MCQs PATHOLOGY: Mechanisms of Pathogenicity

5.1 Which microbial property does NOT interfere with the body's attempt to localize infection? A. Fibrinolysin or Streptococcus pyogenes B. Motility of Salmonella paratyphi B C. Polysaccharide capsule of Streptococcus pneumoniae D. Protein A of Staphylococcus aureus E. Vi antigen of Salmonella typhi.


5.2 Which one of the properties listed here as a characteristic of bacterial exotoxins is FALSE? F. Diffusible, highly toxic, immunogenic protein G. Marked specificity of action H. May mimic disease when injected J. Neutralized by specific IgG antibody K. Produced only by Gram-positive species.


5.3 Which one of the following statements about the nature of diphtheria toxin is FALSE? L. Inhibits protein synthesis in target cells M. Is a slow acting, heat labile, diffusible protein exotoxin N. Production greatly influenced by iron concentration O. Toxigenic cells are invariably lysogenic P. Toxoid is derived from avirulent strains.


5.4 Which one of the following shows if a clinical isolate of Corynebacterium diphtheriae is toxigenic? Q. Bacterial agglutination with specific antisera R. Colonial morphology on blood tellurite medium S. Positive Elek plate T. Positive identification of "gravis" strain U. Positive Schick test.


5.5 Which organism produces a potent exotoxin? V. Shigella boydi W. Shigella dysenteriae X. Shigella flexneri Y. Shigella sonnei Z. None of these.


5.6 Which description of tetanus toxin is FALSE? A. Blocks synaptic inhibitory transmitter B. Converted to toxoid by formalin C. Formed only by virulent strains of Clostridium tetani D. Reaches CNS via motor nerves E. Six serologically distinct forms are known.


5.7 Which organism produces a toxin which blocks neuro-muscular transmission in cholinergic motor nerves? F. Clostridium botulinum G. Clostridium tetani H. Corynebacterium diphtheriae J. Shigella dysenteriae K. Vibrio cholerae.


5.8 Which organism exerts its pathogenic effect by secretion of a potent exotoxin which continuously stimulates the adenyl cyclase activity of mucosal cells? L. Clostridium welchii M. Salmonella typhimurium N. Shigella dysenteriae O. Staphylococcus aureus P. Vibrio cholerae


5.9 Which one of the following is a property of endotoxin from coliform bacilli? Q. Completely neutralized by antisera R. Firmly cell-bound and non-diffusible S. Largely composed of protein T. Purified endotoxin is strongly antigenic U. Toxicity lost by boiling for 1 hour.


5.10 "Cord formation" is characteristically shown by cultures of virulent strains of which organism? V. Bordetella pertussis W. Clostridium tetani X. Corynebacterium diphtheriae Y. Haemophilus influenzae Z. Mycobacterium tuberculosis.


5.11 Which property of Mycobacterium tuberculosis is thought to determine its destructive effect in the body? A. Ability to induce delayed hypersensitivity B. Ability to produce "cord factor" C. Classical endotoxic activity D. Classical exotoxic activity E. Potential for intracellular growth.


5.12 In which of the following is bacteraemia LEAST likely to occur? F. Anthrax G. Brucellosis H. Diphtheria J. Miliary tuberculosis K. Subacute bacterial endocarditis.


5.13 Metastatic pyaemic abscesses occur MOST frequently as a complication of infection with which organism? L. Bruceila abortus M. Cory ne bacterium diphtheriae N. Salmonella typhimurium O. Staphylococcus aureus P. Streptococcus viridans.


ANSWERS


5.1 B. Motility seems to have no influence on invasiveness as is shown by absence of any protection afforded by homologous anti-flagellar antibody and by the finding that non-flagellate variants of invasive pathogens show no related loss of virulence or invasiveness. All the other properties listed contribute to virulence and invasiveness. Bacterial capsules, Vi antigen and protein A all inhibit opsonization and phagocytosis thereby allowing organisms to multiply and spread instead of being killed at the site of infection. Fibrinogen, which escapes from blood vessels in and around the focus of infection, is normally rapidly changed to fibrin to enmesh and localize organisms, but this effect is prevented by fibrinolysin which acts as an aggressin by dissolving fibrin.


5.2 K. Although formed predominantly by Gram-positive species as typified by Cl tetanus (tetanus), C. diphtheria (diphtheria) and Strep, pyogenes (scarlet fever), important exceptions among the Gram-negative species include Sh. dysenteriae (dysentery), V. cholerae (Asiatic cholera) and a limited range of "O" serotypes of E. coli (not infantile gastroenteritis but a benign cholera-like disease).


5.3 P. Diphtheria toxoid is prepared from a potent toxin produced by a virulent strain of C. diphtheriae. The toxin is treated with dilute formalin until all toxicity is lost, while antigenicity and serological specificity are retained. Toxoid can be injected to stimulate the formation of specific antitoxin in active immunization.


5.4 S. Identification of a clinical isolate as C. diphtheriae of a certain serotype or biotype says nothing of its possible toxin producing capacity; a "gravis" strain could be non-toxigenic and therefore non-virulent. The Schick test is quite inappropriate as it is not a test of toxigenicity but a skin test to detect individuals lacking protective immunity. The Elek plate is therefore what is used in most laboratories, although some still use animal toxicity tests and others use a more recently introduced test based on toxicity for tissue culture HeLa cells. The Elek plate method is a double diffusion precipitation-in-gel where the test strain and control strains, are streaked at right angles to a paper strip impregnated with diphtheria antitoxin. A positive result shows precipitation lines of identity with the test and positive control strains.


5.5 W. The severe diarrhoea and profound dehydration which characterize S. dysenteriae infection is due largely to the effect of a heat stable, protein exotoxin lethal to intestinal epithelial cells. Early literature described it as a "neuro-toxin". The other species do not produce an exotoxin but possess the common ability to penetrate epithelial cells and to release endotoxin on lysis.


5.6 E. Although different strains of Clostridium tetani show diversity in somatic and flagellar antigens, all toxigenic strains produce only one type of tetanospasmin with a common serological specificity.


5.7 F. The neurotoxin of Clostridium botulinut,t suppresses the release of acetylcholine at the myoneural junction of cholinergic motor nerves first producing muscle weakness and then paralysis, usually fatal if it involves the respiratory muscles.


5.8 P. Water and electrolyte transport across mucosal cells is normally controlled by intermittent hormonal activation of the mucosal enzyme adenyl cyclase which then catalyses the formation of cyclic adenosine monophosphate (CAMP) from ATP and this activates the cell. Cholera exotoxin causes continuous irreversible activation of adenyl cyclase with resultant "rice water" stools and lethal water and electrolyte depletion.


5.9 R. Endotoxin is a constituent of the Gram-negative cell wall lipopolysaccharide or somatic antigen. Endotoxin activity is most closely associated with the lipid A component. It is normally part of the cell wall and non-diffusible, but may be released as macromolecular disintegration products on lysis of the cell. These complexes are only weakly antigenic and do not induce fully protective antibodies. They are relatively heat stable. They contrast with bacterial exotoxins which are pharmacologically active diffusible protein poisons of high specificity, highly antigenic, fully neutralized by specific anti-serum, heat labile and produced mainly by Gram-positive organisms.


5.10 Z. Virulent strains of Mycobacterium tuberculosis regularly form in culture serpentine cords of longitudinally arranged, pallisaded bundles of strongly acid-fast bacilli, whereas avirulent strains lack this characteristic. "Cord formation" is related to the production of a toxic glycolipid, trehalose-6, 6-dimycolate, which is known as "cord factor".


5.11 A. Although the full mechanism of pathogenicity is still unknown it seems probable that immunologically active surface peptidoglycolipid induces a state of delayed hyper-sensitivity to the bacillary proteins. Once induced, small amounts of bacillary antigen will enhance resistance but large amounts have a distinctly destructive effect due to an exaggerated level of tuberculin hypersensitivity. "Cord factor" may contribute to local tissue damage but it is not an important factor.


5.12 H. Loeffler, who established the aetiological agent of diphtheria in 1884, made the important discovery that even in fatal cases the organism remained localized to the tissue damage at the portal of entry and could never be isolated from the distant lesions in the heart, adrenals, liver and nervous tissue. He postulated the existence of a diffusible toxin which is now known to be the essential mechanism of virulence of C. diphtheriae. Diphtheria and tetanus are often cited as the two best examples of exotoxic disease. Anthrax and brucellosis are characteristically septicaemic. Miliary tuberculosis is due to systemic dissemination of tubercle bacilli through the circulation and may be likened to septicaemic pyaemic abscesses. Bacterial endocarditis is characterized by multiple arterial emboli often containing clumps of bacteria in the fragments of clot. All of these infections, with the exception of tuberculosis, may therefore be diagnosed by blood culture, and even in the case of tuberculosis, Lowenstein claimed to make positive isolation of M. tuberculosis by blood culture although the work could not be repeated by Jensen.


5.13 O. Staphylococcus aureus infections are characterized by suppuration and a tendency to bacteraemic spread. Even minor superficial skin lesions can result in the development of visceral and skeletal abscesses, due to haematogenous spread. Thus minor boils may give rise to major systemic infections, such as acute osteitis, acute bacterial endocarditis, lung, brain and perinephric abscesses, all of which may produce a fatal septicaemia. Of the other organisms listed, C. diphtheriae is virtually non-invasive; S. typhimurium not infrequently enters the blood stream but does not produce systemic abscesses as would the enteric fever and septicaemic salmonellae. Strep. uiridans may cause subacute bacterial endocarditis with an embolie bacteraemia but does not produce pyaemic abscesses; Bruceila abortus generally invades the circulation, but granulomata rather than abscesses are found at its site of lodgement.