Inflammation and Mediators Flashcards
ER
Site where proteins are synthesized
Golgi
Site where secreted proteins are converted to their final forms and packaged for secretion
What is the structural basis of TLR?
Multiple extracellular leucine rich modules
What is the connection between macrophages and CRP?
Macrophages secrete IL-6–> induces synthesis of fibrinogen by hepatocytes–> activates Jak kinas–> increase in CRP
Fc receptors
Bind IgG and enhance phagocytosis
How is nitric oxide made
INOS catalyzes the conversion of arginine to citrulline
Elastase
- One of the most important enzymes in neutrophils
- Broad spectrum serine protease
- Required for killing many types of bacteria
What do Natural Killer cells express?
CD16 (Fc receptor for IgG) and CD56
What types of cells do NK cells recognize?
- cells coated with Fc IgG
- Cells infected with viruses
- cells lacking MHC class I (tumor)
Classical pathway
- Antibody dependent
- Plasma protein C1q detects antibodies bound to surface of microbe or another structure
- Once C1q binds to the Fc portion, two associated serine proteases, C1r and C1s become active and initiate a proteolytic cascade
Alternative pathway
- Not antibody mediated
- Triggered when C3 recognizes certain microbial structures such as bacterial LPS, leading to cleavage to C3b and C3a
Which complement components lead to increased vascular permeability?
- C3a and C5a
Which complement component has chemotactic ability?
- C5a
Which complement can opsonize?
- C3a
How does the MAC complex become formed?
- C5b binds C6 and C7
- They become a high affinity receptor for C8
- C9 binds to C5b-8 to form the fully active MAC
- MAC forms pores in plasma membranes in cells its deposited on–> entry of water–> osmotic swelling and cell rupture
- Expressed on bone marrow derived cells
- Promotes phagocytosis of C3b and C4b opsonized particles
- On erythrocytes, binds circulating immune complexes and transports them to liver and spleen
- Type I complement receptor CR1/CD35
- Stimulates humoral immune response by enhancing B cell activation by antigen and promoting trapping of antigen-antibody complexes in germinal centers
- Type 2 Complement receptor CR2/CD21
- Integrin expressed on neutrophils, mononuclear phagocytes, mast cells and Nk
- Promotes phagocytosis
- Also binds to ICAM1 on endothelial cells–> leukocyte migration
Type 3 CR
CR3/Mac-1, CD11bCD18
Similar to Type 3
Found on DCs
CR4, p150, 95, CD11C, CD18
Expressed on liver macrophages
Involved in clearance of opsonized bacteria and other blood borne pathogens
CRIg
Produced by monocytes and macrophages upon stimulation with IFN g
- Marker of Th1 derived immune activation
Pentraxins
CRP
SAA
IL-2
- Source is T cells
- Growth factor for antigen stimulated T cells
- Can also lead to proliferation and activation of NK cells
iL-4
Inhibition of macrophage activation
IL-10
- Inhibits production of IL12 and TNF by activated macrophages
- Inhibits expression of co stimulators and MHC class II molecules on macrophages
IL-12
- Has both innate and adaptive functions
- Mediator of early innate immune response to intracelluar microbes
- Produced in response to TLR
- Stimulates interferon gamma production by NK cells
- Stimulates diff of CD4 helper into Th1
- Stimulates CD8 to CTL
- Stimulates IFNG production by T cells
Phospholipase A2
Produces arachidonic acid
What are the three major metabolites from Arachidonic acid ?
COX–> Prostagladins, thromboxane
LOX–> Leukotrienes
Inhibits the action of phospholipase 2
Steroids
Which COX is inducible enzyme during inflammation?
COX 2
How to NSAIDs cause ulcers
block Cox –> decreased Prostaglandins–> increased stomach acid, decreased mucous secretion
Mediate bronchoconstriction and vasoconstriction
Leukotrienes
What induces MHC class II on macrophages
- IFN gamma
Proteolytic fragment of C2
Kinin
