Porth's Pathophysiology, 9e

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UNIT IV Infection, Inflammation, and Immunity

­development and remain functional in the newborn for the first few months of life providing passive immunity until Ig production is well established in the newborn. IgG is the only class of Igs able to cross the placenta. 39 Maternally transmit- ted IgG is effective against most microorganisms and viruses that a neonate encounters. The largest amount of IgG crosses the placenta during the last weeks of pregnancy and is stored in fetal tissues. Infants born prematurely may be deficient in maternal antibodies and, therefore, more susceptible to infec- tion. Because of transfer of IgG antibodies to the fetus, an infant born to a mother infected with HIV has a positive HIV antibody test result, although the child may not be infected with the virus. Cord blood does not normally contain IgM or IgA. If present, these antibodies are of fetal origin and represent exposure to intrauterine infection because maternal IgM and IgA antibodies do not readily cross the placenta. Normally, the neonate begins producing IgM antibodies shortly after birth, as a result of exposure to the immense number of antigens normally found in the surrounding environment. However, this IgM is of lower binding affinity and effective against a limited range of antigens. It has also been demonstrated that premature infants can produce IgM as well as term infants. At approximately 6 days of age, the IgM rises sharply, and this rise continues until approximately 1 year of age, when the adult level is achieved. Serum IgA normally is not present at birth but detected in the neonate approximately 13 days after birth. The levels of IgA increase during early childhood and reach between 6 and 7 years of age. While maternal IgA is not transferred in utero, it is transferred to the breast-fed infant in colostrum. Since IgA antibodies as associated with mucosal members, these antibodies provide local immunity for the intestinal system during early life. Immune Response in the Older Adult As we age, the ability of the immune system to protect the body from pathogenic organisms and environmental toxins declines as a result of an overall decline in immune respon- siveness. This results from changes in both cell-mediated and humoral immune responses. As a result, older adults are more susceptible to infections, have more evidence of autoimmune and immune complex disorders, and have a higher incidence of cancer than do younger people. In addition, the immune system of older adults is less likely to respond appropriately to immunization. As a result, older adults have a weakened response to vaccination. Older adults also frequently have many comorbid conditions that impair normal immune func- tion and compromise the immune response. The cause of the altered response in older adults is multifactorial. There is a continued decrease in the size of the thymus gland, which begins during puberty and affects overall T-cell production and function. The size of the thy- mus diminishes to 15% or less of its maximum size. There may also be a decrease in the number of the lymphocytes in

the ­peripheral lymphoid tissue. The most common finding is a slight decrease in the proportion of T cells to other lympho- cytes and a decrease in CD4 + and CD8 + cells. Aging also produces qualitative changes in lymphocyte function. Lymphocytes seem to exhibit altered responses to antigen stimulation with an increased proportion becoming unresponsive to activation. It appears that the CD4 + T lym- phocyte is most severely affected because there is a decreased rate of synthesis of the cytokines that stimulate the prolif- eration of lymphocytes and expression of the specific recep- tors that interact with the circulating cytokines. Specifically, IL-2, IL-4, and IL-12 levels decrease in older adults. While actual B-cell function is compromised with age, the range of antigens that can be recognized by the B cells does not change. IN SUMMARY Neonates are protected against antigens in early life as a result of passive transfer of maternal IgG antibodies through the placenta and IgA antibodies in colostrum. Many changes occur with aging, but the exact mechanisms are not completely understood. References 1. Wen H., Schaller M., Dou Y., et al. (2008). Dendritic cells at the interface of innate and acquired immunity: the role of epigenetic changes. Journal of Leukocyte Biology 83, 439–446. 2. Dubinett S., Lee J., Sharma S., et al. (2010). Chemokines: Can effec- tor cells be redirected to the site of the tumor? The Cancer Journal 16, 325–335. 3. Mogensen T. (2009). Pathogen recognition and inflammatory signaling in innate immune defenses. Clinical Microbiology Reviews 22, 240–273. 4. Zhang X., Zhu C., Wu D., et al. (2010). Possible role of Toll-like receptor 4 in acute pancreatitis. Pancreas 39, 819–824. 5. Guglani L., Khader S. (2010). Th17 cytokines in mucosal immunity and inflammation. Current Opinion in HIV and AIDS 5, 120–127. 6. Balkwill F. (2004). Cancer and the chemokine network. Nature Reviews Cancer 4, 540–550. 7. Yu P., Lee Y., Lui W., et al. (2004). Priming of naive T cells inside tumors leads to eradication of established tumors. Nature Immunology 5, 141–149. 8. Chen T., Guo J., Han C., et al. (2009). Heat shock protein 70, released from heat-stressed tumor cells, initiates antitumor immunity by inducing tumor cell chemokine production and activating dendritic cells via THR4 pathway. Journal of Immunology 182, 1449–1459. 9. Knobloch J., Sibbing B., Jungck D., et al. (2010). Resveratrol impairs the release of steroid-resistant inflammatory cytokines from human airway smooth muscle cells in chronic obstructive pulmonary disease. Journal of Pharmacology and Experimental Therapeutics 335, 788–798. 10. Gordy C., Pua H., Sempowski G., et al. (2011). Regulation of steady-state neutrophil homeostasis by macrophages. Blood 117, 618–629. 11. Niebuhr M., Werfel T. (2010). Innate immunity, allergy and atopic derma- titis. Current Opinion in Allergy and Clinical Immunology 10, 463–468. 12. Asgari E., Zhou W., Sacks S. (2010). Complement in organ transplanta- tion. Current Opinion in Organ Transplantation 15, 486–491. 13. Silva M. (2010). When two is better than one: macrophages and neutro- phils work in concert in innate immunity as complementary and coopera- tive partners of a myeloidphagocyte system. Journal of Leukocyte Biology 87, 93–106.