L13 Guest Lecture

Question 1

When you have an infection, there is both an ___ and ____ immunity that leads to destruction of the pathogen

Answer 1

innate, adaptive

Question 2

examines the interactions between the nervous, immune and endocrine systems

Answer 2

psychoneuroimmunology

Question 3

Originally, the brain was considered ___ and separated from the peripheral immune system. This was due to the presence of the ___ ___ ___ that tightly regulates molecules entering the brain, and the absence of ____ ____. We now know that the brain is ____ and interacts with the peripheral immune system

Answer 3

immunoprivileged, blood brain barrier, lymphatic drainage, immunocompetent

Question 4

There are marked similarities between ___ ___ produced by adaptive neuroimmune function, and ______ ______ produced by pathological neuroimmune function. Both are mediated by brain ___ production

Answer 4

sickness behaviours, neuropsychiatric disorders, cytokine

Question 5

A paper by Rober Ader and Nicholas Cohen found that when sugar water was paired with ____, rats would stop drinking the water. ____ ____ just the water would results in the rats death.

Answer 5

cyclophosphamide, force feeding

Question 6

In a conditioned immunosuppression task, adult male rats were conditioned to _____ paired with saccharin water. On day 3, they were injected with an ____ (___ ____). On day 9, the ______ levels were measured (immune response). They found that conditioned rats given only _____ after the antigen treatment ____ antibody concentration. However, ____ rats, or rats that did not receive saccharin after the antigen showed ____ antibody concentration. Moreover, when sugar water was ____ given, the immune response was suppressed further. This showed that the ___ ___ is able to condition an immune response and there must be a connection between them.

Answer 6

cyclophosphamide, antigen, immune challenge, antibody, saccharin, decreased, unconditioned, high, continuously, nervous system

Question 7

Immunosuppressive drug

Answer 7

cyclophophamide

Question 8

cytokines are ___ protein messenger secreted by immune cells such as ____ and ____. They have both ___ and ___ actions within local tissues, as well as ___ actions via their release into the bloodstream and subsequent signalling to the ___. Examples are _____, and the ____.

Answer 8

soluble, t-cells, b-cells, autocrine, paracrine, endocrine, brain, interleukin, TNF

Question 9

proinflammatory cytokines include ___, ___ and ____

Answer 9

IL-1beta, IL-12, TNF-alpha

Question 10

antiinflammatory cytokines include ___ and ___

Answer 10

IL-4, IL-10

Question 11

microglia are ____ immune cells of the brain that rapidly respond to an ___ ____. They communicate with the _____ system and continuously sample the microenvironment for ____ and ___ _____. Microglia have different ____ depending on the state of activation, though they are never at ____. In a less activated state, they are ___, have thin ___ and ____. In a more active state, they are ____ and have ___ morphology. Microglia are also important for brain development like ____ formation and ____.

Answer 11

resident, immune challenge, neuroendocrine, debris, dead cells, morphology, rest, ramified, projections, processes, amoeboid, round, synapse, elimination

Question 12

in order for peripheral inflammation to signal the brain, cytokines bind to receptors on ___ ____. Activation of the vagus nerve leads to ______ effects to suppress a ____ inflammatory response.

Answer 12

vagal afferents, anti-inflammatory, systemic

Question 13

the main nerve for the parasympathetic system; also regulates immune function

Answer 13

vagus nerve

Question 14

Another way of periphery signalling the brain is cytokine signalling across the ___ ___ ____ via endocrine effects. The cytokine binds to a receptor near the BBB but does not ___ and exerts its effects

Answer 14

blood brain barrier, enter

Question 15

Another way of periphery signalling to the brain involves the cytokine crossing into the brain at _____ ____ where the BBB is ___/leaky. In this way, cytokines can enter ___ ___

Answer 15

circumventricular organs, permeable, brain tissue

Question 16

The last way of peripheral signalling involves the cytokine being _____ _____ across the blood brain barrier via specialized _____

Answer 16

actively transported, transporters

Question 17

sickness behaviours are _____ behaviours in response to an ____. The common phenotype in rodents includes decreased ___ and ____, reduced _____, ___ ____ and impaired ___ and ____.

Answer 17

adaptive, infection, exploration, grooming, locomotion, social interactions, learning memory

Question 18

To show sickness behaviours, a study gave male mice a direct infusion of pro-inflammatory cytokine _____ into the brain via _____ _____. 20 minutes after the injection, those with ___ or _____pg of cytokine showed the most exploration with a ___ object. Any higher concentration of cytokine showed ____ exploration to the same extent. To conclude, ____ signalling in the brain is responsible for reducing exploratory behaviour in the absence of a _____ infection

Answer 18

IL-1, intracerebroventricular injection, saline, 0.4, novel, decreased, IL-1, peripheral

Question 19

In another study, male rats were given IL-1 via ______ injection, in other words, a _____ infection. Then the rats were either given intracerebrospinal ____, or ____ _____ ______. IL-1 paired with saline ____ food motivation and social interaction. IL-1 paired with the antagonist ______ it. In conclusion, the peripheral response travelled to the ___ to induce a response, and blocking the _____ response blocked that first response.

Answer 19

intraperitoneal, peripheral, saline, IL-1 receptor antagonist, decreased, restored, brain, brain

Question 20

In another experiment, all male rats received an intraperitoneal ____ injection, to simulate a ____ infection. Giving the rats a vehicle afterwards depressed ___ ____ for __ hours after the LPS injection. Giving an _______ injection of _____ (anti-inflammatory cytokine) resulted in _____ of social exploration up to 6 hours at high _____. In conclusion, anti-inflammatory cytokines in the ____ was able to decrease sickness behaviour following LPS treatment

Answer 20

lipopolysaccharide, peripheral, social exploration, 6, intracerebrospinal, IL-10, restoration, doses, brain

Question 21

an antigen that stimulates immune activation but doesn’t give a full infection

Answer 21

Lipopolysaccharide

Question 22

peripheral cytokine ____ can travel into the brain

Answer 22

production

Question 23

When there is peripheral immune activation, peripheral immune cells secrete a ______ ____, which activates ___ in the CNS via activation of the __ ___. The microglia secret ___ cytokines of their own, and these activate the ____ to produce glucocorticoids. These glucocorticoids regulate the __ ___ of both peripheral and CNS ___ ____, by binding to glucocorticoid receptors. They act on the HPA axis to inhibit further production of ____ and ____. They also promote the _____ of anti-inflammatory cytokines.

Answer 23

pro-inflammtory cytokine, microglia, vagus nerve, pro-inflammatory, HPA-axis, negative feedback, immune tissues, CRH, ACTH, production

Question 24

To study neonatal exposure to bacteria, male and female rats were given intraperitoneal ______, or _____ on postnatal day ___ and ____. Then in adulthood, animals underwent ___ minutes of ____ stress, or no stress. It was found that have a neonatal immune activation led to a higher ___ peak, and ______ in the hippocampus after the stressor. To conclude, early life infection changes both how you ____ stress and your immune ____

Answer 24

LPS, saline, 3, 5, 30, restraint, corticosterone, IL-1beta, perceive, response

Question 25

Microglia are sensitive to the _____ axis, express ____, ___ and ____ receptors, and can react to stress to help restore _____. A high level of ____ can modulate the ____, ___ and ___ ___ of microglia. They can also prime the microglia for a subsequent _____ _____.

Answer 25

HPA, GRs, MRs, CRH, homeostasis, GCs, proliferation, morphology, cytokine production, immune challenges

Question 26

In studying whether glucocorticoids can alter microglia activity to proinflammatory stimuli, male rats were treated with either _____ (GR antagonist), or a vehicle. An hour later, rats underwent an ____ ___ stressor, or were left undisturbed. The animals were euthanized 24 hours after, and the ___ was dissected for a _____ culture. The Ex-vivo microglia cells were exposed to ___ and ______ was quantified. Microglia from the stressed rats showed increased ____ production following LPS treatment. The _____ blocked the IS-induced sensitization of the pro-inflammatory response.

Answer 26

RU486, inescapable shock, hippocampus, microglia, LPS, IL-1beta, IL-1beta, GR antagonist

Question 27

the neuroimmune system is important for proper brain _____. For example, microglia prune excess _____ during development. Early life ____ can disturb the neuroimmune system and alter ___ _____. Aberrant synaptic pruning were linked to neural disorders such as _____.

Answer 27

maturation, synapses, adversities, brain development, schizophrenia

Question 28

In Bolton et al.’s study, male neonatal mice were given early life adversary by providing limited ____ materials from postnatal days ____, making an ____ environment. The results showed that ELA increased the number of _____ ___ in PVN ____ neurons at P10, and decreased the _____ ____ of excitatory synapses in the same neurons. This showed that ELA ____ the microglia’s ability to prune excess synapses

Answer 28

nesting, 2-10, impoverished, excitatory synapses, CRH, microglia englufment, inhibits

Question 29

a task that elicits an innate fear response in rodents by using a visual stimulus to mimic a predator hovering over the animal

Answer 29

looming shadow test

Question 30

ELA also ____ the latency to respond to a threat during the looming shadow test. This shows that ELA disrupts function to reduced excitatory synapses in _____ ____ neurons, which disrupt the fear response in adulthood.

Answer 30

increases, PVN CRH

Question 31

____ or ____ infections have long lasting impacts on the brain and behaviour. Many ____ ___ have similar pathologies to immune activation. An example is the type A2 ____ epidemic in Finland, which when exposed to in the ___ ____, resulted in an elevated risk for being diagnosed with ______.

Answer 31

neonatal, prenatal, psychiatric disorders, influenza, 2nd trimester, schizophrenia

Question 32

In order to determine whether early life infection altered memory and the response to a subsequent immune challenge, neonatal male rats were subject to ______ or a ____ control. Then in adulthood, the rats underwent a _______ _____ task, where they were conditioned to a footshock. After, they were either given ____ (second hit) or saline, and placed back into the context and given a memory refresher of the footshock. ___ hours later, the rat was returned to the context to measure ___ ____. Results showed that neonatal infection led to and exaggerated ______ response ____ hours after exposure to LPS in the brains of adult rats, as well as ____ ____.

Answer 32

E.coli, PBS, context preexposure, LPS, 24, freezing behaviour, IL-1beta, 1-1.5, memory impairment