Simms Flashcards
A patient is diagnosed with sarcoidosis. What would be strongly associated with this pathology?
TNF-alpha.
Sarcoidosis involves granuloma formation. When there is chronic inflammation, prolonged levels of TNF-alpha leads to granuloma formation.
TNF-alpha can activate what 3 pathways?
- NF-kappaB
- MAPK/ERK
- caspase 8-apoptosis
What secretes TNF-alpha?
Macrophages, lymphocytes, fibroblasts, etc.
Is IL-10 anti or pro inflammatory?
anti-inflammatory
Is IL-4 anti or pro inflammatory?
Both!
IL-4 is a regulatory anti-inflammatory cytokine that down-regulates acute inflammation and promotes eosinophil-based allergic inflammatory state.
…………is an innate immune system pattern recognition receptor that binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria. Binding activates complement, promoting phagocytosis.
C-reactive protein (CRP)
Is granulomatous inflammation synonymous with chronic inflammation?
No!
Granulomatous inflammation is a type of chronic inflammation and, if present, suggests certain disorders (Mycobacterial infection, fungal infection, sarcoidosis, etc.)
A female has severe cramping due to excess prostaglandin production. Prostaglandins are synthasized by which pathway?
Arachadonic acid pathway.
Is IL-1 pro or anti-inflammatory?
pro-inflammatory
But note that IL-1 –> increased ACTH –> increased cortisol (cortisol is anti-inflammatory)
What produces IL-1?
Macrophages, endothelial cells, APC/dendritic cells, and B lymphocytes.
What are the effects of IL-1?
- elevated core temp
- acute phase protein production
- chemotaxis of monocytes and neutrophils
- endothelial adhesion molecule production
- T cell activation, proliferation, IL-2 secretion
- B cell proliferation
- NK activation
- Vasodilation
A 60 year old male is being treated for osteoarthritis with a selective COX-2 inhibitor. He reports acute onset of shortness of breath and chest pain that radiates into his jaw and left arm. What should he have initially been prescribed for his arthritis to avoid this, and why?
A non-selective COX inhibitor such as Asprin!
COX-1 is constitutive. If we block only COX-2 with a selective inhibitor, we still get TXA2 production via COX-1, which can lead to thrombus formation.
Aspirin blocks both COX 1 and 2, which suppresses (via irreversible inhibition) the production of prostaglandins and thromboxanes.
A patients lung biopsy shows marginated neutrophils. Which substance is the most likely cause of the position of the neutrophils?
a. bradykinin
b. C5a
c. histamine
d. NO
e. prostaglandin E2
b. C5a
One of the effects of C5a is activation of immune adhesion molecules, which would allow the neutrophils to adhere and access the site of infection.
What is the major proinflammatory pathway in the immune system?
NFkB pathway
(Nuclear factor kappa light chain enhancer of activated B cells)
NFkB (a transcription factor) exists in the cytoplasm in its inactive form, complexed with………
IkB
* PAMPs or DAMPs bind PRRs, which causes IkB phosphorylation by IKK (a kinase). NFkB dimers can now translocate to the nucleus and bind to DNA.
Early response pattern of acute phase reactants shows elevation primarily in the………. fraction of serum proteins with a small rise in alpha-1 fraction.
alpha-2
Late/Chronic inflammation shows elevation in the alpha-2 fraction, alpha-1 fraction, beta fraction and gamma fraction. Here is the diagram:
………..are single or multiple blue cytoplasmic inclusions adjacent to the cell membrane. They are remnants of rough endoplasmic reticulum.
Dhole bodies
* Commonly seen in band cells in conjunction with toxic granulation.
* common causes: Severe infection with left shift, burns, trauma, malignancy, leukemoid rxn, Fanconi syndrome, May-hegglin anomaly, Chediak-steinbrinck-higashi syndrome.
