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BSI test 3


Connective tissue most diverse and abundant form of tissue
fibrocyte connective tissue proper
cartilage chondrocyte
bone tissue osteocyte
basil lamina a non-cellular supporting sheet between the epithelium and the connective tissue.
basil lamina consists of proteins secretedby epithelial cells
basil lamina acts as a selective filler and scaffolding
tight junctions interlocking junctions of proteins
desmosome intermediate filaments that form linker proteins
gap junction form channels between cells
cyclin CDK inhibitor P21 (S CDK)
cyclin CDK inhibitor P27 (G1/S CDK)
transcription factors myc
transcription factors e2F
transcription factors p53
inhibitors involved with cell cycle Rb
inhibitors involved with cell cycle Wee1
inhibitors involved with cell cycle securin
UBQ ligases in cell cycle control MDM2
UBQ ligases in cell cycle control APC
UBQ ligases in cell cycle control SCF
anaphase the APC triggers separation of chromatids the spindles draw the chromatids to opposite poles
telophase nuclear envelope reassembles around each set of separated chromatids. the chromasomes start to decondense
cytokinesis division of cytoplasm. begins in anaphase and ends in telo phase
prophase the replicated chromosomes condense. the centrosomes move to opposite sides of the nucleus
prometaphase nuclear envelope breaks down. the spindles attach to kinetochores on chromatids.
kinetochores protein complexes on chromosomes
metaphase mitotic spindle aligns the chromosomes at the equator
S-CdK triggers DNA replication in S phase
How does the cell prevent entry into S phase if there is DNA damage? 1)DNA damage leads to phosphorylation and increased stability of 2)p53 increases the transcription of p21 3)p21 binds to G1/S-CdK and S-CdK inhibiting their activity
Potential candidates for knocking gene out will it lead to increased cell proliferation. Rb P27 P21 Wee1 ATM Securin P53
Which enzyme replicates DNA? DNA polymerase
How many chromosomes are copied? 46
What are the phases of mitosis? PPMAT
In what phase do the sister chromatids separate? Anaphase
How does APC trigger anaphase? Ubiquitinates securing
MAPK activates G-CDK and G1?S-CDK by phosphorylating them? (T/F) False
G1-CDK and G1/S CDK activate S-CDK by phosphorylating it. (T/F) False
P 27Inhibits: G1/S CDK
P21 Inhibits G1/S CDK S-CDK
How does S-CDK activate M-CDK? It phosphorylates cdc-25
In mammals an external cellular signal is required to initiate the cell cycle mitogen
The mitogen stimulated activity of G1-CdK and G1/S-CdK leads to transition into S-phase and activation of S-CdK
M-CdK activity is responsible for transition through the M-phase
Mitogen signaling leads to increased activity of G1-CdK and G1/-CdK
Rb phosphorylation leads to increased activity of E2F and entry into S phase
E2F a transcription factor that increases expression of proteins needed for s-phase
S-CdK triggers DNA replication in S phase
CdKs phosphorylate key proteins involved in the cell cycle
CdKs must be bound to cyclins inorder to be active
When cyclins are degraded the CdK becomes inactive
Cyclins degraded by the ubiquitin-proteasome system
There are a variety of CdKs and cyclins that regulate the different phases of the cell cycle. The cyclin-CdK complexes are called G1-CdK, G1/S-CdK, S-CdK, M-CdK.
Aside form cyclin binding, CdKs also require phosphorylation/dephosphorylation to be fully active
Necrosis Death due to injury or severe insult
Physical characteristics of necrosis 1.Cell and organelles swell and rupture releasing intracellular contents 2. Induces an inflammatory response a. Infiltration of immune cells (white blood cells) 3. Damage and/or death to surrounding tissue
Apoptosis Death is tightly regulated and Cell suicide is executed via specific signaling pathways
physical characteristics of apoptosis 1.Cell shrinks 2.Condense nucleus 3.DNA fragments into oligonucleosomes 4. Membrane blebbing and formation of apoptotic bodies ingested by neighboring cells or macrophages 5.No inflammatory response 6. Death of single cell
Signal for phagocytosis of apoptotic bodies exposure of phosphatidylserine on outer layer of plasma membrane
External stimuli (triggers of apoptosis) 1. Withdrawal of growth factors/survival signals 2. Detachment from extracellular matrix 3. Cytokines a. Produced by cells of immune system b. Example: tumor necrosis factor alpha (TNF-alpha) 4. Cytotoxic T cells 5. Toxins
Internal stimuli (triggers of apoptosis) 1. DNA damage 2. Mitochondrial dysfunction a. Decreased ATP production b. Excessive free radical production and damage
Variations in cell type (triggers of apoptosis) 1. Stimuli that induce apoptosis 2. Resistance to apoptosis
Caspases Executioners of Apoptosis, Proteases that cleave proteins
Capases Synthesized as proenzymes-inactive precursors
Cleavage forms large and small subunit which forms the active caspase
Caspases cleave specific substrates
number of capases 14 caspases
Intrinsic Apototic signaling pathways 1. Mitochondrial-mediated apoptosis 2. p53/Nuclear-mediated apoptosis
Extrinsic Apototic signaling pathways 1. Receptor-mediated apoptosis a. Fas/FasL signaling
mitochondrial-mediated apoptotic signaling is triggered by mitochondrial function and apoptotic signaling pathway
mitochondrial functions that trigger mitochondrial-mediated apototic signaling a. Deficient ATP production b. Oxidative stress/ROS production
apoptotic signaling pathway apototic signaling p53/Nuclear-mediated which is Receptor-mediated
mitocondrial-mediated signaling event 1. Cytochrome c release 2. Formation of apoptosome (Procaspase-9, Apaf-1, cytochrome c, dATP) 3. Activation of caspase cascade
Formation of apoptosome Procaspase-9, Apaf-1, cytochrome c, dATP
Caspases proteases which cleave other proteins
Procaspases also known as proenzyme cleaved to active caspases
Procaspase-9 → active caspase-9 auto cleaves itself cleaves procaspase-3 this leads to → Apoptosis
Regulators of apoptosis Bcl-2 family, Inhibitors of Apoptosis Proteins (IAPs)and Repressors of IAPs
Anti-apoptotic: prevents cytochrome c release Bcl-2, (Other: Bcl-XL)
Pro-apoptotic: favors cytochrome c release Bax, tBid (truncated Bid) (Other: Bak, Bim, Bad, Bok, etc)
Inhibitors of Apoptosis Proteins (IAPs) XIAP, (Others: cIAP1, cIAP2, survivin, Binds to cleaved caspases and inhibits activity
XIAP inhibits activity of caspase-9 and caspase-3
Repressors of IAPs Smac/Diablo and Omi/Htra2
Smac/Diablo and Omi/Htra2 i. Released from mitochondria upon stimulation ii. Binds to IAPs and represses their inhibition on caspases allowing caspases to exhibit their activity to execute apoptosis
In cells not undergoing apoptosis ICAD (I =inhibitor) binds to CAD and inhibits its activity
When cells are undergoing apoptosis caspase-3 cleaves and degrades ICAD
CAD is free and active to fragment DNA into mono-and oligonucleosomes after ICAD binds to CAD and inhibits its activity or when capase-3 cleavs and degrades ICAD
Proteins that caspase-3 inactivates by cleavage ICAD,Cleavage of proteins involved in DNA repair, Cytoskeleton, Anti-apoptotic BCL-2 family proteins
Tumor <0.5mm can receive O2 and nutrients by diffusion from blood vessel
Tumor >0.5mm requires proliferation & morphogenesis of vascular endothelial cells to form new blood vessels
The Onset of angiogenesis is due to the imbalance between pro- and anti-angiogenic factors (upregulation of pro-angiogenic proteins/downregulation of anti-angiogenic proteins)
In adults, active angiogenesis is required only for wound healing, endometrial proliferation, and during pregnancy
Angiogenesis required for progression & metastasis of cancer
The most potent stimulus for angiogenesis is VEGF
VEGF stands for Vascular endothelial growth factor
The most potent stimulus for VEGF production by tumor Hypoxia
HIF- binds to VEGF gene and induces transcription Hypoxia-inducible transcription factor-
HIF- binds to VEGF gene and induces transcription
overexpression of VEGF can result from Mutations in p53 and Activation of ras
Step 1 of angiogenesis pericytes detach, blood vessels dilate
Step 2 angiogenesis basement membrabe and extracellular matrix are degraded by MMP's creating a tunnel toward VEGF for tumor cells to crawl through
Step 3 angiogenesis endothelial cells migrate towards angiogenic stimuli (VEGF) produced by tumor cells
Step 4 angiogenesis endothelial cells proliferate
step 5 angiogenesis endothelial cells adhere to each other and create a lumen
step 6 of angiogenesis formation of basement membrane and pericyte re-attachment
lumen tunnel/opening formed by endothelial cells during angiogenesis
MMP stands for matrix metalloproteinase
Agents targeting the VEGF pathway 1)Antibody for vegf (binds to vegf in general) 2)Anti vegf receptor antibody 3)Small molecule vegf receptor inhibitors (binds to the intracellular domain of the receptor)
Invasion is the migration of cells into deeper tissues—cancer cells break through the barrier that keeps them localized
a tumor is malignant if it has The invasive phenotype
Metastasis is the spread of cancer cells from a primary tumor to distant sites in the body
the major causes of cancer treatment failure Invasiveness and metastasis
Steps in matastasis T.AS.AP.SC.EGSS.AST.EIR. (Tri AskedShelley AboutPookie SeeCar EGSS, AshleySlapsTri ExtremelyIrriatableReaction)
To be able to invade a tumor must 1)Increase MMPs, 2)turn on cell motility systems, 3)Decrease expression of adhesion molecules to detach and crawl away to blood supply
Tumor cells can induce apoptosis of cytotoxic T cells
Cytotoxic T cells express FasL & Fas
Tumor cells express Fas L (normal cells usually do not) and downregulate Fas receptor
Tumor cells can upregulate cFLIP (will block caspase 8)
Consequences of Tumor cells can induce apoptosis of cytotoxic T cells 1)Tumor cells (with low Fas) resistant to apoptosis by cytotoxic T cells 2)Tumor cells (due to FasL expression) induce apoptosis in cytotoxic T cells
HPV is a virus that causes cancer and inactivates p53 and Rb
Interphase consists of what 3 phases G1, S, G2
G1 phase Cell growth (Some cells remain in this phase permanently then called G0)
S phase 1)Replication of genome (DNA synthesis) 2)DNA is copied by DNA polymerase 3)The duplicate chromosomes remain bound together by proteins called cohesions (until M-phase when the chromosomes will be separated)
G2 cell growth, again
MPhase consists of Mitosis and cytokinesis
Mitosis consists of Prophase, prometaphase, metaphase, anaphase, telophase
Prophase i. The replicated chromosomes condense ii. Centrosomes (which replicated during S phase) start to move to opposite sides of the nucleus and the mitotic spindle begins to assemble outside the nucleus
prometaphase i. Nuclear envelope breaks down ii. This allows the spindle microtubules to contact the condensed chromosomes iii. The microtubules bind to kinetochores located at centromeres of sister chromatids
kinetochores protein complexes which assemble on the condensed chromosomes
metaphase Mitotic spindle gathers all the chromosomes to the center (equator) of the spindle
anaphase i.sister chromatids split apart 2.Spindle draws them to opposite poles 3. Anaphase begins with the release of linker of sister chromatids iv. chromatids are pulled to the spindle pole v.sets of chromosomes to opposite ends of the spindle
Activation of anaphase promoting complex (APC) triggers the separation of sister chromatids
telophase 1.Nuclear envelope reassembles around each of the two sets of separated chromosomes to form two nuclei 2.Nucleus expands and chromosomes decondense to interphase state 3. Assembly of contractile ring necessary for cytokinesis
Cytokinesis a. Division of the cytoplasm (including all organelles) 2. Begins in anaphase and is complete by the end of telophase
epithelial tissues basic function covering
connective tissue basic function suport
muscle tissue basic function movement
nervous tissue basic function control
epithelial tissue covers a body surface or lines cavities forms glands protects absorbtion, secretion and ion transport filtration slippery
squamous cells wider than tall (squished flat)
cuboidal cells are as wide as tall (cube like)
columnar cells taller than wider (columns, usually have cilia)
ducts carry what? products of exocrine glands to surface
simple ducts ducts that branch
compound duct ducts that branch
simple tubular ducts found in intestinal glands
simple branched tubular ducts found in gastric glands
compound tubular ducts found in duodenal glands of small intestine
coumpound alveolar ducts found in mamary glands
simple alveolar ducts not found in humans
simple branched alveolar ducts found sebaceous (oil) glands
compound tubuloalveolar ducts found in salivary glands
endocrine glands ductless glands, secrete sunstances diretly into clood and produce hormones
basil lamina noncellular supporting sheet between epithelium and connective tissue and consists of proteind secreted bu the epithelial cells
functions of the basil lamina acts as a selective filter to the epithelium,, acts as scaffolding where epithelial cells can migrate
basement membrane consists of the basil lamina and reticular layers of connective tissue
tight junction forming a virtually impermeable barrier to fluid between cells
desmosome junctions form cell-cell adhesions and help to resist shearing forces and are found in simple and stratified squamous epithelium.
gap junctions directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells
Connective tissue Most diverse and abundant tissue Cells separated by large amount of extracellular matrix Common embryonic origin – mesenchyme
main types of connective tissue Connective tissue proper Cartilage Bone tissue Blood
types of loose connective tissue aerolar, adipose, reticular
types of dense connective tissue regular, irregular, eliasic
types of cartilage hyaline, fibro, and elastic
types of bone spongy (callceous), and compact
areolar connective tissue gel like matrix with all three fiber types, wraps and cushions organs
areolar connective tissue is found under epithelium, forms lamina prpria of mucous membranes, packages organs, surrounds capillaries
adipose tissue matrix of adipocytes that have nucleus pushed to the side , provides reserve food fuel, insulates, supports and protects organs
adipose tissue is found under the skin; around kidneys and eyeballs, within abdomen; in breasts
Reticular tissue network of reticular fibers in a lose ground substance, form soft internal skeleton that supports other types of cell types (blood, mast, macrophages)
reticular tissue is found lymphoid organs (lymph nodes, bone marrow, and sleen)
Dense Irregular connective tissue irregulary arranged collagen and some elasic fibers, able to withstand tension exerted in many directions, provides structural strength
Dense Irregular connective tissue is found dermis of the skin, submucosa of digestive tract, fibrous capsules of organs and joints.
Dense regular connective tissue parallel collagen and a few elastin fibers attaches muscles to bones, withstands stress when pulling in one direction
Dense regular connective tissue is found tendons, most ligaments, aponeuroses
Hyaline cartilage amorphous but firm matrix made of collagen fibers, chondroblasts produce the matrix and can lie in lacunae when mature; supports and reinforces
Hyaline cartilage is found embryonic skeleton, covers ends of long bone, forms costal cartilages of the ribs, nose trachea and larynx
Elastic cartilage firm matrix made of elastin fibers; maintains shape whicle allowing flexibility
elastic cartilage location external ear(pinna) epiglottis
fibrocartilage less firm matrix with thich collagen fibers; tensile strength with the ability to absorb shock
fibrocartilage is found intervetebral discs, pubic symphysis, discs of knee joint
Bone tissue hard calcified matrix containing many collagen fibers osteocytes lie in lacunae, very well vascularized; supports and protects stores calcium, minerals and fat, blood cell formation
blood tissue red and white blood cells in a fluid matrix (plasma) transport of respiratory gases, nutrients, wastes and other substances
thoracic cavity heart and lungs
major organs or tissues of circulatory system heart, blood vessels
major organs or tissues of respiratory nose, larynx, trachea, bronchi, and lungs
major organs or tissues of digestive mouth, pharynx, esophagus, stomach, intestines, salivary glands, pancreas, liver, gallbladder
major organs or tissues of urinary kidneys, ureters, bladder, urethra
major organs or tissues of musculoskeletal cartilage, bone, ligaments, tendons, joints, skeletal muscle
major organs or tissues of immune white blood cells, lymph vessels and nodes, spleen, thymus, and other lymphoid tissues
major organs or tissues of nervous brain, spinal cord, peripheral nerves and ganglia, special sense organs
major organs or tissues of endocrine all glands secreting hormones, pancreas, testes, ovaries, hypothalamus, kidneys, pituitary, thyrois, parathyroid, adrenal, intestinal, thymus, heart, and pineal
Most control systems operate by negative feedback which basically means that the change in a sensed body parameter initiates a response that opposes that change in an attempt to maintain homeostasis.
negative feedback which basically means that the change in a sensed body parameter initiates a response that opposes that change in an attempt to maintain homeostasis
Positive feedback is usually inappropriate as it tends to increase the stimulus that was monitored as a deviation from homeostasis
4 main cell types of the integumetory system keratinocytes, melanocytes, Merkel cells and Langerhans cells (can act as APC antigen presenting cells).
Keratinocytes are the most common and are constantly formed from the germinal layer on the underlying basement membrane.
keratinocytes produce tough, fibrous protein keratin, some antibodies and enzymes (for protection: see Immunology). As they ascend from the basement membrane to the surface, they die and form an outer physical barrier (toughened by the keratin).
The deepest layer of the epidermis is the stratum basale which is attached to the underlying dermis and contains, as well as actively dividing keratinocytes, Merkel cells (sensory function) and melanocytes (produce the pigment melanin for UV protection).
the most superficial layer is the stratum corneum which is composed of dead keratinocytes with thickened cell membranes.
the next layer superficially from the stratum basale is the stratum spinosum where keratin is forming and Langerhans cells are found.
Langerhans cells immune cells that present antigenic fragments of pathogens to special T-lymphocytes to activate them and produce a specific immune response. They are part of a very important group of cells known collectively as Antigen Presenting Cells (APCs)
the third layer of skin is stratum granulosum which is primarily made up of maturing keratinocytes containing keratin filaments (tonofilaments) plus a waterproofing glycolipid. And stops water loss as well
In thick skin there is an extra layer known as the stratum lucidum which is composed of now flattening, dead keratinocytes.
what 2 layers is the dermis composed of papillary and reticular (deepest)
the reticular layer is composed of dense, irregular connective tissue
Hair is composed of flexible strands of dead, keratinized cells: there are 3 concentric rings starting with the inner medulla → cortex → cuticle.
Sebaceous glands produce an oily secretion called sebum which helps trap dirt and softens and lubricates both skin and hair (this is holocrine secretion meaning that the entire cell breaks down to release the sebum (and is replaced by new cells).
Created by: jeanieceford