immune system 1 B1 Types of White Blood Cells White blood cells (leukocytes) are immune cells. They are produced in the bone marrow and thymus and are transported to other tissues via the bloodstream. There are three main types of leukocytes in the blood: granulocytes, monocytes, and lymphocytes. Granulocytes (neutrophils, eosinophils, 3. basophils, and mast cells) are inflammatory cells that are involved in killing microbes 2 and in allergic reactions. They have large numbers of intracellular vesicles called granules, which contain degradative 4. enzymes, antìmicrobial peptides, and inflammatory mediators that can be released by degranulation to kill a./? extracellular pathogens and mobilise other ð immune cells. v\ \ Monocytes enter tissues, where they PPv Pant¡¡o¿ies become macrophages. They engulf microbes and clear tissue debris by phagocytosis. Lymphocytes include B cells and T cells. B cells produce antibodies, while T cells can activate other immune cells or kill infected cells. 5 Granulocytes and monocytes are innate immune cells. They are particularly o3o cytoki ne5 6 important in the early stages of immune ":*"" o ooo responses against invading microbes. Other granules innate immune cells include dendritic cells (which activate T cells) and natural killer cells (which release their granules to kill infected cells). Lymphocytes are adaptive oo o 7 o slowly but are responsible for the long-lasting immune memory that 8. confers protection against re-infection. Answers ¿'sê}^roqdu?{l 9'slla)I s'sêtÁrouou t'llor}seu/llqdospq/lr¡ldoursoa €'llqdoJ¡nau o o immune cells. They are mobilised more slla)I)!xolol,{r'g'sllo)Ilodlaq o ¿'sСÁ)olnuel6 L 182 immune system Function of Macrophages and Granulocytes Macrophages patrol tissues, where they clear debris and monitor for invading microbes. They employ phagocytosis to engulf and internalise dead cells and small microbes such as bacteria. Macrophages kill and degrade internalised microbes in acidic intracellular compartments using enzymes and reactive oxygen and nitrogen compounds. When they detect invading microbes, macrophages also produce inflammatory mediators to attract other immune cells. o o oo + Pathogen Uptake for lntracellular Killing c O l L-) o 2. 4 3. (process) 5 o o o o o o ^o o (J 9 6. o 7 8. o o o o Extracellular Pathogen Killing o o o o oo oo T o o (process) Neutrophils are usually the first immune cells recruited to infected tissues. Like macrophages, they undergo phagocytosis to c¿pturc ¿nd killstr¿ll rlicroLres, bul. Lhey c¿n ¿lso kill rnicrobes that are tclo big tcl be internalised. Neutrophils undergo degranulation to release the contents of their intracellular granules (including enzymes and antimicrobial peptides) onto extracellular targets. They can also catch extracellular microbes in a web of extruded DNA known as a neutrophil extracellular trap (NET). The other granulocytes - eosinophils, basophils, and mast cells - also release the contents of their granules. They are particularly important for killing parasitic worms. ln addition, they release histamine, which increases the permeability of blood vessels to allow more leukocytes to enter the tissues to kill invading microbes. Histamine release by these cells also triggers many of the symptoms associated with allergies and asthma. Answers sutalord a¡nuer6 rlxoloúl 6'uorlelnuerbop 8'olrsered ¿ 'sêlnuer6 9'llð) tspu/lrqdospq/llqdoulsoo S 'ouoso6eqd t'srso¡flobeqd E 'ê6eqdojreu Z 'aqol)ru I irnmune system Humoral Defence: B Lymphocytes and Antibody Production B cells are lymphocytes that use 5. immunoglobulins to detect molecular structures known as antigens (e.9. 4. n components of bacteria or viruses). lmmunoglobulins (lgA, lgD, lgE, lgG, lgM) exist both as B cell receptors on the cell surface and as secreted molecules known ¿< -'-\ + B cell activation B Cell Activation .-''-s --2 =< as antibodies. B cells are activated when their B cell 3. receptors detect specific antigens. Activated B cells (known as plasma cells) produce 2 antibodies, which recognise the same antigens as the B cells that produced them. Antibodies therefore coordinate immune responses against specific targets. lgA i is secreted in mucosal tissues (e.9. ntesti nal, respi ratory, a 7 nd u rogenita I tracts). lgG plays several important roles in protection from infection. For example, it 6. can neutralise viruses to limit their spread, attach to bacteria to promote their uptake by macrophages and neutrophils, or identify cells infected with viruses to promote their destruction by cytotoxic T cells and natural killer cells. lgG can 'l 1' also cross the placenta to protect the unborn child. lgE 10' marks extracellular targets such as parasitic worms for destruction by for eosinophils and is also responsible triggering allergic reactions. Some activated B cells 9. become memory cells, which can be reactivated months or even years later if a specific threat is detected again. lmmunoglobulin Answers uor6aJ alqeue^ | I 'uo!6ar luetsuo|o! 'uteql f^eaq 6 'uleq) Ìq6ll I 'uè6rlue rllr)ads-uou '¿ 'uo6!ìue lr}lrads g '(sorpoq!tue) urlnqoloounuu! alqnlos E'llo) Puseld t'llal I a^leu € 'uo6rlue 'Z'(Joldêror llð) €) u!lnqol6ounuul oueJquau ! 184 immune system Cellular Defence: T Lymphocytes and Cell-Med¡ated lmmunity T Cell Activation 5 1 ooo 2 6 1o oooo õ o o oo Y activatio o activation g o o o :3"" o o o I 3. o o I I 7 4 T cells are lymphocytes involved in adaptive immune responses. They are actlvated when their T cell receptors detect specific antigens, but the antigens must be presented to T cells by antigen-presenting cells such as dendritic cells. T cells mature in the thymus and are stored in lymphoid tissues (spleen and lymph nodes). They can be effector cells, memory cells, or regulatory cells. Effector T cells can be helper cells or cytotoxic cells. Helper T cells orchestrate cell-mediated immune responses by releasing inflammatory mediators such as chemokines and cytokines, which attract and activate other immune cells, including macrophages and neutrophils. ln addition, helper T cells assist in the activation of cytotoxic T cells and B cells. Cytotoxic T cells undergo degranulation to release their granule contents to kill targets such as tumour cells or cells infected with viruses. Some activated T cells become memory T cells, which can be reactivated upon subsequent detection of the same threat. Along with memory B cells, they are responsible for the long-lasting immunoprotective effects of vaccines. T cells that recognise self-antigens rather than foreign antigens are deleted in the thymus to avoid autoimmunity. Regulatory T cells also prevent autoimmunity by suppressing immune responses. # Degranulation of Cytotoxic T Cell Answers infected cell 10. Y 1'l o o o oo o o o oo o oO o o o o o integration of function Response to 185 Exerc¡se: Metabolism The regulation of metabolism during exercise is complex and is influenced by a number of factors, including the duration and intensity of exercise (o/oVOrmax). ln general, low-intensity exercìse is primarily reliant on lipìd (fat)as a fuelsource, and as exercise intensrty increases, carbohydrates (glucose) become the primary fuel source. ln contrast, proteins play a small role as a fuel source during exercise and must first be degraded into amino acids. Proteases may be activated during extended exercise periods (two hours or more), and amino acids may contribute as a fuel source during such times. Accordingly, during low-intensity exercise, plasma free fatty acids (FFAs) are the primary source of fuel. As exercise intensity increases from low to moderate, the contributron of plasma FFAs declines and there is an increased reliance upon muscle triglycerides. At higher exercise intensities, the contribution of plasma FFAs and muscle triglycerides are equaland much smaller in comparison to that of muscle glycogen. 100 muscle triglycerides muscle glycogen plasma free fatty acids plasma glucose 80 1 Fill in the colours that represent the contribution of that substrate during a given exercise intensity. t60 o 2._ u L f, o lntegrative Response to Exercise: Metabolism õ Þ =.ii o 40 3 20 4. 0 25 65 85 exercise intensity (% VO, max) Glucose is stored in the liver and skeletal muscle as glycogen. Muscle glycogen stores are affected by training status such that aerobically trained indivrduals are able to store a greater amount of muscle glycogen to serve as a muscle fuel source. Liver glycogen stores primarily serve to maintain blood glucose levels at rest and during low-intensity exercise, and this plasma glucose can serve as a fuel source for muscle. As exercise intensity increases, there is a large increase in the reliance upon muscle glycogen stores as a fuel source. The contribution of skeletal muscle glycogen as a fuel source for exercising muscle ìs an intensity-dependent relationship. Answers sêpuê),{l6lr} al)snu t'spl)e Á}}e} aõr+ euseld € 'aso)nl6 euseld ¿ 'uo6or/{16 aPsnu ! 186 Response integration of function to Exerc¡se: Cardiovascu lar During acute exercise, there is an elevated demand for oxygen from the working muscles. As a means to meet this elevated oxygen demand, blood flow and oxygen delivery increase to the working tissues, in part by elevating cardiac output and redistributing blood flow away from non-working muscles and the viscera, and towards exercising muscles via local vasodilation. ln addition to a redistribution of blood in the periphery. there appears to be significant increase in brain blood flow associated with exercise. Ventilation increases with exercise intensity as a means of oxygenating the blood. Further, a greater surface area of the lung is both ventilated and perfused with blood to maximise loading of oxygen and unloading of carbon dioxide; this is reporled as improved matching of ventilation and perfusion within the lung. lncreased cardiac output facilitates the increased delivery of oxygenated blood to the periphery, mainly through an elevated heart rate. This increased work of the heart leads to an elevated metabolic demand on the cardiac tissue and a subsequent increase in oxygen demand. Accordingly, blood flow within the heart muscle is also elevated to facilitate the matching of oxygen delivery to demand. Skeletal muscle blood flow can increase 1O0{old during high-intensity exercise, due to elevations in cardiac output and blood flow redistribution. Another adaption that occurs during exercise is a reduction in plasma volume through a loss of water to the contracting skeletal muscle. This leads to haemoconcentration of red blood cells, which facilitates extraction of oxygen by the tissue (contracting muscle). Cardiovascular System Response to Acute Exercise brain neural activity _ 6. ventilation and gas exchange 7. _ _ 9. _ 10. _ cardiac output 8. coronary blood flow _ 12. _ 3. _ haemoconcentration 5. skin blood flow 25. ._ 2. _ 3. _ 4. _ 'l blood flow blood distribution metabolism blood flow lungs 24. _ blood flow (possibly) oxygen consumption blood f low distribution? heart digestive system 1 1. 1 oxygen content levels of energy substrates blood _ 15. _ 14. 23. blood flow 22. mechanical strain 21. release of stem cells skeleton circulatory system muscles _ 17. _ 16. 1 8. 19. Indicate the direction of change for each element using t, !, or -. Some answers should have two or three arrows to indicate heightened response. _ _ 20. arterial dilation capillary pressure and energy substrate exchange blood distribution ven oco nstriction metabolism and blood f low oxygen extraction and consumption mechanical strains Answers '!l-li'SZ'1 'VZ'-li'EZ'ii'zz'tt'tz 'i 0¿'iii 6t'iii 8t'i 1l'i'91'ii Sr'¿¿¡ tt'it-'tt'r'zt 'i Il'j Ot'iii 6'iii 8'iii ¿'iii f ii¡'9'1 þ'!'t- z'1,! l integration of function Response to Exercise: Endocrine As exercise ensues there is withdrawal of the (++) parasympathetic nervous system and activation of the sympathetic nervous system (SNS), and the c .9 increase in this branch of the nervous system is I graded with exercise intensity. At approximately 60 per cent of VO, max, there is a marked increase in SNS activity, resulting in elevated catecholamines concentration (noradrenaline (+) CP sû cotr Uõ g,r o o cO) Fc oq c,, and adrenaline). These catecholamines increase heart rate and help redistribute blood flow Ê- to the working muscles by evoking peripheral 2 (-) (u E- vasoconstriction. Additionally, the catecholamines work to help mobilise fuel sources by stimulating (- -) 0 glycogenolysis and lipolysis. Another hormone that aids in mobilising fuels for exercise is cortisol. Released from the adrenal cortex. cortisol 100 increases gluconeogenesis and lipolysis. Additionally, the SNS suppresses insulin secretion during exercise in an effort to maintain blood glucose levels. During exercise, skeletal muscle 50 20 40 60 80 40 60 80 100 3 c,, Ol o glucose uptake occurs in an insulin-independent manner and the rate of glucose uptake during -c u exercise far exceeds that observed during rest. lt o P c 0 o o- that increases in intracellular calcium associated with skeletal muscle contractions drive is believed -50 the insulin-independent uptake of glucose observed with exercise. Additionally, the kidney is -1 00 0 innervated by the SNS and upon activation, blood flow to the organ will decrease in an effort to 20 100 400 redistribute blood to working muscles. Additionally, SNS stimulation increases the secretion of renin from the kidney which, along 300 with aldosterone and angíotensin ll, work to o Ol maintain blood pressure over the long term by affecting fluid and electrolyte balance. c co o Label the hormones in each graph 200 100 o o- Endocrine System Response During Acute Exercise 4. 5. 6. tr 0 ^o -1 00 02040 Answers ¡¡ utsualot6ue 9 f}¡¡tlre urual s'suorolsoplp 60 VO, max (%) t'losr!o) euseld t'u!lnsu|z'uo6p)nl6,losr¡lol,auouroq [¡]aol6,aurlpualperou,autleuðJpe.l 80