Innate Immunity Flashcards
What are the two methods used to get bacteria into a phagocyte?
1- Direct receptor
2- Compliment
What are the three means of innate immunity?
Mechanical, chemical, microbiological
What is an endotoxin?
A component of gram - bacteria cell walls
What is the immunological effect of endotoxins?
gram negative sepsis if it happens at a systemic level
What end of the endotoxin contains the “toxin”?
The hydrophobic lipid rich end
Which end of the endotoxin is usually antigenic?
hydrophilic polysaccharide rich end
How are endotoxins destroyed?
baking at a high temperature
What is IL-1?
Interleukin 1
What effects does IL-1 mediate?
1- activate vascular endothelium
2-activated lymphocytes
3- Local tissue distruction
4- increase accessof effector cells (makes vessels leaky)
What are the side effects of IL-1?
1- Fever
2- Production of IL-6
What induces IL-1?
TNF- alpha
What are the local effects of TNF-alpha?
Activates vascular endothelium and increases vascular permeability
Increased entry of complument and cells to tissues.
Increased fluid drainage to lymph nodes
What are the systemic effects of TN-alpha?
Fever
Mobilization of metabolites
Shock
Where is the overlap in function between TNF-alpha and IL-1?
Stimulation of B cells
Inducing Fever
What cell receptor binds LPS?
CD14
What TLR interacts with CD14?
TLR4
What do superantigens induce?
Through non-specific crosslinking, superantigens induce TNF-alpha and IL-1
What is the compliment system?
A complex system of sequentially interacting serum proteins
What does the compliment system result in?
cell lysis
increased phagocytosis
functional stimulation of macrophages
What is the goal of the compliment system?
Cleavage of C3
What is the membrane attack complex?
C5-C9 components
What do membrane attack complexes achieve?
Lysis of the target cell
What pathway is C1 involved in?
Classical pathway
What is the structure of C1?
3 proteins non covalently bound to one another
What does C1 bind more readily, IgG or IgM?
IgM binds more readily. Need 100X more IgG to trigger compliment.
What does C1s cleave?
C4 and C2
What happends to C4b once C4 is cleaved?
It becomes covalently attached to the microbial surface
What does C2a bind to?
It binds to C4b
What is the function of the C4bC2a complex?
cleave C3
Where does C3b go when it is cleaved?
accumulates of the micobial surface
in the alternative pathway, C3b on the cell surface binds what?
It binds D
What does D cleave?
It cleaves B
Which subunit of B stays attached to C3b?
Bb
For the classical pathway, what is the C3 convertase?
C4bC2a
For the alternative pathway, what is the C3 convertase?
C3bBb
What needs to happen for both pathways to be activated?
C1 needs to bind antibody
What does the deposition of C3b lead to?
Opsonization
Clearance of Immune complexes
What has the ability to stabilize the C4bC2a complex on the cell surface?
properdin
What inactivates C3b
Factor H and Factor I
What disrupts the C3bBb convertase?
DAF and MCP
How does the compliment system destroy immune complexes?
C1 binds and then eventually the immune complex gets coated with C3b
Where does destruction of the immune complexes occur?
In the liver and the spleen
What is the function of C5a?
it is a critically important chemoattractor that causes more leukocytes to come to the area
What allows for the formation of C5a?
Classical: C4bC2aC2b binds and cleaves C5
Alternative: C3bBbC3b binds and cleaves C5
What does C5b do?
Begins the lytic pathway and attracts other factors (C6-C9) that poke holes in the membrane to form a pore
Which two factors act on blood vessel permeability?
C3a and C5a
What has the ability to inhibit C1?
C1INH
Which deficiencies are more severe?
Alternative (C3 or another althernative pathway factors)
If missing C1 what is an individual unable to do?
Clear antibody complexes
