I. BACTERIAL PATHOGENESIS
B. VIRULENCE FACTORS THAT PROMOTE BACTERIAL COLONIZATION OF THE HOST
5. The ability to resist innate immune defenses such as phagocytosis and complement
a. an overview of phagocytosis and the complement pathways
The overall purpose of this Learning Object is to introduce the process of phagocytosis and the functions of the body's complement pathways as an integral part of body defense. These defenses will be discussed in greater detail in later units.
LEARNING OBJECTIVES FOR THIS SECTION
In this section on Bacterial Pathogenesis we are looking at virulence factors that promote bacterial colonization of the host. The following are virulence factors that promote bacterial colonization of the host .
1. The ability to use motility and other means to contact host cells and disseminate within a host.
2. The ability to adhere to host cells and resist physical removal.
3. The ability to invade host cells.
4. The ability to compete for iron and other nutrients.
5. The ability to resist innate immune defenses such as phagocytosis and complement.
6. The ability to evade adaptive immune defenses.
We will now look at virulence factors that enable bacteria to resist innate immune defenses such as phagocytosis and complement.
5. The Ability to Resist Innate Immune Defenses such as Phagocytosis and Complement
a. An Overview of Phagocytosis and the Complement Pathways
1. An Overview of Phagocytosis
As will be seen in Unit 4, there are several steps involved in phagocytosis.
First the surface of the microbe must be attached to the cytoplasmic membrane of the phagocyte. Attachment of microorganisms is necessary for ingestion and may be unenhanced or enhanced.
1. Unenhanced attachment is a general recognition of what are called pathogen-associated molecular patterns or PAMPs (def) - components of common molecules such as peptidoglycan, teichoic acids, lipopolysaccharide, mannans, and glucans common in microbial cell walls but not found on human cells - by means of glycoprotein known as endocytic pattern-recognition receptors (def) on the surface of the phagocytes (see Fig. 1).
2. Enhanced attachment is the attachment of microbes to phagocytes by way of an antibody (def) molecule called IgG or two proteins produced during the complement pathways (def) called C3b and C4b (see Fig. 2). Molecules such as IgG, C3b, and C4b that promote enhanced attachment are called opsonins (def) and the process is called opsonization (def). Enhanced attachment is much more specific and efficient than unenhanced.
Following attachment, polymerization and then depolymerization of actin filaments (def) send pseudopods out to engulf the microbe (see Fig. 3) and place it in a vesicle called a phagosome (def) (see Fig. 4).
During this process, an electron pump brings protons (H+) into the phagosome. This lowers the pH within the phagosome so that when a lysosome fuses with the phagosome, the pH is correct for the acid hydrolases to effectively break down cellular proteins.
1. intracellular destruction
Finally, lysosomes (def), containing digestive enzymes and microbicidal chemicals, fuse with the phagosome containing the ingested microbe and the microbe is destroyed (see Fig. 5).
2. extracellular destruction
If the the infection site contains very large numbers of microorganisms and high levels of inflammatory cytokines and chemokines are being produced in response to PAMPs , the phagocyte will empty the contents of its lysosomes by a process called degranulation in order to kill the microorganisms or cell extracellularly (see Fig. 11).
To view a scanning electron micrograph of a macrophage with pseudopods and phagocytosis of E. coli by a macrophage on a blood vessel, see Dennis Kunkel's Microscopy, University of Hawaii-Manoa.
2. An Overview of the Body's Complement Pathways
Some bacteria are able to interfere with the body's complement pathways. The complement pathways (def) will be discussed in detail later in Unit 4, but a brief summary is relevant here.
There are three complement pathways: the classical complement pathway, the alternative complement pathway, and the lectin pathway. While the three pathways differ in the way they are activated, once activated they all produce the same benificial complement proteins. Basically the complement proteins are a series of serum proteins that when activated participate in four important body defense functions. These include:
Inflammation is the means by which body defense cells and defense chemicals leave the blood and enter the tissue around an injured or infected site. Complement proteins known as C5a, C3a, and C4a lead to vasodilation, increased capillary permeability, and the expression of the adhesion molecules on leukocytes and the vascular endothelium. This enables leukocytes to adhere to the inner wall of the capillaries, pass between the endothelial cells, and enter the surrounding tissue. Vasodilation also enables a variety of defense chemicals in the plasma of the blood to enter the tissue.These defense chemicals include antibodies and complement proteins. C5a also causes neutrophils to release proteases and toxic oxygen radicals for extracellular killing of microbes.
b. Phagocyte Chemotaxis
Complement proteins C3a and C4a are chemoattractants for leukocytes. Chemotaxis enables the phagocytes to move toward the infected area in order to remove microorganisms.
Movie showing chemotaxis by neutrophil as they remove dead liver cells.
From Science Friday on NPR; originally published in Science by Paul Kubes and colleagues.
c. Opsonization (Enhanced Attachment)
The complement proteins C3b and C4b are known as opsonins because they bind microbes to phagocytes (see Fig. 2). One portion of the molecule binds to microbial proteins while the other portion binds to receptors on phagocytes. In this way, microbes can be engulfed by phagocytes more effectively.
d. MAC Lysis of Biological Membranes
A series of complement proteins known as the membrane attack complex or MAC put pores in cellular membranes resulting in lysis. This is used to kill such things as gram-negative bacteria, virus-infected cells, and tumor cells.
These processes will be discussed in greater detail in Unit 4.
3. Certain bacteria can resist antibacterial peptides
The body produces a number of antibacterial peptides such as human defensins (def) that are directly toxic by forming pores in the cytoplasmic membrane of a variety of microorganisms causing leakage of cellular needs. They also activate cells for an inflammatory response. Defensins are produced by leukocytes, epithelial cells, and other cells. They are also found in blood plasma and mucus.
Some bacteria are able to resist phagocytosis and interfere with the body's complement pathways (def). In the next two sections we will look at the following virulence factors:
1. The ability to resist phagocytic engulfment (attachment and ingestion)
2. The ability to resist phagocytic destruction and serum lysis
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Updated: Oct., 2012
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