Chronic Inflammation Flashcards
What is chronic inflammation associated with?
greater tissue destruction
What is inflammatory infiltrate a mixture of?
macrophages and B cells/ T cells
Why are neutrophils not as present in chronic inflammation?
Neutrophils are short-lived cells that can undergo apoptosis and be cleared by macrophages
What is the time period for chronic inflammation?
occurs over months, years and possibly forever
What are the 3 main classes of chronic inflammation?
non-specific
specific (primary)
chronic granulomatous
What are the characteristics of non-specific inflammation?
usually arises from acute inflammation when immune system does not eradicate infection
infiltrate dominated by tissue macrophages, T cells and B cells
characterised by a dynamic balance between tissue destruction and repair
What is an example of non-specific chronic inflammation?
periodontitis
What are characteristics of specific chronic inflammation?
can be non-granulomatous or granulomatous
excessively activated macrophages
no acute phase
What are the causes of specific chronic inflammation?
non immunological agents (foreign body, inert noxious material like silica and asbestos)
immunological agents (infective organisms that grow in cells, hypersensitivity, autoimmune, infection by fungi protozoa or parasites)
What is an autoimmune disease?
unwanted response to body’s own cells
loss (breach of tolerance to self antigens
chronic inflammation generates cells and molecules that destroy tissues
What cells attack what in RA?
auto reactive T cells against antigens of joint synovium
What bacteria can RA arise from?
porphyromonas gingivalis
What enzyme does P gingivalis create?
PAD and proteases (gingipain)
Why does P gingivalis cause an autoimmune reaction?
production of enzymes that cause peptide citrullination which causes a breach of tolerance and production of antibodies that attack citrullinated proteins
What are the characteristics of chronic granulomatous inflammation?
Differs from normal chronic inflammation as the predominant cell types are modified activated macrophages;
– Known as epithelioid macrophages
– Giant cells (multi-nucleated: formed from fused epithelioid macrophages)
– B and T cells present in tissue.
What are the causes of chronic granulomatous inflammation?
– Immunological (delayed hypersensitivity type reaction or invading pathogens)
– Non-immunological (Foreign body in tissue e.g. asbestos particles)
What are the subsets of macrophages?
M1 - pro inflammatory
M2 - anti inflammatory
What do macrophages release to cause tissue injury?
– Toxic oxygen metabolites
– Proteases
– Neutrophil chemotactic factors
– Coagulation factors
– AA metabolites
– Nitric oxide
What do macrophages release to cause tissue repair?
– Process of fibrosis
– Growth factors (PDGF,FGF,TGF beta)
– Fibrogenic cytokines
– Angiogenesis factors (FGF)
– Remodelling collagenases
What cells are in and around a granuloma?
macrophages
epitheloid macrophages
T cells producing IL-12, IL-2, IFN-Y
What is an example of chronic granulomatous inflammation?
Orofacial Granulomatosis
What is intestinal crohns granulomatosis called?
oral crohns
Where are the granulomas in the oral cavity?
soft tissue
What cells produce matrix metalloproteinases (MMPs)?
fibroblasts, dendritic cells, lymphocyte, neutrophil, macrophages, endothelial
What is ECM?
complex structure that supports cells made of protein fibres (mostly collagen)
What remodels the ECM in soft tissues?
MMPs
What do MMPs do?
clear pathway for cell migration and angiogenesis
What is bone formation?
osteoblastogenesis
What is bone resorption?
osteoclastogenesis
When is the skeleton remodelled?
every 10 years
What do osteoclasts differentiate from?
macrophages
What do osteoblasts produce?
Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)
osteoprotogerin (OPG)
What does RANKL activate?
RANK (the receptor) on osteoclasts
If RANKL production is controlled, what is prevented?
bone resorption
What does osteoprotogerin (OPG) do?
OPG inhibits RANKL function – therefore controlling bone resorption
What ratio is important in preventing bone resorption?
RANKL/OPG ratio
What is an excessive immune response concerning bone loss associated with?
increase in the RANKL/OPG ratio and ‘tips the balance’ toward bone loss/resorption
What is the action of RANKL?
binds to RANK receptor on the surface of osteoclast precursor cells, stimulating their differentiation into osteoclasts and activating them.
