Lecture 8: Inflammation Flashcards
what is the main goal of inflammation
restore homeostasis and allow healing
3 roles of inflammation
- deliver effectors and cells from blood –> infection site
- induce localized clotting
- promote repair of damaged tissue
what happens once the acute inflammatory response is triggered
- dilation and increased permeability of vasculature
- influx of neutrophils (PMNs)
what cells exhibit an influx when chronic inflammation occurs
monocytes and lymphocytes
significant tissue damage can result in _____?
granulomas
what are the 3 components of the initial acute inflammation response
- vasodilation to increase blood flow to site of infection
- increased vascular permeability so immune cells can enter tissues
- increased expression of adhesion molecules, causes extravasation of neutrophils to site of infection
what types of receptors do macrophages and dendritic cells have to recognize PAMPs and DAMPs
Pattern Recognition Receptors
what does TLR4 bind to in order to trigger the activation of NkFB
TLR4 binds bacterial lipopolysaccharide (LPS) which triggers activation of NkFB and production of pro-inflammatory cytokines
what are the main pro-inflammatory cytokines
TNF-α, IL-1, IL-6, IL-12, and INF-γ
steps in extravasation
- rolling adhesion
- integrin activation
- stable adhesion
what cell types produce pro-inflammatory cytokines
- Macrophages
- Dendritic cells
- mast cells
- endothelial
what do pro-inflammatory cytokines cause
- induce expression of adhesion molecules allowing for the extravasation of WBCs
what are 2 important adhesion molecules induced by TNF-α and IL-1
selectins and ICAMS
what is the outcome of leukocyte adhesion deficiencies
- no or poor adherence of immune cells to endothelial cells
- poor extravasation
- causes high WBC counts and recurrent infections
what are the 2 types of inflammatory mediators
- plasma derived (liver)
- cell derived
A plasma derived inflammatory mediator…
what is the result of the coagulation and Kinin system in response to damage
- coagulation: production of blood clots
- kinin: production of products w/ pro-inflammatory effects
A plasma derived inflammatory mediator
What is the effect of Anaphylatoxins C3a and C5a on inflammation
- stimulate release of Histamine
- stimulate immune cell chemotaxis and extravasation
- vasodilation, fluid leakage
what are the cell-derived inflammatory mediators
- histamine
- arachidonic acid metabolits
- cytokines
what are the plasma-derived inflammatory mediators
- Coagulation and Kinin systems
- Anaphylatoxins C3a + C5a
what is the effect of Histamine as a cell-derived inflammatory mediator
histamine binds H1 receptors causing
* vasodilation and endothelial cell contraction
* itch perception
what is the effect of Arachidonic Acid Metabolites as cell-derived inflammatory mediators
- production of thromboxanes, prostaglandins, leukotrienes which mediate inflammation
what is the effect of cytokines as a cell-derived inflammatory mediator
- regulate the immune system
- Inflammasome = protein complex that triggers activation of caspases to cleave pro-IL 1β into active IL-1β
what are acute phase proteins
- C-reactive protein (CRP)
- proteins whose concentration in blood plasma either increases or decreases in response to inflammation
- produced in liver
what cytokines stimulate acute phase proteins
TNF-α, IL-1, IL-6
what is the function of C-reactive proteins
- CRP concentration increases dramatically during inflammation
- they bind lysophosphatidylcholine on dead/dying cells to induce classical complement via C1
what is AA Amyloidosis
- systemic condition that can develop in patients w/ chronic inflammatory diseases
- elevated levels of pro-inflammatory cytokines lead to increased APP prouction
- if left untreated, can cause excessive amyloid accumulation = kidney failure
potential causes of prolonged inflammation (chronic)
- persistent injury/infection
- hypersensitivites and autoimmunity
- prolonged exposure to toxins
explain how chronic inflammation can result in tissue damage
- monocytes become macrophages as they enter into tissues
- continued stimulation of macrophages can lead to tissue damage
- Granulomas can form to wall off persistent antigens
what are 2 main inhibitory cytokines of the immune system
IL-10 and TGF-β
Produced by macrophages and T cells
Granuloma formation is initiated by ______, secreted by _______ cells in order to enhacne macrophage activation
INFy, T-cells
what inflammatory mediator do NSAIDs inhibit
prostaglandins
what transcription factors are activated by the binding of a PAMP to a TLR
NFkB and IRF3
which then activate IL-1, IL-6, TNF-α
what does tumor necrosis factor (TNFα) stimulate
- T cell growth
- actue phase response
- triggers inflammation
what interleukin promotes IFNα
IL - 18
what does IL-6 stimulate
- stimulates acute phase responses
- promotes B cell differentiation
what does IL-1 stimuate
- stimulates acute phase response
- costimulator of Th2 cells
innate activation of macrophages occurs in response to…
TLR ligation
what happens in the classical activation of macrophages
- they become M1 cells by exposure to microbial products and Th1 cytokines (INFy)
what happens in alternative activation of macrophages
- they become M2 cells upon exposure to Th2
functions of the reticuloendothelial system
- destroy foregin substances
- clean up dying / apoptoic cells
cDC1 promotes type __?__ responses by producing IL __?__ and activating __?___ cells
type I responses by producing IL-12 and activating Th1 cells
cDC2 promotes type __?__ responses by producing IL __?__ and activating __?___ cells
type II responses by producing IL-6 and IL-23 and activating Th2 and Th17 cells
inflammasomes generate _____ that activates cytokines _____?_____
generate CASPACE1
activates cytokines ILB and IL18
SAA and fibrinogen are examples of what
acute phase proteins
antigen specificity of an antibody is determined by ?
combination of heavy and light chain domains
what are the sickness cytokines?
IL-1, IL-6, HMGB1, TNF-α
