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There are two important processes that play a significant role in parasitism, infections and intoxications.
1. Infection:
Infection refers to entry of a pathogen into host tissues after transmission, and its growth and reproduction resulting in disease.
The events of infection are as below:
(i) Attachment and Colonization by the Pathogen:
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The host contains its own normal microbial flora. A pathogen enters into host and compete normal microbial flora. Pathogens are equipped with certain specialized structure (e.g. haemagglutinin, fimbriae, capsule, lectin, mucus gel, pili, receptors, etc.) that provides high degree of specificity to a particular tissue and help in colonization.
These specialized molecules or structures are also known as adherence factors or adhesins. The adhesins bind to complementary receptor sites present on cell surface of the host.
(ii) Entry of the Pathogen:
After attaching to the surface of epithelium, pathogen enters deeper into the epithelium through:
(a) Producing lytic substances and dissolving host tissues,
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(b) Disrupting the cell surface, or
(c) Degrading carbohydrate-protein complex between the cells.
Moreover, entry of the pathogen inside body is also facilitated by already made breaks, lesions or ulcers in mucus membrane, wounds, bums or abrasions on skin, wounds created by arthropods, etc.
After entering inside host tissues the pathogen disseminates throughout the whole body.
This is accomplished by specific products and/ or enzymes that help spreading as given below:
(a) Coagulase:
Coagulase by Staphylococcus aureus that protects the pathogen from phagocytosis and keeps it isolated from other defense mechanism of the host,
(b) Collagenase:
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Collagenase by Clostridium sp. that breaks collagen and allow to spread the pathogen,
(c) Elastase and Alkaline Protease:
Elastase and alkaline protease by Pseudomonas aeruginosa that breaks laminin associated with basement membrane,
(d) Haemolysins:
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Haemolysins (by staphylococci, E. coli, Clostridium peifringens) that break down erythrocytes causing anaemia and make iron available to the microorganism for growth,
(e) Immunoglobulin:
Immunoglobulin A protease by Streptococcus pneumoniae that cleaves immunoglobulin A into Fab and Fc fragments,
(f) Lecithinase:
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Lecithinase by Clostridium spp. that breaks down lecithin of plasma membrane and helps the pathogen to spread,
(g) Porins:
Porins by Salmonella typhimurium that inhibits leukocyte phagocytosis through activation of the adenylate cyclase system, etc.
(iii) Growth and Multiplication of the Pathogen:
After different mechanisms ultimately the pathogen reaches to terminal lymphatic capillaries surrounding the epithelial cells, which merge into large lymphatic vessels. The lymphatic vessels connect the circulatory system and discharge the pathogen therein.
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Finally, pathogen reaches to all the body organs. The pathogen gets proper nutrients, optimum pH and temperature in certain specific areas. This results in growth and multiplication of the pathogen.
Moreover, some pathogens have evolved specificity to multiply either inside host cells, in tissues, in blood plasma, and also can generate its own nutrient-gathering mechanism. Sometimes the metabolic products of blood become toxic and results in a condition called septicemia.
2. Intoxications:
Intoxications are the diseases caused due to entry of toxins (Latin toxicum means poison) into the host systems or body organs. Intoxications may occur in the presence or absence of the pathogen. The conditions resulted from a toxin is called toxemia. Toxins are of two main types: exotoxins and endotoxins.
(i) Exotoxins:
Exotoxins are heat-labile, soluble proteins secreted by the pathogen that after release is circulated to other part of body tissues or target cells. However, after treatment with formaldehyde the toxicity of exotoxins is lost but their antigenic properties are retained.
They have ability to induce the production of antibodies i.e. antitoxins which react with toxins and neutralize them. In this inactivated form these exotoxins are known as toxoid. Now-a-days toxoids are used as vaccines to immunize against several diseases e.g., tetanus, diphtheria, botulism, etc.
The general characteristics of exotoxins are that these are:
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(a) Synthesized by exotoxin genes present on plasmid of the pathogen,
(b) Heat-labile protein which becomes inactivated between 60 and 80°C,
(c) Toxic in low doses i.e. in µg/kg of substrate,
(c) Specific in their action,
(d) Easily inactivated by iodine, formaldehyde, etc. to form toxoids (which show immunogenic properties),
(e) Highly immunogenic and induce the production of neutralising antibodies (antitoxins),
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(f) Named after the name of disease e.g. botulinum toxin, diphtheria toxin, etc., and
(g) Of different types based on their mode of action such as neurotoxins (affecting nerve tissues), cytotoxins (affecting general tissues), enterotoxins (affecting intestinal mucosa) (Table 23.2).
Table 23.2 : Example of exotoxin producing bacteria.
Mechanism of Action:
The mechanism of transport of exotoxin can be explained with its structural subunits (A and B) of polypeptide chain that constitute it. Enzymatic subunit A has toxic effect on cell after entering inside, whereas the subunit B binds to target cells. Subunit B does not exert toxic effect on the cell. It interacts with its specific receptor sites present on target cell.
Thereafter, subunit A that lacks binding site is delivered inside the cell. This mechanism is called AB model for transport of exotoxins. The mechanism of action of exotoxins is quite complex. It affects by several ways such as: inhibiting the protein synthesis, disrupting the membrane transport, causing damage to plasma membrane, etc.
(ii) Endotoxins:
The outer membrane of cell wall of most of the Gram-negative bacteria consists of lipopolysaccharide (LPS). LPS is toxic in certain conditions and, therefore, it is called endotoxin because it is tightly bound to cell wall and released only after lysis of microorganisms. Lipid A portion is the toxic component of LPS. It is a complex array of lipid residues. Lipid A component is associated with all the properties of the microorganism.
Moreover, endotoxins are:
(a) Heat-labile,
(b) Toxic only at high doses (i.e. mg/ kg amount of substrate),
(c) Capable of producing systemic effects such as fever, shocks, blood coagulation, weakness, diarrhoea, inflammation, and fibrinolysis i.e. enzymatic breakdown of fibrin (which is a major component of blood clots).
Mechanism of Action:
Both in vivo and in vitro endotoxins initially activate Hageman Factor (i.e. blood clotting factor VII) which in turn exerts the following four systemic effects:
(a) They start the blood clotting cascade that leads to blood coagulation, thrombosis, and acute disseminated intravascular coagulation which in turn depletes platelets and various clotting factors and results in clinical bleeding;
(b) They can activate the complement system which leads to inflammation;
(c) They can activate fibrinolysis; and
(d) They can trigger a series of enzymatic reactions that lead to the release of bradykinins (a potent vasoactive peptide causing), and other vasoactive peptides which cause hypotension.
For comparison a summary of characteristics of exotoxins and endotoxins is given in Table 23.3:
