Path: Inflammation 4 Flashcards
Chronic inflammation is inflammation of how long?
prolonged duration: weeks to years
Chronic inflammation consists of what 2 aspects?
- active inflammation
- tissue destruction
- attempted repair
What are 4 example causes of chronic inflammation?
- persistent infections (ex: TB)
- prolonged toxin exposure (ex: silicosis)
- autoimmunity (ex: lupus)
- conditions of unknown etiology, such as atherosclerosis, sarcoidosis, Alzheimer’s
What cell is the key player in chronic inflammation?
macrophages
Macrophages secrete neutrophil chemotactic factor and growth factors such as ___, ___, and ___.
TGF-beta, PDGF, and FGF
*PDGF=platelet derived growth factor
Macrophages and lymphocytes have bi-directional communication. Macrophages present antigens and secrete ___, which stimulate T cells. In turn T cells secrete ___ which activates macrophages.
cytokines (IL-12); IFN-gamma
What draws macrophages to sites of inflammation?
chemotaxis by MCP-1, C5a, PDGF, TGF-alpha, fibronectin, and fibrinopeptide fragments
Examples of ____ predominant diseases include most forms of thyroiditis, rheumatoid arthritis, and myocarditis.
lymphocyte
Examples of ____ predominant diseases include atherosclerosis, subacute phase phenomena, Gaucher disease, gout, and usual interstitial pneumonia.
macrophage
Examples of ____ predominant diseases include osteomyelitis.
neutrophil
Examples of ____ predominant diseases include the fungal infection blastomycosis.
macrophage and neutrophil co-predominant
Resident macrophages in the liver are called ____ cells.
Kupffer
Resident macrophages in the spleen/lymph nodes are called ____ cells.
histiocytes
Resident macrophages in the brain are called ____ cells.
microglia
Resident macrophages in the lungs are called ____ cells.
alveolar macrophages
There are two pathways of macrophage activation. What are they?
- classical
2. alternative
The classical pathway of macrophage activation can start with what three options?
- microbial products sensed by TLRs
- cytokines, from T cells
- foreign substances, like crystals
What is the name of classically activated macrophages?
M1 macrophages
M1 macrophages upregulate production of what to fulfill their role as effector cells?
lysosomal enzymes, nitric oxide, reactive oxygen species
IL-1, IL-12, IL-23, and chemokines are inflammatory mediators secreted by what?
classically activated macrophages
The alternative pathway of macrophage activation can start with what?
cytokines (other than IFN-gamma) including IL-4 and IL-13
True or false: the alternative cytokines inhibits the classical pathway of macrophage activation.
true
What is the name of alternatively activated macrophages?
M2 macrophages
True or false: M2 macrophages are actively microbicidal.
False - they are instead activated to secrete anti-inflammatory factors like IL-10 and TGF-beta
M2 macrophages secrete ____ that promote angiogenesis and stimulate fibroblasts to make ____.
growth factors; collagen
It is presumed that ____ macrophage activation precedes ____ activation in dealing with chronic infections or injuries.
classical preceded alternative
True or false: the classical macrophage activation pathway makes them healers, while the alternative macrophage activation pathway makes them killers.
False - the other way around
What factors recruit lymphocytes to sites of chronic inflammation?
IL-1, TNF-1, and chemokines
True or false: Th1 lymphocytes secrete IFN-gamma, which activates macrophages by the classical pathway to promote killing of intracellular microbes, taking over from the first responder neutrophils.
True
Th2 lymphocytes secrete ____ and ____, which activates macrophages by the alternative pathway to promote healing from infection.
IL-4 and IL-13
In addition to secreting IL-4 and IL-13 to activate macrophages, Th__ lymphocytes can also secrete ____ to recruit and activate eosinophils responding to parasitic infestations and inappropriately responding stimuli in allergies.
TH2 lymphocytes; IL-5
TH17 lymphocytes secrete IL-17, which does what?
recruits neutrophils and monocytes to sites of chronric infammation
Are plasma cells and activated B-cells often found at the site of chronic inflammation?
yes - not sure why
Describe the process of lymphoid organogenesis in chronic inflammation.
sometimes in chronic inflammatory diseases the lymphocytes will form into germinal centers outside of lymphoid tissues; the resulting tissue is called tertiary lymphoid organs; this occurs in the synovium in RA and in the thyroid gland in Hashimoto thyroiditis
What is a granuloma?
an aggregate of activated macrophages working together
True or false: granulomatous conditions are always acute, never chronic.
False - because they are macrophages, they won’t even develop acutely, and they take time to form
What are the two major forms of granulomas?
- foreign body granulomas
2. immune granulomas
Describe foreign body granulomas.
These are granulomas that form around a foreign body that is indigestible by one phagocyte (usually b/c too large), so many macrophages coalesce into one multinucleated foreign body giant cell; many of these cells come together and form a foreign body granuloma
What are the subcategories of immune granulomas?
- those that are due to infection
2. those that are autoimmune
True or false: immune granulomas can be induced by self-perpetuating positive feedback loops that stimulate T cell activation of themselves and macrophages.
True
Immune granulomas tend to have a rim of _____ around the macrophages.
T lymphocytes
What do epithelioid cells, or activated macrophages in granulomas, look like?
they have pink granular cytoplasm with indistinct cell boundaries and they resemble epithelial cells, hence the name “epithelioid cells”
Giant cells in immune granulomas are often called ____ and have what characteristic appearance?
Langhans type cell; nuclei arranged in semi-circle around the periphery of the giant cell
In granulomas due to TB and histoplasmosis, there is sometimes a central area of necrosis attributed to hypoxia + free radical injury. Because this area consists of amorphous, acellular, eosinophilic material without ghost cells, it is common to call this microscopic necrotizing granuloma ____.
caseating
Please name the three distinct types of granulomas.
- foreign body
- infectious immune
- autoimmune
Tuberculosis, syphilis, lupus, cat-scratch disease, and sarcoidosis are examples of ____ disease.
granulomatous
TB starts in the ____ and spread to ____.
lungs; local lymph nodes
Cat-scratch disease starts in the ____ and spreads to ____.
skin; nearby lymph nodes
A granuloma described as “tiny potatoes (tubercles), especially cheesey (caseous) ones” would make you think of what disease?
tuberculosis
A granuloma described as “round or stellate with central necrotic granular debris and neutrophils” would make you think of what disease?
cat-scratch disease
What type of granulomas does sarcoidosis tend to have?
non-necrotizing, non-caseating, tight naked granulomas, without a rim of lymphocytes
Inflammation of lymphatic channels is called ____.
lymphangitis
Inflammation of lymph nodes is called ____.
lymphadenitis
Enlargement of lymph nodes is called ____.
lymphadenopathy
True or false: chronic inflammation has the same systemic effects on the patient as acute inflammation has.
False - it has similar but not the same systemic effects
Compare and contrast the sedimentation rate in acute inflammation and chronic inflammation.
Both inflammation types will elevate the erythrocyte sedimentation rate, but:
- chronic: elevated sed rate because Igs makes RBCs sticky
- acute: higher sed rate because fibrinogen makes the RBCs very sticky.
True or false: chronic inflammation causes anemia but acute does not.
True - acute inflammation will not usually cause anemia unless it’s complicated by hemolysis, DIC, or bleeding, but chronic inflammation will
Why does chronic inflammation cause anemia?
the body thinks the inflammation is due to persistent microbial infection, so it takes up and hides all the iron - but ends up hiding it from RBCs as well
What is ferroportin?
it’s the only iron export protein in iron-transporting cells
What causes down-regulation of ferroportin?
IFN, LPS, TNF-alpha
What does hepcidin do, and what stimulates hepatic production of it?
inhibits duodenal absorption of iron and macrophage iron recycling, as well as binds to ferroportin and leads to its degradation; production stimulated by IL-6 and LPS
The storage and retention of iron within macrophages is stimulated by what factors, which also induce ferritin expression?
TNF-alpha, IL-1, IL-6, and IL-10
___ and ___ inhibit production of erythropoietin in the kidney.
TNF-alpha and IFN-gamma
Anemia of chronic disease will usually only reduce hemoglobin to ___g/dl–so if it’s lower than that, look for another cause of the anemia.
10g/dl
Tuberculosis is cause by what microbe?
mycobacterium tuberculosis
What is sarcoidosis?
multi-system probably autoimmune granulomatous disease
What are the functions of TNF-alpha?
- Downregulates ferroportin
- Induces ferritin
- Promotes retention of iron in macrophages
- Inhibits erythropoietin production in kidney
What are the functions of IFN-gamma?
- Secreted by TH1 cells to activate macrophages by the classical pathway (killer cells)
- Inhibits erythropoietin production in kidney
What are the functions of IL-6?
- Stimulates production of hepcidin
- Induces ferritin
- Promotes retention of iron in macrophages
What are the functions of IL-1?
- Inflammatory mediator secreted by M1 cells
- Recruits lymphocytes to site of inflammation
- Induces ferritin
- Promotes retention of iron in macrophages
What are the functions of IL-12?
- Inflammatory mediator secreted by M1 cells
- Secreted by macrophages to induce T cells
What are the functions of IL-4?
- activates macrophages by the alternative pathway
* secreted by TH2 cells
What are the functions of IL-5?
- recruit and activate eosinophils responding to parasitic infestations and inappropriately responding stimuli in allergies
- secreted by TH2 cells
What are the functions of IL-13?
- activates macrophages by the alternative pathway
* secreted by TH2 cells
