Chronic inflammation, as evident in this
patient, is mediated by _____. Fibrosis can occur from ___________ which can lead to stiffening of the lung parenchyma and a greater FEV1
macrophages.
chronically activated M2 macrophages
What is the major cytokine
involved with fibrosis
tgf-b
Exudate common causes
Pneumonia
– Malignancy
– Tuberculosis
– Pancreatitis
What are the principal sources of chemokines?
Macrophages
endothelial cells
T-cells
Mast cell
What stimulates transcytosis?
What else does it do?
promotes vascular leakage
What are the major opsonins?
C3b and IgG
Increased vascular permeability, contraction of smooth muscle, dilation of blood vessels, pain when injected into skin are all properties of?
Bradykinin
Which CD4+ subsets are involved in defense against many types of bacteria and viruses and in autoimmune diseases?
TH1 and TH17 cells
Granulomatous inflammation is a form of chronic inflammation characterized by what type of cells?
Sometimes associated with what?
- Activated macrophages and T lymphocytes
- Central necrosis
What are the 4 clinically important acute-phase reactants, which are made in the liver.
- CRP
- Fibrinogen
- SAA (Serum amyloid A)
- Hepcidin
IL6 stimulates production of: CRP and fibrinogen
IL1 or TNF stimulation production of SAA.
In granulomatous inflammation the activated macrophages may develop abundant cytoplasm and begin to resemble epithelial cells, and are called?
These then fuse and make?
- Epitheliod cells
- Multinucleate giant cells (AKA Langerhans giant cells)
One of two types of granulomas:
Foreign body granulomas cause what kind of immune response?
FB granulomas made by FB, not T cells.
- Do not incite an immune response or inflammation. Form around things like talc from IV drug use, sutures or other things that cant be phago
One of two types of granulomas.
What causes immune granulomas?
What do macrophages activate and cytokines involved?
- Caused by variety of things that that inducea T-cell response when the microbe is hard to kill or there is a self-ag.
- Macrophages activate T cells to produce cytokines, such as IL-2, which activates other T cells, perpetuating the response, and IFN-y, which activates the macrophages
What is the prototype of a granulomatous disease caused by infection and should always be excluded as the cause when granulomas are identified?
What is the granuloma referred to as in this dease?
- Tuberculosis
- A tubercle
Which cytokines are important mediators of the acute-phase reaction?
- TNF
- IL-1
- IL-6
- Type I interferons
FIbrinogen binds to red cells and causes them to form what?
Basis for measuring what as a simple test for an inflammatory response cause by any stimulus?
- Form stacks (rouleaux) that cause the RBC to break down more rapidly at unit gravity
- Erythrocyte sedimentation rate (ESR)
Which cytokines stimulate CRP, fibrinogen, and SAA?
- IL-6: CRP and fibrinogen
- IL-1 and TNF: SAA
Chronically elevated levels of ______ reduce the availability of iron and are responsible for the anemia associated with chronic inflammation
Hepcidin
Elevated levels of ______ have been proposed as a marker for increased risk of MI in patients with coronary artery disease?
CRP
Bacterial infections are characterized by what cells usually?
Viral?
- Neutrophils (bacterial) = neutrophilia
- Lymphocytes (viral) = lymphocytosis
Extreme elevation of leukocytes are referred to as?
Leukemoid reaction; similar to the white cell count seen in leukemia
Leukocytosis == increased number of leukocytes in the blood (opposed to leukopenia)
- Initially: TNF and IL-1 cause accelerated release of cells from bone marrow post-mitotic pools, causing a rise in number of immature neutrophils in blood (left shift)
IF TNF and IL-1 stay high: this can cause septic shock (triad: coagulation t/o blood, hypotensive shock, disturbances in metbolism like insulin resistance and hyperglycemia)
Acute phase response == cytokine induced systemic reactions mediated by TNF, IL1, IL6 and Type 1 IFN, that can cause a fever.
How do we get fever?
pyrogens (substances) that increase the set point of the hypothalamus.
Exogenous pyrogens (bacterial products) cause leukocytes to release endogenous pyrogens (IL-1 or TNF) => increase COX => covert AA into prostaglandins (esp PGE2) in the vascular and perivascular cells of the hypothlamus => stim prod of a NT in hypothalamus to increase temp set point
The set point in the hypothalamus is changed prostaglandins (especially ______) that stimulate the production of the neurotransmitters that change the set point.
PGE2
