I.
THE INNATE IMMUNE SYSTEM
D.
EARLY INDUCED INNATE IMMUNITY
10. THE ACUTE PHASE RESPONSE
Fundamental Statements for this Learning Object:
1. 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.
2. Inflammatory cytokines produced during innate immunity travel through the blood and stimulate hepatocytes in the liver to synthesize and secrete acute phase proteins.
3. Two important acute phase proteins are C-reactive protein and mannose-binding protein, both functioning as soluble pattern-recognition receptors.
4. C-reactive protein (CRP) binds to certain PAMPs bacterial and fungal cell walls as well as to phosphocholine found on the surface of damaged or dead human cells.
5. CRP functions as an opsonin, sticking the microorganism to phagocytes, and activates the classical complement pathway by binding C1q, the first component in the pathway.
6. Mannan-binding lectin (MBL) - also known as mannan-binding protein or MBP - binds to mannose-rich glycans on microbial cell walls.
7. MBL functions as an opsonin, sticking the microorganism to phagocytes, and activates the lectin pathway.
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:
- phagocytic cells: leukocytes
such as neutrophils, eosinophils, and monocytes; tissue phagocytic cells
in the tissue such as macrophages (def);
- cells that release inflammatory
mediators: inflammatory cells in the tissue such as macrophages and mast
cells (def); leukocytes such as basophils and eosinophils; and
- natural killer cells (NK cells (def)).
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 be recognized as a part of innate immunity. These are often referred to as danger-associated molecular patterns or DAMPs.
Most body defense cells
have pattern-recognition receptors or PRRs (def) for
these common PAMPs (see
Fig. 1) enabling 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.
Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.
Last updated: Feb., 2020
Please send comments and inquiries to Dr.
Gary Kaiser