I. THE INNATE IMMUNE SYSTEM
D. EARLY INDUCED INNATE IMMUNITY
10. THE ACUTE PHASE RESPONSEThe overall purpose of this Learning Object is to learn what is meant by the acute phase response and how it functions in innate immune defenses.
LEARNING OBJECTIVES FOR THIS SECTION
D. Early Induced Innate Immunity
Early induced innate immunity begins 4 - 96 hours after exposure to an infectious agent and involves the recruitment of defense cells as a result of pathogen-associated molecular patterns or PAMPS (def) binding to pattern-recognition receptors or PRRs (def). These recruited defense cells include:
Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize molecules shared by groups of related microbes that are essential for the survival of those organisms and are not found associated with mammalian cells. These unique microbial molecules are called pathogen-associated molecular patterns or PAMPS (def) and include LPS from the gram-negative cell wall, peptidoglycan and lipotechoic acids from the gram-positive cell wall, the sugar mannose (a terminal sugar common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial and viral unmethylated CpG DNA, bacterial flagellin, the amino acid N-formylmethionine found in bacterial proteins, double-stranded and single-stranded RNA from viruses, and glucans from fungal cell walls. In addition, unique molecules displayed on stressed, injured, infected, or transformed human cells also act as PAMPS. (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)
Most body defense cells have pattern-recognition receptors or PRRs (def) for these common PAMPS and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 of these microbial molecular patterns.
We will now take a closer look at the acute phase response.
10. The Acute Phase Response
The acute phase response is an innate body defense seen during acute illnesses and involves the increased production of certain blood proteins termed acute phase proteins (def).
Activated macrophages and other leukocytes release inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) when their pattern-recognition receptors (PRRs) bind pathogen associated molecular patterns or PAMPs (def) - molecular components associated with microorganisms but not found as a part of eukaryotic cells. These include bacterial molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, flagellin, pilin, and bacterial DNA. There are also pattern-recognition molecules for viral double-stranded RNA (dsRNA) and fungal cell walls components such as lipoteichoic acids, glycolipids, mannans, and zymosan.
These cytokines travel through the blood and stimulate hepatocytes in the liver to synthesize and secrete acute phase proteins (def). This response provides an early defense and enables the body to recognize foreign substances early on in the infection process prior to the full activation and implementation of the immune responses. Two important acute phase proteins are C-reactive protein and mannose-binding protein. They function as soluble pattern-recognition receptors.
1. C-reactive protein (CRP) binds to the phosphorylcholine portion of teichoic acids and lipopolysaccharides of bacterial and fungal cell walls. It also binds to the phosphocholine found on the surface of damaged or dead human cells. It functions as an opsonin, sticking the microorganism to phagocytes, and activates the classical complement pathway by binding C1q, the first component in the pathway.
2. Mannan-binding lectin (MBL) - also known as mannan-binding protein or MBP - binds to mannose-rich glycans (short carbohydrate chains with the sugar mannose or fructose as the terminal sugar). These are common in microbial glycoproteins and glycolipids but rare in those of humans. It functions as an opsonin, sticking the microorganism to phagocytes, and activates the lectin pathway.
Products of the complement pathways, in turn, promote inflammation, attach microbes to phagocytes, cause to MAC cytolysis, and chemotactically attract phagocytes to the infected area.
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Updated: Sept., 2012
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