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Chapter 15: The Innate Immune Response. Important Point:. If you are having trouble understanding lecture material: Try reading your text before attending lectures. And take the time to read it well!.
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Important Point: If you are having trouble understanding lecture material: Try reading your text before attending lectures. And take the time to read it well!
“From a microorganism’s standpoint, the tissues and fluids of the human body are much like a warm culture flask filled with a nutrient-rich solution.” • “Considering this, it may be surprising that the interior of the body--including blood, muscles, bones, and organs--is generally sterile.” • “If this were not the case, microbes would simply degrade our tissues, just as they readily decompose the carcass of a dead animal.” • The immunity that keeps us from decomposing like said carcass can be differentiated into an Innate Immunity and an Adaptive Immunity. • This chapter will concentrate on Innate Immunity. Immunity
“From a microorganism’s standpoint, the tissues and fluids of the human body are much like a warm culture flask filled with a nutrient-rich solution.” • “Considering this, it may be surprising that the interior of the body--including blood, muscles, bones, and organs--is generally sterile.” • “If this were not the case, microbes would simply degrade our tissues, just as they readily decompose the carcass of a dead animal.” • The immunity that keeps us from decomposing like said carcass can be differentiated into an Innate Immunity and an Adaptive Immunity. • This chapter will concentrate on Innate Immunity. Immunity Recall that “Sterile” means absence of life, though here we mean absence of microorganisms.
The skin is the most difficult surface to penetrate. • Mucous on mucous membranes helps wash away microbes, in some cases via active propulsion such as via the lung’s mucocilliary escalator. • Lysozyme, an enzyme that destroys particularly Gram-positive cell walls, is found in various body fluids, secretions, and defensive cells. • Lactoferrin sequesters iron within the body; iron is a key nutrient required for bacterial growth. • Defensins are small proteins that create pores in bacterial membranes (killing the bacteria). • Free Fatty Acids essentially are soap. • Normal flora occupies space, utilizes nutrients, and produces antimicrobial substances that together can prevent pathogen colonization of body surfaces. First-Line Defenses
PMNs Polymorphonuclear Neutrophilic Leukocytes, a.k.a., PMNs. They are shorter lived than macrophages but have greater killing power.
Non-Phagocytic Granulocytes Eosinophils are involved in allergic responses, inflammation, and release of Histamine; Histamine is released by Basophils.
Mediators of Adaptive Immunity These are mostly considered in chapter 16.
Toll-Like Receptors Including phagocyte-attracting citokines. Danger, I’m infected! signal.
Complement 2. Complement proteins are activated by various mechanisms. 1. Inactive complement proteins are in constant circulation. 3. These are the consequences...
Complement Activation Let’s just worry about Classical and Alternative Pathways...
Complement Cascade Let’s just worry about C3a, C3b, and C5a. Note, typo!
Note, typo! Complement Action Opsonization signals phagocytes to engulf materials including bacterial cells. C3b serves as an Opsonin. C3b binds to all cells but is actively removed from body cells.
Phagocytosis “It is the toll-like receptors on macrophages that enable them to sense that the material is microbial in origin, and must therefore be eliminated quickly.” Chemotaxis = movement toward infections.
Inflammation gives rise to localized reddening, swelling, increased temperatures, and pain. • The function of inflammation is to localize tissue damage, localize responses, and then to restore tissue function. • The action of localized leukocytes is augmented (i.e., enhanced) via the attraction of neutrophils and monocytes normally found in circulation. • Microbial materials such as LPS, flagellin (making up bacterial flagella), activated complement, and even bacterial DNA serve as indicators of infection which in turn activates the production of pro-inflammatory cytokines (immune-system activating chemicals). • In addition to the cell-to-cell interactions underlying inflammation, the inflammatory response involves localized increases in blood flow, leakage of blood vessels, and attraction of leukocytes from the blood. Inflammation
Inflammation is a great tool, unless it becomes chronic or non-localized. • Chronic inflammation typically has an underlying cause (e.g., ongoing infection). • Non-localized inflammatory responses gives rise to body-wide vessel dilation and leakage, resulting in precipitous drops in blood pressure called Shock. • Endotoxin signals inflammatory responses and systemic infections with Gram-negative bacteria can give rise to a very dangerous condition known as Septic Shock. • Fever is the preferred systemic response to bacterial infection. • Fevers are elevated body temperatures induced either by pathogen molecules or by body molecules produced in response to pathogen molecules. • Fever results in temperatures that, ideally, inhibit microbes while enhancing body defenses. Fever
Interferon: An Antiviral dsRNA normally is not present in cells.
