lecture 11 - immunology in the CNS Flashcards
two types of immunity
Innate Immunity
Non-specific, constitutive and quick
Anatomical (barriers)
Inflammation
Phagocytes and antigen-presenting cells (APCs)
PRRs recognising PAMPs
Monocytes and macrophages
Dendritic cells
Neutrophils and other granulocytes (eosinophils, basophils, mast cells)
Adaptive Immunity (humoral and cell-mediated)
Specific (diversity/polymorphism), induced so slower, memory
Lymphocytes (T and B cells)
T cells:
Helper
Cytotoxic
Regulatory
Memory
B cells:
Plasma ( antibodies)
Memory
Recognition in the immune system:
PAMPS, PRRs, BCRs and TCRs
Myeloid cells of the immune system
- Macrophage (“big eater”)
- Dendritic cell (DCs)
- Neutrophil (polymorphonuclear cells, PMNs)
- Eosinophil
- Basophil
Macrophage (“big eater”)
Phagocytosis
Bactericidal mechanisms
Antigen presentation
Cytokine production
Dendritic cell (DCs)
Antigen uptake in periphery
Antigen presentation in lymph nodes
Cytokine production
Neutrophil (polymorphonuclear cells, PMNs)
Phagocytosis
Bactericidal mechanisms
Eosinophil
Killing of antibody-coated parasites
Basophil
Allergic responses
Augmentation of anti-parasite immunity
Lymphoid cells of the immune system
Lymphocytes
T and B lymphocytes cannot be distinguished by blood smear, instead by surface markers
Mostly small and inactive until they encounter the specific antigen that interacts with the receptor on their surface
T cell subsets include CD4+ helper T cells and CD8+ cytotoxic T cells
Flow cytometry of CD4+ and CD8+ cells
Signalling, communication, activation and inhibition:
cytokines
Meninges and Blood-Brain Barrier (BBB)
Invasion of the central nervous system
Crossing the blood-brain barrier (BBB) encephalitis
Crossing the blood-CSF barrier meningitis
Pathogens can cross these barriers by:
Infecting the cells that comprise the barrier
Being passively transported across in intracellular vacuoles
Carriage across by infected white blood cells
CNS invasion is broadly rare because most microorganisms fail to infiltrate the natural barriers between the blood and the CNS
Rabies virus – From bite to brain
CNS invasion
Viruses increase in lymphocytes (mostly T cells) and monocytes in CSF, increase in protein, CSF remains mostly clear (“aseptic meningitis”)
Bacteria rapid increase in neutrophils and protein, CSF becomes turbid (“septic/purulent meningitis”)
Little extracellular space means most spread is limited to direct cell-to-cell
Dramatic localised inflammation leads to abscess formation, limiting spread
CNS invasion - Limited success
From the point of view of being transmitted to a new host, CNS invasion is generally foolish due to damage to the host
Establishment of latency (HSV and VZV) gives a mechanism for reactivation and later shedding
Rabies - CNS invasion can be part of the route to shedding and invasion of limbic system can lead to helpful behaviour (aggression, hydrophobia and increased likelihood of biting!)
What is inflammation for?
Tissue homeostasis
Tissue defence
Tissue homeostasis
Removal of dead cells/tissue
Promoting death of damaged cells
Promoting wound healing
Tissue defence
Production of cytotoxic substances
Production of chemokines for recruitment of populations of immune cells
Production of cytokines for coordination of immune response in local stromal cells, vasculature and wider immune system
Immunologically privileged sites
Body sites in which antigens do not elicit destructive immune responses.
Previously thought to be passive and barrier-based, now understood to be actively maintained.
Not under constant immune surveillance.
Antigens induce tolerance (immune cells are made unresponsive) or non-destructive responses.
An evolutionary adaptation aimed at protecting especially vulnerable organs from overwhelming inflammation that could abolish their functions
Immunologically privileged sites - Examples:
Brain
Eye
Testis
Uterus (foetus)
Hamster cheek pouch (this is not a typo)
Inflammation in the CNS
Inelastic casing (“the closed box”) – risk of damage/injury
Neurodegeneration
