Introduction to Neuroinflammatory Disorders

by Roy Strowd, MD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides Multiple Sclerosis Inflammatory Disorders of the CNS​.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    00:01 In this talk, we're going to review neuroinflammatory disorders.

    00:05 And we'll begin with an introduction to neuroinflammatory disorders.

    00:10 To begin, let's talk about the pathophysiology.

    00:13 What's going on when there's an immune attack in the brain or central nervous system? Well, we start with the brain.

    00:20 And in the brain lives, the neurons.

    00:22 The neurons are protected from the immune system by the blood–brain barrier.

    00:26 What we see here is a schematic showing the neurons in the brain, a blood vessel and the blood-brain barrier.

    00:33 The immune system is composed as we know of T cells, B cells, and natural killer cells and those are maintained within the blood vessels and separated from the central nervous system by the blood-brain barrier.

    00:45 The blood-brain barrier is made up of astrocytes.

    00:48 Astrocytes form a thick and protective wall between the blood vessels in the brain and prevent immune cells from infiltrating into the central nervous system.

    00:59 In the central nervous system, the primary immune cell in the immune compartment are the microglia.

    01:05 And they're the resident immune mediators that function as immune regulators.

    01:11 And also pericytes.

    01:13 Pericytes are immune cells located around the periphery of the blood vessels, primarily around meningeal blood vessels and serve an immune function.

    01:22 In autoimmune conditions, what we see is that there's infiltration of that systemic immune response, the T cells, the B cells, the natural killer cells, or some combination of the three into the brain through the blood-brain barrier, resulting in damage to the nerve, to the myelin, to the axon, or some aspect of the central nervous system.

    01:44 When I think about autoimmune conditions in the central nervous system, there's five key mechanisms.

    01:49 And I want you to understand and at least appreciate some of the things that happen that cause CNS autoimmunity.

    01:56 The first thing we'll talk about is molecular mimicry.

    01:59 Where an antigen on a virus mimics an antigen in the brain.

    02:03 And as a result of the immune response to the virus, we see an attack in the brain.

    02:08 The second cause or underlying pathophysiology of CNS autoimmunity are sequestered proteins.

    02:15 And we'll talk about how proteins are normally sequestered from the immune system as a result of an infection, they can be released.

    02:21 and this results in an immune attack in the central nervous system.

    02:26 I want you to know about the bystander activation or altered regulation, where as a result of some infectious process.

    02:32 There's activation of cytokines which revs up the immune system and can result in a CNS attack.

    02:39 We'll also talk about an abnormal host development and normally, the thymus is involved in creating B cells and T cells that attack foreign antigens and are not auto reactive.

    02:51 And in some circumstances, the body can generate autoreactive immunity that can result in CNS immune attacks.

    02:59 And then the last thing is we'll talk about paraneoplastic causes of CNS autoimmunity.

    03:03 And I want you to understand each of these five, underlying pathophysiologic processes that contribute to neuroinflammatory disorders.

    03:13 First, let's talk about molecular mimicry.

    03:15 So here we're looking at a schematic of a neuron, the blood-brain barrier, and the blood vessel as well as a new virus that is expressing an antigen.

    03:25 In the setting of molecular mimicry, the immune system responds to the virus, which is normal.

    03:29 That's what you want the body to do to attack the virus and clear it.

    03:33 But in this case, the virus is expressing an antigen that's also expressed in the brain.

    03:39 And so in some circumstances, there is a hyperactive immune response to that antigen to kill the virus, but this also results in attacking of that same antigen in the brain and that contributes to the development of a neuroinflammatory disorder or CNS autoimmunity.

    03:57 This is the first type of CNS autoimmunity.

    04:01 The first cause, underlying cause, of a neuroinflammatory disorder.

    04:06 What about sequestered proteins? How does this work? Well, again, we have our same neurons which are expressing an antigen protected from the systemic circulation by the blood-brain barrier.

    04:16 Here some infectious process results in release of an intracellular antigen that was previously not seen by the immune system.

    04:25 So here you can see in this schematic infection with a virus can result in release of those intracellular proteins.

    04:32 Normally, the body's immune system should attack that antigen recognizing it as unfamiliar.

    04:38 But in this case, the antigen is also contained within the neurons.

    04:42 As a result of a hyperactive immune response, we see infiltration of that systemic inflammatory response into the brain and this can contribute to the development of CNS autoimmunity or a neuroinflammatory disorder.

    04:57 What about bystander activation? How does that work? Well, again, we have the neurons in the brain separated from the systemic circulation by the blood-brain barrier.

    05:05 Here as a result of some process that irritates activates cells, we have release of cytokines due to an infectious process.

    05:13 Those cytokines rev up the immune system, the immune system is able to infiltrate into the brain and that sets off this CNS autoimmune attack.

    05:22 So this is another underlying cause for the development of a neuroinflammatory disorder.

    05:28 What about abnormal host development? How does that work? Normally, the thymus is the organ in the body that results in development of B and T cells, normal immune cells that respond to foreign antigens and destroy potentially autoreactive antibodies, and immune cells.

    05:49 In some circumstances of abnormal development, the body fails to degenerate, discard, and destroy those autoreactive immune effector cells.

    06:00 And as a result, they're able to identify antigens such as those on neurons infiltrate into the brain and result in the development of CNS autoimmune conditions.

    06:11 And then the last underlying process that can contribute to CNS autoimmunity is a paraneoplastic process.

    06:18 Here, patients may develop a tumor.

    06:19 In fact, we're all really developing tumors at all times throughout our lifetime.

    06:24 And the normal process for is for the body's immune system to recognize that tumor, to see it as abnormal and to kill and destroy it.

    06:32 In some circumstances, that antigen that is contained on the tumor is also present on the surface or inside of nerves.

    06:40 The body's immune system is revved up as a result of that cancer.

    06:43 And when the immune system can infiltrate into the brain, we have the development of a paraneoplastic neurologic disorder.

    06:51 In many cases, the neurologic disorder can precede the development or recognition of the cancer.

    06:56 The body's immune system is doing a good job at keeping the cancer at bay, but we see this neurologic syndrome that develops and really should herald additional workup for an underlying cancer.

    07:08 And so these five causes or underlying pathophysiologic mechanisms are the mechanisms by which CNS autoimmunity can develop.

    About the Lecture

    The lecture Introduction to Neuroinflammatory Disorders by Roy Strowd, MD is from the course Multiple Sclerosis (MS) and Inflammatory Disorders of the CNS​.

    Included Quiz Questions

    1. Paraneoplastic
    2. Molecular mimicry
    3. Protein sequestration
    4. Bystander activation
    5. Abnormal host development
    1. Release of sequestered proteins
    2. Molecular mimicry
    3. Paraneoplastic
    4. Bystander activation
    5. Abnormal host development
    1. Abnormal host development
    2. Molecular mimicry
    3. Protein sequestration
    4. Paraneoplastic
    5. Bystander activation

    Author of lecture Introduction to Neuroinflammatory Disorders

     Roy Strowd, MD

    Roy Strowd, MD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star