Chapter 37
Drugs Of Abuse and the Immune System
Toby K. Eisenstein, David E. Kaminsky, Rahil T. Rahim and Thomas J. Rogers
Questions
1.
It is observed that morphine given subcutaneously suppresses responses of spleen cells put into tissue
culture with the T-cell mitogen Concanavalin A (Con A).
a. Mice with a disruption of the gene coding the mu opioid receptor (Mu Opioid Receptor knock-out mice),
would not show suppression to Con A.
b. Morphine acts mainly through the kappa opioid receptor.
c. Morphine is mainly metabolized to heroin when it is injected in vivo.
d. Methyl-morphine could not be used to determine if peripheral receptors or brain receptors are involved in
the immunosuppression.
e. None of the above.
2.
In regard to cannabinoids:
a. They are proteins.
b. They exert their effects primarily by interdigitating into cell membranes.
c. There is evidence that they polarize the immune response towards a Th1 type phenotype.
d. There is evidence that they polarize the immune response towards a Th2 type phenotype.
e. They have no direct effects on cells of the immune system.
3.
In regard to the immune system, morphine has been shown to:
a. Elevate antibody responses to various antigens.
b. Elevate responses to the B-cell mitogen, lipopolysaccharide (LPS).
c. Elevate delayed-type hypersensitivity (DTH) responses.
d. Increase phagocytosis by macrophages.
e. Depress natural killer (NK) cell activity.
4.
Cocaine:
a. Has no effect on the immune system.
b. Exacerbates HIV replication in a mouse/human model of viral replication.
c. Binds to the delta opioid receptor.
d. Depresses IL-2 production.
e. All of the above.
5.
In regard to infections and drugs of abuse:
a. Morphine sensitizes mice to infection with Legionella pneumophila (Legionnaires’ Disease).
b. Δ9-THC sensitizes mice to Salmonella infection.
c. Morphine and Δ9-THC have direct effects on the ability of bacteria to grow in broth cultures.
d. Morphine can affect resistance to infection by altering the activity of phagocytes.
e. Intravenous drug abusers have a rate of infection the same as the general population.
6.
Morphine most probably affects the progression of HIV infection by all of the following EXCEPT:
a. Changing the level of chemokine receptors.
b. Changing the level of chemokines.
c. Causing T-cells to undergo uncontrolled cell division.
d. Mediating heterologous desensitization of chemokine receptors.
e. Altering cytokine levels.
37. Drugs Of Abuse and the Immune System
Toby K. Eisenstein, David E. Kaminsky, Rahil T. Rahim and Thomas J. Rogers
2
7.
Which of the following statements is true:
a. Opioids, cannabinoids, and cocaine uniformly suppress the activity of NK cells.
b. The use of N-methylmorphine substantiated the direct effects of opioid-induced NK cell suppression.
c. Mice lacking the μ-opioid receptor do not have suppressed NK cell activity in
response to morphine treatment.
d. Δ9-THC prevents NK cell proliferation by inhibiting the secretion of TGF-β.
e. Morphine inhibits NK cell activity by inducing endogenous cannabinoid levels.
8.
Opioids modulate phagocyte activity by:
a. Increasing phagocytic uptake of bacteria.
b. Decreasing apoptosis of phagocytic cells.
c. Enhancing maturation of bone marrow cells into macrophages.
d. Decreasing their ability to make microbicidal compounds in vitro.
e. Decreasing maturation of lymphocytes in the bone marrow.
9.
Immune cells treated with morphine:
a. Uniformly have markers of activation.
b. Display altered levels of pro-inflammatory chemokines, but chemokine receptor numbers remained
unchanged.
c. Display bi-directional heterologous desensitization between opioid receptors and
certain chemokine receptors.
d. Clearly have inhibition of Th2 cytokine responses.
e. None of the above
10. Which of the following statements is true:
a. Δ9-THC induces its effects through both CXCR4 and CCR5.
b. Both Δ9-THC and morphine have been shown to induce the expression of
pro-inflammatory chemokines, such as MCP-1 and IL-8.
c. Like cannabinoids and morphine, cocaine treatment increases TNF-α and IL-1.
d. Cocaine uniformly suppresses cytokine and chemokine production when given
in vivo or applied to cells of the immune system in vitro.
e. Opioids have no effect on antibody formation.
11. Morphine and/or DAMGO treatment results in decreases in which of the following?
a. Apoptosis
b. Pro-inflammatory chemokine production
c. Serum antibody responses
d. TGF-β
e. All of the above
12. Inhibition of T cell responses is observed for which of the following drugs of abuse?
a. Morphine
b. Δ9-THC
c. Cocaine
d. All of the above
e. None of the above
13. The initial evidence suggesting that opioid receptors are expressed by cells of the immune system was:
a. Results showing impairment of T cells to rosette to sheep red blood cells in the presence of morphine.
b. Studies examining functions of the CB1 and CB2 receptors.
c. Primate studies examining disease incidence in self-administration of heroin
d. Biochemical analyses of lymph nodes in heroin addicts.
e. Studies showing increased HIV infection in heroin abusers.
37. Drugs Of Abuse and the Immune System
Toby K. Eisenstein, David E. Kaminsky, Rahil T. Rahim and Thomas J. Rogers
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14. All of the following statements are true EXCEPT?
a. In vitro studies have shown Δ9-THC biases the immune response towards a Th2
cytokine profile.
b. Cocaine administration stimulated production of the anti-inflammatory cytokine
IL-10, while simultaneously suppressing IFNγ.
c. Activated human PMNs show enhanced functional activity in response to cocaine.
d. The effects of opioids, cannabinoids, and cocaine on immune system function are compounded by the
involvement of the HPA axis.
e. Chemokine expression is induced by morphine administration.
15. Evaluation of the effects of drugs of abuse can be complicated by a number of factors, including:
a. The effects of the sympathetic nervous system on immune cell function.
b. The effects of the HPA axis on immune cell function.
c. The capacity of cells of the immune system to produce endogenous opioids.
d. The production of endogenous cannabinoids in the periphery.
e. All of the above.
16. The function of G protein-coupled receptors, such as the opioid and cannabinoid receptors, can be
regulated by the process of heterologous desensitization. Which of the following statements is true about
this regulatory mechanism?
a. This process occurs when the activation of one receptor leads to an increased
expression of a second receptor.
b. This process only occurs between receptors expressed on the surfaces of adjacent cells.
c. This process cannot occur between receptors expressed on the same cell.
d. This is a process that appears to involve transphophorylation of G protein-coupled receptors.
e. All of the above
17. Both opioids and cannabinoids have been shown to sensitize animals to a variety of experimental
infections. The impact of drugs of abuse on resistance to infectious agents can be difficult to evaluate
because:
a. Drug abuse rarely involves the administration of a single drug, and the effects of poly-drug abuse are
poorly understood.
b. Drug abusers are exposed more frequently to pathogenic agents than non-abusers.
c. A number of additional factors, which are hard to control, impact on measurement of the immune
competence of drug abusers, including the dose of the drug and the time since it was last taken.
d. The contributions of legal drug use, including nicotine and alcohol, can complicate the effects of illegal
drug abuse.
e. All of the above.
18. All of the following influence the effect of opioids on susceptibility to HIV infection EXCEPT:
a. Opioids alter the expression of chemokine receptors that are co-receptors for HIV-1.
b. Opioids increase the expression of some chemokines, which may promote the attraction of additional
susceptible target cells for HIV infection.
c. Opioids increase the expression of chemokines, which, for an individual cell, may block viral replication by
blockading the chemokine coreceptor.
d. Opioids alter the phagocytic activity of neutrophils, and this would be expected to significantly alter the
kinetics of the infection.
e. Opioids would be expected to alter the expression of cytokines that may, in turn, alter the replication rate of
the virus in monocytes and T cells.
37. Drugs Of Abuse and the Immune System
Toby K. Eisenstein, David E. Kaminsky, Rahil T. Rahim and Thomas J. Rogers
Answers
1.
a
2.
d
3.
e
4.
d
5.
d
6.
c
7.
c
8.
d
9.
c
10.
b
11.
c
12.
d
13.
a
14.
b
15.
e
16.
d
17.
e
18.
d
4