Hd (05-10-06) Pni

Front 1

In what 2 ways are the CNS and immune system connected?

Back 1

1) Neuronal (direct)
2) Hormonal/Neuroendocrine (indirect)

Front 2

Name 5 neuropeptides/neurotransmitters that are released during stress.

Back 2

1) EPI
2) NE
3) GABA
4) ACh
5) Serotonin

Front 3

What do these stress-activated neuropeptides/neurotransmitters stimulate?

Back 3

Paraventricular Nucleus (PVN) of the hypothalamus to release CRH, which will stimulate ACTH release from anterior pituitary, which will result in cortisol release from the adrenal cortex.

Front 4

What is the effect of cortisol on the immune system?

Back 4

Generally, cortisol suppresses immune system cells.

Front 5

How is the adrenal medulla activated to secrete its catecholamines?

Back 5

Direct innervation by sympathetic nerves.
Hypothalamus activates the splanchnic nerves, which trigger chromaffin cells of the adrenal medulla to secrete catecholamines.

Front 6

What activates bone marrow (leukocyte production)?

Back 6

NE.

Front 7

What activates the thymus?

Back 7

NE, ACh, and neuropeptides.

Front 8

What activates the spleen?

Back 8

NE.

Front 9

What activates the lymph nodes?

Back 9

NE and neuropeptides.

Front 10

What are the main functions of cortisol?

Back 10

1) Suppressing inflammation by reducing cytokine production, T,B-cell reactivity, and NK cell activity.
2) Increasing gluconeogenesis

Front 11

What effect does EPI and NE have on leukocytes?

Back 11

Immediate (and short term) increase in leukocyte mobilization to the circulation. Increase NK cell activity.

Front 12

What stimulates POMC and where is it synthesized?

Back 12

CRH activates its release, and it is synthesized in the pituitary. POMC is enzymatically split into ACTH, MSH, and the endorphin opioid. ACTH produces cortisol.

Front 13

What is an enkephalin?

Back 13

An analgesic that binds to the same receptors as endorphins.

Front 14

How do endorphins and enkephalins affect the immune response?

Back 14

Both contribute to analgesic sensations, and also increase T-cell reactivity and NK cell activity.

Front 15

What are the 2 types of stress?

Back 15

1) Acute controllable
2) Chronic uncontrollable

Front 16

During acute controllable stress, what 6 things are seen to increase?

Back 16

1) EPI
2) NE
3) Heart rate
4) Cortisol
5) Circulating leukocytes
6) NK cell activity

Front 17

What are the 5 circulating leukocytes that respond to acute stress and their cell surface markers?

Back 17

1) T cells (CD3)
2) T-helper cells (CD4)
3) Cytotoxic T cells (CD8)
4) Monocytes (CD16)
5) NK cells (CD56)

Front 18

Why does NK cell activity increase in response to acute stress/increased catecholamine levels?

Back 18

Epinephrine and NE seem to cause an increase in the number of circulating NK cells, therefore, an increase in NK cell activity.

Front 19

What happens to leukocyte levels in the serum about 1 hr. following the acute stress?

Back 19

Decreases because these cells localize in the regional lymph nodes, in response to catecholamines and cortisol.

Front 20

What mechanism allows this redistribution to the regional lymph nodes?

Back 20

Hormonal modification of adhesion molecules on leukocyte surfaces (CD11a) and activation of adhesion molecules on endothelial surfaces (ICAM-1).

Front 21

Why is the delayed type hypersensitivity (DTH) reaction used to measure immune function?

Back 21

DTH activates the immune response function.

Front 22

How does the the immune system respond to acute stress?

Back 22

Enhances the immune response (DTH).

Front 23

How does the the immune system respond to very high levels of stress?

Back 23

Dulls the immune response and causes it to be less effective, similar to chronic stress response.

Front 24

How does the immune system respond to chronic levels of stress?

Back 24

Suppresses the immune response.

Front 25

What specifically happens to the immune system in situations of chronic uncontrollable stress?

Back 25

Decreased IL-1 production.
Decreased Ab production.

Front 26

How do the immune systems of high stress patients compare with those of low stress patients?

Back 26

High stress patients: decreased production of IL-2, increase in incidence of colds.

Front 27

Which cytokines are produced as a result of chronic immune or inflammatory processes?

Back 27

IL-1, TNF, IL-6.

Front 28

How do these cytokines affect the CNS?

Back 28

Increase ACTH production from the pituitary, which stimulates cortisol; long-term exposure causes sickness behavior.

Front 29

What 3 components are increased during T and B-cell activation following a response to chronic stress?

Back 29

1) ACTH
2) Endorphins
3) Enkephalins

Front 30

What is sickness behavior?

Back 30

Fever, headache, muscle and joint pain, diminished appetite, lethargy caused by cytokines (IL-1, TNF, IL-6), which not only activate the immune response, but bind to the CNS and modify behavior.

Front 31

By what 2 pathways do cytokines produce sickness behavior?

Back 31

1) Circulation
2) Vagal (afferent) neurons

Front 32

Describe the pathway of cytokines travelling to the CNS via the circulation to produce sickness behavior.

Back 32

IL-1, TNF, and IL-6 cross the blood-brain barrier through circumventricular organs (barrier deficient areas) and bind to neurons that express receptors for IL-1, TNF, and IL-6.

Front 33

What is the pathway of cytokines travelling to the CNS via the nervous system to produce sickness behavior?

Back 33

IL-1 produced by leukocytes travels via the vagal afferents to the brain.

Front 34

Why don't the immune system and the fight or flight response work together over the long term?

Back 34

Both require very high amounts of energy and resources, so when one is activated, the other is suppressed in order to maximize energy.

Front 35

Describe how the immune system responds to increases in catecholamines.

Back 35

Initially, leukocytes are mobilized to the circulation and then to regional lymph nodes. Over time, cortisol will continue to be released which suppresses immune system activity.

Front 36

What advantage is there immediately after the initiation of the fight or flight response?

Back 36

More lymphocytes are present and waiting in regional lymph nodes to react to a potential antigenic challenge.

Front 37

What disadvantage is there after prolonged state of sympathetic response?

Back 37

Longer and larger cortisol release suppresses the immune response.

Front 38

What happens to leukocytes immedately after the sympathetic response?

Back 38

EPI and NE will result in an initial increase in plasma leukocytes, and then a drastic drop as they're mobilized to the regional lymph nodes by EPI and Cortisol.

Front 39

What will restore the plasma levels of leukocytes in the circulation following exposure to long term stress (cortisol)?

Back 39

A drop in EPI, NE, and Cortisol levels.