1. NAJRAN UNIVERSITY College of Medicine NAJRAN UNIVERSITY College of Medicine Microbiology &Immunology Course Lecture No. 9 Microbiology &Immunology Course Lecture No. 9 By Dr. Ahmed Morad Asaad Associate Professor of Microbiology Dr. Ahmed Morad Asaad Associate Professor of Microbiology

2. INFECTION AND DISEASE Infection: Infection is a process by which the microbe enters into a relationship with the host. For this relationship to be established, certain requirements are to be fulfilled : 1. Entrance of the microbe into the host. There are various portals of entry for microbes into their host 2. Multiplication of the microbe in the host after entry.

3. For transmissibility of infection from one host to another, the microbe must have: a)An exit from the body e.g. stools, urine, respiratory or genital discharges or through the skin from the blood stream by an insect. b) A means of transportation from one host to another (vehicle of infection) e.g. food, air, hands, utensils or insects.

4. Infection by microorganisms occurs very frequently. But only few infections result in diseases. In other words, there are infections, which terminate without occurrence of pathological changes and thus not manifested as clinical disease. These are often termed subclinical or silent infections. Whether a given infection will result in disease or not is determined by a complexity of interactions between: (a)microbial factors, and (b) host factors. It is also these factors, which determine whether the resultant disease will be severe or fatal moderately severe, mild or minimal.

5. Microbial Pathogenicity : Microbes are roughly divided into: 1. Pathogens: Those species capable of multiplying in living tissues causing disturbance of physiological functions of the body. This disturbed function is manifested as a disease. 2. Non ‑ pathogens: Those which when introduced into living tissues are not capable of establishing themselves in the body but they easily eliminated by the normal physiological mechanisms, i.e. unable to produce disease.

6. Pathogenicity is a character of the species of microbes, e.g. Salmonella typhi is a pathogenic species but other species in genus Salmonella are non-pathogenic. The term "commensal" refers to those species which normally inhabit the body, e.g. in the intestine, on the surface of the skin and on the mucous membranes of the upper respiratory tract and vagina. Under normal conditions, they are non ‑ pathogenic and even sometimes useful. they must be regarded as potentially pathogenic because under certain conditions, they might be responsible for production of diseases as in: 1.Lowering of natural resistance of the body: e.g. in uncontrolled diabetics or leukaemic cases. 2. Change of natural habitat of the organism: e.g. Escherichia coli,

7. Microbial Virulence (Virulence factors) : While pathogenicity is a character of the species of microbes, virulence is a character of individual strains within the species. A population of a certain pathogenic microbial species, like any other biological population, consists of individual strains with varied ability to produce disease. This ability is called "virulence". a certain strain of diphtheria bacillus is capable of producing severe disease if it is highly virulent, while another strain produces a mild disease if it is of low virulence. Still other strains may be completely unable to produce disease if they are avirulent (attenuated).

8. Virulence Factors : 1. Adherence factors. (by common pilli) 2. Invasiveness. (Ability to grow & multiply in host tissues) 3. Production of toxins. 4. Extracellular enzymes.

9. PropertyExotoxinsEndotoxins SecretionExcreted by living cell. High concentrations in liquid medium (diffusible)  Integral part of the cell wall of gram negative bacteria.  Released on bacterial death and in part during growth  Many do not need to be released to have biologic activity SourceProduced by both gram positive and gram negative bacteria Found only in gram negative bacteria ChemistryProtein in natureLipopolysaccharide Heat stability Heat labile (destroyed at 60ºC) Heat stable (withstands heat over 60ºC)

10. PropertyExotoxinsEndotoxins AntigenicityHighly immunogenicWeakly immunogenic VaccinesConverted to antigenic, non toxic, toxoids by formalin Not converted to toxoids ToxicityHighly toxicModerately toxic BindingUsually bind to specific receptors on cells Specific receptors not found on cells Clinical effects Usually do not produce fever in the host Usually produce fever by release of interleukin 1 and TNF Location of gene Frequently plasmid or phage mediated Chromosomal mediated ExamplesC. diphtheriae, Cl. tetani, Cl. botulinum, staphylococcai, E. coli, V. Cholerae Meningococcemia, sepsis by gram negative rods

11. Septic Shock Septic shock is caused mainly by the endotoxins (LPS) of gram negative bacilli and cocci. The endotoxin acts as a superantigen which stimulates the release of IL ‑ 1, TNF, bradykinin and other mediators. The biological effects of endotoxin include: fever, hypotension, activation of complement, increased vascular permeability, disseminated intravascular coagulation “DIC”, thrombosis, purpural rash and ischemia. Septic shock can cause death of the patient even though antibiotics have killed the bacteria in the blood. Peptidoglycan released during infection with gram positive bacteria may yield many of the same biologic activities as LPS, though much less potent.

12. 4. Extracellular enzymes : Collagenase Coagulase Fibrinolysin Hyaluronidase Leukocidin Protease Lecithinase