1. Burton's Microbiology for the Health Sciences Chapter 15
Burton's Microbiology for the Health Sciences Chapter 15. Nonspecific Host Defense Mechanisms

2. Chapter 15 Outline Introduction Nonspecific Host Defense Mechanisms
First Line of Defense
Second Line of Defense

3. Introduction Host Defense Mechanisms
Ways in which the body protects itself from pathogens – referred to as 3 lines of defense.
First 2 lines of defense are nonspecific.
The 3rd line of defense, the immune response, is very specific.
In the 3rd line of defense, special proteins called antibodies are produced in response to foreign substances called antigens.

4. Lines of Defense

5. Nonspecific Host Defense Mechanisms
Nonspecific host defense mechanisms are general and serve to protect the body against many harmful substances.
Example: innate or inborn resistance.
Exact factors that produce innate resistance are not well understood.
Other nonspecific host defense mechanisms include mechanical and physical barriers to invasion, chemical factors, microbial antagonism, fever, the inflammatory response, and phagocytic white blood cells.

6. First Line of Defense http://www.healthknot.com/body_defense.html
Skin and Mucous Membranes as Physical Barriers
Cellular and Chemical Factors
In addition to the skin as a physical barrier, there are other factors (e.g., pH and temperature of skin, temperature, perspiration, cilia, and various enzymes in secretions such as lysozyme) that are components of the first line of defense.
Microbial Antagonism
When indigenous microflora prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances.

7. Second Line of Defense Transferrin
Levels of this glycoprotein increase in response to systemic bacterial infections; binds to iron, depriving pathogens of this vital nutrient
Fever
Stimulated by pyrogenic (fever-producing) substances (e.g., pathogens and Interleukin 1 [IL-1])
Augments host’s defenses by stimulating leukocytes, reducing available free plasma iron, and inducing the production of IL-1

8. Second Line of Defense, cont.
Interferons
Small antiviral proteins produced by virus-infected cells; they prevent viruses from multiplying
There are 3 types (alpha, beta and gamma), produced by 3 different types of cells
The 3 types are induced by different stimuli (e.g., viruses, tumors, bacteria, and foreign cells)
Interferons are not virus-specific, but they are species-specific
Interferons can cause nonspecific flu-like symptoms

9. Second Line of Defense, cont.
The Complement System
A group of about 30 different proteins found in normal blood plasma – “complementary” to the immune system
Complement components interact with each other in a stepwise manner known as the complement cascade
The complement system assists in the destruction of many different pathogens
Opsonization is a process by which phagocytosis is facilitated by the deposition of opsonins (e.g., antibodies or certain complement fragments) onto objects (e.g., pathogens)

10. Second Line of Defense, cont.
Acute-Phase Proteins
Plasma proteins that increase rapidly in response to infection, inflammation, or tissue injury; one example is C-reactive protein
Cytokines
Chemical mediators released from many different types of cells in the body; enable cells to communicate with each other – within the immune system and between the immune system and other systems of the body
Some cytokines are chemoattractants; they recruit phagocytes to sites where they are needed

11. Second Line of Defense Inflammation
The body responds to any local injury, irritation, microbial invasion, or bacterial toxin by a complex series of events referred to as inflammation; the 3 major events in acute inflammation are:
An increase in the diameter of capillaries (vasodilation) which increases blood flow to the site
Increased permeability of the capillaries, allowing the escape of plasma and plasma proteins
Exit of leukocytes from the capillaries and their accumulation at the site of injury

12. Inflammation, cont.
The primary purposes of the inflammatory response are to:
Localize an infection
Prevent the spread of microbial invaders
Neutralize any toxins being produced at the site
Aid in the repair of damaged tissue
The 4 major signs and symptoms of inflammation are: redness, heat, swelling (edema), and pain
Plasma that escapes from the capillaries into the site causes the area to become edematous (swollen)

13. Sequence of Events in Inflammation
Tissue Injury
Vasodilation
Increased Permeability
Emigration of Leukocytes
Chemotaxis
Phagocytosis
ebs.org/immun ity.htm

14. Inflammation, cont.
The accumulation of fluid, cells, and cellular debris at the inflammation site is known as an inflammatory exudate.
If the exudate is thick and greenish-yellow, containing many live and dead leukocytes, it is known as a purulent exudate or pus.
In many inflammatory responses (e.g., arthritis or pancreatitis) there is no exudate and no invading microorganisms.
Pyogenic microorganisms (pus- producing microorganisms) like staphylococci and streptococci result in additional pus formation.

15. Phagocytosis
Phagocytic white blood cells are called phagocytes, and the process by which they surround and engulf (ingest) foreign material is called phagocytosis.
The 3 major categories of leukocytes (white cells) found in blood are monocytes, lymphocytes, and granulocytes.
The 3 types of granulocytes are: eosinophils, basophils, and neutrophils.
The most important groups of phagocytes in the human body are macrophages and neutrophils.

16. Cellular Elements of Human Blood

18. Opsonization is the coating of microbes with complement components, such as C3b.
Opsonized particles are more easily phagocytosed due to the presence of complement receptors on the plasma membrane of phagocytic cells.

19. Opsonization
Nucleus
Phagocyte, having no surface receptors which can attach to the bacterial capsule.
Phagocyte has receptors which can attach to complement fragments (opsonins) which have been deposited onto the capsule.
Bacterium
Phagocyte has receptors which can attach to antibodies (opsonins) which have been deposited onto the capsule.

20. The Ingestion Phase of Phagocytosis
Bacterial cell
Phagocyte
Attachment
Pseudopodia extend around bacterial cell
Pseudopodia fuse
Bacterial cell is within the phagocyte

21. The Digestion Phase of Phagocytosis
Lysosome with digestive enzymes moves toward phagosome
Lysosome membrane fuses with phagosome membrane
Lysosome and phagosome become a single membrane-bound vesicle
Bacterial cell is digested within the phagolysosome

22. Photomicrograph of Rat Leukocytes, Some of Which Contain Phagocytized Giardia Trophozoites

23. Scanning electron micrographs, illustrating the phagocytosis of Giardia trophozoites; G = Giardia trophozoite, L = leukocyte.

24. Mechanisms by Which Pathogens Escape Destruction by Phagocytes
Capsules; initially serve to protect the organism from phagocytosis (they serve an antiphagocytic function)
Some bacteria produce an exoenzyme called leukocidin, which kills phagocytes.
Some bacteria (e.g., Mycobacterium tuberculosis) are not destroyed within the phagolysosome.
The mechanism by which each pathogen evades digestion by lysosomal enzymes differs from pathogen to pathogen, and is not yet fully understood.

25. Leukopenia - an abnormally low number of circulating leukocytes
Disorders and Conditions that Adversely Affect Phagocytic and Inflammatory Processes
Leukopenia - an abnormally low number of circulating leukocytes
Disorders and Conditions Affecting Leukocyte Motility and Chemotaxis
Inabililty of leukocytes to migrate in response to chemotactic agents may be related to a defect in the production of actin, a structural protein associated with motility
Disorders and Conditions Affecting Intracellular Killing By Phagocytes (e.g., chronic granulomatous disease, CGD)
Additional Factors
Figure 1.Peripheral smear shows no blastocytes but an atypical lymphocyte, mild leukopenia, and thrombocytopenia

26. Additional Factors that Can Impair Host Defense Mechanisms
Nutritional status
Increased iron levels
Stress
Cancer and cancer chemotherapy
Various genetic defects
Age
AIDS
Drugs (e.g., steroids)