NP4A Flashcards
proteins and glycoproteins associated with myelin for which we have autoreactive T cells
privileged antigens
We also have cells that are non-renewable, mainly __________ , making cell loss during an inflammatory process problematic
neurons
Helps create an environment conducive to neuronal conduction and myelin maintenance, keeping out small molecules that may serve as false neurotransmitters or those that might be toxic to oligodendrocytes. Can also help to exclude microorganisms that periodically find their way into the vascular system.
blood brain barrier
The barrier does not prevent ____________ from entering.
immune cells
__________ routinely enter and exit nervous tissue as part of their immune surveillance
Lymphocytes
Tight junctions between endothelial cells can be broken, and the basement membrane modified, and this is particularly the case in an environment of ___________, in which case the barrier is transiently broken down
inflammation
__________ and _______ can produce inflammatory cytokines that initiate the process, but it is microglia in particular that make this happen
Neurons , glia
There are ____________ in the CNS as well, and this allows antigens of CNS origin to be processed by deep cervical lymph node
lymphatics
How can we minimize damage to the CNS during the course of inflammation?
- limit expression of antigen presenting molecules
- you cannot prime an immune response in the CNS
- we have regulatory T cells in the CNS that can dampen certain immune responses
- lymphocytes (T cells) can eliminate intracellular pathogens in neurons without actually killing the cell
Antigen presenting complexes:
MHC I
MHC II
Antigen presenting complexes:
MHC I
MHC II
would present to T cells responsible for cell mediated immunity
MHC I
would present to lymphocytes ultimately that are driving humeral immune responses
MHC II
No CNS resident cell expresses _______at basal levels, and _________ can only be induced in microglia when stimulated by interferons released from activated lymphocytes
MHC II
Only microglia express ________ at basal levels, although interferons released from activated lymphocytes may induce _______ on astrocytes and oligodendrocytes – but not neurons
MHC I
You cannot prime an immune response in the _______
CNS
Priming is done by dendritic cells located in lymph nodes, and so priming immune responses to CNS antigens is no simple matter. You can only stimulate primed lymphocytes through antigen that is presented by ____
glia
But there is a downside: neurons and oligodendrocytes (but particularly neurons) are a great place for intracellular pathogens such as viruses to _____
hide
If the agent finds itself in the blood stream, it may invade the CNS through blood vessels penetrating from the _________or those located in the _________
meninges, choroid plexus
If the agent is a virus, all you need to be able to do is infect endothelial cells (in meningeal vessels) or highjack a _______ that knows how to cross the blood-brain barrier
leukocyte
____________ also enter by infecting the blood vessel lining
Protozoal
_________ and ___________ use a blunt force approach – cause vasculitis, essentially destroying any barrier function
Bacteria, fungi
Alternatively, you can infect a __________ process and this should be relatively easy to do if you infect the upper respiratory tract – hit those olfactory neurons and take a ride through the cribriform plate
peripheral nerve
a portion of the ethmoid bone located at the base of the skull
cribriform plate
(neutrophils) – think bacteria first
Suppurative
Example: suppurative meningitis
(macrophages) – think fungal
Granulomatous
Example: granulomatous encephalitis
Protozoa also cause granulomatous inflammation, but this is only apparent microscopically unless they cause vascular damage with hemorrhage and/or tissue necrosis
(fibrin) – think of an agent that damages vascular walls (e.g., some bacteria or an immune complex disease)
Fibrinous
Example: periventricular fibrinous encephalitis (cat with FIP)
Those infiltrates that you won’t see grossly (unless associated with hemorrhage or necrosis)
Non-suppurative
(lymphocytes, monocytes, and/or plasma cells) – think viral, protozoal, and parasitic infections. The latter may also be associated with eosinophilic infiltrates.
Non-suppurative
comprised of leucocytes that accumulate in the perivascular space around post-capillary venules before their infiltration into the parenchyma of the central nervous system
perivascular cuff
Viruses entering the bloodstream can find multiple ways of entering the brain, but we can survive these infections through adaptive immune (inflammatory) responses. Which of the following properly describes the host response?
Microglia present viral antigens to lymphocytes that have been primed in the periphery and those activated lymphocytes mediate viral clearance.
The nature of the immune response in CNS allows you to survive an initial viral infection, but what are the potential collateral effects?
- virus might persist in neurons, where lack of MHC expression compromises immune surveillance
- prolonged inflammation may result in the presentation of privileged antigens with activation of autoreactive lymphocytes, ultimately causing immune-mediated disease
