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immunology > Interaction of Immune Cells with Cells of the CNS > Flashcards

Interaction of Immune Cells with Cells of the CNS Flashcards

1
Q

What maintains the brain as an immune privilege site?

A 
low expression of MHC class 1 and 11
 presence of partial BBB
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2
Q

What is the observation that the brain is an immune privileged site?

A

Tissue grafts placed in certain anatomical sites can survive for extended periods of time. Low response to antigens in brain compared to periphery

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3
Q

Name 2 main CNS barriers

A

BBB

Blood CSF barrier

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4
Q

How do leukocytes enter the brain?

  1. BBB
  2. Blood Cerebro Spinal Fluid Barrier
A
  1. From the BBB, Leukocytes pass the parenchymal venule migrate into the perivascular space which contains CSF to glia limitans and finally brain parenchyma
  2. BCSF barrier : Leukocytes in the choroid plexus stroma pass EC barrier into the ventricle with CSF
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5
Q

What are sites of immune cell entry into the CNS?

A
  1. Via fenestrated blood vessels of the choroid plexus across the epyndymal layer into CSF
  2. Via postcapillary venules
  3. Via Pericascular/ Virchow-Robin Space
    ie BBB into CNS parenchyma (where meningeal blood vessels brainch into the subarachnoid space)
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6
Q

What are 3 major CNS barriers and what cells are involved in each of these barriers?

A

BBB- wraps around capillaries, blood
cells: epithelial cells, astrocytes,

Blood meningeal barrier/arachnoid epithelium- pia, arachnoid epithelium, subarachnoid CSF blood vessels

Blood CSF barrier- Choroid plexus epithelium, epithelial cells of the choroid plexus, endothelial cells, ventricles, ependyma

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7
Q

Describe the multistep recruitment of leukocytes into the CNS?

A

Blood stream: activation, arrest, crawling, diapedesis
enter perivascular space
Enter CNS parenchyma via glia limitansand releases chemokynes into the brain parenchyma

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8
Q

Which antibody is involved in the migration of cells from blood to brain and what happens when you block it?

A

VLA-4. Blocking arrests cells in migration

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9
Q

Which drug is used to treat immune cells migrationg frrom into the brain from the blood?

A

Natalizumab/ tysabri used in Multiple sclerosis.

side effect: Immune surveillance blocked hence some patients died due to Progressive multifocal Leukoencephalopathy.

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10
Q

What is an example of a virus that causes progressive multifocal leukoencephalopathy?

A

John Cunningham (JC) Virus : infects primary oligos in the CNS causing virus induced killing of oligos and demyelination

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11
Q

How do leukocytes and antigens leave the CNS?

A
  1. At cribriform plate of the olfactory bulb-cells from CSF into the lymphatic system directly
  2. Arachnoid granulation: parenchyma to CSF to sinus via arachnoid granulation
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12
Q

Lymphatic vessels can drain cells from the CSF into the lymphatic system or blood. True or false

A

True

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13
Q

What happens when sinuses are blocked?

A

Supression of CSF accumulation/ oedema

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14
Q

How does immune surveillance look like in a healthy brain versus an infected brain?

A

Immune cells survail, ISF washing in parenchyma, CSF circulating, lymphatics, no infection

Infected brain: antigens in CSF, T cells activated, tissue destruction, neurons collateral damage eg in encephalitis

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15
Q

what are the main divisions of glial cells?

A

macroglia: astrocytes and oligos
microglia: perivascular, parenchymal

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16
Q

Describe interaction of T cells with microglia

A
  1. Th cells from the blood pass epithelial cells
  2. In the Perivascular space, macrophages/PVS microglia/ DCs reactivate T cells by oresenting antigens via MHC class 11 molecules
  3. Penetration into the parenchyma,interaction with parenchymal microglia, activation via MHC class 11
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17
Q

What does an imbalance of pro/anti inflammatory cytokines versus neurotrophic/neurotoxic describe

A

health/pathology

18
Q

How do T cells interact with glial cells ?

A
  1. Astrocytes under some conditions express MHC class 11
  2. Interaction by soluble factors. All glial cells express receptors for different cytokines eg IL-1, IL-6, TNF alpha
  3. Cytotoxic T cells via MHC class 1, activated, may kill oligos and astrocytes
  4. TRAIL- expressed in inflammatory Th cells. Th1 has the TRAIL receptor. When ligand binds to receptor expressing cells, killig of oligos.
19
Q

How do T cells interact with neurons?

A
  1. Soluble factors ie pro inflammatory cytokines eg IFN gamma which induce MHC class I genes in neurons
  2. MHC independent- blockade of electric activity
20
Q

Neurons express MHC class II. True/false

A

False

21
Q

Can CD4 +ve T cells cause neuronal damage?

A

Cause influx of calcium readout due to induction of apoptosis after interaction with neurons.

22
Q

What mediates T cell neuronal degeneration?

A

TRAIL-TRAIL-IR

  1. Antigen depenent- via MHC Class I-cd8+ve can kill
  2. Bystanader/no antigen presentation-eg in TRAIL blocker
23
Q

Name 3 different sites of leukocyte entry into the CNS

A

blood spinal cord barrier
Blood CSF barrier
Blood brain barrier

24
Q

How do leukocytes circulate from CNS to lymphatic circulation?

A
  1. Cribriform plate in the olfactory bulb

2. Dura lymphatics

25
Q

Name 3 CNS disorders

A

Multiple Sclerosis
Devi Syndrome- Neuromyelitis Optica
Rheumatological diseases eg lupus

26
Q

Name 2 examples of antibody mediated immune diseases

A

myastheria gravis- women, AB against nicotinic ACh receptors

Guillain Barre syndrome- acute demyelinating polyradiculoneuropathy

27
Q

What is the hypothesis that governs Giullain Barre syndrome?

A

Molecular mimicry. Bacterial (campylobacter) antigens induces IgG, IgM, IgA auto-antibodies against ganglioside epitopes.

28
Q

What is an example of a chronic inflammatory demyelinating disease?

A

Multiple Sclerosis

29
Q

What are the 2 courses of MS?

A

relapsing remitting- acute attacks then partial/complete recovery
primary progressive-disease progression from onset

30
Q

What evidence shows that MS is a CD4 Tcell mediated autoimmune disease?

A

CD4 cells found in lesion
Genetic association with MHC II
In animals, disease can be transferred by T cells not antibodies

31
Q

What are 2 examples of Experimental Autoimmune Encephalomyelitis mice models?d

A

Passive EAE
Transfer EAE (inject T cells into mouse)
(PLP-myelin peptide)

32
Q

Where is CSF found?

A

In the subarachnoid space

33
Q

What is the trojan horse hypothesis?

A

Migration of infected monocytes which differentiate into perivascular microphages. eg in HIV encephalitis

34
Q

What are opportunistic infections of the CNS asssociated with HIV?

A

toxoplasmosis
CMV retinitis
JC-V
TB

35
Q

How does Rabies Virus evade the immune system?

A

RV enters the CNS without triggering apoptosis of infected neurons and preserving the integrity of neurites
Kills protective migrating T cells

36
Q

High fever, headache, stiff neck are symptoms of

A

meningitis

37
Q

Least common route to the CNS

A

intraneural pathways eg Herpex Virus-trigeminal nerve

Rabies virus-peripheral sensory nerves

38
Q

Name 3 mechanisms of the complement system

A

Classical pathway
lectin pathway
alternative pathway

39
Q

Which protein starts the complement cycle?

A

C3b. It’s an opsonizing agent which puts itself on foreign surfaces, recognized by macrophages, recruits other proteins, creates a cascade

40
Q

Why does neisseria bacteria express factor H binding protein?

A

Binds to factor H which prevents cell lysis by binding to glycosaminoglycans on the surface of host cells, preventing immune response.

41
Q

C5 to C9 form the lytic complex. What is it called?

A

Membrane attack complex, responsible for cell lysis

42
Q

What does C3 a do?

A

Acts as a signal that allows immune cells to be activated in response to an antigen/foreign body to which C3b is bound to

immunology (2 decks)

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