Chapter 14 HOST-PARASITE RELATIONS P.G. REDDY

 

14.1 SUMMARY OF MAJOR OBJECTIVES

This is the first of a series of lectures dealing with host response to invasion by a pathogenic microorganism. Basically, it is a study of the immune system (Immunology).

Please view the following video tapes in AV/AT laboratory at your convenience.

1. Basic Concepts of Immunology - TV 192

2. The Immune System - TV 927 (Parts I, II, III)

3. Lab. Technics in Vet. Clinical Immunology - TV 670

Study of this chapter should enable you to answer questions such as:

1) What are all the possible outcomes of an infection? 2) What is meant by "Innate immunity"? Specifically, you should be able to explain in detail about "first and second lines of defense mechanisms". 3) What are phagocytic cells? Explain the mechanisms used by these cells to destroy organisms that have entered the body.

14.2 HOST-PARASITE RELATIONS

An infection when occurs, may have several possible outcomes. These outcomes are controlled by strong effecter mechanisms of the host ranged against sophisticated evasion strategies of the invading parasite.

In order to understand the infectious process it is necessary to understand the nature of the parasite and its preferences for growth; the response of the host, and the environment in which the host and parasite interact. The concept of multicausational factors focuses on this interaction.

From hosts view point - the ideal is: complete elimination of the invading organism with establishment of resistance to reinfection from the same organism. The above is true in many infections. However, the following outcomes are possible:

14.3 NON SPECIFIC HOST RESISTANCE

Invertebrates and veterbrates must have an effective set of mechanisms to avoid microbial invasion. Since all organisms are potential sources of nutrients for microorganisms, an effective defense is essential. Immunity is directed toward preventing the agent from gaining entry or becoming infectious and causing disease. In order to facilitate the understanding of the host immune system, the following categories of immunity will be characterized:

First Line of Defense:

anatomical, physiological and ecological barriers.

Second Line of Defense:

the aggressive defense mechanism (phagocytes, complement etc.). The above two are considered as Innate Immunity (Lecture #14 and 15).

Third Line of Defense:

specific acquired immunity (Lectures #16 and 17).

Please note that this presentation is a course of study for general understanding and does not represent the well-programmed interactions that occur among different systems, cell types and molecules.

14.3.1 First Line of Defense

This category represents the combined protective effects of anatomical and physiological barriers modified by nutritional, hormonal and genetic properties of the individual and the species. This defense mechanism is general or non-specific; well developed at birth; does not alter significantly from one infectious episode to the next.

Physical barriers:

Most important physical barrier is skin. When there is a loss of skin (burns and wounds) infection becomes a major problem. The muco-ciliary escalator acts as a clearing mechanism coupled with reflex responses such as coughing and sneezing.

Mechanical barriers:

mucus, washing action of tears, saliva and urine.

Chemical barriers:

lysozyme, lactoferrin, transferring, bactericidins and natural antibiotics, acid in gastric juice, altered pH, 0-R potential, lipids, glycoproteins, etc.

 Ecological barriers:

colonization by normal bacterial flora causing competition for space. Thus they suppress the growth of pathogenic bacteria.

 Nutritional Immunity:

a consistent host response to bacterial infection is the reduction of plasma iron levels. It appears that the role of iron-specific nutritional immunity is most important between the time of microbial invasion and the onset of cell multiplication. Two important iron-binding proteins, serum transferring and lactoferrin, function to sequester iron. It is important to note that some pathogens produce siderophores that compete with the host's iron sequestering abilities. 

Fever:

its role as a defense mechanism is not understood. There are a variety of activators ( endotoxin, microorganisms) that interact with a variety of cell types such as monocytes and granulocytes to induce the release of interleukin-1 (IL-1; endogenous pyrogen; please refer to page 276 of Vet. Immunology by Tizard). The IL-1 may stimulate: fever, neutrophilia, immune stimulation, and complement activation and release of acute phase proteins some of which act as iron binding proteins. Example: microbial invasion---host becomes hyperferremic---host resistance is enhanced by transferring withholding the iron that the microbes might utilize.

14.3.2 Second Line of Defense:

This category includes those non-specific resistance factors of the host and their response to infection and disease.

 14.3.3 Phagocytosis:

Organisms that succeed in entering the tissues are rapidly exposed to phagocytic cells. These cells recognize, attach to, endocytose and digest foreign material.

1. Cell Types:

a. microphages: polymorphonuclear neutrophils (PMN's)

b. macrophages:

Bone marrow promonocytes Blood monocytes Tissue macrophages

2. Chemotaxis:

process by which phagocytes are attracted to sites of inflammation. Phagocytes migrate up a concentration gradient of C5a, a component of the complement. PMN's traverse capillaries to the site of inflammation (infection) by attachment and diapedesis. 

3. Phagocytic cells

have receptors on their surface which allow attachment to microbes. Attachment is enhanced by opsonization by the C3b component of complement and antibody.

 4. Phagocytes

engulf microbes by extending pseudopodia which fuse to form a phagosome. Lysosome fuses with phagosome to form a phagolysosome and the microbe is killed by a discharge of cytoplasmic granules (degranulation) with different microbicidal mechanisms.

5. Killing: 

a. Oxygen-dependent mechanisms:

increase in activity of the hexose monophosphate shunt generating NADPH _ burst of oxygen consumption. As a result oxygen is converted into superoxide anion, hydrogen peroxide, singlet O2, and hydroxy radicals - all these substances are powerful microbicidal agents. Further, the combination of peroxide, myeloperoxidase and halide ions constitute a powerful agent to kill both bacteria and viruses.

b. Oxygen-independent mechanisms:

low mol. wt. defensins, cathepsin G, high mol. wt. cationic proteins, bactericidal permeability increasing protein - all are capable of causing damage to microbial membranes. Lysozyme - damage to cell wall. Lactoferrin - sequestration of iron. Other proteolytic enzymes - digestion of killed organism.