Innate Immunity Flashcards
Endotoxins
Heat-stable (pyrogen) cell-associated toxin
NOT directly TOXIN
Induces body to produce toxic molecules
LPS
Endotoxin on gram - bacteria
Pathology of LPS
LPS responsible for many of the body’s responses to gram negative bacteria
- profound inflammatory response
- infiltration of neutrophils and MOs
- increases permeability
- swelling
Septic shock
Endotoxin shock - associated w/ gram - infection
- lethal
- can lead to DIC, necrosis, ARDS
How to avoid Endotoxins
Test for pyrogen using LAL
-if dev DIC - there is LPS present
What toxic about LPS?
Proteins produced by LPS-stimulated MOs are the endogenous mediator (inflammatory cytokines)
- *IL-1
- *TNF-Alpha
TNF-Alpha
Important cytotoxic molecule produced by MO and is an important immunoregulator molecule
- Has overlapping function w/ IL1
- -stimulating B and T cells
- -inducing fever
IL-1
Cytokine secreted by activated and stimulated MOS
_produced as a pro-cytokine (must be cleaved prior to release)
_cleavage often by caspase 1 activated by inflammation sensitive complex (inflammasome)
Super Agtigenic Toxins
TSST-1 - endotoxin causing toxic show syndrom
-In response to the binding of toxin
__both T cells and APC produce many cytokines
–>TNF-alpha and IL1
Complement System
- Much more than lead to cell lysis
- Imp inflammatory mediators
- Role in opsonization
- Imp in clearing immune complexes
- Terminal complement imp in killing Neisseria
Complement
Is the collective term for a complex of sequentially interacting serum proteins
What occurs as a result of complement activation cascade?
Cell lysis Increased phagocytosis Increased vascular permeability Enhance leukocyte chemotaxis Functional stimulation of MOs
What are the two PWs for complement?
Classical PW
Alternative PW
**both lead to cleavage of C3 –>C3a and C3b
C3b attaches to surface of pathogen
Classical PW
- Initiation by IgM or IgG binding to Ag on a pathogen surface
- C1 binds single molecule of IgM (pentamer) or 2 or more IgG
- Activated C1s cleave C4 and C2
- C2a binds to surface C4b - forming C3b convertase (C4b2a)
- binds to C3b and cleaves it
- C3b binds covalently to microbial surface
Alternative PW
Formation and action of the soluable C3 convertase iC3Bb that initiates this PW
- -formation and action of the C3 convertase (C3bBb) at a pathogen surface
- -C3 continuously cleaved and C3b put on pathogen surface