Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

NEUR4305 Immune-Brain Interactions > Midterm > Flashcards

Midterm Flashcards

You may prefer our related Brainscape-certified flashcards:
The Brain flashcards
1
Q

Immune cells

A

Dynamic set of specialized cells that search for, deal with and eliminate danger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Pathogens

A

Things that our immune system defends against. Can include viruses, bacteria, fungi, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Immune system

A

A network of blood derived cellular operations that orchestrates protection against the microbial world.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Innate immune system

A

A nonspecific response that includes the first and second line of defence.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Leukocytes

A

Specialized cells of the immune system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

First line of defence for innate immune system

A

Barriers that block entry/invasion. These include ears, eyes, mouth and nasal cavity, skin, stomach, trachea and bronchi, vagina, urethra and anus.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Second line of defence for innate immune system

A

Once a pathogen has made it past the first line of defence, the second line of defence is activated and involves cells and fluid attacking invaders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Adaptive immune response

A

Specific response that involves the 3rd line of defence. develops after exposure to a pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

True or false: the innate and adaptive immune systems are mutually exclusive.

A

False, they typically work together; the innate system informing the adaptive immune system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Defensins

A

Antimicrobial peptides which can kill and inhibit growth of pathogens - found in the mucous layer surrounding the GI tract.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Overall function of innate immune cells (IICs)

A
  • getting rid of pathogen by “eating” it or releasing signals that destroy it
  • send signals to recruit other immune cells for help
  • send signals to alert and mobilize the adaptive branch
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Mast cells will recognize bacteria and then release _____________

A

Heparin/histamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Heparin/histamine

A

Causes blood vessels to dilate which increase in white blood cell concentration at the affected area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do innate immune cells recognize pathogens?

A

Pathogens have PAMPs attached to them which is recognized by receptors on the innate immune cells (PRRs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

PAMPs (Pathogen associated molecular patterns)

A

Non-specific shared characteristic of different types of pathogens that are not present on human cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What do innate immune cells do once their PRRs are activated?

A

Initiates phagocytosis which includes engulfing, breaking down and digesting the pathogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the main cell type involved in phagocytosis

A

Macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Neutrophils and Phagocytosis

A

The most abundant and rapid responders who roam through blood and infectious tissue - they engulf and destroy microbes (especially bacteria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Macrophages and Phagocytosis

A

Found throughout the body as roamers and reside in various tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Eosinophils and phagocytosis

A

embedded in tissue and are used to kill parasites larger than bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Dendritic cells and phaogcytosis

A

Embedded in tissue and are antigen presenting cells - they phagocytize part of the antigen and then present its parts to the adaptive immune system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Describe the 3 methods of attack for neutrophils

A

1) Phagocytosis

2) Degranulation - this involves releasing chemicals such as defensins(which are attracted to the pathogen’s membrane) which then poke holes into the membrane of the pathogen inducing apoptosis

3) Release of Neutrophil Extracellular Traps (NETS): involves a net like extension which will trap the pathogen and then bring it to the neutrophil to perform phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do innate immune cells attack very large pathogens?

A

Phagocytic cells will act to destroy it as well as release toxic chemicals such as defensins, ROS (reactive oxygen species) and lysosomes to chemically break it down.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Cytokines

A

Small glycoproteins that are involved in chemical signalling in which are released into the blood stream by IICs upon recognition of a pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Primary role of cytokines

A

Recruits, activate/deactivate, and/or stimulate production of immune cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Autocrine signalling

A

Signal that acts on the same cell it was released from

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Paracrine signalling

A

Signalling the affects cells in the immediate vicinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Endocrine signalling

A

Signalling that affects cells remote from the secreting cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Pro-Inflammatory cytokines

A

Used to amplify the immune response.
Examples: TNFa, IFN-gamma, Interleukin-6 (IL-6)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Anti-inflammatory cytokines

A

Used to decrease an inflammatory response
Examples: IL-4,IL-10, IL-20

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Complement system

A

A set of 20 proteins present in the blood (compliment proteins) that are activated by pathogens. Their role is to enhance inflammation, cause opsonization, cytolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Opsonization

A

Tagging of a pathogen for destruction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Cell types involved in the adaptive immune system

A

B cells and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Cellular immunity typically involves __________

A

T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Humoral immunity typically involves ___________

A

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Antigen

A

Specific molecular markers of different bacteria (sometimes a pathogen can be referred to as an antigen)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How does a B cell recognize a pathogen?

A

B cells have B cell receptors that can recognize one specific antigen on a pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Antibody specificity

A

A B cell can only recognize one type of pathogen - one that can recognize influenza cannot recognize herpes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

How do B cells proliferate?

A

An antigen binding to a BCR will cause a cascade that will lead to the proliferation of that B cell. The b cell will make effector B cells which will then mature into plasma cells. Plasma cells will release the antibodies against the antigen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is the main function of an antibody

A

To neutralize and/or eliminate a pathogen/antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How does an antibody neutralize a pathogen?

A

It does so by binding to the antigen which anchors it - therefore it cannot enter cells and replicate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is an antibody’s role in opsonization?

A

The antibody’s constant region is exposed which signals macrophages and other phagocytes to come engulf the pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Variable region of an antibody

A

Binds to the antigen on the pathogen, leaving constant region exposed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Constant region of the antibody

A

Not attached to the antigen: they recruit macrophages and phagocytes to the pathogen to be phagocytized.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Fc Region

A

receptor on a phagocyte which allows them to recognize antibodies that are bound to pathogens.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Active immunity

A

Immunity that occurs by exposing someone to the virus (vaccinations)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Passive immunity

A

Natural immunity that is derived from without activating the individuals immune system.
Example: mother’s breast milk or blood plasma transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Memory b cells

A

Created during the B cell proliferation stage and remain once a pathogen has been eliminated. Allows prompt recognition of that same pathogen should we be infected again.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Function of T cells

A

1) Help other immune cells
2) Regulate immune response
3) Kill and mobilize a response against infected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What are the 4 types of T cells

A

1) CD 8+ Cytotoxic T cells (Tc)
2) CD 4+ T helper cells (Th)
3) CD4+ T Regulatory cells (Treg)
4) T memory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Role of Cytotoxic T cells

A

To kill infect cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

MHC proteins

A

Major histocompatibility complex that all cells have. Once infected, the MHC will turn the virus into fragments, hold its parts on its cells surface and it present it outside the cell for the Tc to kill.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

MHC1

A

All nucleated cells in the body have this complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

MHC2

A

Found in antigen presenting cells such as phagocytic Innate Immune Cells (dendritic cells) and B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

How does a Tc recognize and initiate elimination of an infected cell.

A

The CD8 protein in Tc will recognize the MHC1 on the infected cell and bind to it. The CD8 protein will move the cell closer to the TCR and if it recognizes the pathogen it will initiate apoptosis of the cell. The Tc and the infected cell will also release cytokines that will call the Tc to make clones of itself. The clones (Effector Tc cells) will now be circulating to find more infected cells. They will bind and force the cell to self destruct through exocytosing perforin and granzymes that will poke holes in the infected cells membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Role of the T helper cells

A

They help engage an immune response by secreting cytokines which help activate other cells of the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Lymphatic system

A

part of a vascular system comprising a large network of lymphatic vessels that contain fluid called lymph

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Proliferation of Th cells

A

When the MHC2 binds to the Th cell cytokines are released. These cytokines will initiate proliferation of 2 types of TH cells: Th1 or Th2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What cytokine initiates Th1 proliferation?

A

IL-12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Sterile inflammation

A

Factors that cause an immune activation in our body that is not provoked by a pathogen.
Example: Trauma, stroke, toxins, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is the blood brain barrier?

A

A membrane that assists in making our peripheral immune system decentralized, prevents harmful substances from entering into the brain, and allows selective passage of essential nutrients such as oxygen and hormones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What cells make up the BBB?

A

Brain capillary endothelial cells (BCECs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is the neurovascular unit(NVU) made up of?

A

BCECs, pericytes and astrocytic endfeet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

How does the BBB restrict things from entering the brain?

A

The BCECs are joined together by tight junction proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Paracellular transport across BBB

A

Refers to transport that occurs in between cells, passing through an intercellular hollow pathway. Not tightly regulated and relatively unselective (based on size and charge). (H2O, electrolytes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Transcellular Diffusion across BBB (Passive diffusion)

A

Transport of small lipophillic molecules through brain capillary endothelial cells from the blood into the brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Carrier Mediated Transcytosis across BBB

A

Molecules carried across the BCECs via specific solute carriers/carrier proteins. Solute will bind to the protein transporter leading to a conformational change, allowing the carrier to then transport the substance to the other side of the membrane (typically with its concentration gradient) (if against gradient, ATP is used)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Absorptive Mediated Transcytosis across BBB

A

Positively charged substance in bloodstream is attracted to negatively charged membrane, this induces membrane invagination and vesicle formation. The substance-containing vesicle will enter intracellular space and move to the brain side of the capillary endothelium – then integrating with the cell membrane and releasing its contents.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Receptor mediated transcytosis across BBB ** will be an exam question **

A

Macromolecules enter via receptor binding which triggers an endocytotic event and subsequent transport across the BBB. The ligand binds to the receptor, initiates invagination of membrane and endocytosis; in cell, the vesicle can be 1) recycled back out into the capillary, 2) fuse with membrane on the other side for content release, or 3) fuse with lysosome and be degraded.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Flaw of the BBB

A

Prevents treatment administration for certain brain illnesses.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

How might scientists overcome the flaw of the BBB when administering brain treatments

A

We can inject antibodies into the brain were created to target certain brain pathogens or proteins for destruction or for tagging.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

How are antibodies created for immunostaining?

A

Inject antigens into an animal species (rat, rabbit, etc). Antigen will activate the B cells and then produce antibodies against that antigen. We then collect the plasma and extract the antibodies from the plasma. (Primary antibody)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Method for utilizing antibodies against Alzeimer’s (removal of beta ameloid plaques)

A

Using the Receptor mediated transcytosis system, there are many transcytosis receptors (TfR) on the BCECs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Antibody conjugation

A

Method of antibody delivery that involves taking a part of the protein that binds to TfR and fusing it with the antibody. This antibody/protein complex can then cross the BBB and bind to the antigen in the brain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

True or false: Antibodies are immunoglobulin proteins?

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Antigen binding region

A

Portion of the antibody that binds to the antigen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

5 classes of antibodies

A

IgG, IgM, IgD, IgA, IgE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Role of IgG

A

To neutralize toxins and perform opsinization.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Bispecific antibodies

A

An antibody that binds to 2 different antigens, one being the BBB receptor and the second being the Ag target.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

Other methods of treatment delivery into the brain (not including receptor mediated transcytosis)

A

1) Utilizing other receptors on BCECs
2) Linking drugs with amino acids that are known to cross BBB
3) Using BBB permeability enhancers.
4) Non-invasive techniques

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

Leaky BBB

A

This describes when the BBB becomes compromised and leads to infiltration of toxic substances into the brain.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Microglia

A

The brain’s immune cells, they act as guards detecting first signs of pathogenic invasion, tissue damage, cancerous or defective cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

True or False: Microglia come from the same source as other cells of the CNS

A

False, they are though to come from progenitor cells in our yolk sac.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Characteristics of microglia as surveyors

A

They are in their non-reactive form where they move around our neurons and cells looking for “trouble”. Microglia in this state have a small cell body and highly ramified branches.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Overall function of microglia in their non-reactive form

A
  • Clean up cellular debris and foreign materials in the environment.
  • Maintain homeostasis to ensure integrity of neuronal circuits.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What causes microglia to exit their non-reactive form

A

If their recognition receptors are activated they will morph into their reactive form which consists of reactive-non-phagocytic or reactive phagocytic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Two pathways of morph from a non-reactive microglia

A

1) Non- reactive –> Reactive-non-phagocytic –> reactive phagocytic

2) Non-reactive –> reactive non-phagocytic

Non-reactive can turn into either RNP or RP, depends on whether phagocytic receptors get activated or not.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Role of microglia in their reactive form

A
  • Release molecules to recruit and activate other immune cells
  • Release factors that induce destruction/protection of neurons and dendrites.
  • Regulate amount of inflammation
  • engage in phagocytosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

5 Steps in phagocytosis guaranteed exam question

A

1) recognition of pathogen, debris or apoptotic cells
2) ingestion and formation of phagosome
3) formation of the phagolysosome (merging of a phagosome and a lysosome)
4) killing of target molecule
5) elimination and exocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Are non reactive microglia typically pro- or anti- inflammatory?

A

Anti-inflammatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

Are reactive microglia typically pro- or anti- inflammatory?

A

Pro-inflammatory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Two types of receptors present on microglia

A

1) Damage recognition receptors (DRRs) - recognize damage/apoptotic cells (DAMPs)

2) Pattern/pathogen recognition receptors (PRRs) - recognize PAMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

How do microglia recognize damage?

A

Their DRRs will be activated by nuclear or cytosolic proteins released by the damaged cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What happens when a DRR is activated?

A

It will engage in chemotaxis, release cytokines and engage in phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Chemotaxis

A

Process where microglia and other cells move in response to a signal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

NFKB pathway resulted from PRR activation

A

1) the NFKB complex is resting in the cytosol and not moving because it is attached to IKB.
2) When TLR4 is activated, IKB gets broken down which leads NKFB to be free to act as a transcription factor
3) NFKB will translocate from cytosol into nucleus to interact with DNA/promoter regions of pro-inflammatory cytokines to be transcribed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Neuroinflammation

A

Brain’s inflammatory response to various triggers, such as injury, infection, stress or neurodegen. conditions. It involved the accumulation of reactive microglia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

Acute neuroinflammation

A

Rapid inflammatory response which occurs immediately following CNS injury or xenobiotic detection in the brain, often involving activated microglia (RNP and RP) for a period of time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

How can microglia protect against stroke damage?

A

1) Swiftly clearing debris, removing dead cells and preventing harm to neurons.
2) Release growth factors like VEGF and BDNF.
3) Promote formation and maintenance of tight junctions for the BBB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

How microglia can be more damaging in terms of stroke damage?

A

Instead of being strictly anti-inflammatory, microglia can promote inflammation thru the release of pro-inflammatory cytokines and ROS which can cause damage to surrounding tissue.

101
Q

VEGF

A

Vascular endothelial growth factor. It promotes angiogenesis (growth of blood vessels)

102
Q

BDNF

A

Brain derived neurotropic factor. Its a factor that is engaged to protect neurons, involved in synaptic plasticity, growing of dendrites to make new connections following an ischemic stroke.

103
Q

Minocycline

A

An antibiotic that has been shown to have neuroprotective factors as it promotes an anti-inflammatory environment.

104
Q

Chronic neuroinflammation

A

prolonged and sustained inflammatory response within the CNS, characterized by a presence of reactive microglia.

105
Q

Pathogen that can inhibit phagocytosis/induce cell death

A

Listeria monocytogenes

106
Q

What cells do microglia recruit in order to replenish?

A

BMDMs and PVMs, they can replace lost microglia.

107
Q

How do microglia distinguish between active vs inactive synapases?

A

1) Detecting number of AMPA receptors on the synapses. More AMPA receptors = preservation of that synapse
2) Unused synapses will send out filopodia projections to the microglia to be engulfed.
3) Unused synapses will use chemokine signalling to attract the microglia to engulf them.

108
Q

What did Ader & Cohen’s 1950 experiment with rats, saccharin water and Cyclophosphamide (CP) demonstrate? Recall in this experiment saccharin water was
paired with CP (a chemotherapy drug that attacks dividing cells) and then the CP was taken away. Following CP removal rats only drank saccharin water. Despite this they still had a reduction in their immune response.

A

This showed that the CNS can influence our immune response.

109
Q

Which cells are activated by MHC1-peptide/Ag complex in response to viruses?

A

CD8 cytotoxic T cells

110
Q

What does the Type 1 Interferon Response primarily defend against?

A

Viral infections

111
Q

What role do Type I Interferons (e.g., IFN-alpha & IFN-beta) play?

A

They have powerful antiviral properties.

112
Q

How do type 1 interferons pose an antiviral defense mechanism?

A
  1. block viral replication
  2. enhance the activity of other immune cells like cd8 and nk cells
  3. increase the expression of mhc1 molecules on infected cells
  4. induce apoptosis in virus infected cells
113
Q

if a person exhibiting high loneliness scores is exposed to a virus, what might you expect
in their immune response?

A

impaired ability to clear the virus

114
Q

In a lab study, lonely monkeys exposed to the SIV virus showed __________

A

reduced type 1 IFN response.

115
Q

What is sickness behaviour?

A

constellation of behavioural effects that an organism uses to defend against an immunological threat.

116
Q

Anhedonia

A

Loss of pleasure in things we once found pleasurable.

117
Q

If a mouse shows reduced grooming and disturbed sleep rhythms, what can be inferred?

A

The mouse is likely experiencing sickness behaviour.

118
Q

According to theorists, what is the primary purpose of adopting sickness behaviors?

A

To reorganize priorities for survival.

119
Q

What is the primary cause of sickness behavior?

A

Cytokines (endogenous pyrogens) influencing the brain.

120
Q

What happens when the body exceeds normal set point?

A

Warm-sensitive neurons in the pre-optic nucleus of the hypothalamus (PNOH) become activated and signal to the automatic nervous system (sweat glands and blood vessels) telling them to dilate and secrete fluids in order to decrease heat.

121
Q

What happens when the body’s temperature decreases?

A

Cold sensitive neurons become activated and signal to blood vessels to constrict and sweat glands to remain inactive in order to conserve body heat.

122
Q

Fever

A

An increase in the set point for temp regulation set by the hypothalamus.

123
Q

Endogenous pyrogens

A

Pro-inflammatory cytokines such as IL1beta

124
Q

Exogenous pyrogens

A

Different pathogens such as parasites, bacteria and viruses.

125
Q

What is the fever inducing prostaglandin?

A

(PG)E2

126
Q

How is PG(E2) synthesized?

A

Arachidonic acid (fatty acid) is converted into prostaglandin H2 (PGE2) by cyclo-oxygenase.

127
Q

How do prostaglandins affect the warm-sensitive neurons in the pre-optic nucleus of the hypothalamus (PNOH) during fever?

A

When PG(E2) binds to its receptor in the PNOH (EP3R), there is a decrease in neuronal firing therefore the hypothalamus will not send any signals to the blood vessels and the sweat glands, this ultimately increases the hypothalamic set point.

128
Q

Besides interacting with cells of the OVLT to increase prostaglandin release leading to fever, how else do pyrogens contribute to fever?

A

Through activation of vagal nerve afferents (the neural pathway)

129
Q

Circumventricular organs

A

Areas in the brain that lack a BBB. Lines the 3rd and 4th ventricle close to the hypothalamus.

130
Q

How do immune cells respond to increased body temperature?

A

By enhancing phagocytosis of the innate immune cells

131
Q

What is the effect of COX-2 inhibitors like ibuprofen on fever?

A

To decrease fever by inhibiting the synthesis of PG(E2) through antagonizing its enzyme (cyclooxygenase).

132
Q

How do pyrogens induce anorexia during sickness?

A

By suppressing AgRP neurons, which inhibits the inhibition of satiety neurons, therefore they continue to tell us we are full

133
Q

If a person’s body temperature rises during an infection, how might POMC neurons respond?

A

By reducing appetite, through activation of satiety neurons that tell us we are full.

134
Q

What is the role of the sympathetic nervous system (SNS) in the initial immune response?

A

To enhance the immune response.

135
Q

Steps to transrepression

A

1) cortisol will bind to GR which will become activated and undergo a conformational change
2) activated GRs translocate from the cytoplasm into the cell nucleus
3)within the cell nucleus, activated GRs interact with pro-inflammatory transcription factors (TFs)
4) this interaction prevents the activation of these TFs and ultimately their ability to promote pro-inflammatory cytokine transcription

end game one = reduced expression of pro-inflammatory cytokines.

136
Q

Steps to transactivation

A

1) cortisol will bind to GR which will become activated and undergo a conformational change
2) activated GRs translocate from the cytoplasm into the cell nucleus
3) within the cell nucleus, GRs bind to specific DNA sequences call glucocorticoid response elements (GREs) which are typically located in the promotor regions of anti-inflammatory target genes
4) this interaction of GRs binding to GREs results in the production of anti-inflammatory cytokines.

end game 2 = increased expression of anti-inflammatory cytokines

137
Q

Which receptors are expressed by B cells, T cells, and macrophages to allow for their mobilization during the initial stages of the stress response?

A

Adrenergic receptor

138
Q

What is the primary purpose of cortisol release during an immune response?

A

To serve as an anti-inflammatory agent

139
Q

What can prolonged cortisol elevation lead to as a result of chronic stress?

A

Chronic inflammation and immune dysregulation

140
Q

In an infection, what is a direct consequence of (PG)E2 interacting with GABA neurons they inhibit CRH neurons in the stress response?

A

To decrease GABA neuron firing

141
Q

Biological hallmarks of PD

A

1) degeneration of dopamine neurons in the substantia nigra
2)presence of Lewy body inclusions
3)neuroinflammation

142
Q

Symptoms of PD

A
  • Bradykinesia
  • Rigidity and postural instability
  • Tremors
  • Walking or gait difficulties
  • Gastro dysfunction
  • Fatigue
  • Anxiety
  • Depression
143
Q

How pathogens may trigger microglia activation leading to DA cell death in PD?

A

1) entry of pathogen
2) triggers immune response
3)cytokine gain entry/or cause more cytokine activation which causes prolonged proinflammatory microglia
4) leads to death of DA neurons in the SNc
5) results in PD motor characteristics.

144
Q

Non-cell autonomous theory (neuroinflammation)

A

1) pathogen enters into the brain
2) reactive microglia become activated and release things like ROS and proinflammatory cytokines
3)that leads to cell death of DA cells in the area
4) those dead cells are gonna release DAMPS which signals microglia to come clean up and initiate apoptosis
5) this cycle continues and triggers a cascade of events

145
Q

Cell autonomous theory (neuroinflammation)

A

1) Problem in the DA neuron which leads to the activation of microglia
2) Toxin will enter DA neuron and DA neuron will die and release DAMPs that will cause activation of microglia
3)Activated microglia will release ROS and proinflammatory cytokines which results in the cyclic cycle of killing DA cells.

146
Q

How are the peripheral immune cells recruited from the CNS?

A

1) Activated microglia recruit peripheral pro-inflammatory immune cells through cytokine release - decreasing the selectivity of the BBB, allowing peripheral immune cells to enter.

2) Infiltration of peripheral immune cells

3) Peripheral immune cells contribute to neuroinflammation

147
Q

Proposed role of peripheral immune cells in parkinsons

A

1) Macrophages assist the microglia in phagocytosis

2) B cells release auto-antibodies to coat neurons with misfolded alpha-synuclein aggregates (least supported theory of PD)

3) T cells (depending on the type)
- Th(CD4+) cells amplify neuroimmune response
- May be involved in contributing to cell death (CD8+)

148
Q

How do CD4+/CD8+ cells induce cell death in DA neurons?

A

Involved RP and RNP microglia.
- A DA neuron will die and then release lewy bodies, subsequently releasing a-syn. The microglia will phagocytosize the a-syn and break it down and the present it on cell surface. RNP will release pro-inflammatory cytokines to recruit immune cells to the site (CD4). When they enter the brain, the T cells will turn into effector cells and then proliferate. THe effector T cells will have a FAS ligand and that will bind to the FAS receptor on the DA cells, inducing apoptosis.

149
Q

Describe what happens to KO CD4+ T cells in mouse model exposed to MPTP.

A

MPTP is a compound that exerts the death of DA neurons. KO CD4+ cells showed less DA cell death when exposed to MPTP compared to wildtype mice exposed to MPTP.

150
Q

Immune priming effect (in terms of PD)

A

Something that occurs that predisposes us to another “hit” in PD. For example - we may have genetic vulnerability/early pathogen exposure and then we are more primed to be vulnerable to envio toxins - which can subsequently lead to PD

151
Q

Paraquat

A

Herbicide used to spray crops to prevent weeds.

152
Q

What did they find in the paraquat animal model of PD

A

Expose animal to paraquat and find that it induces behavioural abnormalities associated with PD: motor coordination deficits, decreased home cage activity, impaired fine motor skills, increased anxiety, increased behavioural despair, increased cognitive deficits.

153
Q

1 genetic contributor to PD

A

Mutations are typically genetically inherited on the LRRK2 gene

154
Q

What does LRRK2 do?

A

Strongly upregulated in our leukocytes and microglia after the have been exposed to immune activating agents. Seem to be involved in chemotaxis.

155
Q

How do G2019S mutation mice react to LPS

A

Increased chemotaxis

156
Q

How do LRRK2 KO mice react to LPS

A

No microglia activation/no increase in microglia staining. This is exactly how a mouse would react to a saline injection as well.

157
Q

TNF alpha receptors

A

TNFR1 (p55) or TNFR2(p75). TNFR1 is found in most cells and TNFR2 are found in the cells of the innate immune system.

158
Q

TNFR1 levels are ________ in brains of PD patients

A

increased

159
Q

How does TNFalpha induce death of DA neurons?

A

activation of the TNFR1 receptor induces signalling cascades, first causing activation of TRADD. Following TRADD, there are 2 pathways that lead to apoptosis: death signalling pathway, and the MAPK pathways. It can also activate a 3rd pathway to enhance neuroinflammation: NfKB pathway.

160
Q

Antibiotic used to block TNFalpha production

A

Minocycline

161
Q

IFNgamma

A

Microglia signalling factor that leads to inflammation and apoptosis when bound to its receptor expressed on neurons and microglia. Effects on microglia/neurons occur via JAK/STAT pathway

162
Q

Key steps to JAK/STAT pathway

A

1) IFNgamma binds to receptor
2) JAK then phosphorylates receptor
3) Two STAT proteins then bind to phosphates
4) JAK will then phosphorylate stats and then form a dimer
5) Dimer enters into nucleus and acts as transcription factor binding to target genes (e.g FAS, IFNgamma)

163
Q

How might cannabis protect against PD?

A

Different components in cannabis can activate the CB2 receptor found on the microglia. Binding of the CB2 receptor can reduce microglia activation thus reducing microglia’s contribution to inflammation and thus contribution to DA cell death.

164
Q

Gut brain axis

A

bidirectional communication network that links the CNS with the gastrointestinal tract and its resident microbiota

165
Q

How does the gut communicate with the brain?

A

Through neural pathways such as the vagal nerve, endocrine signalling, immune responses (cytokines) and microbial metabolites (SCFAs)

166
Q

Gut

A

The entire tract from mouth to anus

167
Q

Organization of the intestines

A

Small intestine comprised of the duodenum, jejunum and the ileum. Then the large intestine (colon).

168
Q

4 specialized cells of the intestines

A

Enterocytes, enteroendocrine, goblet and paneth cells.

169
Q

Enterocytes

A

Epithelial cell responsible for nutrient uptake, tightly joined together to make up intestinal barrier

170
Q

Enteroendocrine cells

A

Cells that produce hormones (hunger/satiety hormones)

171
Q

Goblet cells

A

Creates mucus that lines the gastrointestinal tract which prevents microbes from interacting with our enterocytes/human cells because if they do it can result in gut inflammation (they can activate TLR4 on enterocytes)

172
Q

Paneth cells

A

Specialized immune cell that releases antimicrobial peptides such as defensins

173
Q

The _____________ connects our gut to the rest of the body

A

lamina propria

174
Q

Where do most of our immune cells reside?

A

70% of our immune cells exist in our lamina propria waiting for a pathogen to breach intestinal barrier. Consists primarily of innate immune cells, but consists of some adaptive immune cells.

175
Q

Peyers patches

A

Lymphoid structures in the gut that contain adaptive immune cells, waiting to be activated by innate immune system (where antigen presentation takes place)

176
Q

Gut microbiome

A

collection of genes from microbiota in the gut (balance between of good and bad microbes)

177
Q

How does our immune system know to not attack the good microbes in our gut?

A

Early in dev, our microbiota trains our immune system to not attack it therefore immune cells learn what microbiota are good vs bad.

178
Q

Functions of gut microbiota

A

1) protection against pathogens
2) essential nutrients
3) digestion and NRG
4) train immune system
5) critical defense mec. of the brain

179
Q

Delivery important in training immune response to fetus

A

Vaginal birth

180
Q

Individuals more likely to get asthma and immune deficiency are born ___________

A

via c-section

181
Q

2 tight junction proteins

A

Occludin and claudin-5

182
Q

3 types of SCFA metabolites

A

acetate, propionate, and butyrate.

183
Q

Multifactorial etiology of gut microbiome

A

sex differences, genetics, Diet, delivery method, medication, social interaction, environment

184
Q

Germ Free (GF) mice when compared to control (Pathogen Free; PF) mice show what in regard to BBB?

A

GF mice has increased permeability in BBB and decreased expression of TJ proteins (increased Evans Blue in brain)

185
Q

What in the diet cant normally be digested?

A

Fibre (plant polysaccharides)

186
Q

What helps digest fibre?

A

different bacteria microbiota

187
Q

Short Chain Fatty Acids (SCFA)

A

resulting end product from fibre digestion, which is important in the integrity of BBB

188
Q

What did mice that had colonized bacteria and produce SCFA (CONV mice) show when compared to GF mice?

A

Restored BBB integrity and increased TJP (claudins/occludin); (reduction in Evans blue in brain)

189
Q

what does Clostridium tyrobutyricum produce?

A

butyrate

190
Q

What does Bacteroides thetaiotaomicron produce?

A

acetate and propionate

191
Q

What does R4A (NMDA receptor for Ab) do?

A

induce cell death

192
Q

Microbiota play what role in relation to microglia

A
  1. Promoting microglia maturation
  2. Training microglia to appropriately respond to pathogens
193
Q

Microglia from adult GF mice show what when compared to PF mice?

A

increase in immature markers; decreased inflammatory response genes

194
Q

Dysbiosis

A

ecological balance of our gut microbiota disrupted in a way that shifts this balance so there are more bad bacteria compared to good bacteria

195
Q

Has been linked to reduction in bacterial diversity

A

old age and a variety of pathologies

196
Q

What do obese individuals have greater proportions of?

A

more firmicutes than Bacteroidetes

197
Q

SCFA act to __________ food intake directly & indirectly via activation of ___________ neurons

A

decrease, pomc

198
Q

Increase Lipoprotein lipase results in

A

increased energy storage by increasing uptake of fatty acids and triglycerides.

199
Q

Fasting-induced adipocyte factor (FiaF)

A

released from enteroendocrine cells which inhibit LPL therefore LPL cannot induce storage of fatty acids and triglyceride.

200
Q

FiaF in obese individuals

A

FiaF levels are reduced therefore LPL activity is increased and therefore an increase in energy storage in fat cells leading to an increase in fat tissues

201
Q

FiaF in lean individuals

A

FiaF levels are increased which leads to a decrease in LPL activity.

202
Q

Emulsifier

A

chemical compound added to processed food to prevent separation between liquids. exposure to this might result in decreased microbiota diversity which enhances inflammation which can in turn induce anxiety like behaviours.

203
Q

What can emulsifiers do regarding intestinal permeability?

A

increase permeability of gut barrier -> increased peripheral inflammation measured by antibodies specific to bacterial components of LPS & Flagellin (ie. activated innate & adaptive immune system)

204
Q

What neuropsychiatric disorder has been linked with dysbiosis of microbiota? also inflammation

A

anxiety

205
Q

structures involved in the neurobiology of anxiety

A

amygdala, hippocampus, hypothalamus (PVN) & PFC

206
Q

Clinical evidence of patients with GAD have shown___________

A

increased serum pro-inflammatory cytokines compared to anti-inflammatory cytokine ratios

207
Q

Emulsifiers overall…….

A
  1. alter gut mcirobitoa
  2. increase gut permeability
  3. increase systemic inflammation (ie. peripheral)
  4. increase anxiety-like behaviours
208
Q

Amygdala activation occurs via release of _______________

A

glutamate

209
Q

2 parts of amygdala

A

basolateral amygdala (BLA) & central amygdala (CeA)

210
Q

BLA receives glutamate that then activates _________________

A

Central amygdala (CeA)

211
Q

What makes BLA more responsive to glutamatergic input?

A

Pro-inflammatory cytokines

212
Q

Mice exposed to emulsifiers show what in BlA?

A

Increased genes related to amygdala hyperactivity

213
Q

Immediately following a break in the skin, phagocytes engulf bacteria within the wound. This is an example of an _________ immune response which is __________ against a pathogen

A

innate, nonspecific

214
Q

____________ are responsible for the production of antibody against pathogens.

A

B cells

215
Q

Virus, bacteria and fungi can be considered:

A

A pathogen

216
Q

Passive immunity in a developing infant can happen as a result of:

A

Exposure to breast milk

217
Q

Humoral immunity is a type of adaptive immunity that results in the circulation of which of the following throughout the blood?

A

B cells/antibodies

217
Q

Defensins can be considered:

A

an antimicrobial peptide which can kill or inhibit the growth of pathogens

218
Q

Cells of lymphoid origin include:

A

T cells and b cells

219
Q

T or F: The adaptive branch of the immune system is a slower response that the innate branch of the immune system

A

True

220
Q

At the preclinical level, in an Alzheimer’s disease transgenic (Tg) mouse model, researchers have conjugated an antibody to the portion of the transferrin protein that binds to the transferrin receptor (TfR) creating a protein complex. In the brain of these mice, as discussed in class, what is the primary outcome of injecting the protein complex into Tg mice engineered to express Aβ plaques?

A

Tagging of Aβ plaques for destruction by the brains immune cells

221
Q

In adsorptive mediated transcytosis what is the primary process that occurs when a positively charged substance in the bloodstream associates with a negatively charged membrane surface?

A

Membrane invagination and vesicle formation

222
Q

A professional antigen presenting cells like dendritic cells express which MHC protein?:

A

MHC2

223
Q

Which type of T cell is primarily responsible for assisting other cells of the immune system, including B cells and cytotoxic T cells?

A

CD4+ T helper cells

224
Q

What is the key feature of active immunity?

A

It involves the production of antibodies by the individual’s own immune system (e.g., via vaccination)

225
Q

What is the primary characteristic of passive immunity?

A

It involves the transfer of pre-formed antibodies or immune cells from another individual or source.

226
Q

What is the primary role of T cell receptors (TCRs) on T cells?

A

To recognize and bind to a specific antigen-presenting complex

227
Q

Which of the following is the primary function of cytotoxic T cells in the immune system?

A

Killing infected or cancerous cells

228
Q

What typically happens to the concentration of antibodies in the blood following a secondary exposure to the same antigen?

A

The concentration of antibodies increases rapidly and significantly.

229
Q

Otis’s neurologist is considering the use of minocycline as a potential therapeutic approach to modulate microglial activation and promote a protective phenotype in her ischemic stroke. What is minocycline typically used for?

A

Antibiotic treatment

230
Q

During chronic neuroinflammation, microglia primarily exhibit which phenotypic state?

A

Proinflammatory

231
Q

What growth factor released by microglia helps fortify the Blood-Brain Barrier (BBB) by promoting the formation and maintenance of tight junctions?

A

Transforming Growth Factor-β (TGF-β)

232
Q

How does microglia’s release of VEGF contribute to their protective role in response to stroke?

A

By promoting angiogenesis and ensuring adequate blood flow

233
Q

Which action by activated microglia contributes to their protective role in response to stroke?

A

Swiftly clearing debris and dead cells

234
Q

In a study involving the OCD-like HoxB microglia deficient mouse, researchers replaced the deficient microglia with peripheral bone marrow-derived macrophages (BMDMs). What was the outcome of this intervention?

A

The OCD-like behavior improved and was reduced.

235
Q

What role do peripheral bone marrow-derived macrophages (BMDMs) and perivascular macrophages (PVMs) play when recruited by microglia during distress in the CNS?

A

BMDMs and PVMs replace lost microglia to supplement the population

236
Q

How does Listeria monocytogenes primarily impair microglia during infection?

A

Listeria interferes with phagolysosome formation, reducing microglial effectiveness.

237
Q

Case Study Scenario: In a research study investigating the role of microglia in neuroinflammation, scientists exposed microglial cells to various pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). They aimed to determine how microglia recognize and respond to different types of cellular damage.

Question: During their experiments, the researchers observed that microglial cells rapidly detected and responded to the presence of certain molecules released during cellular damage. Which type of receptors on microglia are primarily responsible for recognizing these molecules?

A

Damage recognition receptors (DRRs)

238
Q

Which of the following best describes the role of pyrogens in relation to fever?

A

Pyrogens are substances that initiate fever, either endogenously or exogenously.

239
Q

When the hypothalamic set point is adjusted, resulting in fever, which of the following molecules moves to the PNOH and influences the firing tone of warm-sensitive neurons?

A

(PG)E2

240
Q

Dr. Smith is studying the physiological response of the body during fever. He noticed that certain neurons in the PNOH are not firing as frequently as they typically would. Which of the following is the most likely reason for the reduced firing of these neurons during a fever?

A

Interaction of IL-1β with EP3R receptors on warm-sensitive neurons.

241
Q

Sarah is studying the vagus nerve’s role in fever. After extensive research, she concludes that there’s a specific pathway that allows the vagus nerve to influence fever. What is this pathway termed as?

A

Neural pathway

242
Q

aria is working on a research project to explore the feedback mechanisms in immune cells. She observes that when there’s a rise in temperature, the immune cells show a notable change in one of their functions. What is this specific change?

A

Enhanced phagocytosis of pathogens

243
Q

Which enzyme is responsible for the production of prostaglandins, specifically (PG)E2, and is targeted by drugs like ibuprofen to reduce fever?

A

Cyclooxygenase-2 (COX-2)

243
Q

Dr. Evans is conducting a ground-breaking experiment to understand the intricacies of feeding behavior. After days of research, she notices a specific set of neurons that become highly active when subjects are deprived of food or exposed to a hormone known as ghrelin. However, when she introduces LPS to simulate immune activation, the activity of these neurons decreases, suggesting the involvement of certain cytokines and the vagus nerve. Which neurons is Dr. Evans most likely studying

A

AgRP neurons

244
Q

A student asks Professor Chris about the mechanisms by which immune factors activate the stress response. Chris explains that there are several pathways, emphasizing one route involving the production of (PG)E2 from BCECs. How does this particular route impact CRH neurons?A student asks Professor Chris about the mechanisms by which immune factors activate the stress response. Chris explains that there are several pathways, emphasizing one route involving the production of (PG)E2 from BCECs. How does this particular route impact CRH neurons?

A

It causes a reduction in GABA neuron firing, leading to an increase in CRH.

245
Q

Dr. Martinez is treating a 68-year-old patient diagnosed with Parkinson’s disease. The patient has been on L-DOPA therapy and reports diminished effectiveness of the medication. Upon further testing, Dr. Martinez discovers an infection in the patient’s stomach. The bacterium responsible for this infection is known to colonize the stomach lining, often causing chronic gastritis, and can potentially affect the absorption of L-DOPA. Which bacterium is most likely responsible for the patient’s infection?

A

Helicobacter pylori

246
Q

Which theory suggests that the degeneration in DA cells is driven by harmful factors originating from neighboring non-neuronal cells, such as microglia?

A

Non-cell-autonomous (NCA) theory

NEUR4305 Immune-Brain Interactions (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions