Exotoxins

Exotoxins, unlike the lipopolysaccharide endotoxin, are protein toxins released from viable bacteria. They form a class of poisons that is among the most potent, per unit weight, of all toxic substances. Most of the higher molecular-sized exotoxin proteins are heat labile; however, numerous low molecular-sized exotoxins are heat-stable peptides. Unlike endotoxin, which is a structural component of all Gram-negative cells, exotoxins are produced by some members of both Gram-positive and Gram-negative genera. The functions of these exotoxins for the bacteria are usually unknown, and the genes for most can be deleted with no noticeable effect on bacterial growth. In contrast to the extensive systemic and immune-system effects of endotoxin on the host, the site of action of most exotoxins is more localized and is confined to particular cell types or cell receptors. Tetanus toxin, for example, affects only internuncial neurons. In general, exotoxins are excellent antigens that elicit specific antibodies called antitoxins. Not all antibodies to exotoxins are protective, but some react with important binding sites or enzymatic sites on the exotoxin, resulting in complete inhibition of the toxic activity (i.e., neutralization).

Exotoxins can be grouped into several categories (e.g., neurotoxins, cytotoxins, and enterotoxins) based on their biologic effect on host cells. Neurotoxins are best exemplified by the toxins produced by Clostridium spp., for example, the botulinum toxin formed by C. botulinum. This potent neurotoxin acts on motor neurons by preventing the release of acetylcholine at the myoneural junctions, thereby preventing muscle excitation and producing flaccid paralysis. The cytotoxins constitute a larger, more heterogeneous grouping with a wide array of host cell specificities and toxic manifestations. One cytotoxin is diphtheria toxin, which is produced by Corynebacterium diphtheriae. This cytotoxin inhibits protein synthesis in many cell types by catalyzing the ADP-ribosylation of elongation factor II, which blocks elongation of the growing peptide chain.

Properties of exotoxins

• Thermostable and thermolabile

• Localization of intra- and extracellular

• Highly toxic

• Specific

• Under the action of formalin pass into the toxoid (anatoxin)

• Gram “+” and Gram “-” bacteria are formed.

Classification of protein toxins by mechanism of action

1.Cytotoxins - block protein synthesis at the subcellular level (histotoxin of diphtheria causative agent).

2. Membranotoxins - destroy the membranes of erythrocytes and leukocytes.

3. Functional blockers - disrupt the function of tissue systems (neurotoxins, enterotoxins).

4. Exfoliatins and erythrogens - disrupt the interaction of cells between themselves and the intercellular substance.

Preparation of exotoxins

• 1) cultivation of a toxigenic culture in a liquid nutrient medium;

• 2) filtration through bacterial filters (separation of exotoxin from bacterial cells); Other methods of cleaning can be used.

• 3) exotoxins are then used to prepare anatoxins (molecular vaccine).

Preparation of endotoxins

• Various methods of destruction of the microbial cell are used, and then purification is carried out, i.e. separation of endotoxin from other components of the cell.

• Because Endotoxins are lipopolysaccharides, they can be extracted from a microbial cell by destroying TCA followed by dialysis.

• Dialysis allows to purify lipopolysaccharides from proteins. In dialysis, semipermeable membranes are used, which retard high-molecular compounds, i.e. proteins and pass low-molecular compounds, i.e. lipopolysaccharides.

Other factors should be considered in describing the agent. The infecting dose (the number of organisms necessary to cause disease) varies according to the organism, method of transmission, site of entrance of the organism into the host, host defenses, and host species. Another agent factor is specificity; some agents (for example, Salmonella typhimurium)can infect a broad range of hosts; others have a narrow range of hosts. Styphi,for example, infects only humans. Other agent factors include antigenic composition, which can vary within a species (as in influenza virus or Streptococcus species); antibiotic sensitivity; resistance transfer plasmids and enzyme production.

The role of the macroorganism in the infectious process

1. Sex, age (childhood infections).

2. The state of the immune and nervous systems - their oppression contributes to a more severe course of the disease.

3. The state of the endocrine system (diabetes enhance of inflammatory processes).

4. Nutrition - lack of proteins, vitamins, trace elements predisposes to infections.

5. Normal microflora.

The role of the environment in the infectious process

1. Climate and season (intestinal infections is more often in summer, in winter - respiratory infections);

2. Ecological situation (proximity of industrial facilities, quality of water).

• 3. Social factors (working and living conditions, material and cultural level, health status)

Peculiarities of the infectious disease

1. Specificity: pathogenic m / o causes "his", inherent only to him an infectious disease

2. Contagiousness - transmission from patient to healthy

3.Cyclicity - a succession of periods of illness

4. Formation of immunity

5. Specific microbiological and immunological methods of diagnosis

6. The use of specific drugs for treatment and prevention

THE PERIODS OF INFECTIOUS DISEASES

1. Incubation - from infection to the first clinical symptoms (several hours (influenza, plague) to 30 years- (leprosy))

2. Prodromal-non-specific symptoms (1-2 days)

3.The period of the height of the disease: is the emergence and growth of specific clinical and laboratory signs (it can end up lethal or go to the next stage)

4.The period of the extinction of symptoms

5. Reconvalescence (recovery) - the disappearance of symptoms of the disease, restoration of body functions: complete or incomplete with residual changes in organs and tissues

The names of infectious diseases are formed from the name of the pathogen (species, genus, family) with the addition of suffixes "osis" or "asis" (salmonellosis, rickettsiosis, amoebiasis, etc.).

Forms of infectious process

By origin: endogenous (with activation of M / O of normal microflora) and exogenous

(M / O from the environment).

By the number of pathogens: - monoinfection, mixed (measles + tuberculosis)

By the duration: acute (influenza, typhus) and chronic (malaria, tuberculosis)

By the localization - focal (furunculosis, angina), generalized (as a result of the spread of the pathogen from the primary focus of lympho-, hemato-, bronchogenic or perineural)

By manifestation:

a) manifest - with a typical complete symptomatology;

b) abortive - incomplete symptomatology;

c) latent (asymptomatic) - there are no clinical manifestations, there is an increase in antibodies.

Secondary infection- infection by another type of pathogen in the presence of the primary disease.

Reinfection - re-infection with the same kind of pathogen after recovery (dysentery)

Superinfection - a new infection by the same pathogen during the current infection

Relapse - return symptoms of the disease (malaria) due to the remaining pathogens in the body.

Elements of epidemiology

Epidemiology is the study of the determinants, occurrence, and distribution of health and disease in a defined population.