Embryology Biology 441 Spring 2011 Albert Harris
Last list of review questions:Which of the following is closest to the reason that people don't normally make antibodies against their bodies' own antigens?
b) Genetic linkage prevents anybody who inherits the gene for the A antigen from also inheriting the gene for antibodies that bind to the A antigen, and likewise for every combination of antigens and antibodies. c) Transcription of RNA is selectively inhibited for any antibody whose binding site would fit any of a person's own antigens. d) Because some mechanism weeds out those V, D and J regions of DNA that would code for antibodies that would fit any of that person's own antigens. e) Some mechanism selectively kills, inactivates or sequesters all B and T lymphocytes whose combinations of V, D and J regions of DNA actually do code for antibodies (or T-cell receptors) that actually do fit any of that person's own antigens. f) When antibodies bind to antigens that are present in large enough amounts, then those antibodies are quickly filtered out of the blood. ) Some other mechanism? Put it in your own words.
T-lymphocytes bind to antigens at a binding site called what?
Suggest two major reasons why it's necessary that the great majority of lymphocytes undergo apoptosis.
Explain each of the following newly-invented-just-for-this-exam (but really might work!) cures for cancer
b) A twenty-some amino acid peptide that can be cleaved in two to produce any amino acid sequence very similar in conformation to an amino acid sequence found in vaccines against measles, polio or whooping cough. c) An analog to GTP (guanosine triphosphate) that binds to Ras proteins, but which in this bound state stimulates apoptosis unless its third phosphate is quickly cleaved off. d) A chemical that de-represses caspase enzymes in response to disorganization of the cytoskeleton. e) A chemical that inhibits one or more of the cell cycle checkpoints, thereby allowing mitosis to continue even if the chromosomes are not aligned on the spindle, or that allows DNA synthesis to begin regardless of damage to the DNA. f) A chemical that kills cells in which the bcl-2 protein somehow becomes too concentrated.
g) A chemotactic attractant that stimulates migration of cancerous cells toward the direction of increased concentration of this substance. i) A drug that slows down DNA synthesis and/or mitosis more in normal cells than in cancer cells. j) A drug that creates holes through plasma membranes wherever certain growth factor receptor proteins are over-active.
Please invent several more new methods for taking advantage of (1) The abnormalities observed in cancer cells, (2) The biochemical effects of oncogenes, (3) And the mechanism of apoptosis for the purpose of selective killing of cancer cells, while harming normal cells as little as possible. Name and describe three different birth defects that occur in humans that are caused by failure of epithelia to fuse with each other. For each of these three, what spaces fail to become separated from each other? One of these birth defects can be detected in embryos by presence in the amniotic fluid of certain proteins that are normally found only of cerebrospinal fluid. Can you explain this by a drawing of the location of the neural tube relative to the amnion. What would happen if the margins of the amnion failed to fuse with each other? Draw the position of the extraembryonic coelom relative to the amniotic cavity, the chorion, the allantois and the yolk sac. What are at least six specific examples of apoptosis in normal embryonic development? Although nematode worms have been shown to develop almost normal bodies when deprived of particular genes that are necessary for apoptosis to occur, list at least six major abnormalities that would occur in a human or other vertebrate embryo that lacked genes necessary for apoptosis. What are some of the proteins needed for normal apoptosis? What is one protein needed to prevent excess apoptosis? Several viruses' genomes have been discovered to contain genes with very nearly the same base sequence as this protein; please explain how these proteins help block the immune system's ability to prevent infection by these viruses. (Hint: This wasn't discussed in lecture, but you ought to be able to figure it out, based on one of the functions served by apoptosis.) What are caspases? Where are they normally located? Are they enzymes? Why are their active sites normally blocked? How and when are they activated? Which kinds of cancer cells contain inactive caspases in their cytoplasm? (hint: All kinds!) What are the differences between sarcomas and carcinomas? What is a difference between leukemia and lymphoma? What is metastasis? Compare the invasive locomotion of cancer cells with the normal cell motility of neural crest cells, myoblast cells, ingression of future mesoderm and endoderm cells in normal gastrulation in human embryos. Is there any difference between apoptosis and necrosis? In other words, is apoptosis a synonym for cell death? Or a special kind of cell death? If you had a method for distinguishing active caspases from inactive caspases, how could you use it to distinguish apoptosis from necrosis? Please use the youtube addresses listed on the apoptosis web page of this course to observe movies of cells actually undergoing apoptosis: Be ready to draw and to describe in your own words what cells look like while undergoing apoptosis. Please look at the videos on the cancer page of the course web site, and the histological section of cancer cells, that show differences and abnormalities of malignant versus non-cancerous behaviors of tissue culture cells: Be ready to draw and describe these differences in your own words, and list as many differences as you can between cancer cells and normal ones. * Suggest how an increased ability of cells to crawl from more adhesive surfaces onto less adhesive surfaces may be related to spreading of cancer cells by metastasis. * Discuss why it might not be possible for sponges to have cancers. Describe how the coelomic cavity is formed in human and other mammal embryos. What is cavitation, in the sense of embryological cell rearrangements? What is the difference between the somatic and the splanchnic layers of the lateral plate mesoderm? From what part of what germ layer does the vertebrate heart develop? What happens if an experimenter puts a barrier between the outer edges of the anterior lateral plate mesoderm, so that they cannot fuse? How is the result similar to the phenomenon discovered by Driesch in early echinoderm embryos? What can happen if you split the outer end of an early developing vertebrate limb bud? Or if you graft tissue from the posterior side of one limb bud to the anterior side of an early developing embryo? Or if you cut off the outer end of a developing limb bud, rotate it 180 degrees, and graft it back to the stump oriented so that the anterior side of the cut-off part is next to the posterior side of the stump, and vice-versa? Why does the heart need to start pumping blood very early in development, long before there is any need for skeletal muscles to contract or for the brain to control the contractions of muscles? Why do the kidneys also need to begin functioning very early in development, almost as soon as the heart begins to pump? What is the function of the pronephros? From what does it develop? By what duct does urine from the pronephros move to the allantois? What is the function of the mesonephros? From what does it develop? By what duct does urine from the mesonephros reach to the allantois? What is the function of the metanephros? From what does it develop? Through what duct is urine from the metanephros carried to the allantois? From what does the sperm duct develop, in the human embryo? From what does the oviduct develop, in human embryos? Why is it logically possible for an embryo to develop both these ducts, two sperm ducts in addition to two oviducts? What are two different ways in which the development of the heart is like the development of the uterus in mammal embryos? Contrast development of the heart and the kidney, as two very different solutions to the problem of beginning to function very early in development, combined with eventually developing a very much more complex organ for post-embryonic life.
Hint: Imagine a kind of animal whose embryos form a succession of three different hearts, first in the neck, the second in the chest, and the third in the abdomen, with only the third remaining in the body after birth. What is the ductus arteriosus? What does it connect to what? What function does it serve in mammal embryos before birth? When does it close by constriction? How would the developing embryo be harmed if the ductus arteriosus closed before birth? What bad consequences would result if the ductus arteriosus remained open after birth? What and where is the foramen ovale? What function is served by the foramen ovale? When does blood flow through the foramen ovale, and when does this flow of blood normally stop?
After birth, the left ventricle of mammals pumps blood at higher pressure than the right ventricle. Eventually, in a normal person, the left ventricle pumps blood at about four times the pressure; and the muscle layer in the wall of the left ventricle is four times as thick as the wall of the right ventricle.
The blood-containing cavity of the left ventricle becomes circular in cross section, in contrast to the shape of the right ventricle, which is shaped like a crescent moon. Compare the situation to that of two soap bubbles, one large and one small, that share one side: remember? Does the little one bulge into the larger one? Or vice versa? Does the left ventricle bulge into the right ventricle (hint: Yes!), or the reverse? Or neither? Lifting weights is well-known to stimulate strengthening and thickening of skeletal muscles: but what about cardiac muscles? Do they get stronger and thicker in response to being forced to exert more force? Hint: yes. How does this help explain the changes in shapes (and differences in geometrical cross-sections) of the two ventricles after birth? "Septal defects" are a serious and important category of birth defects of the heart, in which a hole remains through which blood can flow freely from one ventricle to the other. Would you expect this to cause any harm before birth? (Hint, no!) Explain why or why not. If the hole is not closed by surgery, what bad results will there be? Would you expect the walls of the two ventricle to remain the same thickness? (if this hole is not closed) What would you deduce about the mechanism that controls heart muscle strengths if the right ventricle wall develops the same strength as the left ventricle wall? (i.e. in a baby whose heart has a hole connecting the two ventricles) From the web page on immunology:
What two differentiated cell types do the attacking? Do they ever attack anything other than germs? 2 examples. An "antigen" is any molecule that is selectively bound to by (what parts of?) proteins called what? Which are made and secreted by what differentiated cells? Virus-infected cells are induced to do what? This is accomplished by what other differentiated cell type? The "Generator of Diversity" accomplishes what? What is unusual about the genes for antibody binding sites? Which is more surprising? That people EVER make anti-self binding sites, or that this doesn't happen much more frequently?
Where are blood cells formed in an embryo? Why is this not the same location as their site of formation in adults? What is fetal hemoglobin? What would happen if an adult continued to make it? What are blood islands? Describe the circulatory system in an early mammalian embryo, and compare it to the circulation of an adult fish. Draw a diagram of blood flow before and after birth, and answer the following questions (from the web page on heart and kidney development):
b) Which direction does blood flow through the ductus arteriosus before birth? c) Why doesn't the blood flow in the other direction in the foramen ovale? d) Why doesn't it flow in the other direction in the ductus arteriosus?
What might be different about salamanders that allows them to regenerate entire limbs? How would you go about trying to identify a substance involved in the control of this process, either by stimulating regeneration in salamanders, or prohibiting it in other vertebrates? What are glial cells? What are Schwann cells? How do axons and dendrites differ from each other? What very important scientific method was developed by Ross Harrison, and what connection did it have to nerve cell growth? What are motor nerves? autonomic nerves? sensory nerves? spinal sensory ganglia? ganglion cells? When do nerve cells replicate their DNA? Describe the composition of the brain and spinal cord. What is the optic tectum? What is a neural projection? The retino-tectal projection? What are ephrins? Describe how they are thought to work in formation of neural connections. What are the three ways in which human identical twins are formed? Which can lead to formation of conjoined twins? Propose some new methods for treating cancer, different from those now being used:
Choose another two specific questions about which you can suggest experiments that could solve that problem, and write two short essays summarizing the research that you would suppose.
This completes the list of review questions. The exam will cover the entire course, although emphasis will be on material presented since the last exam. You should review all the web pages, including the figures, and the sets of study questions for the past two exams.
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