The concept that disease were infectious and caused by an unknown “something” appears in human history long period before the discovery of the microorganisms. In 1546 Fracastoro proposed a “germ theory of disease”. After opening of microorganisms by Leeuwenhoek people began to suspect that microorganisms might cause disease in human and other animals. Only Paster has proved that microbes can cause infectious disease. Robert Koch offered proof of the germ theory of disease. His approach led to the formulation of “Koch’s postulates”, which are criteria that he proposed must be satisfied to confirm the causal role of microorganisms. These criteria are as follows:
The type and severity of an infection depend on numerous factors, most of which are related to the pathogenicity of the microbe and the condition of the host. Pathogenicity describes a microorganism's potential to cause an infection or disease.
Pathogenic microbes have been traditionally divided into two categories, depending upon the nature of the microbe-host relationship. Examples include the influenza virus, plague bacillus, rabies virus, and other microorganisms with well-developed qualities of virulence
Differences in pathogenicity can be accounted for on the basis of virulence. Virulence takes into account the ability of microbes to invade a host and produce toxins (toxigenicity). These properties are called virulence factors All these factors are realized during of infectious disease and conditioned pathogenesis
Progression or resolution of the disease: 1. Death 2. Carrying formation 3. Convalescence
It is a place or organism where microorganisms can multiply and where from they are spread and infect other organisms
The ID varied widely among microbial species and depends on virulence of microorganisms.
Vector are arthropods which are carriers of disease agents. In case of biological vectors, microorganisms multiply in their organism. Yellow fever, caused by virus, is transmitted by mosquito vectors, rocky Mountain spotted fever is transmitted by ticks.
Certain bacteria have specialized structures, eg pili, or produce substance, eg. capsule or glycocalyces, that allow them to adhere to the surface of human cells, thereby enhancing their ability to cause disease. Mutants that lack these mechanisms are often nonpathogenic. For example, the pili of N.gonorrhoeae and E.coli mediate the attachment of the organisms to urinary epithelium. A lot of viruses have spikes on the calsid or supercalsid for adhesion on host cell.
A toxin molecule secreted by a living bacterial cell into the infected tissues is an exotoxin. A toxin that is not secreted but is released only after the cell is damaged or lysed is an endotoxin.
Fever due to the release by macrophages of endogenous pyrogen (interleukin-1), which acts on the hypothalamic temperature-regulatory center. Activation of the alternative pathway of the complement cascade, resulting in inflammation and tissue damage Disseminated intravascular coagulation due to action of the coagulation system through Hageman factor, resulting in thrombosis and tissue ischemia Endotoxins do not cause these effects directly. Rather, they induce synthesis of host factors such as interleudin-1 and TNF (tumor necrosis factor) by macrophages.
Several factors contribute to invasiveness by limiting the ability of the host defense mechanisms, especially phagocytosis. Phagocytosis is ineffective for several reasons. For example, some pathogens have a protective coating that makes them hard to engulf (in top) , or the phagocyte ingests them but the microbes can still multiply.
Infectious process and infectious disease are different conception.
When focal infection microorganisms spreads from local site to entire body.
The time of incubation period varies from hours to days to weeks depending on the microorganisms.
During incubation stage, the microorganisms has invaded the host and is migrating to various tissue but has not yet increased to sufficient numbers to cause discomfort or infectivity. In beginning of prodromal period the patient suffer discomfort but does not have sufficient precise symptoms to permit the clinician to make a diagnosis. When this stage patient is contagious to others. During clinical stage the disease is most severe. Communication of infection occurs from prodromal to dicline period when the human is beginning to recover.
Adherence of bacteria Vibrio holerae on the surface of enterocytes Gonococci on the surface of urinary epithelium
Action of enzymes Exoenzymes dissolve extracellular barrier and make possible penetration of bacteria through or between cells to underlying tissues Collagenase and hyaluronidase , which degrade collagen and hyaluronic acid, respectively, thereby allowing the bacteria to spread through subcutaneous tissue.
Pathogenic enzymes Dissolves blood clots Fibrinolysin Destroys red blood cells and other tissue cells Lecithinase Breaks down DNA Deoxyribonuclease Breaks down fat Lipase Breaks down hyaluronic acid, a tissue component Hyaluronidase (spreading factor) Breaks down collagen (connective tissue fiber) Collagenase Coagulates plasma; blood clots Coagulase Breaks down lecithin, a lipid component of mammalian cell membrane Phospholipase Function Enzyme
Action of toxins Exotoxins diffuse to target cells, which are poisoned and disrupted
Differential characteristics of bacterial exotoxins and endotoxins (1) Stable at 100 0 C for 1 hour Destroyed rapidly at 60 0 C Heat stability Bacterial chromosome Bacterial chromosome, plasmid or bacteriophage Location of genes Lipopilysaccharide (LPS) Polypeptide Chemical Released by cell during lysis Secreted from live cell Manner of release Most of gram-negative bacteria A few gram-positive and gram-negative bacteria Source Endotoxin Exotoxin Property
Differential characteristics of bacterial exotoxins and endotoxins (2) Low (toxic in high dose) High (toxic in minute amounts) Toxicity Systemic: fever, inflammation Specific to a cell type Clinical effects Do not convert to toxoid Convert to toxoid that used as vaccines Toxoid formation Low. Poorly antigenic High. Induces high titer antibodies called antitoxins Antigenicity Yes Usually not Fever stimulation Endotoxin Exotoxin Property
Classification of exotoxins based on mechanism of action Staphylococcus aureus Cytotoxin that causes the lysis of human erythrocytes and some other cells. Hemolysin Corynebacte-rium diphtheriae Causes cell death, often by lysis and/or interference with protein synthesis Cytotoxin Vibrio cholerae Inflammation of the gastrointestinal tract; typically causes excessive secretions of fluid and electrolytes from the lining of the gastrointestinal tract Enterotoxin Clostridium botulinum Interference with nerve transmission Neurotoxin Bacterium-producer General site and mode of action Type of toxin
Effects of endotoxin Activation of Hageman factor Coagulation Alternative pathway of complement (C3a,C5a) Inflammation Bradykinin, nitric oxide Hypotension (shock) Interleukin-1 Fever Mediator or mechanism Clinical findings