The Immune Response in Infectious Diseases



The Immune Response in Infectious Diseases





Characteristics of Infectious Diseases


The acquisition of an infectious disease (e.g., viral, bacterial, parasitic, fungal) is influenced by factors related to the microorganism and host. The following factors can influence exposure to and development of an infectious disease:



In many cases, the successful dissemination of a microorganism results from spread of the microorganism over long distances by insect vectors or rapidly from country to country by global travelers. Also, some microorganisms are able to multiply in an intracellular habitat, such as in macrophages, and others can display antigen variation, which makes normal immune mechanism control difficult.


Host factors, such as the general health and age of an individual, influence the likelihood of developing an infectious disease and are important determinants of its severity. The very young and older populations develop infectious diseases more frequently than individuals in other age groups. In addition, a history of previous exposure to a disease or harboring of an organism such as a virus in a dormant condition is also a determining factor in disease development.



Development of Infectious Diseases


For an infectious disease to develop in a host, the organism must penetrate the skin or mucous membrane barrier (first line of defense) and survive other natural and adaptive body defense mechanisms (see Chapter 1). These mechanisms include phagocytosis, antibody and cell-mediated immunity or complement activation, and associated interacting effector mechanisms. Phagocytosis and complement activation may be initiated within minutes of invasion by a microorganism; however, unless primed by previous contact with the same or similar antigen, antibody and cell-mediated responses do not become activated for several days. Complement and antibodies are the most active constituents against microorganisms free in the blood or tissues, whereas cell-mediated responses are most active against microorganisms associated with cells.


The most effective mechanism of body defense in a healthy host depends on factors such as an appropriate portal of entry and the characteristics of each microorganism. The routes of infection or portals of entry can include transmission through oral routes (e.g., foodborne or water-borne contamination), maternal-fetal transmission, insect vectors, sexual transmission, parenteral routes (e.g., injection or transfusion of infected blood), and respiratory transmission. Development of an infectious disease occurs only if a microorganism can evade, overcome, or inhibit normal body defense mechanisms.




Parasitic Diseases


Parasites are relatively large, may have resistant body walls, and may avoid being phagocytized because of their ability to migrate away from an inflamed area. These differences set parasitic infections apart from bacterial and viral infections to which some forms of natural and adaptive immunity afford protection. (Toxoplasmosis, a representative disease, is discussed in Chapter 20.)


Immune responses (effectors) to parasitic infections include immunoglobulins, complement, antibody-dependent, cell-mediated cytotoxicity, and cellular defenses such as eosinophils and T cells. Some cestodes, especially in their larval stages, may be eradicated by complement-fixing immunoglobulin G (IgG) antibodies. In addition, some antibodies may cross-react with other parasitic antigens. Increased levels of IgE may be noted in many helminth infections. Activation of the classic and alternate complement pathways may occur in some cases of schistosomiasis, and the alternate pathway of complement activation may kill larvae in the absence of antibody (see Chapter 5).


Phagocytosis may have some direct activity against parasitic organisms, but the most effective protection in some parasitic infections is provided by antibody-dependent, cell-mediated cytotoxicity. Macrophages, neutrophils, and eosinophils may demonstrate direct toxicity or phagocytosis toward parasites. The actual attachment of the cytotoxic cells is usually mediated by IgG, although IgE may be effective. The role of eosinophils is complex. They may phagocytize immune complexes and act as effector cells in mediating local (type I) reactions, primarily in tissue stage parasites. T cells are frequently involved in body defenses against parasites. Sequestration of microorganisms is a classic T-cell–dependent hypersensitivity response. In addition, helper T cells may sensitize B cells to specific parasitic antigens.


Other nonspecific factors (e.g., nonstimulated monocytes) are a major protective mechanism against parasites such as Giardia spp. Natural killer (NK) cells also have a direct activity against cancer cells and some parasites. Delayed hypersensitivity may be helpful in preventing some parasitic infections but may cause disease in other cases. Deposition of antigen-antibody complexes, demonstrated by Raji cell assays, is responsible for severe pathologic lesions in some parasitic infections. In addition, high levels of circulating IgE may cause hypersensitivity reactions in helminth and cestode infections. Anaphylaxis is a clear risk in echinococcal infections, especially with spontaneous or surgical rupture of a hydatid cyst.



Fungal Diseases


Fungal, or mycotic, infections are normally superficial, but a few fungi can cause serious systemic disease, usually entering through the respiratory tract in the form of spores. Disease manifestation depends on the degree and type of immune response elicited by the host. Fungi are common and harmless inhabitants of skin and mucous membranes under normal conditions (e.g., Candida albicans). In immunocompromised hosts, Candida spp. and other fungi become opportunistic agents that take advantage of the host’s weakened resistance. Manifestations of fungal disease may range from unnoticed respiratory episodes to rapid, fatal dissemination of a violent hypersensitivity reaction.


Survival mechanisms of fungi that successfully invade the body are similar to bacterial characteristics and include the following: (1) presence of an antiphagocytic capsule; (2) resistance to digestion within macrophages; and (3) destruction of phagocytes (e.g., neutrophils). Some types of yeast activate complement through the alternative pathway, but it is unknown whether this activation has any effect on the microorganism’s survival.


Fungal infections are increasing worldwide for a variety of reasons, including the use of immunosuppressive drugs and the development of diseases that result in an immunocompromised host (e.g., acquired immune deficiency syndrome [AIDS]). Serologic tests often play an important role in the diagnosis of these fungal infections (Table 15-1).



Several species of fungi are associated with respiratory disease in human beings. These diseases are acquired by inhaling spores from exogenous reservoirs, including dust, bird droppings, and soil.



Histoplasmosis


Histoplasma capsulatum can be found in soil contaminated with chicken, bird, or bat excreta. Spore-laden dust is the source of histoplasmosis, caused by inhalation.


Histoplasmosis can be difficult to diagnose and can range from asymptomatic to chronic pulmonary disease. In addition, a disseminated form manifesting hepatosplenomegaly with diffuse lymphadenopathy is usually present in varying degrees of severity because of the propensity of the fungus to invade the cells of the mononuclear phagocyte system. Disseminated disease is characterized by fever, anemia, leukopenia, weight loss, and lassitude.


Definitive diagnosis requires isolation in culture and microscopic identification of the fungus, as well as serologic evidence. If an immunodiffusion technique is used, H and M bands appearing together indicate active infection. If only an M band is present, it indicates early infection, chronic infection, or a recent reactive skin test. An H band appears later than the M band and disappears earlier. Disappearance of an H band suggests regression of the infection.


Delayed hypersensitivity skin testing is confirmed by a rise in complement-fixing antibodies to Histoplasma antigens. Titers of 8 and 16 (dilutions of 1:8 and 1:16) are highly suggestive of infection. A titer of 32 or higher usually indicates active infection. A rising titer indicates progressive infection; a decreasing titer suggests regression. Some disseminated infections are nonreactive in complement fixation (CF) tests. In addition, recent skin tests in individuals with prior exposure to Histoplasma capsulatum will produce a rise in the CF titer in 17% to 20% of patients. Cross-reactions in the CF test occur in patients with aspergillosis, blastomycosis, or coccidioidomycosis, but the titers are usually lower. Several follow-up serum samples should be tested at 2- to 3-week intervals.



Aspergillosis


Another opportunistic mycotic infection occurring in human beings is aspergillosis, which can be allergic, invasive, or disseminating, depending on pathologic findings in the host. Aspergillosis is usually secondary to another disease. Allergic bronchopulmonary aspergillosis is characterized by allergic reactions to the toxins and endotoxins of Aspergillus spp.


Species identification of aspergillosis can be made microscopically. Serologically, skin reactions and immunodiffusion are useful tools for identification, especially if the culture is negative.


Immunodiffusion antibody test with reference antisera and known antigen is a frequently used test for the identification of Aspergillus spp. in almost all clinical types of aspergillosis. Precipitin formation by immunodiffusion is useful for identifying patients with pulmonary eosinophilia, severe allergic aspergillosis, and aspergillomas. The presence of one or more precipitin bands suggests active infection. The precipitin bands correlate with CF titers. In this test, the greater the number of bands, the higher is the titer. In general, immunodiffusion measures IgG and a positive result may suggest past infection. The test is positive in about 90% of sera from patients with aspergilloma and 50% to 70% of patients with allergic bronchopulmonary aspergillosis. A negative test does not exclude aspergillosis.


In addition, the enzyme immunoassay (EIA) can be used to detect IgE and IgG antibodies. ImmunoCAP is a newer method used to detect Aspergillus niger IgE in serum.


Enzyme immunoassay is used to detect Aspergillus galactomannan antigen in serum. Negative results do not exclude the diagnosis of invasive aspergillosis. A single positive test result should be confirmed by testing a separate serum specimen. Many agents (e.g., antibiotics, food) can cross-react with the assay. The false-positive rate is higher in children than in adults. If invasive aspergillosis is suspected in high-risk patients, serial sampling is recommended.


Hypersensitivity testing is characterized by immediate and delayed-type hypersensitivity reactions as a result of the presence of Aspergillus-specific immunoglobulin. IgE titers are greatly increased in allergic bronchopulmonary aspergillosis.



Coccidioidomycosis


Coccidioidomycosis is also known as desert fever, San Joaquin fever, or valley fever. The disease may assume several forms, including primary pulmonary, primary cutaneous, and disseminated. The disease is contracted from inhalation of soil or dust containing the arthrospores of Coccidioides immitis.


Hypersensitivity testing using intradermal injections is useful in screening for C. immitis. It is usually the first immunologic test to be positive in asymptomatic and symptomatic cases. Skin testing does not differentiate between recent and past exposures to C. immitis. A positive skin test should be followed by other serodiagnostic tests. A negative test in a previously positive person can indicate a disseminated infection and a state of anergy.


The fluorescent antibody (FA) test can be applied directly to clinical specimens. This procedure is invaluable for making a rapid and specific identification of fungal structures. In addition to culturing the organism, serologic tests used to confirm the diagnosis of coccidioidomycosis include the tube precipitin test, immunodiffusion, CF, and latex agglutination. The CF test is the most widely used quantitative serodiagnostic test to identify infection with C. immitis. It is very effective in detecting disseminated disease. The tube precipitin test is positive in more than 90% of primary symptomatic cases.


Immunodiffusion is equivalent to CF; it can be used as a screening test, but the results should be confirmed by CF. Latex agglutination is not usually a recommended method because it lacks specificity, which leads to many false-positive results.


Two antigens have been developed for the serologic identification of circulating antibodies to C. immitis. IgM appears 1 to 3 weeks after infection in 90% of symptomatic patients. IgG develops 3 to 6 months after the onset of symptoms. Titers of 1:2 to 1:4 are presumptive evidence of an early infection and should be repeated in 3 to 4 weeks. Titers of 1:8 to 1:16 are evidence of active infection, particularly when accompanied by a positive immunodiffusion test. Titers higher than 1:16 occur in 90% to 95% of patients with disseminated coccidioidomycosis.



Jun 12, 2016 | Posted by in IMMUNOLOGY | Comments Off on The Immune Response in Infectious Diseases

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