Lecture 15; Brain Immunity 1

Question 1

What two systems are linked?

Answer 1

The nervous and immune systems

Neuroimmunology

Question 2

Give an example of how the immune system and the nervous systems are linked;

Answer 2

Recognised pathogens lead to immune cell cytokine release which activates the PNS and CNS to start fever and other factors associated with disease such as fatigue and inability to concentrate

Acts as a sensory mechanism

Question 3

Whats the function of the blood brain barrier?

Answer 3

Prevents drugs, immune cells from entering the brain

Question 4

What is the BBB composed of?

Answer 4

• Endothelial cells (tight junctions)
• Basement membrane
• Pericytes + Astrocytes (gap junctions)

Question 5

How is the brain an immunologically privileged organ?

Answer 5

• Existence of BBB
• Lack of antigen presentation in CNS
• Absence of lymphatic drainage

Question 6

What cells in the brain act as immune cells?

Answer 6

Microglia + Astroyctes are not strictly immune cells but adapt to this role

Question 7

Despite being considered immunologically privileged, is this necessarily true?

Answer 7

Possibly not

• Cells of the immune system pass through the CNS
• Immunoglobulins diffuse in at low levels
• Microglia and astrocytes have antigen presentation role in the brain
• Lymphatic drainage does actually occur (Virchow robin spaces)

= Immunologically selective not privileged

Question 8

How can a immune response to an antigen be considered?

Answer 8

As a circuit divided into afferent and efferent limbs

Question 9

Describe the role of the afferent and efferent limbs;

Answer 9

Afferent limbs involves;

• Recognition of antigen
• Generation of effector cells

Efferent limbs involve;

• Passage of activated lymphocytes and antibodies into the tissue
• Elimination of antigen by antibodies and effector cells

Question 10

What typically can activated the CNS immune response?

Answer 10

Recognition of antigens in the cervical lymph nodes and spleen.

Peripheral response

This is where the immune reaction for the brain starts

Mostly humoral (immunoglobulin)

Question 11

Describe the immune system and brain circuit;

Answer 11

Recognition of antigens in spleen and cervical lymph nodes

Effectors cells (B and T) and antibodies can enter the brain and cause;

• Leakage (inc permeability)
• Intrathecal antibody synthesis
• Cellular immunity

Question 12

Which cells are involved in the brain immune response?

Answer 12

Same immune cells as the rest of the body

Question 13

What is great about NK cells?

Answer 13

They dont need to specifically recognise targets

Question 14

What is neuroimmunology?

Answer 14

• The interplay between components of the nervous system with cells and mediators of the immune system
• Neuroimmunology was originally concerned with diseases of the nervous system, and with a series of animal models of diseases.

Question 15

Describe the neuroendocrine immune interactions;

Answer 15

Bi directional between the following factors

• CNS
• Stress
• Endocrine system
• Immune system

Question 16

Describe the features of neuroendocrine immune interactions;

Answer 16

The interactions between the brain and immune system are complicated;

• Bidirectional b/c shared receptors, ligands
• Neurotransmitters, cytokines, hormones are the communicators
• Stress response included as adrenal gland releases corticosteroids which can induce response

Question 17

What two pathways can influence the immune system from the brain?

Answer 17

ANS

HPA neuroendocrine

Question 18

Describe the neuroendocrine pathway of communication between the brain and the immune system;

Answer 18

The immune and neuroendocrine systems share many ligands and receptors that result in constant and important bi-directional communication.

Specifically ;

brain to IS ; ACTH and endorphins

IS to brain; IL1 and IL6

During periods of immune response, there is communication to the brain and this allows for the brain to dampen down the immune response

Question 19

What is the role of the immune system in neuroactivation;

Answer 19

Acts as a sensory system for things the brain cannot detect

• The brain, - signals - prevent uncontrolled activation of the immune system.
• The immune recognition of viruses, bacteria, tumor cells, or antigens could lead to physiological changes specific for every immune response and autoimmune disease.

Question 20

What neuropeptides affects the immune response?

Answer 20

ACTH - Inhibs B cells and AB prod
Endorpins - Inc Tc and NK effects
TSH - Inc AB
GH -inc O3 by macros

Question 21

Describe some of the cytokines that affects the CNS;

Answer 21

IL1 = Enhanced CRH release, ACTH, decreased GnRH

IL6; Enhanced CRH

Question 22

What cytokines are implicated in immune + inflam brain responses;

Answer 22

IL1
IL6
TNFa
IFN g

Question 23

What is very important in brain/immune response?

Answer 23

Context

Question 24

Write some notes on IL1 role;

Answer 24

Produced mainly by macros

Activates HPA axis

Drives ACTH and endorphin release

Question 25

IL6 role;

Answer 25

IL-6 is the principal cytokine to terminal differentiation of activated B cells into immunoglobulin-secreting plasma cells.

Question 26

TNF a role;

Answer 26

TNF-α causes inflammation, apoptotic cell death, cell proliferation, differentiation, tumorigenesis, and viral replication.

Question 27

IFNg role

Answer 27

IFN-γ is a cytokine with antiviral activity, produced predominantly by activated T cells.

Question 28

TGF b role;

Answer 28

TGF-β inhibits the proliferation of many cell types, and production of numerous cytokines. This cytokine functions as a negative regulator of immune and inflammatory responses.

Question 29

CSFs role;

Answer 29

CSFs are cytokines with potent stimulatory effects on the growth and differentiation of bone marrow progenitor cells. Acting this way, they also generate inflammatory leukocytes.

Question 30

What cells in the CNS are primary sources of cytokines?

Answer 30

Activated astrocytes and microglia secrete cytokines and contribute to the propagation of intracerebral immune and inflammatory responses initiated by immune cells.

Question 31

What may changes in cytokine genes lead to?

Answer 31

Changes in cytokine gene expression and function may contribute to various neurological disorders (MS, EAE).

Question 32

What is the COMMS for the ANS pathway?

Answer 32

* Catecholamines * Acetylcholine * Neuropeptides (VIP, NPY, Substance P, CGRP, opioid peptides)

Question 33

What does the ANS do?

Answer 33

Neurotransmitters and neuropeptides alter the immune cell function and trafficking in primary (thymus, bone marrow) and secondary lymphoid organs (spleen, lymph nodes).

Question 34

What did the tyrosine hydroxylase in rats show?

Answer 34

Role of neurotransmitter release TH is rate limiting enzyme in NE production *theyre marked Nerve fibres are in white pulp of spleen These nerve terminals are in direct contact with immune cells

Question 35

What other models found neurotransmitter to interact with immune cells?

Answer 35

Substance P positive nerves in thymocytes CGRP+ positive bundle runs through the rat splenic white pulp Not just the thymus and spleen that are neurologically innervated in terms of lymphoid tissues

Question 36

What is Psychoneuroimmunology?

Answer 36

Stress and immunity

Question 37

What does stress do?

Answer 37

Alters the expression of catecholamines and glucocorticoids (stress hormones) that can act on all lymphoid tissues

Question 38

What do corticosteroids do?

Answer 38

* Profound lympholytic effect on lymphoid organs * Inhibit lymphocytic function * Ability to suppress immune responses * Suppress inflammation

Question 39

Which areas of the brain become active during stress?

Answer 39

* Several regions in the hypothalamus * Amygdala * Basal ganglia of the thalamus * Brain stem neurones (ventral lateral medulla, nucleus of the solitary tract, locus coeruleus, periaqueductal gray, raphe nuclei) These become activated and effect the reponse (immune)

Question 40

How do we recognise areas activated by stress?

Answer 40

C-Fos positive brain cells in the locus coeruleus