Unit 4

How stem cells are maintained by stem cell niche, examples?

-microenvironment maintains undifferentiated state

Genetic changes and evolution of cancer cells -oncogenes, tumor-suppressor genes, DNA damage repair

-Dominant GoF mutations in proto-oncogenes -Recessive LoF mutations in tumor-suppressor genes -Recessive LoF in DNA damage repair genes

Describe signaling pathways associated with CAM (integrins)

-Integrins interact by adapter proteins to influence cell survival, gene transcription, cell prolif Outside-in: focal adhesion kinase [FAK]

Describe unidirectional action potential propagation

-Voltage gated channels are located at Nodes of ranvier -Unidirectional conduction occurs due to refractory period of voltage dependent Na+ channels

Oncogenes vs. tumor suppressor genes

-oncogenes promote the cell cycle; like stepping on the gas pedal -mutated tumor suppressors can no longer slow the cell cycle; like cutting the brakes

Identify 4 major types of cell adhesion molecules and what they bind

1. Cadherins: form Ca2+ dependent interactions with other cadherins (cis/trans) 2. Immunoglobulin family: homophilic and heterophilic linkages 3. Integrins: heterodimeric (a/b chains) adhere to large substrates like fibronectin 4. Selectins: lectin domain binds to carbs (glycoproteins/glycolipids)

1) totipotent 2) pluripotent 3) multipotent 4) unipotent

1. Generates all cell types, tissues, structures (zygote 2 cell or 4 cell) 2. All ES cell types (blastocyst ICM) 3. Many cell types (hematopoietic stem cell) 4. One cell type

Which glycosaminoglycan (GAG) is NOT part of a proteoglycan? 1. Hyalauronan 2. Chondroitan sulfate 3. Heparin sulfate 4. Keratan sulfate

1. Hyalauronan

Describe major components of the basal lamina and their function

1. Laminins: a heterotrimeric protein shaped like a cross that crosslinks receptors and ECM, Ca2+ mediator 2. Collagen type IV: a trimeric protein with a triple-helix structure, that forms a two-dimensional sheet 3. Perlecan: large multidomain proteoglylcan that cross-links ECM components and cell surface molecules 4. Nidogen: a rod-like molecule that cross-links type IV collagen, perlecan and laminin

Other ECM components: 1. Proteoglycans 2. Plant cell wall

1. O-linked and N-linked glycosaminoglycans (repeated disaccharides) 2. Laminate of cellulose fibrils in a matrix of glycoproteins, plasmodesmata for communication

Apoptosis pathway 1. What differentiates pro-survival from pro-apoptotic? 2. Pathway

1. Pro-survival has BH4/Bcl-2, Pro-apoptotic Bax/Bak kept monomeric by Bcl-2 2. Apoptotic signals (BH3 only proteins) disrupt Bcl-2-Bak interaction -> Bak oligomerizes and forms channel for Cyt C exit -> Cyt C binds & activates APAF -> activates initiator caspase -> activates effector caspases through proteolytic cleavage Bh3: Bad, Bid, Bim, Puma, Noxa

How tumor cells differ

1. abnormal genomes/karyotypes 2. aerobic glycolysis (Warburg effect) 3. unique metabolites for growth advantage 4. Metastasis and migration

Describe 1. properties of stem cells 2. how ES cells and iPSC are created**

1. asymmetric cell division, telomerase 2. -inner cell mass of blastocyst forms embryo (ES cells) -Oct4, Sox2, Nanog necessary for self-renewal and pluripotency

Describe cell-cell junctions and their CAMs 1. adherens junctions 2. desmosomes 3. hemidesmosomes 4. tight junctions 5. gap junctions 6. focal adhesions

1. cadherins, shape & tension 2. cadherins; intermediate filaments 3. integrins, shape 4. occludin, claudins, JAMs; solute flow and diffusion control 5. Connexins; communication & small-molecule transport 6. integrins; shape

Describe how asymmetric cell division is mediated by internal and external signals

1. localized cue 2. sensing cue 3. signal transduction -> reorganize cytoskeleton 4. movement of polarity determinants 5. reinforcement of polarity determinants

1. oligodendrocytes 2. astrocytes 3. Schwann cells

1. myelin sheaths around neurons in CNS 2. interact with endothelial cells at the BBB, interconnected by gap junctions, produce ECM proteins, capillary tight junctions 3. form myelin sheaths around neurons in PNS

Describe major proteins of connective tissue and their structures and functions 1. fibrillar collagens nonfibrillar collagens 2. Tendons 3. Cartilage

1. propeptides form triple helix with Gly-X-Y (proline, hydroxyproline) -> procollagen -> collagen fibril 2. Type I fibrils bound by type VI collagens and proteoglycans 3. Type IX collagen bound along type II fibrils, chondroitin sulfate change at flexible kink, globular N-terminal

In adult mammals, multipotent stem cells are found in the (select all that apply) A. Bone marrow B. intestinal crypts C. liver

A, B

Explain how neurons and effector cells communicate across synaptic junction

Action potential -> opening of voltage gated Ca+ channel -> membrane fusion -> release of NT in synaptic cleft -> bind to receptors at neuromuscular junction -> voltage gated Na+ channel -> calcium release in SR for muscular contraction -Multiple signals are integrated until threshold is reached (~ 40 mV)

The adaptive immune system uses many types of APC (dendritic cells, for example) to _____. Activate T and B lymphocytes Produce antibodies Terminate T and B lymphocyte activation

Activate T and B lymphocytes

Antibody diversity is created by the random selection of ________. The Ig gene segments to be recombined the ability of the heavy and light chains produced from rearranged Ig genes to associate with many different light chains and heavy chains Junctional imprecision somatic hypermutation Pick this if all of the above are correct.

All of the above

Compare and contrast antibodies and T-cell receptors--structures & antigens bound

Antibody (IgE/B cell): 2 light chains, 2 heavy chains, undergo somatic recombination for high variability and unique antibodies, 5 isotypes -SOMATIC HYPERMUTATION by deamination T-Cell recptor: alpha and beta chains undergo somatic recombination

Describe mechanisms that generate antigen receptor diversity in B cells and T cells

B-Cell: somatic recombination, somatic hypermutation by deamination T-cell: somatic recombination

Which of the following are involved in important immulogic checkpoints of relevance to cancer? CTLA1 myc PD-1 Bax PKC

CTLA1, PD-1

Describe Class I and Class II MHC molecules in antigen presentation

Class I: ALL cells express MHC I antigens, present to CD8+ T cells Class II: Only professional antigen-presenting cells, external antigens, present to CD4+ T cells

EMT and MET in Cancer Metastasis

Epithelial: adherent stage Mesenchymal: prliferative, migrating

Which region of an antibody binds to the antigen? Fab Fc Fd all of the above

Fab

Identify isotypes and multimers

IgG, M, A, D, E IgA and IgM

Distinguish innate and adaptive defenses w/ respect to timing and antigen specificity

Innate: minutes to hours, macrophage, dendritic cell, neutrophil, NK cell -BROAD Adaptive: Days; (macrophage, dendritic, neutrophil, NK cell) B/T cells! -SPECIFIC -dendritic cells present antigen to B/T cells

Match the structures labeled with letters A-E with their correct names

LAPTOP

How is cell polarity established?

Localized cue leads to cytoskeletal reorganization and asymmetric cell division (Cdc42 marks anterior)

Upon activation, dendritic cell migrate to

Lymph Nodes

Describe interactions between dendritic cells, CD4+ T cells, B cells, and CD8+ T cells to defend against pathogens

Mature T/B cells go to lymph nodes, B cell binds antigen presented by dendritic cell, T cell activated , T cells interact with B cell leading to B-cell differentiation and antibody production

Multi-hit model for cancers

Multiple mutations are required to cause cancers

Perforin and granzymes are used in the killing mechanism of _______ Neutrophils macrophages NK cells the complement system CTLs (activated CD8+ T cells)

NK cells, CTLs (activated CD8+ T cells)

Apoptosis vs. necrosis

Necrosis causes cells to swell and burst, whereas apoptotic cells shrink and condense -Necrosis damages surrounding cells

What "reloads" a secretory vesicle with neurotransmitters?

a V-class proton pump plus H+-antiporter drive neurotransmitter uptake

Draw an action potential and explain ion channels

Resting: Nongated K+ partly open Depolarization (-70mV -> +50mV): Na+ channels open and voltage-sensing alpha helix moves -> movement of channel-inactivating segment inactivates channel -> refractory period -> repolarization & displacement of channel-inactivating segment Repolarization: K+ efflux Hyperpolarization: Na+/K+ normalizes

In mammalian development, cells in which of the following stages are NOT totipotent? blastocyst zygote compacted morula 4-cell 8-cell

blastocyst

The vertebrate apoptosome is composed of Apaf 1, _____, and caspase 9

cytochrome C

Explain clonal selection

encounters with antigen selects which lymphocyte will divide to produce a clonal population= clonal selection

In the mouse embryo, pluripotent stem cells are found in the inner cell mass trophectoderm zona pellucida only at the 8-cell stage or before

inner cell mass

Mutations in the APC gene (APC adenomatous polyposis coli) contribute to abnormal cell proliferation because they _____. stimulate capillaries to grow into tumors and provide nutrients for cancer cell growth. interfere with the normal mechanism for proteosomal degradation of β-catenin. eliminate the ability of connexins to form and control transport of small molecules between neighboring cells. none of the above are related to APC mutations.

interfere with the normal mechanism for proteosomal degradation of β-catenin.

Class II molecules bind to extracellular materials internalized by_________. phagocytosis receptor-mediated endocytosis the SRP receptor for ER transit Mitochondrial inner membrane transport

phagocytosis, receptor-mediated endocytosis