Inflammation Mediators Flashcards
Toll-Like Receptors
Activated by PAMPs; upregulated NF-kB leading to activation of immune response genes to multiple immune mediators (also seen on lymphocytes for both acute and chronic)
PGI2, PGD2, PGE2
Vasodilation and increased vascular permeability; PGE2 also mediates pain and fever
LTB4
Attracts and activates neutrophils
LTC4, LTD4, LTE4
Vasoconstriction, broncospasm, and increased vascular permeability (by contracting smooth muscle)
Mast Cells
Activated by tissue trauma, C3a, C5a or cross-linking of cell surface IgE by antigen; release of histamine granules (vasodilation and increased vascular permeability)
What are Rubor (redness) and Calor (warmth) due to?
Due to vasodilation, resulting in increased blood flow; mediated by histamine, bradykinin, and prostaglandin
What is Tumor (swelling) due to?
Leakage of fluid from post-capillary venules into interstitial space (exudate); mediated by histamine (endothelial cell contraction) and tissue damage (endothelial cell disruption)
What is Dolor (pain) mediated by?
Bradykinin and PGE2 that sensitive free nerve endings
What is Fever mediated by?
Pyrogens (such as LPS) from bacteria that cause macrophages to release IL-1 and TNF, increases COX in perivascular cells of the hypothalamus
What mediator raises set point temperature?
PGE2
What causes margination?
Vasodilation, slowing down flow in POST-CAP VENULE; allowing cells to marginate from center to periphery
What releases and mediates P-selectin?
Released from: Weibel-Palade bodies
Mediated by: histamine
What induces E-selectin?
TNF & IL-1
How does rolling occur?
Selectins bind to Sialyl-Lewis X found on leukocytes
Where and how are I-CAM and V-CAM regulated?
Upregulated on endothelium by TNF and IL-1
What do I-CAM and V-CAM interact with, what does it cause, and how does it happen?
I-CAM and V-CAM interact with Integrins on leukocytes; via C5a and LTB4 causing firm adheshion
What is LAD due to, and what type of disease is it? (x-linked, autosomal dominant, autosomal recessive)
Autosomal recessive defect of Integrins (CD 18)
How does LAD present?
First is delayed separation of umbilical cord, will see increased circulation of neutrophils, and recurrent bacterial infections that lack bus
What are neutrophils attracted by?
IL-8, C5a, LTB4
What do IgG and C3b do?
Phagocytosis; consumption of pathogens or necrotic tissue
What is Chediak-Higashi due to, and what type of disease is it? (x-linked, autosomal dominant, autosomal recessive)
Autosomal recessive defect in protein trafficking leading to impaired phagolysosome formation
How does Chediak-Higashi present?
Increased risk for pyogenic infections, neutropenia, giant granules in leukocytes, albinism, peripheral neuropathy
Fill in the enzymes on top of the arrows:
O2 —> O2* —> H2O2 —> HOCl (bleach)
- NADPH oxidase (oxidative burst)
- Superoxide dismutase
- Myeloperoxidase
What is CGD due to, and what type of disease is it?
NADPH Oxidase deficiency leading to poor O2-dependent killing; x-linked recessive
How does CGD present?
Infection and granuloma formation by catalase positive organisms such as Staph Aureus, Nocardia, etc.
Results of nitroblue tetrazolium test in CGD?
Positive; means it’s colorless, if it turns blue, that would be the NORMAL.
What is MPO deficiency due to and how does it present?
Myeloperoxidase enzyme missing; most patients are asymptomatic but at increased risk for Candida infections
What do macrophages secrete for resolution and healing?
IL-10 & TGF-beta (anti-inflammator)
What do macrophages secrete to continue an acute infection?
IL-8 (attracts neutrophils)
What do macrophages secrete to form an abscess?
FGF & cytokines (fibrosis around inflammation)
What are MHC-Class II linked to, and what type of antigen?
CD4+ T Cells; Extracellular
What are MHC-Class I linked to, and what type of antigen?
CD8+ T Cells; Intracellular
What does the Th1 subset of CD4+ T Cells secrete?
IL-2 (T-cell growth factor and CD8 activator), and IFN-gamma (activates macrophage)
What does the Th2 subset of CD4+ T Cells secrete?
IL-4 (class switch IgG and IgE), IL-5 (eosinophil chemotaxis, and mature B-cell class switch to IgA), and IL-10 (inhibits Th1)
How do CD8+ Cytotoxic T Cells kill?
Perforins and granzymes to induce apoptosis
What is the characteristic cell of granuloma formation?
Epitheliod histiocytes (macrophages with abundant pink cytoplasm)
What are the steps of a granuloma formation?
- Macrophages process and present antigen via MHC Class II-CD4+ Helper T Cells
- Interaction leads to macrophage secretion of IL-12 causing Helper T to form Th1
- Th1 cells secrete IFN-gamma which differentiates macrophages into epithelioid histiocytes
Where would you see a non-caseating granulatoma?
Reaction to foreign material, sarcoidosis, beryllium exposure, Chron’s, Cat Scratch
Where would you see a caseating granuloma?
Tuberculosis and Fungi
What causes Bruton’s and what do you expect to find?
Deficiency of IgG so opsinization through C3b only; recurrent infections from things such as Haemophilus, Strep, Hepatitis. Will have lymphoid hypoplasia (tonsils & adenoids)
SIGNIFICANT DROP IN ALL Ig LEVELS!
What does the interaction of CD31 and PCAM-1 cause?
Diapedesis.
