S4 Flashcards

1
Q

cell expression basic concept for N and E cadherin

A

can sort by type or by level of cellular expression

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2
Q

cell adheisoon molecuels vs cell junctions

A

membrane proteins vs aggregates of transmembrane and intracellular proteins
inuitive complexity, size, transience and stability differences

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3
Q

epithelial tissue

A

mechanical stress cell to cell by cytoskeletal filaments

anchored to cell matric and cell to cell adhestin sites

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4
Q

connective tissue

A

ECM directly bears mechanical stress

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5
Q

metastasis

A

cells leave tumor then enter blood stream then extravasation to new tissue to colonize

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6
Q

neural development and adhesion

A

cells in epitheliem and then lose adheision when dividing then adhere to radial glia to move up

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7
Q

anchoring junctions

A

actin filament attacchment sites

intermediate filament attatchment sites

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8
Q

actin filament attatchment sites

A

cell cell junctions (adherins junctions)

cell matrix junctions (actin linked cell matrix adhesions)

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9
Q

intermediate filament attatchment sites

A

cell cell is desmosomes

cell matrix is hemidesmosomes

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10
Q

Occluding junctions

A

tight junctions in vertes

septate in invertes

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11
Q

signal relay junctions

A

chemical synapses
immunological synnapes
transmembrane lignad - receptor and cell cell signaling contancts

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12
Q

role of extra junctional adehesion molecuels

A

involved in forming junctions but not direcly part of it

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13
Q

ways to measure adhesion/junction force

A
centrifugation
atomic force microsopy
dual pippette assay
flipping assay
magnetic bead
FRET
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14
Q

this section TEM vs Freeze fracture TEM

A

close vs overview?

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15
Q

freeze fracture

A

separate leaflits of PM
E face is smooth exoplasmic
P face is rough protoplasmic

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16
Q

occluding junctions on endothelim of intestings

A

tight junctions
apical
usually top down is tight,adherin, desomosomal, hemidesmosomal
visible as terminal bar
protein occludin
sealing strands with actin microfilaments
polarize cells

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17
Q

2 anchoring junction protein types

A

intracellular anchoring proteins

transmembrane adheision proteins (adheision molecuels)

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18
Q

adherins junction

A
cell to cell
classical cadheirins
bind to same on other cell
actin filaments
alpha and beta cateinn
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19
Q

desomosomes

A
non classiscal cadherines
cell to cell
bind desmoglein and desmocollin on other cell
intermediate filaments
plakoglobin
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20
Q

adherens and development

A

contract to create invaginations for like epithelial tube
E cadherins outside tube
N cadherins in the ring

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21
Q

mechanotransduction

A

when stretched more actin recruited

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22
Q

hemi vs desmosome

A

both link to intermediate
hemi to basal lamina,
desmo is cell cell

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23
Q

pemphigus vulgaris

A

autoimmune disease affecting desomosmes

antibodies disrupt in skin causing blisters, flfluid loss and infection

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24
Q

hemidesmosomes in EM

A

look like half desmosomes
anchor basal lamina to intermediate filaments
disrupted in bullous pemphigold

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25
focal adhesions
link actin to ECM cell movement and wound healing integreins
26
integrin activation
ligand for outside in or tallin for inside out
27
Talin as a mechanotradducoer
vinculin binding site exposed from tension | intracellular
28
selectins
adhesion molecules that dont participate in junctions | transient adhesions
29
extravasation
weak adhesion and rolling (selectin dependent) strong adhesion and emigration (integrin dependent) white blood cells leave blood stream to chase inflammation
30
neurexin and neurolign
involved in cell cell connections at synapes and signaling for developing and maintaintng neural contacts
31
integrin receptor basics
membrane spanning bind to ECM proteins transduce bidirectionsally
32
GAGs
glycosamino glyicans amino sugar 4 groups mainly hylauran
33
hylauronan
simples GAG | not bownd to core protein
34
proteoglycan
GAGs covalentlybound to core preotiens | gel like ground substances
35
functions of GAGS and proteoglycans
regulate chemical signaling regulate other secreted proteins act as co receptors resist compressive force
36
hurlers syndrome
accumulation of the GAG heparan sulfate | deficincy in degration enzyme
37
fibrous proteins in ECM
collagen elastic fibers fibronectin
38
collagen
tensile strength triple helix hydoxyproline and hydroxylisine residues are critical for fibril formation cells determine size/ organizaation via gene expression
39
types of collagen
I most comman for like skin and bone IX and XII for link fibrils IV network forming VII anchorning
40
collagen assembly steps
``` syn of pro alpha chain hydroxylation of prolines and lysines glycosylation of selected hydroxylysines self assmbly of 3 pro alhpha chains procollagen triple helix formation via inter chain H bonds at hydroxylated residues secretion cleaveage of propetides self aseembly into crosslinked fibriles ```
41
fibril associated collagens
wickerwork is perpindicular | budneled is parallel
42
scurvy
vitamin C deficiency | no hydroxylation so no collagen
43
osteogeneis imperfecta
colllagen Type I mutated | weak bones
44
scleroderma
autoimmune scar tissue buildup and collagen in dkinand organs
45
elastic fibers
recoil after trasent stretch elastin with loos random coil model microfibril coat eleastin core as scaffold made of fibrillin
46
marfans syndrom
mutation of fibrilin gene lense displacement, skin joints weird predisposint ot aortic rupture
47
fibronectin
``` cell-ECM interaction specific binding sites for matrix macromleucles and cell surface receptors dimers with repeated domains Type III binds integrin at RGD sequence needs to bind integrin to form fibril ```
48
basal lamina
ECM under epithelial cells laminin is primary component, cross shaped, cue from cell to form sheet type IV collagen
49
basal lamina functions
``` mechanical support compartmentalize tissue selective filter scaffold migration cell polarity ```
50
epidermolysis bullosa
defece in basmemtn membrane leading to blisters
51
ECM turnover
``` remodleing matrix metalloproteasses serine proteases regulated by local activaaiotn cell surface receptors secreted inhibtiros protease specificity ```
52
integrin receptors
``` heterodimerice transmembrane ECM receptors alpha and beta subunites distinct dimers short C tails and large N heads Tail link integrin to cytoskeleton head to ECM proeins ```
53
receptor mediated signaling
dynamic inactive - bent, tighlty folded heads, tail tail contact active - separate tails, unfolded heads
54
outside in signaling
ligand binds head makes active conformation exposing binding site on tail talin binds beta subuinit and anchors integrin to cytoskeleton
55
inside out signaling
talin activated binds to Beta subunit creating cross talk on surface
56
allosteric regulation
ligan binding make conform change on both sides so bidirectional signals basically cuz dimers, changes in one affects both
57
integrin clustering
receptors in high concentratin with low affinity for ligand velcro principle: bunhch of weak make strong activated integrins associate laterally
58
focal adheison
ECM binds integrins | downstream effects, no intrinsic kinase in integrins
59
focal adhesion kinase
binding site revealed when talin binds integrin | FAK gets activted
60
growth factor receptor regulation
direct is independent because GFRs cross phosphorylate | indirect is depended
61
leukocyte adhesion deficiency
Beta 2 deficient so WBCs cant get to infection
62
glanzmans disease
Beta 3 | platelates cant clot ucz cant interact with fibrinogen
63
ECM-integrin cell morphology
spatial signals agar for 2D layers but spherical in ECM for mammilary mechanical signals bidirectionally reciperocal communication btwn cells and environment
64
ECM-integrin cell survivial
``` biochemical cues integrins and GFRs anchorage dependent growth contact promotion detatchment and apoptosis ```
65
anoikis
cell death as resuld of ECM detatchment | cancer cells resist this
66
ECM-integrin and Migration
mechanical support and chemical cues dor dirceting | differential integrin activation for moving
67
ECM integrin dysfunction and cancer progressin
break through basal lamina matrix protease activation invadopodia are membrane protrutions
68
ECM integrin dysfunction and cancer | matrix stiffness
tumor progresssion | matrix not tumor is whats felt
69
LOX
inhibit this and increase collagen cross links
70
volociximab
against alha5beta | slows tumor growth
71
cilengitide
targets avb5 and avb 3
72
inner vs outter blastocyst
inner is animal, forms disc | outer forms placenta
73
3 germ layers
endoderm mesoderm ectoderm
74
gastrulation
endoderm - epeithelial cells mesoderm - heart, muscles, bone ectoderm - nervous system, epidermis
75
epithelial cell movmentn
``` out of mesenchymal loss of cellcell junctions lose apical basal polarity alpha SMA expression for front back polarity MMP upregulate ```
76
heart organogenesis
``` cardiogenic area near head u shaped primitive blood cells 2 tubes fuse bulbos folding and lifting into compartments controll of transcription factors by microRNA ```
77
lung organogenesis
tracheal buds then branching surfactant Tbx5, Wnt, Bmp FGF and Shh to create branches
78
limb development
initiation has antiror Gli3 and Wnt and posterior Hand2 and Wnt early secification has ZPA with Shh posterior and AER distal with FGF apoptosis to separate
79
teratology
study for birth defects | knockouts cool if they work in vivo but might be embyronically lethal and useless
80
in vitro fertilization
create permanant collections of embryonic stem cells
81
genetic engineernig steps
take special stem cells inject in to blastocyst inner cell mass implant in foster mother making chimeric mouse
82
Crispr Cas 9
dont need ES cells | can just inject DNA changes
83
stem cell stages
self renewal specification differentiation
84
specificatoin
make stem cells pic a path autonomous - genome, asymmetric division not external factors syncytial - unusual, nuculus not cytoplasm divides conditional - environment: indirect with paracrinn Shh or integrines; direct with cell cell contact via juxtacrin or notch
85
differentiation
take specified scells and specialize them into cell type
86
key characteristics of stem cells
self renewal without loss of differntation potential | can make differentaited daughter cells
87
diabetes stem cell treatment
beta cell transplant
88
potency
number of possible fates
89
totipotency
can be anything | found in zygotes for 8 days
90
pluripotents
can make all embryo cells in innerc cell mass till day 10 make teratoma in tumor in mice that hass all 3 germ layers oct4, nanog, sox2
91
multipotent
all tissues of an organ hematopoeitic for blood mesenchymal for connective tissue
92
unipotent
one type | like spermatogonia
93
Lineage tracing
have reporter gene so can tell all the progeny of a single cell
94
stem cell niche basics
microenvironment and cells next to stem cells that support and tell when/how to divide daugther cells divide away from niches so dont get SC signals stem cells start doing stuff before niche is formed
95
drosophila stem cell niches male
male of SC have hub cells at apical end attached side stays SC unattached activates JAK STAT pathway to divide and differentiate
96
drosophila stem cell niche female
cap cells at apical end signal through cadherin junctinos TGF beta ligands promote MAD+P which turns off BAM but BAM is on in daughter cells and leads to differentation
97
intestinal stem cell niche
Lrg5+ at crytp base for rapid Bmi1+ for slowly (further up) alpi+ can dedifferentiate back to Lrg5+
98
neural stem cell niche
in V-SVz
99
serial transplantatio
``` take out tag culture put back regenerate organ ```
100
label retention
stem cells can turn off cell cycle to
101
damage repair
queiscent by NHEJ | cycleing by HR will have higher fidelity but also ROS so bad
102
plasticity of differentiatied cells
dedifferentiation to same lineage happens in instestines with Alpi+ trandifferentiation when daugter cells become multiple types (pancrease) important for regeneration
103
lineage tracing
cre with stem cell promoter and a marker
104
mTor
nutreint sensing | related to insulin and insulin like receptors
105
senescence
cell lineage lifespan defined by number of doublings telomeres
106
hayflick limit
human cells do not spontaneously immortalize except for tumors mouse cells do
107
3T3 cells
cells per square centimeter is 3x10^5 | concentration where they immortalize but retain normal phenotype
108
SV40LT
viral protein inactivates p53 and pRb creates crisis and apoptosis but surviviors immortalize as tumors
109
papilloma virus
imortalizes by targeting E proteins
110
Li faumeni syndrome
heterozygous mutation for p53
111
p53 and sensecence
+P activates p53 which activates p21 and arrests cell cycle or activates PUMA and apoptosis
112
senscenes char that are opposite of apoptosis
``` maintain viablity cells persist secrete stuff pro inflame natural killer cell response impact tissues ```
113
4 triggers of p53 and senescence
telomere attrition oncogenic activation oxidative stress mitochondrial stress
114
telomere attritions
end gets shorter cuz overhang and okaziki fragments T loop stuff not able to recover full length humans dont have telomerase DNA damage once too short activated p53
115
oncogenic transformation
immortal cells with activated ras proteins become tumors but mortal ones senesce
116
pluiipotent blood stem cells
CD34+ and Lin Negative | 1/1000 in bone marrow
117
neutrophil
most abundant granulocyte phagocitic line of defense against bacteria
118
basophil
least numerous | histamine and allergies
119
eosinophils
kill parasitic worms
120
monocytes
become macrophages in tissue
121
function of WBCs
innate non specific immune response | extravasation from blood stream to inflammation
122
lymphocytes
adaptive immune cels make antibodies B cells have antibody in membrane and makes more T cells eat then present antigen to make more helpers and killers
123
chars of hematopoitic ontageny timing
mesoblastic 2 weeks to 2 months hepatic 6 weeks to birth (liver and soome spleen) myeloid - bone marrow red for intrauterine life
124
stromal cells
stem cells in niche bound to these stay stem cells otherwise differentiate has kit ligand and SCF
125
early hematopoietic colony stimulating factors CSFs
stem cell factor SCF/kit ligand | IL-3 / multi csf
126
intermediate hematopoietic colony stimulating factors CSFs
lineage commitment GM-CSF -> myelocytes IL-7 -> lymphocytes
127
late hematopoietic colony stimulating factors CSFs
``` single lineage G-CSF -> neutrophils IL-5 -> eosinophils M-CSF -> monocytes/macrophages IL-4 -> mast cells EPO -> erythrocytes ```
128
red blood cell development
extrudes nuclesu with division loses 'dont eat me' with age oxygen does not stimulate ECO which makes sense cuz if theres less oxygen then you need more blood for efficiecny
129
counting precursors
cell surface makers tell where in process | cd34 early on
130
leukemia and lymphoma basics
mutation of white blood cells philadelphia chromosome when 9 translocates with 22 stem cells
131
Acute L
blast form ready to divide | CD19 negative in B cell precusor
132
CAR T therapy
chimeric antigen receptors change T cell targets to CD19 postive
133
chronic leukemia
malignant | insidious
134
adult T cell LL
Rash
135
mycosis fungoides
invades skin then blood
136
multiple myeloma
IL6 | infectino risk
137
Non hodgkin lymphoma
CD19 | more frequent
138
Burkitt lymphoma
jaw c-myc CD20
139
hodkin lymphoma
lymph nodes CD15,30 cytokines attract other cell types antibody treatments inneffective
140
autosomal dominant
vertical pattern think punnet square only one parent needs it and then theres a 50% chance regardless of gender paternal age effect
141
autosomal recessive
horizontal cuz only one generation effected heterozygous carriers need two heterozygous parents to be affected 25% affected 25% no mutation 50% carrier punnet square
142
Y chromosome inheretance
males only affected and transmitting
143
mitochondrial inheretance
miDNA | maternal transmition only but can effect male
144
x linked inheritance
males are hemizygous so no male to male transmision all daugters of affected male are heterozygous female give 50/50 affected to sons and 50/50 carrier daughters
145
obligate carrier
heterozygous who have affected offspring
146
EcoR1 and XLA gene mapping
creates two short segments short means mutated long if not both if carrier X linked only one for male, 2 for female
147
LOD scores
>3 linkage of mednelian trati | >2 for multigene trait
148
c
% recombination | recombinates/(progeny+R)
149
highest Z
log(c) | best hypothesis
150
brutons diseas
x linked agammaglobulinemia | BTK mutant arrests B cell development