Flashcards in L15_Innate Immunity Deck (29):
Are endotoxins directly toxic to cells?
No, they induce the body to produce toxic particles.
Which portion of LPS is antigenic and which portion is the actual toxic component?
The polysaccharide end is often antigenic and is the determinant of the O-antigen. The actual toxicity resides in the lipid A region
What are some of the symptoms of septic shock?
Fever, headache, vomiting, decreased BP and cardiac output, possible DIC or ARDS
What is DIC?
Disseminated Intravascular Coagulation, formation of platelet thrombi and blood clotting in multiple sites leading to a depletion of clotting components often followed by widespread hemorrhage.
What does ARDS stand for?
Acute Respiratory Distress Syndrome
What is a pyrogen?
something that can cause fever. All IV bags will say pyrogen free.
What is most likely the cause of toxicity in septic shock?
proteins produced by LPS-stimulated macrophages: IL-1 TNF alpha, and IL 6
What are some of the local effects of TNF alpha and IL1
TNF- activates endothelium and increases vascular permeability, which leads to increased entry of complement and cells to tissues and increased fluid drainage to lymph nodes.
IL1 - Activates vascular endothelium, Activates lymphocytes, local tissues destruction, increases access of effector cells.
What class of receptors recognize invading pathogens?
Toll Like Receptors. All of the TLRs have a common signal transduction pathways which explain why so many diverse molecules induce similar patterns of cytokine.
What is the difference between Septic Shock and Toxic Shock.
Septic shock is usually caused by GRAM neg bacteria, LPS induces inflammatory factors that lead to shock, Toxic shock causes some of the same effects but initiates the shock via a different pathway, a super antigen binds TCR and APCs in a non specific way causing a wave of cytokines that activate similar pathways to those in Septic shock.
What complement components for the membrane attack complex?
What does the activation of the complement cascade result in?
Cell lysis, increased phagocytosis, increased vascular permeability, enhanced leukocyte chemotaxis, and functional stimulation of macrophages.
How do you tell a complement protein involved in the classical pathway or alternate pathway apart by nomenclature?
Classical C#, Alternative capital letters other than C
What is the first to act, the alternate or classical pathway?
What receptor does LPS bind to?
All else being equal, what fixes complement better IgG or IgM?
IgM because it only take 1 molecule of pentameric IgM, it takes two molecules of IgG situated close together.
How do self cells protect against the alternative complement pathway?
They have proteins such as DAF and MCP that disrupt C3bBb on human cell surfaces
Briefly describe how the classical leads to the fixation of C3b
IgM or IgG binds to pathogen surface, C1 binds to 1 IgM or two IgGs, C1 cleaves both C2 and C4, C4bC2a is then a C3 convertase.
Briefly describe how the alternative pathway leads to fixation of C3b on pathogen surface
naturally dissociated C3b bind pathogen surface, Protein B binds C3b, Protein D cleave protein B, C3bBb is then an active C3 convertase
how C3bBb is stabilized
Properdin stabilizes it
How is the alternative pathway inhibited?
Facter H and I work to cleave C3b, C3bi is no longer active but still works as an opsonin
What is the most important role of complement
To fix on bacterial surface and induce phagocytosis without the aid of antibody
how are circulating antibody complexes disposed of?
Complement (C1,2,4) will bind and fixe C3b which then is most likely bound by erythrocytes with C3b receptors that will bring it to macrophages in the liver or spleen for disposal.
Briefly describe the lytic pathway, how is this inhibited on host cells?
C3b forms a complex that can cleave C5, C5b then interacts with 6,7, and 8 to poke a hole in the membrane, multiple C9 are then recruited and help form a pore. C5a is the most important chemotactic factor in the complement system. (CD59 on host cells binds to C5b678 and inhibits pore formation)
What are the 3 most anaphalaxic toxins in the complement pathway? what do they do?
C3a, C5a, and C4a, they increase vascular permeability and C5a helps attract polymorphonuclear leukocytes and macrophages to the site of inflammation
What is the only bacterial infection in which the lytic pathway of complement is absolutely necessary to clear the pathogen?
What would be the result of a C1, C2, C4 defect?
Immune complex disease (looks like a systemic lupus) this is the most important role of these complement factors
What is the most abundant complement component?