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Relaxation therapy is primarily used to manage anxiety produced by exposure but has no direct affect on O purchase simvastatin 40mg without prescription cholesterol levels 70 year old. Daily exposure to cues avoided because of associated discomfort and rituals discount 10 mg simvastatin free shipping cholesterol score of 3, and 2 purchase 10mg simvastatin with amex cholesterol chart conversion. Maintaining exposure and not ritualizing for at least an hour or until discomfort subsides order simvastatin 40 mg online cholesterol test normal value. Anti-obsessive efficacy of fluoxetine, fluvoxamine and sertraline has been reported by controlled trials (March et. Patients should be told trials of more than one agent may be required, at times with augumenting agents. In controlled trials reduction in baseline symptom rating with treatment of upto 16 weeks has been relatively consistent, although modest, ranging from 18 to 44 percent (Geller et. Studies including long term observation report continued symptom reduction upto one year. The comorbidity of tic disorders may require the addition of a-agonists or neuroleptics. Whenever discontinuation is attempted, tapering should be gradual usually over several weeks. Majority of patients should experience significant relief and return to functioning. Reducing delays in diagnosis and aggressive treatment, often with combined approaches goes a long way in minimizing impact of the disorder on children development. Selective Mutism: Data on treatment of selective mutism is mostly limited to single case studies. In spite of this, the conviction that behavioral techniques are an essential component of management of selective mutism is widespread. Reports describe successful use of techniques such as contingency management, stimulus fading, systematic desensitization, negative reinforcement and shaping. A combination of behavioral techniques is probably the most common and successful treatment approach (Anstending K, 1998; Dow et. Then, the child is guided to systematically engage in speaking- related behaviors (e. With repeated attempts, associated anxiety dissipates through autonomic habituation. When the feared consequences of speaking fail to occur anxiety is further reduced. The young age of most children with selective mutism and the fact that most of these children initially do not speak to the therapist necessitates parental involvement in treatment. Traditional anxiety-reducing behavioral techniques like shaping, gradual exposure and reinforcement are often used in initial sessions. Involvement of school personnel for providing regular communication and support in school is also highly recommended. Other Psychosocial therapies: Although behavior therapy is most commonly employed, accounts of successful treatment of selective mutism with use of play therapy, family therapy, psychodynamic therapy, and group therapy are also available (Watson et. It is common for children with selective mutism to have some degree of speech or language difficulties which exacerbate speech- related anxiety. In such cases speech therapy should be considered as an adjunct to other interventions. A double-blind, placebo controlled trial of fluoxetine in children with selective mutism indicated significant benefit (Black & Uhde, 1995). As of now, behavior therapy when available and practical should be considered the initial intervention strategy. Journal of the American Academy of Child & Adolescent Psychiatry:Vol 44(3) March 2005 pp 258-264. Melissa; Manassis, K (2001); Familial Predictions of Treatment outcome in Childhood Anxiety Disorders. Journal of the American Academy of Child & Adolescent Psychiatry:Vol 40(10) pp 1182-1189. Mullin B, Farrell C, Wagner K, Emslie G (2002): Carpenter D Impact of comorbidity on treatment response to paroxetine in pediatric obsessive compulsive disorder. Is the use of exclusion criteria empirically supported in randomized clinical trials. A meta-analysis of pharmacotherapy trials in pediatric obsessive compulsive disorder. L (1988):Development of social anxiety scale for children revised : Factor structure and concurrent validity. L (1993): Anxiety scale for children revised : Factor structure and concurrent validity. Journal of the American Academiy of Child and Adolescent Psychiatry, 35,1502-1510. Toni C, Mucci M, Millepiedi S, Mata B, Perugi G (2001), Paroxetine in child and adolescent outpatients with panic disorder. Abali O, Kaynak N (2003): Citalopram treatment of children and adolescents with obsessive compulsive disorder: A preliminary report Psychiatry Clin Neuroscl. J Am Acad Child Adoles Psychiatry 42:331-339 96- Muris P, Schmidt H, Merckelbach H (1999): The structure of specific phobia symptoms among children and adolescents. Behavioural and cognitive behavioural therapy for obsessive compulsive disorder in children and adolescents. Journal of the American Academy of Child & Adolescent Psychiatry:Vol 37(10S) Supplement Oct. Walkup J (2001): Fluvoxamine for children and adolescents with obsessive compulsive disorder: A randomized, controlled multicenter trial. J Child Psychol Psychiatry 41:713-726 (239) 133- Target M, Fonagy P (1994) : Efficacy of psychoanalysis for children with emotional disorders. Methods: These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. Results: These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Conclusions: Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments. This guideline docu- Anxiety and related disorders are among the most com- ment is not focused on any individual type of clinician mon of mental disorders. Lifetime prevalence of anxiety but rather on assessing the data and making recommen- disorders is reportedly as high as 31%; higher than the dations. Subsequent “user friendly” tools and other lifetime prevalence of mood disorders and substance use initiatives are planned. Unfortunately, anxiety disorders The guidelines include panic disorder, agoraphobia, are under-diagnosed  and under-treated [5,7,8]. Also included are brief discussions of clinically pists, and nurses with the diagnosis and treatment of relevant issues in the management of anxiety and related anxiety and related disorders by providing practical, disorders in children and adolescents, women who are pregnant or lactating, and elderly patients, and patients with comorbid conditions. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. Treatment strategies were rated on subsequently, draft guidelines were prepared by the sub- strength of evidence for the intervention (Table 1).
Ceftiofur and cefapirin also degraded immediately and completely in kidney extract resulting in both formerly reported metabolites as well as not previously reported products purchase simvastatin 20 mg line cholesterol ratio mercola. It is shown that conditions often occurring during the analysis of ceftiofur or cefapirin can result in rapid degradation of both compounds simvastatin 20 mg without a prescription cholesterol levels good. From this discount 10 mg simvastatin with amex cholesterol targets, on a theoretical basis discount 40 mg simvastatin with visa cholesterol what to eat, it is concluded that underestimation of the determined amounts of ceftiofur and cefapirin is likely to occur when using conventional methods for the quantitative analysis of these compounds in tissue, and that a new approach is needed that takes the metabolism and degradation into account. To effectively detect off-label ceftiofur usage an analytical method is needed that, besides the native compound, also detects its active metabolites. It was found that approach A is not suited for quantitative analysis of total ceftiofur concentration nor for effectively detecting off-label use of ceftiofur. Approach B resulted in adequate quantitative results, but is considered to be a single compound method. Approach C showed adequate quantitative results as well, but in contrast to approach B, this approach is applicable to a range of cephalosporin antibiotics and therefore applicable as a broad quantitative analysis method for cephalosporin compounds in poultry tissue samples. It was shown that this method is suitable for the quantitative analysis of 21 out of 22 compounds included and that it is effective for the detection of off-label ceftiofur use, because protein bound metabolites are included. A study comparable to the work described in chapter 3 is needed to assess the selectivity of that technique. Other methods have become available to further enhance the selectivity of a method. Research is needed to determine optimal and compatible conditions for both dimensions and to effectively couple the two chromatographic systems. Due to the fast diffusion rate and the limited back pressure, fast separation at high resolution can be obtained. The national monitoring plan will become more risk based and therefore, a more generic and flexible approach is needed. The most efficient would be to use generic screening methods that include a broad range of compounds in combination with highly selective confirmatory methods. Also, due to the increasing bacterial resistance, the focus of regulatory control will be more on antibiotic usage in general next to the control of food products itself. In this, detection limits should be as low as reasonably possible and the use of other matrices should be investigated, e. Based on the outcome of these studies, the banned status of the drug should be reconsidered. Based on the findings in this thesis we can now answer the question: “What selectivity is adequate? Usually there is a trade-off between selectivity and the number of compounds that can be included in a method. For a screening method a low selectivity is acceptable (as long as the number of false positives remains limited), whereas selectivity should be high for a confirmatory method. Furthermore, the selectivity needed depends on the interferences that can be expected. To conclude, whenever developing or validating a method, it is of extreme importance to consider the parameter selectivity in detail. Antibiotica worden gebruikt om bacterie-infecties te behandelen, maar worden ook toegepast als preventief middel. Het verantwoordelijk gebruik van antibiotica is van belang vanuit het oogpunt van dierlijk welzijn en humane gezondheid. Om antibioticumgebruik in de veehouderij te controleren bestaan er wettelijke monitoringsprogramma’s. In de residuanalyse van antibiotica in producten van dierlijke oorsprong spelen kwantitatieve en kwalitatieve aspecten een rol in het bepalen of een monster conform de regelgeving is. Het kwantitatieve aspect betreft de bepaling van de hoeveelheid van het aanwezig antibioticum en het kwalitatieve aspect betreft het vaststellen van de identiteit van het antibioticum. Selectiviteit wordt gedefinieerd als ‘het vermogen van een methode om onderscheid te maken tussen de te analyseren component en andere aanwezige componenten’. In hoofdstuk 1 wordt de achtergrond van antibioticumgebruik in de veehouderij en de wetgeving omtrent de monitoring hiervan besproken. Ten gevolge van de laatste instrumentele ontwikkelingen is het mogelijk geworden een groot aantal verschillende componenten tegelijkertijd te detecteren. Om componenten met verschillende fysische en chemische eigenschappen tegelijkertijd te kunnen analyseren, dient een generieke monstervoorbewerking toegepast te worden. Deze multi- componentmethoden, die soms meer dan 150 componenten bevatten, leiden tot een verlaging van de analysekosten, maar een nadeel is dat de kans op matrixeffecten groot is, waardoor ingeleverd wordt op detectielimieten, kwantitatieve aspecten, de onderhoudsfrequentie en de selectiviteit. Validatierichtlijnen voor het bepalen van de onzekerheid van het kwantitatieve resultaat van een methode, dat wordt meegenomen in de besluitvorming, zijn voorhanden. Deze criteria betreffen de minimaal toe te passen instrumentele techniek, de retentietijd en relatieve ion-intensiteit. Procedures om de onzekerheid van het kwalitatieve resultaat te bepalen zijn niet voorhanden. Daarom is het vaststellen of een methode voldoende specifiek is een kwestie van de inschatting van experts. Een maat voor de (on)zekerheid van de selectiviteit is de kans dat een component eenzelfde precursor-ion, product- ionen en retentietijd heeft als de component die van belang is. In de ontwikkelde procedure wordt dit bepaald op basis van empirische modellen, opgesteld aan de hand van drie stofdatabanken. Op basis van de verkregen schatting kunnen aanvullende maatregelen genomen worden om te komen tot een eenduidige bevestiging van de identiteit, zoals de selectie van andere product-ionen of de selectie van een additioneel product-ion. De gerapporteerde procedure in combinatie met de gestelde wettelijke criteria voor relatieve ion-intensiteiten resulteert in een krachtige techniek om de onzekerheid van de bevestigingsanalyse te bepalen, zodat het risico op een vals-positief resultaat beperkt wordt. Om het belang van selectiviteit te illustreren, zijn in dit proefschrift twee uitdagingen gepresenteerd waarin selectiviteit een belangrijke rol speelt. Ten eerste een methode waarin de selectiviteit extreem hoog moet zijn om verschil te kunnen maken tussen een verboden antibioticum en haar antimicrobiologisch inactieve isomeren. Ten tweede een methode waarbij de selectiviteit bewust wordt gecompromitteerd zodat een effectieve monitoringsstrategie wordt verkregen waarbij niet alleen het antibioticum zelf wordt gedetecteerd, maar ook eiwitgebonden metabolieten daarvan. Doordat dit antibioticum verdacht carcinogeen is en geassocieerd wordt met aplastische anemie bij de mens, is het verboden voor gebruik bij voedselproducerende dieren. Als dat zo is, 333 heeft dit mogelijk invloed op de bestaande wetgeving en de interpretatie van analytische resultaten. De isomeerscheiding op de analytische kolom, de selectiviteit van de gemonitorde product-ionen en de monstervoorbewerking zijn kritische parameters. Om reproduceerbare retentietijden te verkrijgen wordt isocratische elutie toegepast op een α-zuurglycoproteïnekolom. In het geval van urinemonsters zijn matrixcomponenten in het eindextract aanwezig die ervoor zorgen dat de retentietijden van alle isomeren afnemen, waardoor onvoldoende chromatografische resolutie wordt verkregen. Om dit te voorkomen is een intensieve opschoning van de monsterextracten ontwikkeld, bestaande uit een vaste fase extractie met daarna een vloeistof-vloeistofextractie. De ontwikkelde methode is volledig gevalideerd en voldoet aan de gestelde criteria voor alle -1 isomeren. Met name penicillines worden veelvuldig gebruikt in de veehouderij en als humaan medicijn. Resistentie voor cefalosporines en in minder mate carbapenems komt tevens voor, wat een gevaar vormt voor de volksgezondheid. De uitdagingen voor de analyse van ß-lactams zijn (1) de instabiliteit van enkele componenten behorende tot deze groep en (2) het metabolisme van ceftiofur en cefapirine, en eiwitbinding van ceftiofurresiduen. Een beperkte instabiliteit van cefapirine en desfuroylceftiofur is waargenomen bij verhoogde temperatuur.
Aminobenzoic acid: This neutralizes the action of sulphonamides should these be present in the blood generic 40 mg simvastatin visa cholesterol medication best. Collect and culture the specimen Blood • It should be collected before antimicrobial treatement has been started and at the time the patient’s temperature is beginning to rise best 20 mg simvastatin cholesterol in eggs is dangerous. Insert the needle through the rubber line of the bottle cap and dispense 5ml of blood into each culture bottle simvastatin 10mg on-line cholesterol levels on atkins diet. Incubate the inoculated media: Thioglycollate broth 0 At 35-37 C for up to 2 weeks cheap simvastatin 40 mg cholesterol levels chart in uk, examining and sub-culturing • Look for visible signs of bacterial growth such as turbidity above the red cell layer, colonies growing on top of the red cells (“cotton balls”), haemolysis, gas bubbles and clots. Synovitis means inflammation of the synovial membrane (living of a joint capsule). Arthritis may be caused by bacteria (infective arthritis), rheumatoid arthritis, gout and pseudogout, osteoatrhtitus 3. The term pleural effusion is used to describe a non-purulent serous effusion which sometimes forms in pneumonia, tuberculosis, malignante disease etc Empyema is used to describe a purulent pleural effusion when pus is found in the pleural space. Peritonitis means inflammation of the peritoneum, which is the serous membrane that lines the peritoneal cavity. Ascites refers to the accumulation of fluid in the pentional cary causing abdominal swelling. Commensales No microbial flora Collection is carried out by a medical officer - 2-3ml without anticogulent, to see whether clotting occurs. Staphylococcus warneri • Can readily grow in ordinary media under aerobic and micro- aerophilic conditions • grow most rapidly at 37 0c but form pigment best at room temperature of 20-25 oc • Colonies in solid media are round, smooth, raised and glistening. Peptidoglycan( Mucopeptide): Polysaccharide polymer which provide the rigid exoskeleton of the cell wall. It is important in the pathogenesis of infection like eliciting production of cytokines and opsonic antibodies; chemoattractant for polymorphs;and activate complement 2. Catalase- Produced by staphylococci Converts H202 into H20 and 02 175 Catalase test differentiates staphylococci(catalase-positive) from streptococci(catalase-negative). Coagulase may deposit fibrin on the surface of organism and alter ingestion by phagocytic cells. Clumping factor: A surface compound that is responsible for adherence of the organism to fibrinogen and fibrin Produced by Staphylococcus aureus Determines Invasive potential of the organism. Multiple (A-E, G-I, K-M) soluble heat-stable, gut enzyme resistant toxins which act on neural receptors 176 in the gut to stimulate vomiting center in the central nervous system. Epidermolytic toxin A: Chromosomal gene product and heat stable Epidermolytic toxin B: Plamid mediated and heat labile. Endocarditis and meningitis: Infection of heart tissue and leptomeninges respectively. Characterized by abrupt onset of high fever, vomiting, diarrhea, myalgia, scarlatiform rash,and hypotension with cardiac and renal failure in the most severe disease. Catalaseproducing Bacteria (Staphlococci) No active bubbling…………Non-catalase producing bacteria (streptococci) 2. Serologic specificity of the cell wall group specific substance and other cellwall capsular antigens 3. Partial Greenish discoloration Alpha(α) Viridans streptococci (reduced hemoglobin). None No change Gamma(δ) Enterococci Lancefield grouping of streptococci: Streptococci produce group specific carbohydrates(C carbohydrates) identified using group specific antiserum. Group-specific cell wall antigen Streptococcal cell wall obtained carbohydrate is the basis for serologic grouping of streptococci (Lancefield groups A-H, K-U) 183 2. M protein They are found in hair-like projections of the streptococcal surfaceand determine virulence Major virulent factor for group A streptococci. T substance: Acid and heat labile unlike M protein, and has no relation to virulence of streptococci. R protein Streptococcus pyogenes (Group A β-hemolytic streptococci) The most pathogenic member of the genus It is present as a commensal in the nasopharynx in a variable proportion of healthy individuals. It is an active proteolytic enzyme which lyses fibrin by catalytic conversion of plasminogen to plasmin. Has been given intravenously for the the treatment of pulmonary edema and of arterial and venous thrombosis 2. Streptodornase: Streptococcal deoxyribonuclease 184 Mixtures of streptokinase and streptodornase are used in “enzymatic debridement” 3. Hyaluronidase: Spreading factor It degrades the ground substance of connective tissue (hyaluronic acid) and aids in spreading infectious micro- organoism 5. Hemolysins: Two types Streptolysin O and Streptolysin S Antistreptolysin O antibody titer > 1:200 todd: Supportive evidence for Acute reheumatic fever 2. Erythrogenic toxin: Pyrogenic exotoxins It is responsible for the erythematous rash in scarlet fever. Acute rheumatic fever 185 Immunological damage to the heart valves and muscle following Streptococcal upper respiratory tract infection It clinically presents with fever, malaise, migratory non- sppurative polyarthritis, carditis, erythema marginatum and subcutaneous nodules 2. Post streptococcal acute glomerulonephritis Immunological damage to the kidney following infection of skin with streptococci It clinically manifests with generalized body edema, elevated bloood pressure, protein and blood in the urine, bloood urea nitrogen retention and low complement level. Necrotizing fascitis(Streptococcal gangrene): Extensive and rapidly spreading necrosis of skin and subcutaneous tissue S. Streptococcus mitis Streptococcus mutans Streptococcus salivarius Streptococcus sanguis Clinical features. Grow in ordinary media with shiny or dry colonies with grey-white or colorless appearance. Penicillin + Gentamicin 188 Streptococcus pneumoniae • Fastidious, lancet-shaped gram positive diplococci. Septic arthritis Laboratory Diagnosis: Specimen: Sputum, blood, cerebrospinal fluid, ear discharge and sinus drainage. Look for the appearance of capsule swelling under the 100X objective microscope Treatment: Amoxicillin Chloramphenicol Thid generation Cephalosporins Prevention and control: Pneumococcal conjugate vaccine: Immunization of individuals with type specific polysaccharide vaccine Biochemical reaction to diagnose streptococci. Cutaneous anthrax (Malignant pustule): 95 % of anthrax presentation Characterized by a black necrotic lesion with a definite edematous margin onhands, arms, face or neck with regional lymphadenitis associated systemic symptoms. Intestinal anthrax: Presents with abdominal pain, vomiting, and bloody diarrhea Bacteremic and intestinal anthrax are rare to occur Laboratory diagnosis: Specimen: Fluid or pus from skin lesion, Blood, sputum Smear: Non-capsulated gram-positive rods with centrally located spores from culture Large capsulated gram-positive rods with out spores from primary specimen. Non-hemolytic,large, dense, grey-white irregular colonies with colony margin of “Medussa Head” or “curled-hair lock” appearance due to composition of parallel chaining of cells. Biochemical reaction: Gelatin-stab culture: Gelatin liquefaction Growth along the track of the wire with lateral spikes longest near the surface Providing “inverted fur tree” appearance. Ocular infection Ocular disease following trauma from non-sugical penetrating objects 196 Manifests with keratitis, endophthalmitis, and panophthalmitis Treatment: Clindamycin + Aminoglycosides 2. Genus: Clostridium Characteristics: • Clostridia are anaerobic, spore-forming motile, gram-positive rods. PhospholipaseC (α toxin) It has lethal, necrotizing and hemolytic effect on tissue. It causes cell lysis due to lecithinase action on the lecithin which is found in mammalian cell membrane. Clostridial food poisoning It causes secretory diarrhea due to release of enterotoxin in the intestine Self-limiting diarrhea similar to that produced by B. Saccharolytic property showing reddening of the meat with a rancid smell due to carbohydrate decomposition. Proteolytic property showing blackening of the meat with unpleasant smell due to protein decomposition. Nagler reaction: Lecithinase C activity- Opacity in the egg-yolk medium due to lecithin break down 199 Procedure: 1. Treatment: Penicillin Prompt and extensive wound debridement Polyvalent antitoxin Prevention and control Early adequate contaminated wound cleansing and debridement 200 Closridium difficile General characteristics:.
Antibodies are also likely to make a major contribution to the host-parasite balance occur- ring during chronic parasitic infections purchase simvastatin 10mg fast delivery foods by cholesterol content. Usage subject to terms and conditions of license Immune Defenses against Infection and Tumor Immunity 101 General Schemes of Infectious Diseases 2 Fig purchase simvastatin 10 mg online cholesterol & shrimp levels. Infection by cytopathic pathogens can only be controlled if pathogenic proliferation is slow and the pathogen remains localized; otherwise the outcome is usually fatal generic simvastatin 20mg visa cholesterol risk ratio ldl hdl. In the case of noncytopathic pathogens buy 10 mg simvastatin otc cholesterol medication names australia, the cytotoxic T-cell response is the critical parameter. The T-cell response can be halted by pathogens which proliferate rapidly and spread widely due to the deletion of responding Tcells. For pathogens which exhibit moderate rates of proliferation and spread, the T-cell response may cause extensive immunopathological damage, and thus reduce the proportion of surviving hosts, some of which will controll virus, some not. A weakened immune defense system may not progress beyond an unfavorable virus-host balance, even when confronted with a static or slowly replicating patho- gen which represents an initially favorable balance. Although de- tails of the process are still sketchy, IgE-dependent basophil and eosinophil defense mechanisms have been described for model schistosomal infections. Usage subject to terms and conditions of license 102 2 Basic Principles of Immunology & Avoidance strategies. Infectious agents have developed a variety of stra- tegies by which they can sometimes succeed in circumventing or escaping immune responses, often by inhibiting cytokine action. Short-lived IgM responses can control bacteria in the blood effectively, but are usually insufficient in the controlof toxins. In such cases, immunoglobulinsof the IgGclass are more efficient, as a result of their longer half-life and greater facility for diffusing into tissues. Avoidance Mechanisms of Pathogens (with examples) Influence on the complement system. Some pathogens prevent complement fac- tors from binding to their surfaces: & Prevention of C4b binding; herpes virus, smallpox virus. Viruses can avoid confrontation with the immune defenses by restricting their location to peripheral cells and or- gans located outside of lymphoid tissues: & Papilloma viruses; infect keratinocytes. Infection agents can avoid immune defenses by mutating or reducing their expression of T- or B-cell epitopes. Usage subject to terms and conditions of license Immune Defenses against Infection and Tumor Immunity 103 Continued: Avoidance Mechanisms of Pathogens (with examples) Influence on lymphocytes and immunosuppression. Immune Protection and Immunopathology Whether the consequences of an immune response are protective or harmful depends on the balance between infectious spread and the strength of the ensuing immune response. As for most biological systems, the immune de- fense system is optimized to succeed in 50–90% of cases, not for 100% of cases. For example, immune destruction of virus-infested host cells during the eclipse phase of a virus infection represents a potent means of preventing virus replication (Fig. If a noncytopathic virus is not brought under im- mediate control, the primary illness is not severe—however, the delayed cy- totoxic response may then lead to the destruction of very large numbers of infected host cells and thus exacerbate disease (Tables 2. Since an infection with noncytopathic viruses is not in itself life-threatening to the Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license 104 2 Basic Principles of Immunology Table 2. Auto- “Healthy” or unknown infections, immunity occult carrier viruses, bacteria, (although infec- and endogenous tious agent is retroviruses unknown) Clinical None Chronic Variable disease symptoms disease symptoms, some- times delayed or asymptomatic Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Usage subject to terms and conditions of license Immune Defenses against Infection and Tumor Immunity 105 Table 2. A similar situation is also observed for the cellular immune response against facultative intracellular tuberculosis and leprosy bacilli which themselves have relatively low levels of pathogenicity (Table 2. A healthy immune system will normally bring such infectious agents under control efficiently, and the immunological cell and tissue damage (which oc- curs in parallel with the elimination of the pathogen) will be minimal, en- suring that there is little by wayof pathological or clinical consequence. How- ever, should the immune system allow these agents to spread further, the result will be a chronic immunopathological response and resultant tissue destruction—as seen during hepatitis B as chronic or acute aggressive hepatitis and in leprosy as the tuberculoid form. Should a rapidly spreading infection result in exhaustion of the T cell response, or should an insufficient level of immunity be generated, the infected host will become a carrier. This carrier state, which only occurs during infections characterized by an absent or low- level of cytopathology, is convincingly demonstrated in hepatitis B carriers and sufferers of lepromatous leprosy. Because the im- muneresponse also acts toinhibit virus proliferation, the process of cellulardestruc- tion is generally a gradual process. Paradoxically, the process of immunological cell destruction would helpthevirus survivefor longer periodsin the host and hence facilitate its transmission. From the point of view of the virus this would be an as- tounding, and highly advantageous, strategy—butone with tragic consequences for the host following, in most cases, a lengthy illness. Influence of Prophylactic Immunization on the Immune Defenses Vaccines provide protection from diseases, but in most cases cannot entirely prevent re-infection. Vaccination normally results in a limited infection by an attenuated pathogen, orinduces immunity through the useofkilled patho- gens or toxoids. The former type of vaccine produces a very mild infection or illness capable of inducing an immune response and which subsequently protects the host against re-infection. The successful eradication of smallpox in the seventies so far represents the greatest success story in the history of vaccination. The fact is that vaccinations never offer absolute security, but instead improve the chances of survival by a factor of 100 to 10 000. A special situation applies to infections with noncytopathic agents in which disease results from the immune response itself (see above). Under certain circum- stances, and in a small number of vaccinated persons, the vaccination pro- cedure may therefore shift the balance between immune defense and infec- tion towards an unfavorable outcome, such that the vaccination will actually strengthen the disease. Rare examples of this phenomenon may include the Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Generally, it should be kept in mind that most of the successful immunization programs developed to datehavemediated protectionvia antibodies. This par- 2 ticularly applies to the classic protective vaccines listed inTable 1. This ex- plains why successful vaccines all protect via neutralizing antibodies, because this pathway has been selected by co-evolution. As mentioned earlier, with regard to immunological memory, memory T cells appear to be essential to host immune protection, particularly in those situations when antigen per- sistence is controlled efficiently by means of infection-immunity (e. Tumor Immunity Our knowledge concerning the immune control of tumors is still modest. However this is apparently not sufficient for induction of an efficient immune defense. There is also the problem of tumor diagnosis; the presence of tumors is sometimes confirmed using a functional or immunological basis, yet the tumor cannot be located because conventional examinations are often unable to discover them until they reach a size of about 109 cells (i. Factors important in immune defense reactions include the location and rate of proliferation, vascularization or the lack thereof, and necrosis with pha- gocytosis of disintegrating tumor tissue. We never actually get to see those rare tumors against which immune control might have been successfully eli- cited, instead we only see those clinically relevant tumors that have unfortu- nately become successful tumors which have escaped immune control. Evidence of the immune system’s role in tumor control includes: & Greater than 85% of all tumors are carcinomas and sarcomas, that is non- lymphohematopoietic tumors which arise in the periphery, outside of orga- nized lymphoid tissues. The immune system, in a manner similar to that seen for many strictly extra-lymphatic self antigens, ignores such tumors at first. Interestingly, experimental carcinogens are frequently also immunosuppres- 2 sive. Other tumors side-step im- mune defenses by down-regulating tumor-specific antigens.