Chronic Inflammation II: Granulomatous Inflammation Flashcards
What is a granuloma?
- they have EPITHELIOID CELLS which aggregate in the middle of the granuloma
- they contain macrophages and giant cells, which are many macrophages that have merged together (usually present with a horseshoe nucleus)
- type of chronic inflammation that occurs when the body cannot digest/engulf/break down foreign material and wall it off
- lymphocytes can be seen around the edge of the granuloma
- NOT granulation tissue, which is highly vascular and involved in wound healing
Granulation tissue (NOT GRANULOMA) contain what?
- young collagen
- vessels
- fibrin
(fibroblasts starting to lay down collagen)
Describe a granuloma histologically
- focus of chronic inflammation consisting of macrophages transformed into epithelioid cells/histiocytes, surrounded by a collar of mononuclear leukocytes (mostly lymphocytes and occasional plasma cells)
What cells are involved in a granuloma?
- monocytes (source of macrophages, epithelioid cells, and giant cells)
- macrophages (histiocytes)
- epithelioid cells (derived from macrophages)
- multinucleate giant cells (fusion of macrophages)
- lymphocytes (mostly helper T, but suppressor T and B lymph also present)
- plasma cells (related to IG secretion)
- neutrophils and eosinophils
- fibroblasts
What are the two main situations in which granulomas occur? (non-immune and immune)
- for infections (ie TB-bacterial, cocidiodes- fungal), body has no good way to fight infection. Signals immune system to wall off area, keep neutrophils out and monocytes in. Monocytes turn into histiocytes in tissue and then either macrophges when they engulf something or epithelioid cells when they don’t
- granulomas can also occur when a non-infectious foreign object is located int he body, like a suture. the body will wall it off because it can’t break it down or remove it
What are the six common causative agents of granuloma formation?
- fungi: cocidioides, histoplasma, blastomyces, cryptococcus
- mycobacteria (TB)
- some bacteria
- foreign materials, like suture
- parasites, e.g. shistosomes
- soluble antigens, such as beryllium, if it becomes attached to a protein
What are the dynamic cellular events and mediators in granuloma formation?
- macrophage presents insoluble antigen to CD4+ T cell
- CD4+ T cell secretes IL-1, IL-2
- CD4+ cells clonally expand and secrete IFN-gamma, IL-2, TNF-alpha
- draws blood monocytes to the area and repels neutrophils
- monocytes turn into epithelioid cells and secrete IL-8
What is the relationship between blood monocyte, macrophages, epithelioid cells and giant cells?
- monocytes are in the blood; once they enter the tissues they become known as histiocytes
- if a macrophage is signaled it will turn into an epithelioid cell
- if the histiocyte phagocytizes something then it becomes a macrophage
- macrophages fuse to form giant cells
What are the possible consequences for granulomas?
- granulomas can resolve; they may heal completely or leave varying amounts of scar tissue behind
- they can become necrotic
Compare/contrast granulomatous with nongranulomatous inflammation
- nongranulomatous inflammation does not form giant cells and does not ‘wall off’ from other areas. Neutrophils present in acute inflammatory response and other WBCs follow; lymphocytes will be more involved as the response becomes chronic (as will macrophages). The body will secrete antibodies or use cytotoxic T cells to eliminate the foreign invader
- granulomatous inflammation repels neutrophils. It is organized into round-ish nodules. The epithelioid cells aggregate and do not move like WBCs do in tissue in normal inflammation. Macrophages merge together.
What is the difference between granulomas and granulation tissue?
Granulomas occur in inflammation. They have a round shape with the presence of giant cells and epithelioid cells, which look epithelial but are not. The epithelioid cells aggregate and do not move. There is a ring of lymphocytes outside the granuloma.
granulation tissue has no organization. It is highly vascular. It has type III collagen. Granulation tissue is involved in healing.
Give a brief summary of sarcoidosis as a clinicopathologic disease
- cuase of sarcoidosis is unknonw. causes granulomas and 1/3 of time patient gets better, 1/3 pt stays same, 1/3 pt gets wors. death from sarcoidosis is rare
- tissue must be biopsied and other organisms ruled out. Once the other known causes of granulomas are ruled out, then diagnosis of sarcoidosis can be given
- the granulomas appear very clean under a microscope. They are easy to identify.
