Infections Of The Nervous System

Front 1

Neuroinflammation is a major pathogenic component in most neurological diseases including: (6)

Back 1

-multiple sclerosis
-alzheimer disease
-stroke
-HIV dementia
-brain tumours
-several peripheral neuopathies

Front 2

Which of the two contributing immune mechanisms of neuroinflammation: adaptive and innate predominates?

Back 2

adaptive mechanisms

Front 3

What three things dictate the type and severity of neuroinflammation? (3)

Back 3

cell type involved, immunogen, and the host genetic background

Front 4

Neuroinflammation can be initiated outside the CNS, or initiated within the CNS with what aiding it?

Back 4

subsequent leukocyte infiltration or ensuing leukocyte infiltration

Front 5

What may be counter-productive in the long term?

Back 5

immuno-suppressants

Front 6

What is a favourable therapeutic strategy for inflammation?

Back 6

an anti-inflammatory drug with selective sparing of the beneficial aspects of inflammation

Front 7

What are bone marrow-derived brain cells? What happens to them when disease-activated?

Back 7

microglia, that proliferate when disease-activated

Front 8

What is different about microglia in different locations?

Back 8

morphology (eg. shape)

Front 9

Function of normal microglia

Back 9

immune sensors

Front 10

Functions of activated microglia (7)

Back 10

-phagocytosis
-chemotaxis
-antigen presentation
-cytotoxicity
-morphological changes
-proliferation
-respiratory burst

Front 11

What is the most abundant cell in the brain?

Back 11

astrocyte

Front 12

Which cells contribute to the endogenous (2) and exogenous (5) aspects of innate immunity?

Back 12

endogenous: microglia/macrophages, astrocytes
exogenous:
neutrophils, mast cells, dendritic cells, NK and gamma cells

Front 13

What are the processes involved in adaptive immunity?

Back 13

-cell-mediated immunity (CTL/CD8; DTH/CD4)
-antibody-dependent cell-mediated cytotoxicity
-molecular mimicry (B and T cells)

Front 14

What are four potential antigen presenting cells in the brain, and which proteins are they involved with?

Back 14

-astrocytes possible for MHC class I and II in vivo, and yes for both in vitro
-microglia, perivascular cells and other CNS macrophages possible for MHC class I, and yes for MHC class II in vivo

Front 15

What are seven mediators of neuroinflammation, and which two do not have anti-inflammatory types?

Back 15

-interferons, cytokines, chemokines, eicosinoids, complement fragment, proteases, and neuropeptides
-chemokines and complement fragments don't have anti-inflammatory types

Front 16

What are two unique aspects of CNS infections?

Back 16

-localization of the infection dictates the clinical presentation (CNS vs PNS)
-brain is an immune privileged organ with the blood brain barrier and innate (macrophages, neutrophils) vs adaptive (CTL and Abs) immunity

Front 17

General pathway to a neuroinvasion (5)

Back 17

-viral entry
-growth in extraneural tissues
-maintenance of viremia
-choroid plexus to cerebrospinal fluid
-small vessels to brain

Front 18

What are four primary replication sites, and five secondary sites?

Back 18

-primary: subcutaneous tissue/muscle, lymph nodes, respiratory or gastrointestinal tract
-secondary: muscle, vascular endothelium, bone marrow, liver, or spleen

Front 19

Maintenance of viremia (2)

Back 19

virus replication/amplification in leukocytes, and clearance by macrophages, neutrophils, and antibodies

Front 20

How does a virus cross the blood brain barrier?

Back 20

through the use of infected leukocytes

Front 21

Which virus can infect neural cells, microglia, macrophages, and endothelia?

Back 21

cytomegalovirus (CMV)

Front 22

Which virus infects only the neurone?

Back 22

vericella zoster virus (VZV)

Front 23

Human endogenous retrovirus (HERVs)

Back 23

present in germline for >30M years but usually replication defective and is mitogen stimulation-dependent gene expression

Front 24

HERVs implications in autoimmune diseases (4)

Back 24

multiple sclerosis (MS), systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC), and diabetes mellitus (IDDM)

Front 25

Emerging neurological infections (5)

Back 25

-variant CJD
-nipah virus encephalitis
-west nile virus encephalitis
-enterovirus 71 encephalitis
-usually xenotropic and usually RNA viruses

Front 26

What is the presumed source of HIV-I?

Back 26

chimpanzee

Front 27

How many people are invected with HIV today, how many new infections each year worldwide, and in canada?

Back 27

-42 million HIV positive today
-5 million new/year worldwide
-4000 new infections/year in canada

Front 28

HIV is associated with which four factors of dementia/neurocognitive disorders?

Back 28

memory loss, neuropsychiatric dysfunction, immune-deficiency, and motor abnormalities

Front 29

HIV-associated dementia (HAD)

Back 29

affects 10-20% of patients with HIV, usually after the development of aids and heralds a poorer survival prognosis

Front 30

What usually proceeds HAD?

Back 30

minor cognitive-motor disorder (MCMD)

Front 31

Risk factors associated with HAD (4)

Back 31

extremes of age, CCR5 32, APOE 4, polymorphisms in promoters of TNF-alpha and MCP-1

Front 32

Highly active antiretroviral therapy (HAART)

Back 32

used for cases of HIV, with some success where recovery is dependent on dementia severity and prior ART exposure (MSK scale)

Front 33

Neuropathological features of HIV

Back 33

-atrophy and white matter pallor
-mulrinucleated giant cells
-perivascular cuffing
-HIV antigen detection

Front 34

Expression of what gene is associated with severe dementia?

Back 34

TNFalpha

Front 35

Rank the blood-brain barrier perturbation in HIV infection for myelin, glia, and neurons.

Back 35

+ve subcortical glia>+ve cortical neurons>diffuse myelin pallor

Front 36

What are the cellular components in HIV neuropathogenesis passed form infected macrophage/microglia to apoptotic neuron? (5)

Back 36

cytokines, ROS, MMPs, gp120, and Vpr

Front 37

What are the cellular components in HIV neuropathogenesis passed from infected macrophage/microglia to activated astrocyte? (4)

Back 37

cytokines, ROS, gp120, and Nef

Front 38

What are the cellular components in HIV neuropathogenesis passed from a infected activated astrocyte to apoptotic neurone? (3)

Back 38

cytokines, chemokines, and ROS

Front 39

Neuroprotective drug treatments for HIV-related neurodisorders (6)

Back 39

-NMDA receptor antagonists (memantidine/amantidine)
-minocycline
-PAF/TNF inhibitors
-valproate
-growth hormone
-SSRIs

Front 40

Symptomatic drug treatment for HIV-related neurodisorders (2)

Back 40

quetiapine and olanzapine

Front 41

What are herpes simplex virus encephalitis (HSE) annual incidence, mortality when reduced, and likelihood of reoccurrence?

Back 41

-2-5/million annual
-mortality reduced to 20% with acyclovir
-reoccurance is low >3% in adults

Front 42

What are two new techniques being explored in relation to neurological infection?

Back 42

metagenomics and microarrays