10. Promoting an Inflammatory Response
Antigen-antibody reactions can also promote an inflammatory response:
a. IgG and IgM can activate the classical complement pathway (see Fig. 1).
As learned under innate immunity in Unit 5, the classical complement pathway is primarily activated when a complement protein complex called C1 interacts with the Fc (def) portion of the antibody molecules (def) IgG or IgM after they have bound to their specific antigen via their Fab portion (def). C1 is also able to directly bind to the surfaces of some pathogens.
The C1 complex is composed of three complement proteins called C1q, C1r, and C1s.
- The C1q is the portion of the C1 complex that binds to the antibodies or the microbe.
by 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: August, 2019
Please send comments and inquiries to Dr. Gary Kaiser
- The binding of C1q activates the C1r portion of C1 which, in turn, activates C1s. This activation gives C1s enzymatic activity to cleave complement protein C4 into C4a and C4b and C2 into C2a and C2b and begin the classical complement pathway.
The beneficial results of the activated complement proteins include :
1. Triggering inflammation (def): C5a>C3a>C4a.
2. Chemotactically attracting phagocytes to the infection site: C5a;
3. Promoting the attachment of antigens (def) to phagocytes via enhanced attachment or opsonization (def): C3b>C4b (discussed earlier under opsonization);
4. Causing the lysis of Gram-negative bacteria, viral envelopes, and human cells displaying foreign epitopes (def) (discussed earlier under MAC cytolysis).
b. IgA can activate the lectin complement pathway and the alternative complement pathway and C5a, C3a, and C4a can trigger inflammation.
c. IgE can bind to mast cells and basophils and trigger the release of inflammatory mediators.
The Fc portion of IgE can bind to receptors on mast cells and basophils (def). Cross linking of the cell-bound IgE by antigen triggers the release of vasodilators and other inflammatory mediators for an inflammatory response (see Fig 2).
As learned under inflammation in Unit 5, most of the body defense elements are located in the blood and inflammation is the means by which body defense cells and defense chemicals leave the blood and enter the tissue around the injured or infected site.
The inflammatory response produces vasodilators that increase capillary permeability. As a result of this increased permeability:
a. Plasma (def) flows out of the blood into the tissue.
Beneficial molecules in the plasma include:
1. Clotting factors. Tissue damage activates the coagulation cascade causing fibrin clots to form to localize the infection, stop the bleeding, and chemotactically attract phagocytes.
2. Antibodies (def). These help remove or block the action of microbes through a variety of methods described in this section.
3. Proteins of the complement pathways (def). These, in turn: 1) stimulate more inflammation (C5a, C3a, and C4a), 2) stick microorganisms to phagocytes (C3b and C4b), 3) chemotactically attract phagocytes ( C5a), and 4) lyse membrane-bound cells displaying foreign antigens (membrane attack complex or MAC).
4. Nutrients. These feed the cells of the inflamed tissue.
5. Lysozyme (def), cathelicidins (def), phospholipase A2 (def), and human defensins (def). Lysozyme degrades peptidoglycan. Cathelicidins are cleaved into two peptides that are directly toxic to microbes and can neutralize LPS from the gram-negative bacterial cell wall. Phospholipase A2 hydrolyzes the phospholipids in the bacterial cytoplasmic membrane. Human defensins put pores in the cytoplasmic membranes of many bacteria. Defensins also activate cells involved in the inflammatory response.
6. Transferrin (def). Transferrin deprives microbes of needed iron.b. Leukocytes enter the tissue through a process called diapedesis (def) or extravasation.
Benefits of diapedesis (def) include:
1. Increased phagocytosis. Phagocytes such as neutrophils, monocytes that differentiate into macrophages when they enter the tissue, and eosinophils are phagocytic leukocytes.
2. More vasodilation. Basophils, eosinophils, neutrophils, and platelets enter the tissue and release or stimulate the production of vasoactive agents that promote inflammation.
3. Cytotoxic T-lymphocytes (CTLs) (def), effector T4-cells (def), and NK cells (def) enter the tissue to kill cells such as infected cells and cancer cells that are displaying foreign antigens (def) on their surface (discussed in Unit 6).