2. Inflammation Flashcards
a complex array of interactions among soluble biologically active factors and cells of the immune system that arise in any tissue in response to trauma, infections, post-ischemic, or toxic injury
definition of inflammation
why is inflammation a double-edged sword
essential for normal immune response (allows tissues to return to homeostasis) but can be pathogenic when unresolved
___ plays a major role in pathogenesis of most chronic diseases (periodontal disease, endocarditis, autoimmunity, heart disease, Alzheimer’s, allergies, obesity, cancer)
inflammation
5 signs of inflammation
- heat
- redness
- swelling
- pain
- loss of function
acute inflammation
occurs immediately after injury (lasts for a few days)
__ __ starts after injury that will cause soluble mediators like cytokines, acute phase proteins, and chemokines to promote the migration of neutrophils and macrophages to the area of inflammation. These cells are part of innate immunity that have an active role in __ __.
acute inflammation
subacute inflammation
transformational period from acute to chronic (lasts 2 to 6 weeks)
if this inflammation does not resolve after 6 weeks, chronic form develops with migration of T lymphocytes and plasma cells to site of inflammation
subacute inflammation
chronic inflammation
lasts for months or even years when acute inflammation fails to resolve; occurs with persistence of antigen (viruses, autoimmunity, cancer)
if this persists with no recovery, then tissue damage and fibrosis will ensue. There are other varieties of cells such as the macrophages and monocytes that play a role in both acute and chronic inflammation.
chronic inflammation
true or false: inflammation may be localized or systemic
true
steps of local infection with gram-negative bacteria
- macrophage activated to secrete TNFalpha in the tissue
- increased release of plasma proteins into tissue; increased phagocyte and lymphocyte migration into tissue; increased platelet adhesion to blood vessel wall
- phagocytosis of bacteria; local vessel occlusion; plasma and cells drain to local lymph node
- removal of infection; adaptive immunity
steps of systemic infection with gram-negative bacteria (sepsis)
- macrophages activated in the liver and spleen secrete TNFalpha into the bloodstream
- systemic edema causing decreased blood volume, hypoproteinemia, and neuropenia, followed by neutrophilia; decreased blood volume causes collapse of vessels
- disseminated intravascular coagulation leading to wasting and multiple organ failure
- death
under homeostatic conditions, what does inflammation promote?
clearance of microbes and tissue healing
3 steps of homeostatic conditions of inflammation
- mobilization of immune effector cells and molecules to the site of infection or tissue damage to mediate destruction of microbes
- clot formation to control bleeding and prevent spreading of infection into bloodstream
- promotes remodeling and healing of damaged tissues
causes of inflammation (2 types of inducers)
- endogenous inducers
- exogenous inducers
endogenous inducers
- released by tissues that are either dead, damaged, or stressed
- referred to as damage associated molecular patterns (DAMPs)
- inflammation caused by our own tissues!
exogenous inducers: microbial and nonmicrobial
microbial: two classes
- pathogen-associated molecular patterns (PAMPs)
- virulence factors restricted to pathogens
nonmicrobial
- causes include allergens, toxic compounds, irritants, and foreign bodies that are too large to be digested or cause phagosomal damage in macrophages (foreign bodies such as silica and asbestos) – derived from environment
- also classified as exogenous DAMPs
generation of inflammation requires
receptor activation
in order to generate inflammation, cells must first be able to recognize a specific stimulus (___ or ___). This recognition is mediated by ___ expressed on the cells. These receptors are located on the cell ___ and ___ the cell.
DAMP, PAMP, receptors, surface, within
DAMPs bind specific receptors to generate inflammation. Many different types of endogenous molecules can act as DAMP:
- proteoglycans/glycosaminoglycans
- proteins/peptides
- nucleic acids/protein nucleic acid complexes
- fatty acids/lipoproteins
DAMPs bind to specific cellular receptors. Many types of receptors recognize DAMP:
- toll-like receptors (TLRs) bind diverse ligands (proteoglycans and nucleic acids)
- inflammasomes bind self DNA
- P2X7 receptor binds ATP
toll-like receptors (TLR)
- type of pattern recognition receptor
- expressed on cell surface and intracellularly
- bind diverse ligands such as proteoglycans and nucleic acids
AIM2 and NLRP3
types of inflammasomes
true or false: self-derived DAMP bind to our own receptors to cause inflammation
true
Inflammation is also generated by PAMPs that bind to the same receptors as DAMPs. Many types of receptors recognize PAMPs:
- TLRs: bind bacteria, fungi, viruses
- inflammasomes: bind viral DNA
- NOD receptors: bind bacterial components
true or false: pathogens do not bind to the same receptors as DAMP to cause inflammation
false: they do
what happens following binding of the DAMP or PAMP to its cognate receptor?
- activation of signaling cascades leads to translocation of transcription factors (TFs) from the cytoplasm to the nucleus
- TFs bind to DNA in nucleus and initiate transcription of inflammatory genes
- leads to production of proteins integral to immune response
- pre-formed mediators are also important in immune response
cell-derived mediators of inflammation that are pre-formed mediators in secretory granules
- histamine: mast cells, basophils, platelets
- serotonin: platelets
*these are fast
cell-derived mediators of inflammation that are newly synthesized
- prostaglandins: all leukocytes, mast cells
- leukotrienes: all leukocytes, mast cells
- platelet-activating factor: all leukocytes, endothelium
- reactive oxygen species: all leukocytes
- nitric oxide: macrophages, endothelium
- cytokines: macrophages, endothelium
- neuropeptides: lymphocytes, mast cells, leukocytes, nerve fibers
*these are slow
