Chronic Inflammation

What is chronic inflammation?

inflammation of prolonged duration (weeks to lifelong) in which active inflammation, tissue destruction, and attempts at repair are proceeding simultaneously

What are the hallmarks of chronic inflammation?

macrophages and proliferation (fibrosis)

What are the general characteristics of chronic inflammation?

infiltration is primarily composed of mononuclear cells, especially macrophages, tissue destruction, attempts at healing/repair

What is critical for the failure of acute inflammation and progression to chronic inflammation?

inciting stimulus persists for weeks to months or even more

What is the shift in cellular response during the progression to chronic inflammation?

neutrophils to macrophages ± giant cells (in granulomatous inflammation), lymphocytes

What leads to fibrosis in chronic inflammation?

extensive connective tissue reorganization

What is fibrosing chronic inflammation?

region of chronic inflammation predominantly composed of fibrous connective tissue (ex: chronic traumatic pericarditis (hardware disease) of cattle)

What is chronic-active inflammation?

chronic inflammation that also contains neutrophils and fibrin (constituents of acute inflammation). Chronic-active inflammation occurs when the inciting stimulus has not been removed.

What is granulomatous inflammation?

specific type of chronic inflammatory process (activated macrophages, epithelioid macrophages, multinucleated giants cells, lymphocytes and plasma cells). Nodular (ex: tuberculosis, fungal granulomas) or diffuse (paratuberculosis-Johne’s disease)

What is pyogranulomatous inflammation?

granulomatous inflammation accompanied by neutrophils. Occurs when the inciting stimulus has not been removed from the exudate

What is granulomatous inflammation in simpler terms?

distinct type of chronic inflammation in which macrophages predominate

What are the driving factors of granulomatous inflammation?

1. inciting agent usually with indigestible, poorly degradable, and persistent antigens

2. host immune response

3. interplay of various cytokines/chemokines

What is a nodular granulomatous inflammation?

associated with Th1 cell mediated immune response

What are the three layers of nodular granulomatous inflammation?

1. often a central area of necrosis ± mineralization

2. zone of epithelioid macrophages ± multinucleated giant cells

3. zone of lymphocytes, plasma cells and fibrosis (granuloma)

What is another term for nodular?

tuberculoid

What is an example of nodular (tuberculoid) granulomatous inflammation?

myocbacterium bovis (bovine TB)

What is a diffuse granulomatous inflammation?

associated Th2 humoral immune response

What are the characteristics of diffuse (lepromatous)?

disease is usually more poorly controlled, infiltrate is composed of macrophages, epithelioid cells, ± multinucleate giant cells

What are the mediators of chronic inflammation?

switch from CXC to CC chemokines, recruitement of mononuclear cells rather than polymorphonuclear cells

What are the characteristics of macrophages during chronic inflammation?

longer tissue lifespan than neutrophils, transformation of macrophages into epithelioid macrophages

What are epithelioid macrophages?

less phagocytic, more secretory function, more abundant eosinophilic cytoplasm, cell mediated immunity is key

What are multinucleated giant cells?

fusion of multiple macrophages

What are the two types of multinucleated giants cells?

foreign body type and langhan’s type

What is a foreign body type?

haphazard or centrally located nuclei

What is langhan’s type?

nuclei arranged at periphery in semicircle/horseshoe

What is a classical activation of macrophages?

Th1 response by IFNy, IL-12; they will go on to release IL-1, NO, and respiratory burst

What is an alternative activation of macrophages?

Th2 response by IL-4, IL-13; they will go on t secrete IL-10 TGFB (resolution and proliferation) with increased MHC II and mannose receptors (humoral)

What are B cells?

plasma cells and produce antibody, one of the major opsonins