Infection Pathogenesis Flashcards
What is immunopathologic damage?
Tissue injury caused by a dysregulated immune response, often leading to inflammation and functional impairment
How does cytokine release by macrophages lead to immunopathologic damage?
Leads to the symptoms of influenza
How does cell killing by CTL lead to immunopathologic damage?
May result in organ damage
How does dead cells lead to immunopathologic damage?
Secondary inflammatory response to cellular components(DAMPs) such as DNA and RNA
What are prostaglandins (PG)?
Lipid compounds derived from anachronic acid, a fatty acid present in cell membranes.
Known mediators of the inflammatory response
What are the proinflammatory effects of Prostaglandins (PGs)?
Promoting vasodilation
Increasing vascular permeability,
Sensitizing nociceptors (pain receptors)
What is the role of Prostaglandins in immune response?
Recruit immune cells
Amplify inflammatory response
Modulate immune function
What is PGE2’s role in inflammation?
Promotes vasodilation
Increases vascular permeability
Sensitizes pain receptor
How does PGE2 cause a fever?
PGE2 acts on the hypothalamus to raise body temperature leading to fever.
It is synthesized locally in response to pyrogenic (fever-inducing) substances such as endotoxins or cytokines.
How do PGs have a role in pain sensing?
By sensitizing pain receptors and lowering the threshold for pain perception.
How do PG cause inflammatory pain?
Damaged tissue release pro-inflammatory cytokines (IL-1 and TNF-alpha).
This stimulates the production of PGs, E2.
How does PGE2 sentisation of nociceptors?
PGE2 sensitizes nociceptors by acting on receptors EP1, EP2, and EP4 receptors, which are expressed on sensory nerve fibers.
This sensitization lowers the threshold for activation of nociceptors, making them more responsive to mechanical, thermal, and chemical stimuli.
How does PGE2 enhance neurotransmitter release?
PGE2 enhances the release of excitatory neurotransmitters, such as substance P and glutamate, from sensory nerve terminals in the spinal cord.
This amplifies the transmission of pain signals to higher brain centres, contributing to the perception of pain.
What is the role of PGE2 in chronic pain?
PGE2 is implicated in the pathophysiology of chronic pain conditions, such as osteoarthritis, rheumatoid arthritis, and neuropathic pain.
Persistent inflammation and dysregulation of PG production contribute to the maintenance of chronic pain states.
How does infection cause metabolic changes that affect neuronal activity?
Release of inflammatory mediators.
Disruption of energy metabolism and neurotransmitter synthesis.
Blood-brain barrier dysfunction.
Imbalance of neurotransmitters.
Activation of immune cells in the CNS.
What is IDO?
Indoleamine 2,3-dioxygenase (IDO) is an enzyme involved in the metabolism of tryptophan, an essential amino acid. In the context of flu infection, IDO activation has been implicated in increasing pain sensitivity.
Through what mechanisms does IDO activation in flu infection increase sensitivity?
Immunomodulation via tryptophan metabolism.
Neuroinflammation and glial cell activation.
Direct activation of pain-sensing neurons.
Contribution to neuropathic pain development.
What is type 1 interferon?
Type I interferons (IFNs) are a group of cytokines that play a crucial role in the innate immune response to viral infections and other pathogens.
They are primarily produced by cells such as plasmacytoid dendritic cells, macrophages, and fibroblasts
What are acute interferons?
Inhibit virus replication and promote immune response
What are chronic interferon
Can contribute to pathogen evasion thus promote pathogen persistence
What is the role of interferons?
Induce immune immune suppressive mechanisms including PDL1 and indoleamine 2,3 dioxygenase (IDO)
What is the antiviral activity of interferons?
Inducing the expression of numerous interferon-stimulated genes (ISGs) in both infected and neighbouring cells.
ISGs encode proteins involved in various antiviral mechanisms.
How are interferons important in immune modulation?
By regulating the activation, differentiation, and function of immune cells, including dendritic cells, T cells, B cells, and natural killer (NK) cells.
How are interferons used in induction pathways?
Induced in response to viral infection through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and cytosolic DNA sensors.
