neuroinflammation Flashcards
innate immunity
first line of defence
Skin & hair: physical barrier to microbes
Mucous membranes: mucus secreted to trap and kill
Bodily functions that expel microbes (mechanical)
Gastric secretions, tears, perspiration, lysozyme (chemical)
innate immunity
second line of defence
interferons (interfere with viral replication)
complement (inflammation)
iron binding proteins (reducing iron available for bacterial growth)
antimicrobial proteins (peptides with antimicrobial activity)
innate immunity
if second line of defence fails
NK cells (attack any unusual cell by perforin that causes catalysis)
Macrophages (phagocytosis, antigen presenting cells)
adaptive immunity
specificity & memory
against specific invaders
t cells, b cells & antibodies
microglia
resident immune cells of the brain (80% of brain immune cells)
what makes central capillaries so different?
Structural Differences:
- Central has NO fenestrations (gaps between)
- More extensive tight junctions
Functional Differences:
- Impermeable to most substances
- Sparse pinocytic vesciular transport
- Increase expression of transport and carrier proteins: receptor mediated endocytosis
- Limited paracellular and transcellular transport
3 complement pathways
lectin, alternate, classic
alternative pathway?
inflammation via destruction of microbes by leukocytes (via C3a)
classical pathway
phagocytosis via bounding of C3b to C3b receptor
lectin pathway
cell lysis via MAC
cytokines in degenerative disease (e.g. alzheimers)
resident CNS cells are predominant producers of pro-inflammatory cytokines
cytokines in neuroinflammatory disease (e.g. MS)
pro-inflammatory cytokines are the majoy factor delivered by tissue-invasing leukocytes
is neuroinflammation beneficial?
initial response is beneficial, long-term chronic overproduction of cytokines is detrimental
fuels degeneration
cytokines
allow cells to communicate with one another, orchestrating complex processes
(a chemokine is also a cytokine)
where are cytokines synthesised?
cns vs pns
cns: glial cells
pns: immune cells
cytokines role
Host response to infection
Immune cell signalling
Inflammation
TNF-a
microglia and astrocyte activation, regulation of BBB, febrile responses, glutamatergic transmission, synaptic plasticity
TGF-B
Ability to transform cell lines, and induce cells to not need intracellular matrix (anchorage-independent)
Signals through receptors I, II, or III
Regulation of neuroinflammation and apoptosis in traumatic brain injury
chemokines
stimulate chemotaxis of macrophages, neutrophils, regulate infiltration across BBB during inflammation and disease
pro-inflammatory
IL-1a
IL-1B
TNF-a
IFN-y
IL-6
IL-17
anti-inflammatory
IL-4
IL-10
TGF-B
microglia during disease, injury, illness
Large scale cytokine production
Recruitment of peripheral immune cells
Pathogen destruction
Debris clearance
Tissue repair
astrocyte activation
upregulation of GFAP
interact with endothelial cells -> increase BBB permeability and facilitate leukocyte infiltration
NF-KB
pro-inflammatory responses
activated via cytokines from microglia
inactivated by AHR
