Host responses in the infected brain

Question 1

Describe the phenotypic changes following T-cell activation.

Answer 1

• increased expression of adhesion molecules on endothelium at site of infection –> stable binding of activated T-cells
• effector T-cells enter peripheral tissues

Question 2

What are some of the distant effects of respiratory tract infection on the hypothalamic oligodendrocytes?

Answer 2

• up-regulation of diverse transport processes during early and accute infection
  –> development of a specific subcluster at acute infection
  –> metabolic and NT support

Question 3

What are some of the distant effects of respiratory tract infection on the hypothalamic neurons?

Answer 3

• long term inhibition of metabolic processes, protein translation and apoptotic processes
  –> protective processes to avoid viral entry and replication

Question 4

What are some of the distant effects of respiratory tract infection on the hypothalamic astrocytes?

Answer 4

• potentially mildly affected by glucocorticoids
• activation of oxidoreductase systems
  –> development of a specific subcluster at acute infection
  –> NT regulation via glutamate release/uptake
  –> regulation of microglia activation states via OR system

Question 5

What are some of the distant effects of respiratory tract infection on the hypothalamic microglia?

Answer 5

• increased transcription of proinflammatory genes and cell-to-cell communication genes
• decreased transcription of complement system, microglia state genes and protein synthesis
  –> surviallance and communication with surrounding tissues and cell populations

Question 6

Mention an important chemokine and its receptor for immunerepsone in viral infections. What cells are the predominant producers of this?

Answer 6

Chemokine: CXCL10
R: CXCR3
Predominant producer: CXCL10

Question 7

Which molecule induce CXCL10 production?

Answer 7

IFN-alpha/beta

Question 8

What are SOCS1/3 and what are they associated with?

Answer 8

Suppressor of cytokine signal 1/3
An upregulation of these are associated with virus-induced inflammation

Question 9

What are the two pathways of SOCS upregulation?

Answer 9

• one which involves T-cells and IFN-gamma
• one which are T-cells and IFN-gamma independent

Question 10

What are the rules for T-cell accumulation in the CNS?

Answer 10

• initial recruitment is non-specific and inflammation driven
• local antigen encounter augments accumulation of antigen-specific T-cells
• following resolution tissue-resident memory T-cells persist in the tissue
• triggering of these forms a first line of defense to reinfection