin caps thin fil's.
Golgi Tendon Organ axon pinched when tensed
Muscle spindle encapsulated intrafusal fibers: nuclear bag= nuclei @ center of fiber. Nuclear chain= nuclei strung along length of fiber. Annulospiral nerve ending = rate of extension ->both types. Flowerspray ending = degree of extension ->nuclear chain only.
layers of heart (out to in) pericardium (parietal then visceral), epicardium (connective tissue), myocardium + Purkinje cells, endocardium
cardiac vs. skeletal muscle structure central single nucleus, branched cells, diad located @ Z-bands. skeletal muscle = multinucleate peripheral nuclei unbranched.
Intercalated disks transverse = fascia adherens (thin filaments transmit force across cells), desmosomes (int. filaments transmit force). longitudinal = desmosomes, gap jxns (pass excitation)
caveolae intracellulares in smooth muscle. stimulation triggers Ca influx & SR Ca release.
myoepithelial cells contractile epithelial cells forcibly squeeze gland. located in glandular epithelium. long cytoplasmic processes. iris, sweat/salivary/mammary glands.
myofibroblasts contractile fibroblasts help in wound healing. prominent rough ER
tissue layers of peripheral nerves epineurium (type I collagen, fibroblasts, adipocytes, major vessels). Perineurium (stratified squamous cells w/zonula occludens, small vessels). Endoneurium (Type I collagen around axons, fibroblasts, Schwann & mast cells, capillaries w/zonula occludens).
Auerbach's plexus located b/tw CIRCULAR & LONGITUDINAL MUSCLE LAYERS. receive parasymp. innervation in the myenteric plexus of the intestines. neurons w/enteric glial cells
Meissner's plexus SUBMUCOSA. receive parasymp. innervation in the myenteric plexus of the intestines. neurons w/enteric glial cells.
Neuronal fascicle Perineurium + enclosed endoneurium
Internode axonal area covered by 1 Schwann cell
Schmidt-Lanterman clefts periodic interruptions in the myelin sheath
Pacinian Corpuscle encapsulated nerve ending (sensory, touch)
location of 3 diff. types capillary walls 1) Continuous (lung, skeletal muscle, heart, skin). 2) Fenestrated (GI mucosa, renal capillaries). 3) Discontinuous (liver sinusoids)
characteristics of continuous capillary walls 1) fascia occludens (10nM transport); zonula occludens in BBB & thymus, 2) continuous basal lamina, 3) caveolae & vesicles (50-70nM transport)
characteristics of fenestrated capillary walls 1) 80-100 nm gaps, covered w/"slit membranes", 2) continuous basal lamina, 3) 100x faster exchange than continuous walls
characteristics of discontinuous/sinusoid vascular endothelium 1) large gaps b/tw ECs, 2) basal lamina is patchy
diapedesis extravasation of leukocytes
elastic arteries (large) > 1 cm. tunica intima subendothelium = very prominent. multi-laminae of elastin in tunica media. thin tunica adventitia w/ vasa vasorum @ outer edge.
muscular arteries 2-10 mm diam. thin tunicas intima & adventitia, multi-laminae of elastin in tunica media. sometimes external elastic lamin b/tw tunicas media & adventitia.
atherosclerosis histology macrophage foam cells, smooth muscle hypertrophy, calcification. lumenal occlusion via tunica intima.
arterioles 10-100 microns diam. 1-2 smooth muscle layers in tunica media. no real elastin laminae.
capillaries 1 layer EC's + basal lamina. flow = 1% of elastic artery flow.
post-capillary venules 10=50 microns diam. basal lamina, pericytes. no smooth muscle. site of WBC margination & diapedesis.
muscular venules 50-100 microns diam. 1-2 layers smooth muscle in tunica media.
small vs. medium veins 0.1-1mm diam small, 1-10 mm diam medium
large veins >10 mm, 2-15 layers smooth muscle. indistinct layers. tunica adventitia contains bulk of smooth muscle (longitudinal), NOT media! (mechanical support for "hanging veins")
lymph capillaries discontinuous endothelium, no pericytes, few junctions, anchoring microfibrils maintain vessel patency
larger lymphatics indistinct layers, thin walls, passive lymph movement. large, irregularly shaped lumen. tunica media has both circular and oblique smooth muscle cells 1-2 layers thick.
lymphatic ducts spiral smooth muscle
tunica intima simple squamous epithelium, basal lamina, subendothelial connective tissue. internal elastic lamina in arteries & large veins @ jxn of tunica media.
tunica media smooth muscle (circular; maintains blood pressure) + elastin + pericytes (in capillaries). resists pressures. largest in arteries.
tunica adventitia loose connective tissue & smooth muscle (longitudinal smooth muscle = provides structural support), vasa vasorum in larger vessels.
vasa vasorum provides blood supply to larger arteries & veins.
pericytes nucleus does not protrude into vessel lumen. long processes interact with endothelial cells.
hyaline cartilage homogenous matrix. in adults, remains @ joint surfaces as articular cartilage & in some parts of respiratory system. in rheumatoid arthritis, replaced by synovial connective tissue.
elastic cartilage contains elastic fibers. found in auditory canal, epiglottis, larynx. same organization as hyaline but + elastic fibers & type II collagen in matrix. NO CALCIFICATION!!!
fibrocartilage fibrous connective tissue resists compression & shear, high tensile strength. found in intervertebral discs, joint menisci. dense type I collagen around chondrocytes. no perichondrium.
layers of cartilage & cell types (avascular: matrix diffusion) out to in: PERICHONDRIUM (perichondrial & chondrogenic cells); CARTILAGE (CHONDROBLASTS @ edge, CHONDROCYTES in lacunae of matrix, CHONDROCLASTS/OSTSEOCLASTS degrade cartilage)
type I collagen tendons, bone, skin, capsules/septa/trabeculae; banded fibers, 50-200 nm diam.
type II collagen in cartilage matrix, 20 nm diam.
type III collagen in reticular fibers, distensible connective tissue (banded fibers stain silver). can be branched.
type IV collagen in basal lamina. forms meshwork
cartilage extracellular matrix type II collagen, chondronectin adhesion protein. proteoglycan aggrecan in ground substance = highly hydrated (60-80%) -> resilience!
AGGRECAN proteoglycan in ground substance of hyaline cartilage, binds HA backbone, w/chondroitin sulfate & keratan sulfate. binds water.
Territorial Matrix high proteoglycan sulfate content near lacunae. INTERTERRITORIAL MATRIX = in between territorial.
Perichondrium dense connective tissue surrounding catilage similar to capsule. outer layer = type I collagen + fibroblasts & blood vessels. inner layer = chondroblasts & chondrogenic cells.
Initial Deposition of hyaline cartilage BMP's -> mesenchymal cells (CHONDROBLASTS) secrete matrix. Adjacent cells become perichondrium.
Appositional Growth of cartilage chondrogenic cells in perichondrium become chondroblasts. new cartilage added to surface of existing. chondroblasts become chondrocytes after entrapment in matrix -> type II collagen.
Interstitial growth of cartilage new cartilage added within existing. chondrocyte mitosis -> rows of ISOGENOUS groups. cells separated by novel matrix.
cartilage repair O2 tension too high, so is instead replaced by dense connective tissue of (if band new) calcifies into bone
calcification of cartilage NORMAL = hydroxyapatite crystals form during endochondral growth & in areas adjacent to bone. ABNORMAL = "ectopic bone" in walls of blood vessels or in osteogenic tumors.
ruptured/slipped discs tear in fibrocartilage
bone composition osteoid = organic component: 90% type I collagen (difficult to break or deform). hydroxyapatite = inorganic component (50% dry weight of bone) (stiffness, resists stress).
rickets/osteomalacia vitamin D deficiency prevents normal Ca++ absorption -> decreased stiffness & rigidity deforms bone shape.
scurvy vitamin C deficiency = insufficient collagen -> thinner fragile bone shafts.
bone cell types OSTEOGENIC/OSTEOPROGENITOR CELLS -> osteoblasts. OSTEOBLASTS secrete matrix. OSTEOCYTES in matrix maintain bone. OSTEOCLASTS absorb bone & remodel.
tissues included in bones vessels, nerves, fat, hematopoietic, cartilage (@ joints), bone (structural tissues)
periosteum outer layer fibroblasts & inner layer osteoprogenitor cells. SHARPEY'S FIBERS attach periosteum to bone matrix.
endosteum single layer of osteoprogenitor cells. lines haversion canals, trabeculae, compact bone around marrow.
compact bone dense, outside layer of bone, predominates along shaft. lamellae= deposition of Type I collagen. osteon/Haversian system ~200 microns diam. Outer & inner bone shaft surfaces = no Haversian systems.
spongy bone interlacing trabecular meshwork inside bone housing marrow, predominates @ ends of bone
bone marrow red marrow turns into fat (yellow marrow) w/aging
contents of Haversian canals (osteons) vessels, nerve, connective tissue, sometimes osteoclasts, endosteum (contains osteoblasts). surrounded by concentric lamellae of bone (contain osteocytes). spaces b/tw osteons = intestitial lamellae (old osteons).
Volkmann's canals interconnect Haversian canals. Outer & inner bone shaft surfaces = no Haversian systems.
immature bone "woven" bone (collagen fibrils web-like). VERY cellular. low minerals. active remodeling. no cellular organization.
osteogenic cells fibroblast-like. BMP -> differentiate into osteoblasts (can also -> fibroblasts, adipose). found in periosteum & endosteum.
osteoblasts cuboidal, synthesize bone, cell extensions in matrix form canacliculi. secrete osteoid & release matrix vesicles that locally increase Ca++ & Phosphate. when isolated in matrix-> osteocyte.
osteoid bone extracellular matrix. collagen I w/nucleation sites for mineralization.
osteocalcin Binds Ca++, abundant non-collagenous glycoprotein in osteoid. serum marker for bone turnover.
osteocytes 90% of bone cells. live in lacunae. gap jxns w/other osteocytes & -blasts. cell processes in canaliculi. non-dividing. osteolysis. recruit blasts & clasts in response to gravity, shear force (fluid flow in canaliculi). released from matrix -> blasts.
osteoclasts resorb bone when osteocyte dies. calcitonin inhibits ruffled cell border. parathyroid-> osteoclast-diferentiation factor released by osteoblasts. secrete carbonate/citrate-> dissolves Ca-phosphate. lysosomal hydrolase degrades organic material.
Howship's lacunae region of osteoclast attachment to bone & bone absorption
flat bone (intramembranous) ossification e.g. flat bones of skull & face. mesenchyme -> osteoblasts, peri & endosteum. osteoid secreted, then hydroxyapatite mineralization. cells trapped in matrix -> osteocytes. bone spicules -> trabeculae. osteoclasts remodel. Haversian canals fill out->in.
fetal biosynthesis of long bones hyaline cartilage = model. perichondral cells -> bone collar (E3-months). adjacent chondrocytes swell, release Ca-phosphate. osteoclasts Y periosteal bud enter collar. osteoblasts secrete osteoid -> hydroxyapatite forms. clasts & blasts remodel.
periosteal bud osteogenic cells, blood vessels, mesenchyme in fetal developing bone.
growth & remodeling of bone periosteal bud invasion in epiphysis bt/w 1-2 years. bone gets longer as long as interstitial cartilage growth = cartilage replacement. clasts & blasts remodel to maintain appropriate bone shape
zone of reserve (growing long bone) in epiphyseal plate, cartilage distal to diaphysis divides + interstitial growth = zone of proliferation.
zone of hypertrophy (growing long bone) cartilage proximal to diaphysis hypertrophies, calcifies & is replaced by bone = zone of ossification.
HGH growth hormone regulates cartilage growth & epiphyseal plate closure. childhood deficiency = pituitary dwarfism, excess = gigantism. adult excess = acromegaly (esp. digits & facial bones)
Formation of Haversion System osteoclasts -> 200 micron channels in compact bone (diaphysis). osteogenics deposit lamellae of osteoid (followed by calcification) on walls of channels from cement line (out->in). channel fills w/concentric lamellae except Haversion Canal
estrogen effects on bone 1) inhibits osteoblast activation of osteoclast differentiation . 2) promotes osteoclast apoptosis
osteoporosis resorption >>> deposition
osteopetrosis deposition >>> resorption
bone repair bony callus: fibrous connective tissue & hyaline tissue form in fracture. endochondral bone replaces cartilage. primary bone remodeled. NOTE: demineralized bone matrix promotes healing (contains BMP's)
lifespan of RBCs & WBCs in blood RBCs 120 days. WBCs 2 days.
complete blood count =hemogram. counts blood cell precursors in periphery or marrow.
extramedullary hematopoiesis MESOBLASTIC PHASE: E2weeks, blood island in yolk sac, Basophilic cell aggregates-> erythroblasts->erythrocytes (nucleated RBCs w/ embyronic Hb). HEPATIC PHASE: E6weeks, blood islands in liver (spleen joins @ 2 months), anucleate RBCs + fetal Hb.
Medullary Phase of RBC development =Myeloid Phase. E5months. yellow marrow can revert to red. liver & spleen retain ability to make RBCs.
bone blood flow primary nutrient artery, bone is nourished, venous sinuses = new cells enter circulation, central sinus, circulation
connective tissue stroma reticular cells (make reticular fibers), adipocytes, macrophages (incl. nurse cells)
nurse cells serve several RBCs each in Erythroblastic Island, phagocytose extruded RBC nuclei, feed RBCs Fe/cytokines/nutrients
RBC entry into circulation from medulla transcellular migration through endothelial cell cytoplasm!
stem cell properties 1) undifferentiated, 2) progressive restrictions toward differentiation, 3) self-renewing
erythropoeitin mechanism low O2 in kidneys ->epo released -> CFU-E cells, early precursors of RBCs
bone marrow aspirates needle, sample, Wright Giemsa stain
platelet production megakaryoblast -> multilobed polyploid nucleus in megakaryocyte. invaginations of plasma membrane extended into circulation = proplatelet (~6/cell). @ capillary bed, each proplatelet -> 1200 platelets.
proerythroblast large round violet central nucleus w/euchromatin, VERY basophilic cytoplasm. replicative.
basophilic erythroblast 2nd stage. condensed nucleus, basophilic cytoplasm, starts Hb synthesis. reliant on nurse cell due to "shut-down" of nuclear fxns. replicative.
Polychromatophilic erythroblast 3d stage. nucleus more condensed. cytoplasm = mixed baso- (ribosomes) & eosinophilic (Hb). LOW proliferative potential. last stage of replicative.
Orthochromatic erythroblast 4th stage. nucleus & chromatin v. condensed. eosinophilic cytoplasm. v. few ribosomes & mitochondria. water pumped out. NUCLEUS EXTRUDED. NO proliferative potential.
Reticulocyte 5th stage of RBC development. some organelles, lots of Hb, maturation in 1 day in spleen. ~1% of RBCs, indicator of RBC formation.
Mature Erythrocytes NO MORE organelles, water pumped out, biconcave shape. V. concentrated Hb.
Neutrophil life cycle born, in marrow 5 days, released into circulation 6 hours. migrate to peripheral tissue 2-5 days, then die. large pools avail. in marrow.
pro-neutrophil development signaling molecules IL-1, GM-CSF, G-CSF
Promyelocyte 1st stage. nucleus = off-center, oddly shaped. basophilic cytoplasm. azurophilic primary granules. replicative.
Myelocyte 2nd stage. specific granules synthesized (can see eosinophils, basophils, neutrophils). oval nucleus. replicative.
Metamyelocyte 3d stage. oval/indented nucleus. neutrophil-type most common. Replicative.
Band cell =Stab cell. 4th stage. granulocyte w/condensed horseshoe nucleus. found in peripheral blood. pale pink cytoplasm + blue nucleus (H&E). non-replicative
Wright-Giemsa stain accentuates nuclear & cytoplasmic features to distinguish (i.e. blood) cell types
organization of keratinocytes in the epidermis (4-6 week turnover). Stratum basale, Stratum spinosum, Stratum granulosum, Stratum lucidum, Stratum corneum
Stratum Basale keratinocytes in 4th layer of epidermis. cuboidal & low columnar cells, attached to basement membrane. keratin "tonofilaments" around nucleus attach to (hemi)desmosomes. melanin granules. migrate lateral in wound repair.
Stratum spinosum keratinocytes in prickle cell layer (3d) of epidermis. stratified cuboidal cells. tonofilaments around nucleus & into desmosomes. prickles/spines. lamellar bodies (w/lipid acylglucosylceramide). usually thickest layer (?)
Stratum granulosum 2nd layer of skin. keratinocytes in epidermis. squamous keratinocytes w/organelles. keratohyalin granules (histidine rich). secretion of lamellar bodies -> waterproof glycolipid complex under stratum corneum. keratinization 2-6 hours. free nerve endings.
Stratum corneum Top layer of skin. Keratohyalin granules -> "soft" keratin-filaggrin matrix. dissolution of cellular organelles. DNA fragmentation, dessication -> squames. most variable in thickness.
Filaggrin protein that binds keratin into bundles, epidermis
Tonofilaments Keratin filaments inside epidermis cells
squames fully keratinized cells of the stratum corneum
psoriasis keratinocytes in superbasal layers divide continuously -> immature cells reach the stratum corneum
warts keratinocytes infected w/papilloma virus -> epidermal hyperplasia & skin thickening
melanocytes derived from neural crest. round/columnar, branching processes. 1 per 4-10 keratinocytes. melanosomes (cytocrine) but no desmosomes. color dpdt on melanin production & distribution (not # melanocytes). melanin made from tyrosine by tyrosinase enzyme.
moles = melanocyte aggregates (epidermis/dermis) that appear after birth.
melanoma cancer of melanocytes. most severe.
Langerhans cells wander in stratum spinosum of epidermis, no desmosomes. dendritic. antigen presentation, contact allergy, skin-graft rejection. derive from monocytes.
Merkel cells fine touch sensation. release neurotransmitters. located in stratum basale.
thick skin differences from thin increased area of stratum basale produces extra Stratum corneum. parallel ridges predominate (e.g. fingerprint).
epidermal attachment to basement membrane hemidesmosomes: 1) integrin, 2) bullous pemphigoid antigen
basement membrane of epidermis, layers Lamina lucida = heparan sulfate proteoglycan + laminin (just below basement membrane). Lamina densa = type 4 collagen. Sublamina densa = fibronectin. Anchoring fibrils = type 7 collagen!! type 1 collagen also present.
components of dermis collagen 80%, elastin 2%, glycosaminoglycans provide hydration. deep dermis = Pacinian corpuscles.
Papillary layer of the skin dermis. superficial, type 3 collagen (reticular fibers), loose connective tissue, capillary loops, nerve terminals, macrophages (w/melanin granules). Meissner's corpuscles @ tips of dermal papillae.
Reticular layer of the skin dermis. dense connective tissue. type 1 collagen & proteoglycans.
Subdermis adipose, nerves & blood vessels, secretory portions of glands. Pacinian corpuscles.
blisters plasma leakage b/tw dermis & epidermis
Pacinian corpuscles deep dermis & subdermis, mechanoreceptor
Meissner's corpuscles tips of dermal papillae, touch receptors
Ruffini endings mechanoreceptors, respond to collagen displacement, in dermis
Hairs downgrowth of epidermis into dermis = outer root sheath surrounded by dermal sheath. base of follicle = epidermal cells next to dermal papillae (zone of differentiation where cells divide -> hair shaft). melanocytes in epidermal matrix give color.
hard vs. soft keratin skin = soft. hair = hard (more covalent cross-linkage)
arrector pili muscle smooth muscle, attaches connective tissue sheath around folicle to papillary dermis. goose bumps.
hair stem cells epidermal stem cells in epidermal bulge. dermal stem cells in dermal sheath.
terminal vs. vellus hairs terminal = large course hairs in large follicles (e.g. pubic) . Vellus = short fine hairs in small follicles.
hair growth phases Telogen = rest. Anagen = new hair develops (can last several years for large follicles). Catagen = growth ends & epidermal matrix recedes. Baldness = large follicles convert to small (testosterone based)
sebaceous glands external root sheath cells. several glands/follicle. cells fill w/sebum. holocrine secretion. lubricates/protects hair & skin. develop from hair root sheath.
Acne impacted sebum within hair follicle + anaerobic bacteria
apocrine sweat glands "body odor". axilla/areola/nipple/external genitalia/circumnal. begin @ puberty. associated w/hair follicles. simple epithelial secretory cells, merocrine (misnamed!). duct= stratified cuboidal. empties into hair follicles. develop from hair root sheath.
eccrine sweat glands entire body. Temp control: ACh, forehead & scalp 1st, palms & soles last. Emotional Stress: E/NE, palms & soles 1st. pseudostratified epithel w/secretory & duct=cuboidal, enters dermis @ epidermal pegs.
eccrine sweat body temp/emotional stress. up to 10 L/day
epidermal aging 1 derm-epiderm jxn flattens, 2 fewer basal projections. 3 basal cell cycle slows= thinner epidermis. 4 fewer melanocytes & langerhans. 5 stratum spinosum-> disorganized. 6 vitamin D3 activation decreased -> bone weakness. 7 Stratum corneum dries out.
dermis aging papillary dermis loses elastin (fibrillin remodeling). remaining fibers ->thick & clumped = WRINKLING. less collagen + altered crosslinking = stiff & more damage-proned. decreased sweat gland activity.
nuclear Gemini "gems" = site of snRNP genesis. SMN protein associated w/Gemin 2.
fibronectin glycoprotein that promotes wound covering by EC's
laminin found in basal lamina, associated w/type IV collagen, made by EC's for adhesion to basal lamina.
cellular inclusions 1) melanin. 2) lipofuscin. 3) secretory granules. 4) glycogen.
retroviral proteins & the nucleolus redistribute fibrillar & granular materials to favor viral replication.
PC1-PC2 complex in primary cilia. =stretch activated Ca++ Ch -> RyR opens -> AP generated.
dense bodies smooth muscle: where actin filaments insert. contain alpha-actinin & desmin.
Created by: rbxbrown



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