Articles Blocks 1-2

Question 1

Two major pathways of cell senescence

Answer 1

Replicative and stress-induced

Question 2

What mediates the DNA damage response?

Answer 2

p53, p21, p16

Question 3

Morphology of senescent cells

Answer 3

Enlarged, flattened, multinucleated, vacuolated
Accumulate lipofuscin
Increased beta-galactosidase

Question 4

What part of the immune system do corals lack? What do they have that mammals don’t have?

Answer 4

Acquired; Amoebocytes are main cells of the innate immune system

Question 5

Anoikis prevents

Answer 5

Adherent-independent cell growth

Question 6

Relationship between anoikis and tumor invasion/metastasis

Answer 6

Resistance to anoikis=invasion and metastasis

Question 7

What gives cells ability to resist anoikis?

Answer 7

EMT, antiapoptotic pathways (PI3K/Akt)

Question 8

What has to be present for ferroptosis to occur?

Answer 8

Free iron in cell, lipid peroxides

Question 9

What impairs glutathione peroxidase function?

Answer 9

GSH depletion, lack of cysteine

Question 10

What causes the fenton reaction? What is the result?

Answer 10

free intracellular iron (ferrous iron) interacting with H2O2, forming ROS that cause lipid peroxidation (forms lipid peroxides)

Question 11

When are NETs required?

Answer 11

Large microbial structures (fungal hyphae, bacterial aggregates)

Question 12

What initiates NETosis?

Answer 12

LPS, flagella, immune complexes, complement products, DAMPs, cytokines, activated platelets

Question 13

What causes proteolysis of histones and nucleosomes in NETs?

Answer 13

Neutrophil Elastase

Question 14

NETosis pathway initiation

Answer 14

High levels of ROS activate PAD4, which mediates citrullination of histones, and dissolve cell membranes, so decondensed chromatin mixes with granule contents

Question 15

What causes Parthanatos? What does this overactivate?

Answer 15

Extreme genomic stress with extensive DNA damage; PARP1

Question 16

What phenotype are cells that undergo Mitochondrial Permeability Transition RCD; What triggers MPT RCD?

Answer 16

Necrotic; Severe oxidative stress and Ca overload

Question 17

What does pyroptosis require? What is the outcome?

Answer 17

Caspase 1 (activated by inflammasome) and NFkappaB transcription via TLRs; inflammation

Question 18

What is the effector of pyroptosis?

Answer 18

Gasdermin D (forms pore)

Question 19

What is responsible for carrying out Lysosomal-Dependent Cell Death?

Answer 19

ROS causes lysosomal membrane permeabilization, which releases cathepsins

Question 20

What is the result of lysosomal dependent cell death?

Answer 20

Either apoptosis through MOMP or necrosis (if severe LMP)

Question 21

What is entosis? What triggers it?

Answer 21

Actomyosin-dependent cell in cell internalization; Epithelial cells lacking attachment to basement membrane or ECM

Question 22

What is the hallmark of entosis that sets it apart from anoikis?

Answer 22

Cells drive their uptake into neighboring cells in endocytic membrane

Question 23

What is the main morphological feature of entosis?

Answer 23

Bird’s eye cells, caused by accumulation of actomyosin chains and formation of cell in cell structures

Question 24

Features of necroptosis

Answer 24

Pro-inflammatory
Caspase-independent

Question 25

What is necroptosis dependent on? What inhibits it?

Answer 25

RIPK3; necrostatin, caspase 8 (cleaves RIPK)

Question 26

What initiates necroptosis?

Answer 26

TNF-alpha binding death receptors

Question 27

Possible outcomes of TNFalpha binding death receptor

Answer 27

RIPK ubiquitinated = NFkappaB survival RIPK de-ubiquitinated = either Apoptosis if caspase 8, or necroptosis

Question 28

Effector in necroptosis

Answer 28

MLKL

Question 29

Possible outcome of necroptosis

Answer 29

PGAM5 causes membrane permeability transition pore formation

Question 30

In atherosclerosis, how is the vasa vasorum affected? Major driver?

Answer 30

Increased in density; hypoxia-->VEGF

Question 31

Difference between hepatic stellate cells and hepatic progenitor cells?

Answer 31

HSCs- in space of Disse, known as Ito cells, produce ECM and store vitamin A HPCs- in Canals of Hering, known as oval cells, hepatocyte regeneration

Question 32

How do HSCs cause fibrosis?

Answer 32

Differentiate into myofibroblasts that produce fibrogenic proteins

Question 33

What activates hepatic stellate cells? Three fibrotic genes activated during this process? What holds these in inactive state when not stressed?

Answer 33

Unfolded protein response (ER stress); IRE1alpha, ATF6alpha, PERK; BiP (chaperone)

Question 34

Inhibition of what molecule promotes atherogenesis?

Answer 34

NO

Question 35

Membrane attack complex effect on nucleated cells

Answer 35

Less lytic than microbes due to cell defenses, initiates pro-inflammatory signaling

Question 36

MAC induced effects on nucleated cells (

Answer 36

NLRP3 inflammasome and pyroptosis Apoptosis Necroptosis NFkappaB mediated cell survival

Question 37

What is the path for ICAM and VCAM expression on endothelial cells?

Answer 37

TNF, IL-1, Substance P stimulate GPCR, phospholipase converts PIP2 to DAG and IP3, which causes Ca influx from ER, which causes transcription of ICAM1 and VCAM1 via TF NFAT

Question 38

What is the path for endothelial retraction?

Answer 38

Thrombin binds PAR1, which increases intracellular Ca (GPCR), which activates MLCK and MaMKIIdelta to cause actomyosin contraction, and activates annexin A2 to disassemble VE-Cadherin

Question 39

Potent inducer of acute phase protein production

Answer 39

IL-6

Question 40

Downregulated (negative) acute phase proteins

Answer 40

Albumin Transferrin

Question 41

Hepcidin's role as acute phase protein

Answer 41

Bind transmembrane ferroportin to regulate transport of iron into plasma

Question 42

Haptoglobin's role as acute phase protein

Answer 42

Bind heme to prevent lipid peroxidation

Question 43

Platelets express these adhesive molecules involved in NETosis (and their ligands/receptors on neutrophils)

Answer 43

P selectin - binds PSGL-1 Fibrinogen and integrin alphaIIBbetaIII - binds MAC1 GpIb and vWF binds MAC1

Question 44

Platelets express these soluble molecules involved in NETosis (and their ligands/receptors on neutrophils)

Answer 44

HMGB-1 binds RAGE PF4 and CCL5 (RANTES) chemokines bind GPCR

Question 45

What mechanisms guide leukocyte-endothelial interactions

Answer 45

Cell number Platelet bridging/chemokine signaling Receptor density Ligand affinity- clustering, conformational changes, post-translational mods

Question 46

What is the purpose of In Situ Hybridization?

Answer 46

Localization of a specific (known) nucleic acid sequence using a complementary probe