Innate Immunity

Question 1

Endotoxins and Toll Like Receptors

Answer 1

• most bacteria could grow without any apparent tissue damage if toxins were not produced
• in many cases the targets of the toxins are immune cells whose death or inhibition of function would be beneficial to the microorganisms
• some toxins are not directly toxic to the host, but instead induce leukocytes to produce IF mediators that are toxic

Question 2

endotoxin

Answer 2

• LPS
• membrane component of the cell wall
• not directly toxic
• induces the body to produce toxic molecules
• hydrophobic lipid rich end and a hydrophilic polysaccharide end
• polysaccharide is often antigenic and is the O antigen-epitope of 3 or 4 monosaccharides that may be repeated-type bacteria this way
• Lipid A region is toxic region

Question 3

Lipid A region

Answer 3

• disaccharide of glucosamine with a beta1-6 linkage

- often phosphorylated and highly substituted with lipids in both ester and amide linkages

Question 4

LPS and shock

Answer 4

• LPS binds to macrophage and causes release of TNF systemically leads to:
• systemic bacterial infection
• infusion with contaminated IV solution
• hypovolemic shock with decreased BP
• decreased cardiac output
• disseminated intravascular coagulation-platelet thrombi and blood clotting in multiple sites-depletion of clotting factos and hemorrhage
• acute respiratory distress syndrome
• can have necrosis in liver, kidneys, intestine, or lungs without a generalized DIC

Question 5

LPS hard to get rid of

Answer 5

• heat stable
• goes through many filters
• can be destroyed by baking glassware at high temp
• measure using Limulus amebocyte lysate assay
• negative reagents are referred to as pyrogen free

Question 6

local vs systemic

Answer 6

• local response to LPS brings neutrophils and macrophages which secrete TNF
• causes isolated leaky tissues, increased platelet adhesion
• makes it easier to clear
• systemic leads to leaky vessels all over–bad

Question 7

TNFa

Answer 7

• 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
• fever, mobilization of metabolites, shock
• leads to metabolism of fat-cachectin

Question 8

IL1B

Answer 8

• activates vascular endothelium
• activates lymphocytes
• local tissue destruction increases access of effector cells
• fever, production of IL6

Question 9

IL6

Answer 9

• fever

- induces acute phase protein production by hepatocytes

Question 10

liver

Answer 10

• acute phase proteins

- activation of complement opsonization

Question 11

bone-marrow endothelium

Answer 11

• neutrophil mobilization

- phagocytosis

Question 12

hypothalamus

Answer 12

• increased temperature
• decreased viral and bacterial replication
• increased antigen processing
• facilitates adaptive immune response

Question 13

fat/muscle

Answer 13

• protein and energy mobilization to generate increased temperature
• -decreased viral and bacterial replication
• increased antigen processing
• facilitates adaptive immune response

Question 14

dendritic cells

Answer 14

• TNFa stimulates migration to lymph nodes and maturation

- initiation of adaptive immune response

Question 15

recognition of LPS

Answer 15

• LPS receptor (CD14) brings bacteria to surface of macrophage
• TLR is actual receptor- TLR4
• macrophage releases TNF