L13 Guest Lecture Flashcards
When you have an infection, there is both an ___ and ____ immunity that leads to destruction of the pathogen
innate, adaptive
examines the interactions between the nervous, immune and endocrine systems
psychoneuroimmunology
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
immunoprivileged, blood brain barrier, lymphatic drainage, immunocompetent
There are marked similarities between ___ ___ produced by adaptive neuroimmune function, and ______ ______ produced by pathological neuroimmune function. Both are mediated by brain ___ production
sickness behaviours, neuropsychiatric disorders, cytokine
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.
cyclophosphamide, force feeding
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.
cyclophosphamide, antigen, immune challenge, antibody, saccharin, decreased, unconditioned, high, continuously, nervous system
Immunosuppressive drug
cyclophophamide
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 ____.
soluble, t-cells, b-cells, autocrine, paracrine, endocrine, brain, interleukin, TNF
proinflammatory cytokines include ___, ___ and ____
IL-1beta, IL-12, TNF-alpha
antiinflammatory cytokines include ___ and ___
IL-4, IL-10
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 ____.
resident, immune challenge, neuroendocrine, debris, dead cells, morphology, rest, ramified, projections, processes, amoeboid, round, synapse, elimination
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.
vagal afferents, anti-inflammatory, systemic
the main nerve for the parasympathetic system; also regulates immune function
vagus nerve
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
blood brain barrier, enter
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 ___ ___
circumventricular organs, permeable, brain tissue
The last way of peripheral signalling involves the cytokine being _____ _____ across the blood brain barrier via specialized _____
actively transported, transporters
sickness behaviours are _____ behaviours in response to an ____. The common phenotype in rodents includes decreased ___ and ____, reduced _____, ___ ____ and impaired ___ and ____.
adaptive, infection, exploration, grooming, locomotion, social interactions, learning memory
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
IL-1, intracerebroventricular injection, saline, 0.4, novel, decreased, IL-1, peripheral
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.
intraperitoneal, peripheral, saline, IL-1 receptor antagonist, decreased, restored, brain, brain
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
lipopolysaccharide, peripheral, social exploration, 6, intracerebrospinal, IL-10, restoration, doses, brain
an antigen that stimulates immune activation but doesn’t give a full infection
Lipopolysaccharide
peripheral cytokine ____ can travel into the brain
production
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.
pro-inflammtory cytokine, microglia, vagus nerve, pro-inflammatory, HPA-axis, negative feedback, immune tissues, CRH, ACTH, production
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 ____
LPS, saline, 3, 5, 30, restraint, corticosterone, IL-1beta, perceive, response
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 _____ _____.
HPA, GRs, MRs, CRH, homeostasis, GCs, proliferation, morphology, cytokine production, immune challenges
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.
RU486, inescapable shock, hippocampus, microglia, LPS, IL-1beta, IL-1beta, GR antagonist
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 _____.
maturation, synapses, adversities, brain development, schizophrenia
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
nesting, 2-10, impoverished, excitatory synapses, CRH, microglia englufment, inhibits
a task that elicits an innate fear response in rodents by using a visual stimulus to mimic a predator hovering over the animal
looming shadow test
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.
increases, PVN CRH
____ 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 ______.
neonatal, prenatal, psychiatric disorders, influenza, 2nd trimester, schizophrenia
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 ____ ____.
E.coli, PBS, context preexposure, LPS, 24, freezing behaviour, IL-1beta, 1-1.5, memory impairment
