Innate Immunity Flashcards
What is rule one?
most bacterial die inside phagocyte
endotoxins
recognized by our immune cells to give us a response, one way to recognize bacteria and pick them up, not necessarily toxic, membrane component of cell wall, could cause our body to produce toxic molecules
Lipopolysaccharide (LPS)
gram negative bacteria, heat stable, will go through filters, measured using Limulus Amebocyte Lysate assay, negative reagents are called pyrogen free (does not cause fever in rabbits), can be destroyed by baking glassware at high temperature
toxic component of some gram negative bacteria
gram negative sepsis
caused by body’s response to endotoxins, can be the result of a major trauma, car accident, or contaminated IV solution. results in Disseminated Intravascular Coagulation (DIC), Acute Respiratory Distress Syndrome (ARDS), hypovolemic shock with decreased blood pressure
Limulus Amebocyte Lysate assay
used to measure LPS
IL-6
secreted by macrophages, fever, induces acute phase product production by hepatocytes
TNF alpha
activates vascular endothelium and increases vascular permeability, which leads to increased entry of complement and cells to tissues and increased fluid drainage to lymph nodes
IL-1 beta
activates vascular endothelium, activates lymphocytes, local tissue destruction, increase access of effector cells
Toll Like Receptor (TLR)
binds bacterial LPS, assisted by CD14
bacterial superantigen
made by some bacteria, crosses constant region of MHC and TCR, binding results in large amount of IL-1 and TNF, results in symptoms that look like gram negative sepsis
Complement
one of the critical ways we recognize foreign particles when they come into our body. easily killed by heat, does not increase during immunization (unlike antibodies).
alternative pathway (overview)
pathogen surface creates local environment conducive to complement activation
innate pathway that leads to pathogen surface recognition that leads to recruitment of inflammatory cells, opsonization of pathogens, facilitating uptake and killing by phagocytes, perforation of pathogen cell membranes
classical pathway (overview)
C reactive protein or antibody binds to specific antigen on pathogen surface
classical pathway steps
C1q/C1r/C1s binds to single IgM (or 2 IgG) and cleaves C4 leaving C4b bound to the pathogen surface. C1 complex cleaves C2 leaving C2a bound to C4b. C4b2a cleaves C3 to leave C3b bound to pathogen surface.
alternative pathway steps
C3 spontaneously lyses with B to create C3bBb on pathogen surface. C3bBb lyses C3 to leave C3b bound on pathogen surface
Two types of C3 convertase
C4b2a from classical, C3bBb from alternative pathway.
Properdin
stabilizes C3 convertase C3bBb on a pathogen surface
factor H and factor I
inactivates C3b to leave iC3b on pathogen surface. iC3b can still be target for activation
DAF and MCP
disrupts C3 convertase C3bBb on human cell surface. Inhibits production of C3bBb complex.
Deposition of C3b leads to
binding to complement receptors that allow opsonization and clearance of immune complexes
immune complexes
cleared by complement system with the help of RBC
C5a
critically important chemotactic factor, causes leukocytes to come to bacteria, starts lytic pathway
lytic pathway
results in C9 creating a complex on the pathogen that punches pore in the membrane
C1, C2, C4 (classical pathway) deficiency
cannot clear antibody complexes
C3 (opsonization pathway) deficiency
susceptible to serious bacterial infections
C5-C9 (lytic pathway) deficiency
susceptibility only to Neisseria
what molecules made by our bodies can mediate septic shock
TNF alpha and IL-1
membrane attack complex
formed by components C5-C9, lyses target cell
CR1
receptor on phagocytes that bind C3b
