W3006  Physiology   Problem Set #6      Stress and the immune system

1. In class, we discussed whether stress (sensed by the nervous system) can affect the immune system.  Other scientists have asked whether the immune system can affect the central nervous system.  For example, when our immune system is active in fighting infection, we often decide to change our behavior (decrease locomotion, stay in bed, watch daytime TV, etc.).  Some scientists question the claim that the immune system can affect the brain, because, they say, lymphocytes are unable to get into the brain cells.   A. Describe how lymphocytes might be kept out of the brain.  B. If lymphocytes don't enter the brain, how might they nevertheless have an affect on brain cells and behavior?

2. Scientists have found that neurons from the sympathetic nervous system innervate the lymph nodes, sometimes finding terminals right next to lymphocytes.   You would expect that these lymphoctes would have receptors for _______ (which neurotransmitter?) and that cutting these neurons would lead to (an increased) (a decreased) immune response.   Explain briefly. 

3. All of the following secrete acetylcholine except
a. sympathetic preganglionic fibers  b. parasympathetic preganglionic fibers c. sympathetic postganglionic fibers d. parasympathetic postganglionic fibers  e. motor neurons

4. The human fetus has large amounts of tissue that combine with histological stains to give an appearance similar to that ofcells in the adrenal medulla.  It is thought that this tissue might act in place of the (sympathetic) (parasympathetic) nervous system, which is not completely developed at birth.  Explain your choice.

5. The dogfish shark has adrenal medulla-type tissue and adrenal cortex-type tissue in totally separate parts of the body.  In this species, medulla-type cells produce only norepinephrine, not epinephrine.  How does this differ from the case in humans?  What does this suggest about the relationship between the medulla and the cortex in the human adrenal?

6. Choose which is larger, x or y, or circle both if they're equal in size
A. x. size of monocyte  y. size of macrophage
B. x. amount of perforin secreted by B cell   y. amount of perforin secreted by natural killer cell
C. x. length of POMC  y. length of ACTH

7. What symptoms might you find in someone with a tumor of the adrenal medulla that results in hypersecretion of hormone?

8. Two groups of patients with insufficient blood cortisol are treated by giving them cortisol injections.  Group A are people whose pituitary gland doesn't produce ACTH.   Group B are people who lack any adrenal glands. 
A. To produce normal blood levels of cortisol, more cortisol must be injected into patients of Group B than into Group A.  Suggest two possible reasons for this difference.
B. Human leukocytes have been found to express mRNA for POMC.  With this additional information, which of the two reasons in A seems more reasonable? 
C. What might be the advantage of POMC production by leukocytes?

9. Medical school students are required to remain awake for many hours at a time.   Scientists wondered whether this kind of sleep deprivation produces stress that will decrease the effectiveness of a person's immune system.  In one experiment, they took blood samples before and after 72 hours of wakefulness and found that (in vitro) phagocytic activity of white blood cells was decreased after sleep deprivation.  You are asked to decide whether this finding implies that residents should be allowed to sleep more.  You decide that additional experiments need to be done.  Describe the details of the experiment you plan to do, and the considerations that go into why you designed the experiment this way.  (eg, what subjects, what do you measure, how long your study lasts, etc).

10. It has long been known that African-American men are more likely to develop high blood pressure than are other-American men. This was assumed to be due to genetic differences, but recently a more environmental explanation has been offered: African-American men face more discrimination in our society, and so are exposed to more stress, and long-term stress can lead to high blood pressure.
A. Briefly describe the neuronal/hormonal changes during long-term stress that could lead to high blood pressure.
B. To determine which of these explanations is more important, a scientist goes to a small Caribbean island, where all the inhabitants are of African descent. He finds that there is no difference, on average, in blood pressure, between the wealthy townspeople and the poorer folk living out in the country, and he concludes that genes must be more important than socioeconomic conditions in determining who gets high blood pressure. Discuss whether or not you agree with his conclusion, and if not, suggest a more appropriate experimental design to determine which explanation is more important


1.a. The capillaries that deliver blood to the brain are made of endothelial cells with tight junctions between them. They lack the pores found in most capillaries and so blood probably can’t get from the blood to the neurons.

b. Besides affecting target cells via direct contact, the immune cells can affect targets via secreted chemicals, the cytokines. We saw earlier that IL-1 is able to stimulate prostaglandin synthesis in the hypothalamus and so increase the set point for body temperature and so you might conclude that IL-1 is able to pass through the blood-brain barrier. In fact, the bbb is not 100% effective, and there are certain regions where peripheral blood can reach specific areas of the brain, such as near the hypothalamus.

2. Norepinephrine (is the neurotransmitter in the final synapse in sympathetic neurons)   Increase. We saw various studies showing that stress-> increased sympathetic response -> decreased immune response. If the message gets from the brain to the immune system via the neuronal connections, you’d expect that cutting these neurons would remove an inhibitory control and lead to an increase in immune response.

3.  c

4. Sympathetic. The adrenal medulla derives from SNS tissue, and has the enzymes to produce both norepinephrine (the NT of the SNS) and epinephrine.

5. In humans the adrenal medulla 1) is adjacent to the cortex and 2) converts norepinephrine to epinephrine, and secretes mostly epinephrine. This suggests that the conversion of NE to epi requires some paracrine secretion from the cortex, which is not found near the medulla in the dogfish shark, but is possible in human adrenal..

6. A. y  B. y  C. x

7. Excess epinephrine (adrenaline) will cause high blood pressure, rapid heart rate, high blood glucose.

8.A. The question says that to get blood cotisol levels in the normal range, more cortisol must be injected into people without adrenal glands than into people without pituitary ACTH. This implies that people with an adrenal gland (but without pituitary ACTH) are already producing some cortisol, so a smaller amount of exogenous cortisol is required. This could be because:

a. cortisol secretion is partly constitutive, with some being secreted even without ACTH., or

b.ACTH is still stimulating the adrenal, but the ACTH comes form some site other than the pituitary.

B. Suggests that b is true: POMC is the precursor of ACTH, so leukocytes might be producing the ACTH that stimulates the adrenals to release cortisol even in the absence of ACTH.

C. Leukocytes are more numerous when needed to fight infection, so the presence of leukocytes implies the body is ill.  When ill, the body needs to repair diseased tissue, requiring increased supplies of molecular building blocks.  So the leukocytes may be producing a message (POMC, ACTH) to the adrenals, to release cortisol, which raises blood glucose and amino acids.  Alternately, perhaps the ACTH isn't important, but rather some POMC derivative is.  One of these derivates, beta-endorphin, decreases the sensation of pain, which would be helpful for a diseased body.

9.  Some suggestions:

-Is phagocytic activity the only aspect of the immune system that changes? – Study other cells and signalling molecules
- Perhaps this is a response to a novel event, and occurs only the first time somebody is sleep-deprived. - Repeatedly sleep-deprive the subjects to find out.
- Perhaps the body recovers so rapidly after this change in leukocyte function, that it doesn't really have any long lasting effects on the development of disease.  How long lasting is the affect? Measure after recovery sleep.
- This decreased WBC activity may be statistically significant, but not of any biological significance.  Does it really cause an increase in disease? Study health problems of people who go without sleep for years.
- Perhaps this decrease in WBC function occurs only in the lab, but when residents are working in a more natural situation, like the emergency room.  Do study on actual residents, not the less stressful lab situation
- Vary the number of hours of deprivation – 72 hours is longer than most people stay awake.

10. A. Sympathetic nervous system activation stimulates vasoconstriction > increases blood pressure. Adrenal gland secretion of epinephrine stimulates increase in heart rate, increase strength heart contraction > increase blood pressure Aldosterone increases Na+ retention and thereby water reabsorption in nephrons, > increase blood volume >increase blood pressure ADH increases water retention > increase blood volume > increase blood pressure
B. A wide variety of answers were accepted on the exam: Some criticisms of this experiment included the question of whether socioeconomic condition on a Caribbean island is a good model for racial discrimination in the US. Some of you pointed out that it's not clear whether one of these groups had more stress, or whether the stress was simply different: Poor country folk may have worried about having food and clothing, but the stress might have been greater for city folk who worried about how to invest their money.... Others pointed out that the investigator didn't control for dietary factors, such as sugar and salt consumption, which may be important factors in developing high blood pressure. Some of you suggested that these observational studies are not as useful as interventional ones, in which people are intentionally exposed to some stressful event, or in which individuals from one culture/country are moved to the other. While these may be useful ways of thinking about experimental design, there are obvious ethical problems with some of these ideas... We'll discuss this more when we talk about cardiovascular disease.