Lecture 15; Brain Immunity 1 Flashcards
What two systems are linked?
The nervous and immune systems
Neuroimmunology
Give an example of how the immune system and the nervous systems are linked;
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
Whats the function of the blood brain barrier?
Prevents drugs, immune cells from entering the brain
What is the BBB composed of?
- Endothelial cells (tight junctions)
- Basement membrane
- Pericytes + Astrocytes (gap junctions)
How is the brain an immunologically privileged organ?
- Existence of BBB
- Lack of antigen presentation in CNS
- Absence of lymphatic drainage
What cells in the brain act as immune cells?
Microglia + Astroyctes are not strictly immune cells but adapt to this role
Despite being considered immunologically privileged, is this necessarily true?
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
How can a immune response to an antigen be considered?
As a circuit divided into afferent and efferent limbs
Describe the role of the afferent and efferent limbs;
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
What typically can activated the CNS immune response?
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)
Describe the immune system and brain circuit;
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
Which cells are involved in the brain immune response?
Same immune cells as the rest of the body
What is great about NK cells?
They dont need to specifically recognise targets
What is neuroimmunology?
- 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.
Describe the neuroendocrine immune interactions;
Bi directional between the following factors
- CNS
- Stress
- Endocrine system
- Immune system
Describe the features of neuroendocrine immune interactions;
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
What two pathways can influence the immune system from the brain?
ANS
HPA neuroendocrine
Describe the neuroendocrine pathway of communication between the brain and the immune system;
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
What is the role of the immune system in neuroactivation;
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.
What neuropeptides affects the immune response?
ACTH - Inhibs B cells and AB prod
Endorpins - Inc Tc and NK effects
TSH - Inc AB
GH -inc O3 by macros
Describe some of the cytokines that affects the CNS;
IL1 = Enhanced CRH release, ACTH, decreased GnRH
IL6; Enhanced CRH
What cytokines are implicated in immune + inflam brain responses;
IL1
IL6
TNFa
IFN g
What is very important in brain/immune response?
Context
Write some notes on IL1 role;
Produced mainly by macros
Activates HPA axis
Drives ACTH and endorphin release
IL6 role;
IL-6 is the principal cytokine to terminal differentiation of activated B cells into immunoglobulin-secreting plasma cells.
TNF a role;
TNF-α causes inflammation, apoptotic cell death, cell proliferation, differentiation, tumorigenesis, and viral replication.
IFNg role
IFN-γ is a cytokine with antiviral activity, produced predominantly by activated T cells.
TGF b role;
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.
CSFs role;
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.
What cells in the CNS are primary sources of cytokines?
Activated astrocytes and microglia secrete cytokines and contribute to the propagation of intracerebral immune and inflammatory responses initiated by immune cells.
What may changes in cytokine genes lead to?
Changes in cytokine gene expression and function may contribute to various neurological disorders (MS, EAE).
What is the COMMS for the ANS pathway?
- Catecholamines
- Acetylcholine
- Neuropeptides (VIP, NPY, Substance P, CGRP, opioid peptides)
What does the ANS do?
Neurotransmitters and neuropeptides alter the immune cell function and trafficking in primary (thymus, bone marrow) and secondary lymphoid organs (spleen, lymph nodes).
What did the tyrosine hydroxylase in rats show?
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
What other models found neurotransmitter to interact with immune cells?
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
What is Psychoneuroimmunology?
Stress and immunity
What does stress do?
Alters the expression of catecholamines and glucocorticoids (stress hormones) that can act on all lymphoid tissues
What do corticosteroids do?
- Profound lympholytic effect on lymphoid organs
- Inhibit lymphocytic function
- Ability to suppress immune responses
- Suppress inflammation
Which areas of the brain become active during stress?
- 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)
How do we recognise areas activated by stress?
C-Fos positive brain cells in the locus coeruleus
