Psychoneuroimmunology

Question 1

What is PNI?

Answer 1

The mechanisms whereby the nervous system and the immune system communicate with one another

Question 2

Describe the direct connection between the CNS and the immune system

Answer 2

Innervation of primary and secondary lymphoid organs as well as the adrenal medulla

Question 3

Describe the indirect connection between the CNS and the immune system

Answer 3

The CNS communicates hormonally with the immune system

Question 4

Name 4 neurotransmitters/hormones that are activated by the CNS and affect the immune system

Answer 4

1) Catecholamines
2) GABA
3) ACh
4) Serotonin

These 4 chemicals are released by stress and lead to the release of CRH from the PVN of the hypothalamus

Question 5

What is the general effect of cortisol on the immune system?

Answer 5

Most cells of the immune system are sensitive to cortisol and are inhibited in their function by this hormone

Question 6

Bone marrow is primarily stimulated by what hormone?

Answer 6

NE

Question 7

The thymus is stimulated by what chemicals?

Answer 7

NE, ACh and neuropeptides

Question 8

The spleen is stimulated by what chemicals?

Answer 8

NE

Question 9

Lymph Nodes are stimulated by what chemicals?

Answer 9

NE and neuropeptides

Question 10

Describe how splanchnic nerves can affect the immune system

Answer 10

Stress –> stimulation of splanchnic nerves –> stimulation of adrenal medulla –> release of NE and E –> ACh release –> T-cells, B-cells, neutrophils, mononuclear cells and NK cells affected

Question 11

What is the general effects of NE and Epi on the immune system?

Answer 11

NE and E increase leukocyte mobilization resulting in an increase in NK cells activity

Question 12

What is the general effect of endorphins?

Answer 12

Endorphins, originate from POMC –> important role in analgesia (inability to feel pain) and feelings of happiness

Question 13

What is the general role of enkephalins

Answer 13

Play a role in analgesia –> they can bind to the same opioid receptors as endorphins

Question 14

How do endorphins and enkephalins affect the immune system?

Answer 14

Endorphins and enkephalins increase T cell and NK cell activity

Endorphins act more like hormones, whereas enkephalins act more like neurotransmitters

Question 15

How does acute stress affect catecholamine levels?

Answer 15

Acute stress is associated with increased catecholamine levels

Question 16

How is cortisol affected by acute stress?

Answer 16

Cortisol is increased and maintains higher levels for awhile

Question 17

What happens to the number of lymphocytes in circulation in response to acute stress?

Answer 17

Initially they increases, but one hour later the various mononuclear cell populations decrease because the cells have localized to the regional lymph nodes

Question 18

What causes immediate leukocyte mobilization in circulation in times of acute stress?

Answer 18

Catecholamines (Epi and NE release from the adrenal medulla)

Question 19

What causes the leukocytes to redistribute to the lymph nodes where they can respond quickly to antigenic challenge?

Answer 19

Catecholamines and cortisol

-Cortisol mobilizes glucose/the ability to use muscles, and leukocytes are stored for later use should a challenge be presented

Question 20

What is CD11a?

Answer 20

CD11a is an adhesion molecule on the surface of the leukocyte that binds to ICAM-1 for extravasation into the lymph nodes

Question 21

How do moderate levels of cortisol affect the DTH response?

Answer 21

Moderate levels of acute cortisol enhance the DTH response (more cells in circulation lead to a greater response)

Question 22

How do high levels of cortisol injected acutely affect the DTH response?

Answer 22

High levels of cortisol suppress the DTH response

Question 23

How does chronic stress affect the DTH response?

Answer 23

Chronic stress ablates the DTH response completely

Question 24

Compare the DTH response under conditions of acute vs chronic stress

Answer 24

Acute stress: enhance DTH

Chronic: ablated DTH

Question 25

How does chronic uncontrollable negative stress affect the immune system? Name a few aspects that are specifically affected

Answer 25

Causes immune suppression

Decreased IL-1
Decreased antibody production
Decreased response to vaccines (IL-2 production reduced)
Increase in the number of colds

Question 26

How does IL-1, TNF-alpha and IL-6 production (due to chronic inflammation) affect the CNS?

Answer 26

Cytokines change the firing frequencies of nerve cells in the CNS and influence the secretion of neuroendocrine factors of the HPA axis, especially ATCH production

Question 27

Activated T and B lymphocytes can produce what three neurotransmitters?

Answer 27

ACTH
Beta-endorphins
Enkephalins

Question 28

What is sickness behavior?

Answer 28

Activation of the immune system by an infectious agent induces the production of cytokines (IL-1, IL-6, TNF) which, in addition to activating the immune system also send signals to the CNS that modify behavior. This behavior modification is known as “sickness behavior”

Characteristics: fever, headache, muscle and joint pain, diminished appetite, and lethargy are a consequence of these cytokines

Question 29

How do cytokines induce sickness behavior?

Answer 29

Circulation: cytokines cross the BBB and activate the production of prostaglandins

Vagal Afferent neurons: IL-1 stimulates the related regions of the brain

Question 30

How does the CNS interact with the immune system to prevent excessive inflammation?

Answer 30

CNS interactions with the immune system to regulate excessive inflammation via efferent vagus and the splenic nerve

Action potentials transit the splenic nerve releasing NE, which stimulates the production of ACh by T lymphocytes (ACh binds beta 2AR). ACh interacts with macrophages (via alpha 7 receptors) within the spleen and inhibits IL-1, IL-6 and TNF–> reduction of pro-inflammatory cytokines