1) The integrity of the plasma membrane is essential for cellular survival. Could the immune system utilize this fact to destroy foreign cells that have invaded the body? How might cells of the immune system disrupt membranes of foreign cells? (Two hints: virtually all cells can secrete proteins, and some proteins form pores in membranes.) 2) Most cells are very small. What physical and metabolic constraints limit cell size? What problems would an enormous cell encounter? What adaptations might help a very large cell to survive? 3) Some species of bacteria that live at the surface of sediment on the bottom of lakes are facultative anaerobes; that is, they are capable of either aerobic or anaerobic respiration. How will their metabolism change during the summer when the deep water becomes anoxic (deoxygenated)? If the bacteria continue to grow at the same rate, will glycolysis increase, decrease, or remain the same after the lake becomes anoxic? Explain why. Solution: (1) The integrity of the plasma membrane is essential for cellular survival. Could the immune system utilize this fact to destroy foreign cells that have invaded the body? How might cells of the immune system disrupt membranes of foreign cells? (Two hints: virtually all cells can secrete proteins, and some proteins form pores in membranes.) Answer: The immune response is how your body recognizes and defends itself against bacteria, viruses, and substances that appear foreign and harmful to the body. The first and, arguably, most important barrier is the skin. The skin cannot penetrated by most organisms unless it already has an opening, such as a nick, scratch, or cut. The immune system includes certain types of white blood cells. It also includes chemicals and proteins in the blood (such as complement proteins and interferon). Some of these directly attack foreign substances in the body, and others work together to help the immune system cells. A phagocyte is a cell that attracts (by chemotaxis), adheres to, engulfs, and ingests foreign bodies. Promonocytes are made in the bone marrow, after which they are released into the blood and called circulating monocytes, which eventually mature into macrophages (meaning "big eaters", see below). The complement system is a major triggered enzyme plasma system. It coats microbes with molecules that make them more susceptible to engulfment by phagocytes. Vascular permeability mediators increase the permeability of the capillaries to allow more plasma and complement fluid to flow to the site of infection. They also encourage polys to adhere to the walls of capillaries (margination) from which they can squeeze through in a matter of minutes to arrive at a damaged area. Once phagocytes do their job, they die and their "corpses," pockets of damaged tissue, and fluid form pus. Cell-mediated immunity: Macrophages engulf antigens, process them internally, then display parts of them on their surface together with some of their own proteins. This sensitizes the T cells to recognize these antigens. All cells are coated with various substances. CD stands for cluster of differentiation and there are more than one hundred and sixty clusters, each of which is a different chemical molecule that coats the surface. CD8+ is read "CD8 positive. B cells are coated with CD21, CD35, CD40, and CD45 in addition to other nonCD molecules. T cells have CD2, CD3, CD4, CD28, CD45R, and other non-CD molecules on their surfaces. Some macrophages are concentrated in the lungs, liver (Kupffer cells), lining of the lymph nodes and spleen, brain microglia, kidney mesoangial cells, synovial A cells, and osteoclasts. They are long-lived, depend on mitochondria for energy, and are best at attacking dead cells and pathogens capable of living within cells. Once a macrophage phagocytizes a cell, it places some of its proteins, called epitopes, on its surface—much like a fighter plane displaying its hits. These surface markers serve as an alarm to other immune cells that then infer the form of the invader. All cells that do this are called antigen presenting cells (APCs). The large number of molecules on the surfaces of lymphocytes allows huge variability in the forms of the receptors. They are produced with random configurations on their surfaces. There are some 1018 different structurally different receptors. Essentially, an antigen may find a near-perfect fit with a very small number of lymphocytes, perhaps as few as one. T cells are primed in the thymus, where they undergo two selection processes. The first positive selection process weeds out only those T cells with the correct set of receptors that can recognize the MHC molecules responsible for self-recognition. Then a negative selection process begins whereby T cells that can recognize MHC molecules complexed with foreign peptides are allowed to pass out of the thymus. Cytotoxic or killer T cells (CD8+) do their work by releasing lymphotoxins, which cause cell lysis. Helper T cells (CD4+) serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes. Suppressor T cells inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary. Memory T cells are programmed to recognize and respond to a pathogen once it has invaded and been repelled. Humoral immunity An immunocompetent but as yet immature B-lymphocyte is stimulated to maturity when an antigen binds to its surface receptors and there is a T helper cell nearby (to release a cytokine). This sensitizes or primes the B cell and it undergoes clonal selection, which means it reproduces asexually by mitosis. Most of the family of clones become plasma cells. These cells, after an initial lag, produce highly specific antibodies at a rate of as many as 2000 molecules per second for four to five days. The other B cells become long-lived memory cells. Antibodies, also called immunoglobulins or Igs [with molecular weights of 150– 900 Md], constitute the gamma globulin part of the blood proteins. They are soluble proteins secreted by the plasma offspring (clones) of primed B cells. The antibodies inactivate antigens by, (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), (c) agglutination (clumping), (d) precipitation (forcing insolubility and settling out of solution), and other more arcane methods. The immune system is the collection of organs and tissues involved in the adaptive defense of a body against foreign biological material. It may be broken down into the adaptive immune system, composed of four lymphoid organs (thymus, lymph nodes, spleen and submucosal lymphoid nodules) and the group motile cells that are involved in the body's defense against foreign bodies. The term may also be used to refer to the totality of a body's defense systems, encompassing both the adaptive immune system. 2. Most cells are very small. What physical and metabolic constraints limit cell size? What problems would an enormous cell encounter? What adaptations might help a very large cell to survive? Answer: For each square micrometer of the plasma membrane that surrounds the cell, there is a limit to the amount of waste or biological product that can cross its protective barrier. Thus, the surface area of the cell (i.e. its plasma membrane) must be able to accommodate all of the metabolic reactions that occur within its interior. Although a large cell would be able to withstand more metabolic reactions (due to its larger volume) than a smaller cell, the larger cell would have much less plasma membrane. "Physical inactivity is certainly a major, if not the primary, cause of obesity. A certain minimal level of activity might be necessary for us to accurately balance our caloric intake to our caloric expenditure. With too little activity, we appear to lose the fine control we normally have to maintain this incredible balance”. Cell growth is highly regulated. Cells respond to nutrients or other appropriate growth stimuli by upregulating macromolecular synthesis, and thereby increasing in size. Conversely, cells respond to nutrient limitation or other types of stress by downregulating macromolecular synthesis and enhancing turnover of excess mass. Thus, the control of cell growth involves balancing positive regulation of anabolic processes with negative regulation of catabolic processes. Growth is also controlled relative to cell division. In proliferating cells, growth is linked to the cell cycle such that most cells precisely double their mass before dividing. In other physiological contexts, such as loadinduced muscle hypertrophy or growth factor-induced neuronal growth, cell growth is controlled independently of the cell cycle. Growth of individual cells is controlled relative to overall body growth such that the organs and tissues constituting the organism are properly proportioned. The terms overweight and obesity are often used interchangeably, but this is technically incorrect as they have different meanings. Overweight is defined as a body weight that exceeds the normal or standard weight for a particular person, based on his or her height and frame size. These standards are established solely on the basis of population averages. It is quite possible to be overweight according to these standard tables and yet have a body fat content that is average or even below average. For example, almost all college and professional football players are overweight by these tables, but few are overfat. There are also people who are within the normal range of body weights for their height and frame size by the standard tables, but who have, in fact, excessive body fat. It has often been stated that physical activity has only a limited influence on changing body composition, and that even exercise of vigorous nature results in the expenditure of too few calories to lead to substantial reductions in body fat. Yet, research has conclusively demonstrated the effectiveness of exercise training in promoting major alterations in body composition. Hormonal imbalance also helps to produce large cell size so the main function of insulin is to control glucose level in blood. So most of the carbohydrates are converted into fat bodies, which is stored in liver. If, insulin secretion exerts that will cause low glucose level in blood and which affects the cell size. In the cause of thyroxine, if it secretion exerts or decrease that will affect the cell growth or size. Hormonal imbalance also affects the cell growth. The main treatments for these defects are gene therapy, drugs and hormonal tabelets. Exercize is the best treatment for large cell size so that we can exert waste water or metabolic exerts. 3. Some species of bacteria that live at the surface of sediment on the bottom of lakes are facultative anaerobes; that is, they are capable of either aerobic or anaerobic respiration. How will their metabolism change during the summer when the deep water becomes anoxic (deoxygenated)? If the bacteria continue to grow at the same rate, will glycolysis increase, decrease, or remain the same after the lake becomes anoxic? Explain why. Answer: Oxidation of glucose is known as glycolysis. Glucose is oxidized to either lactate or pyruvate. Under aerobic conditions, the dominant product in most tissues is pyruvate and the pathway is known as aerobic glycolysis. When oxygen is depleted, the dominant glycolytic product in many tissues is lactate and the process is known as anaerobic glycolysis. Alternatives to Glycolysis 1. The pentose phosphate pathway (hexose monophosphate shunt; phosphogluconate pathway) is used to metabolize five-carbon sugars and to generate reducing power in the form of NADPH; one ATP and 12 NADPH molecules are produced from a glucose molecule. Operates simultaneously with glycolysis. Some bacteria have required enzymes (e.g., Bacillus subtilis, Escherichia coli, Enterococcus faecalis, Leuconostoc mesenteroides) 2. The Entner-Doudoroff pathway yields one ATP and two NADPH molecules from one glucose molecule. Some gram-negative bacteria have required enzymes (e.g., Pseudomonas, Rhizobium, Agrobacterium) Facultative anaerobes do not require oxygen for growth, but do grows better in its presence. A facultative anaerobe is an organism that makes ATP by aerobic respiration if oxygen is present but that switches to fermentation under anaerobic conditions. Phosphorus is one of the key elements necessary for growth of plants and animals and in lake ecosystems it tends to be the growth limiting nutrient and is a backbone of the Kreb's Cycle and DNA. The presence of phosphorus is often scarce in the welloxygenated lake waters and importantly, the low levels of phosphorus limit the production of freshwater systems (Ricklefs, 1993). The phosphate becomes incorporated into the biological system but the key areas include: ATP, DNA, and RNA. ATP (adenosine triphosphate) is important in the storage and use of energy and a key stage in the Kreb's Cycle. During aerobic conditions, Bacteria try to decompose the organic waste, consuming the oxygen, and releasing more phosphate, which is known as "recycling or internal cycling". Some of the phosphate may be precipitated as iron phosphate and stored in the sediment where it can then be released if anoxic conditions develop. In anaerobic conditions (absence of oxygen), as conditions worsen as more phosphates and nitrates may be added to the water, all of the oxygen may be used up by bacteria in trying to decompose all of the waste. Different bacteria continue to carry on decomposition reactions, however the products are drastically different. The carbon is converted to methane gas instead of carbon dioxide, sulfur is converted to hydrogen sulfide gas. Some of the sulfide may be precipitated as iron sulfide. Under anaerobic conditions the iron phosphate precipitates in the sediments may be released from the sediments making the phosphate bioavailable. This is a key component of the growth and decay cycle. Adaptation to low oxygen level 1. Denitrifiication: -True anaerobic respiration. ATP synthesis in the lack of oxygen Nitrate is a terminal electron acceptor similar to oxygen It has most of the positive features associated with oxygen based (aerobic) respiration. Most organisms however, cannot switch to an alternative high free energy-ATP generating system in the face of declining oxygen availability. “The product of the glycolytic pathyway is varying according to the oxygen availability. And there are some alternate pathways to glycolysis, we have seen before and if in depletion in oxygen bacteria can go for other alternatives. So there is no chance to increase glycolysis during deoxygenated stage, and there may be possibility to decrease in glycolysis.” Three strategies for effective anaerobic metabolism 1. Store more endogenous glycogen 2. Utilize more efficient fermentations 3. Reduction in metabolic rates Problem - acidification is a hazard of anaerobiosis 2. Utilize more efficient fermentations Classic glycolysis Instead of HMP (hexose monophosphate pathway), bacteria undergoes glycolysis with production of lactate instead of pyruic acid, which implies that there is no change in glycolysis rate, that is it remain constant, but the product only vary it because of oxygen depletion. References: "Roitt's Essential Immunology http://uhaweb.hartford.edu/BUGL/immune.htm http://iai.asm.org/ http://www.academicdb.com/most_cells_are_very_small_physical_metabolic_const_ 16543/ http://www.evolutionary-ecology.com/sample/eear1850.pdf http://jeq.scijournals.org/cgi/content/abstract/34/2/724 http://www.bioweb.uncc.edu/faculty/Menhinick/Ecology/I_COMMUNITY_ECOLO GY.htm http://facstaff.bloomu.edu/chansen/cap/7