Chapter 3: Chronic Inflammation Flashcards
What is all occurring during chronic inflammation?
inflammation, tissue injury, and attempts at repair coexist in varying combinations
what are 3 different settings that chronic inflammation arises?
1) persistent infection by organisms that are difficult to eradicate 2) hypersensitivity diseases 3) prolonged exposure to potentially toxic agents (exogenous or endogenous) such as silica
what is an example of a difficult organism to eradicate?
mycobacteria and parasitic infection where it can be associated with a granulomatous reaction
what are three examples of hypersensitivity diseases?
1) immune reaction against self (multiple sclerosis) 2) unregulated immune responses against microbes (IBD) 3) immune responses against common environmental substances (asthma)
what is the onset like of chronic inflammation?
slow: days
what is the cellular infiltrate of chronic inflammation?
monocytes/macrophages and lymphocytes
what is the cellular infiltrate of acute inflammation?
mainly neutrophils
what is the tissue injury/ fibrosis like of chronic inflammation?
often severe and progressive
are the local and systemic signs prominent or less in chronic inflammation?
less
what are the dominant cells in most chronic inflammatory reactions? and how do they contribute to the reaction?
macrophages- which contribute to the reaction by secreting cytokines and growth factors that act on various cells, destroying foreign invaders and tissues, and activating other cells, notably T lymphocytes
What exactly are macrophages?
tissue cells derived from hematopoietic stem cells in the bone marrow in postnatal life
what are macrophages circulating in the blood called?
monocytes
what are liver macrophages called?
kupffer cells
what are spleen/lymph node macrophages called?
sinus histiocytes
what are macrophages in the CNS called?
microglial cells
what are macrophages in the lungs called?
alveolar macrophages
what are macrophages in the skin called?
langerhans cells
what is the half life of a blood monocyte?
about one day
what is the lifespan of tissue macrophages?
may be several months or years
Macrophages secrete mediators of inflammation such as cytokines. What are some of these cytokines? What else do macrophages secrete
TNF, IL-1, chemokines; eicosanoids
where do macrophages display the antigen to?
to T lymphocytes
what causes classically activated macrophages?
IFN-gamma (microbial products)
what do classically activated macrophages secrete to cause microbicidal actions of phagocytosis and killing of many bacteria and fungi?
ROS, NO, lysosomal enzymes
what do classically activated macrophages secrete to cause inflammation?
IL-1, IL-12, and IL-23
what causes alternatively activated macrophages?
IL-13 and IL-4
what do alternatively activated macrophages secrete to cause tissue repair and fibrosis?
growth factors and TGF-beta
what do alternatively activated macrophages secrete to causes anti-inflammatory effects?
IL-10 and TGF-beta
what amplifies and propagates chronic inflammation?
when microbes and other environmental antigens activate T and B lymphocytes
what happens when T and B lymphocytes are involved in the inflammatory reaction?
the inflammation tends to be persistent and severe, in part because lymphocyte activation leads to the generation of long-lived memory cells
In some chronic inflammatory reactions, the accumulated lymphocytes, antigen presenting cells, and plasma cells cluster together to form what?
lymphoid tissues resembling lymph nodes. These are called tertiary lymphoid organs or lymphoid aggregates
when might eosinophils be abundant?
in immune reactions mediated by IgE and in parasitic infections (think eosinophil in the setting of hypersensitivity, allergy, and parasitic infection)
what recruits eosinophils?
specific chemokines- eotaxin and IL-5
what do the granules of eosinophils contain?
major basic protein, a highly cationic protein that is toxic to parasites but also causes lysis of mammalian epithelial cells
what could be used to treat severe asthma?
a unique IL-5 inhibitor: Benralizumab
what is granulomatous inflammation?
a form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes and sometimes associated with central necrosis
what is one example of a disease with granulomatous inflammation; what is the cause of this disease; and what is the tissue reaction?
Tuberculosis; mycobacterium tuberculosis; caseating granuloma
what should always be excluded as the cause when granulomas are identified?
tuberculosis
