Chronic Inflammation Flashcards
what is the difference between acute and chronic inflammation?
acute inflammation occurs rapidly whilst chronic inflammation is persistent and occurs over months, years and possibly forever
what is chronic inflammation associated with?
greater tissue destruction and generally less fluid build up in infected tissue
what is inflammatory infiltrate?
a mixture of macrophages and lymphocytes (neutrophils are not prominent)
what are the three types of chronic inflammation?
non-specific chronic inflammation, specific (primary) chronic inflammation, chronic granulomatous inflammation
what is non-specific chronic inflammation
failure to resolve, acute inflammation, persistent bouts of acute inflammation, excessive suppuration
what is specific (primary) chronic inflammation
arises without prior warning, persistent exposure to agent, autoimmune diseases
what is chronic granulomatous inflammation?
subset of specific chronic inflammation
when does chronic inflammation arise from acute inflammation?
when the immune system is not sufficient enough to eradicate stimulus
what is the infiltrate of non-specific chronic inflammation dominated by?
tissue macrophages, T cells and B cells
what is non-specific chronic inflammation characterised by?
a dynamic balance between tissue destruction and repair
what may disease pathogenesis of non-specific chronic inflammation include?
repeated acute phases and chronic phases with ongoing repair
give an example of non-specific chronic inflammation
periodontitis
is specific chronic inflammation granulomatous or non-granulomatous?
either
what is specific chronic inflammation characterised by?
excessively activated macrophages
what non-immunological agents induce specific chronic inflammation?
foreign body reactions, inert noxious material (silica and asbestos)
what immunological agents induce specific chronic inflammation
infective organisms that grow in cells (viruses, mycobacteria), hypersensitivity reactions, autoimmune reactions, infection by fungi, protozoa or parasites
what is specific chronic inflammation induced by?
non-immunological agents or immunological agents
what is an autoimmune disease?
unwanted response to body’s own cells and tissues or commensal bacteria, loss of tolerance to self antigens or commensal bacteria, sustained immune response that generates cells and molecules that destroy tissues
give an example of an autoimmune disease
rheumatoid arthritis
what is the disease mechanism of rheumatoid arthritis?
autoreactive T cells against antigens of joint synovium
what is the consequence of rheumatoid arthritis?
joint inflammation and destruction causing arthritis
how is periodontal disease associated with rheumatoid arthritis?
periodontal disease - porphyromonas gingivalis infection - local and systemic inflammatory syndrome - rheumatoid arthritis OR porphyromonas gingivalis infection - production of enzymes: PAD and proteases - peptide citrullination - loss of tolerance: production of antibodies to citrullinated proteins - rheumatid arthritis
what are PAD enzymes and where are they produced from?
peptidyl arginine deiminase and are naturally produced by host cells such as neutrophils but also produced by P. gingivalis
what does PAD enzyme do?
citrullinates proteins (arginine conversion to citrulline which is not a normal naturally occurring amino acid)
how does chronic granulomatous inflammation differ from normal chronic inflammation?
the predominant cell types are modified activated macrophages
what are the modified activated macrophages in chronic granulomatous inflammation?
known as epithelioid macrophages, giant cells (mulit-nucleated formed from fused epithelioid macrophages) and B and T cells present in tissue
what are the immunological causes of chronic granulomatous inflammation?
delayed hypersensitivity type reaction or invading pathogens
what are the non-immunological causes of chronic granulomatous inflammation?
foreign body in tissue e.g. asbestos particles
what are epithelioid cells?
modified macrophages
what is the main aim of macrophages?
to phagocytose and present antigen
what are M1 macrophages?
pro-inflammatory
what are M2 macrophages?
anti-inflammatory
what is included in macrophage tissue injury?
toxic oxygen metabolites, proteases, neutrophil chemotactic factors, coagulation factors, AA metabolites and nitric oxide
what is included in macrophage tissue repair?
process of fibrosis, growth factors, fibrogenic cytokines, angiogenesis factors, remodelling collagenases
what do fibroblasts do?
drive the process of fibrosis - they synthesis the extracellular matrix/collagen that make up the connective tissue
what is angiogensis?
the formation of new blood vessels
what is the process of granuloma formation?
1 - macrophages present antigen to lymphocytes, 2 - lymphocytes produce IL-2 IL-12 and IFN - y , 3 - induces formation of epithelioid macrophages, 4 - contribute further to giant cells formation , 5 - giant cell - macrophages engulfing foreign material
give an example of chronic granulomatous inflammation
orofacial granulomatosis
what is orofacial granulomatosis?
granulomas in soft tissues of oral cavity and swelling
what is orofacial granulomatosis termed if the patient also presents with intestinal crohns?
oral crohns
what is orofacial granulomatosis termed if the patient does not present with intestinal crohns?
orofacial granulomatosis
what are the 2 main classes of chronic inflammation?
specific and non-specific (specific can be granulomatous or non-granulomatous)
what are M1 and M2 macrophages essential in?
injury and repair
what is the inflammatory infiltrate of chronic periodontitis?
defence cells which have been recruited to the tissue in response to microbial biofilm present on the tooth surface
what are the steps of tissue destruction in periodontitis?
1 - initiation of immune response, 2 - recruitment of immune cells, 3 - immune cell activation, 4 - RANKL production, 5 - activation of osteoclasts, 6 - reduced function of osteoblasts, 7 - activation of MMPs
what are the matrix metalloproteinases
fibroblast, endothelial cells, macrophage, neutrophil, lymphocyte, dendritic cell, myofibroblast
what is the ECM?
complex structure that supports cells
what is the ECM made of?
protein fibres (mainly collagen)
what is the ECM remodelled by?
matrix metalloproteinases (MMPs)
what is osteoblastogenesis?
bone formation
what is osteoclastogenesis?
bone resorption
what is osteoclastogenesis mediated by?
osteoclasts
where do osteoclasts come from?
they differentiate from macrophages
what are RANKLs produced by?
osteoblasts
what do RANKLs do?
activates the RANK (receptor on osteoclasts)
why is RANKL production controlled?
so there is no bone resorption
what does RANKL mean?
receptor activator of nuclear factor kappa-b ligand
what is osteoblastogenesis mediated by?
osteoblasts
what do osteoblasts secrete?
osteoprotogerin (OPG)
what does OPG do?
inhibit RANKL function therefore controlling bone resorption
what is excessive immune response in alveolar bone destruction associated with?
an increase in the RANKL/OPG ratio and tips the balance towards the bone loss/resorption
what does soft tissue destruction involve?
matrix metalloproteinases
what do MMPs do in periodontitis?
remodel the gingival tissue causing soft tissue destruction
