390 PART I The Immune System in Health and Disease and a new drug-resistant strain of Mycobacterium tuberculo- sis is spreading at an alarming rate in the United St: Over age five In this chapter, the concepts described in earlier chapters, ntigenicity( Chapter 3)and immune effector mechanisms Under age five (Chapters 12-16), as well as vaccine development(which will be considered in Chapter 18)are applied to selected infec tious diseases caused by viruses, bacteria, protozoa, and helminths-the four main types of pathogens Viral infections A number of specific immune effector mechanisms, together with nonspecific defense mechanisms, are called into play to eliminate an infecting virus (Table 17-1). At the same time the virus acts to subvert one or more of these mechanisms to AIDs Diarrhea Malaria Measles respiratory diseases prolong its own survival. The outcome of the infection de- infections pends on how effectively the host's defensive mechanisms (including resist the offensive tactics of the virus pneumonia and The innate immune response to viral infection is primar ily through the induction of type I interferons(IFN-c and IFN-B)and the activation of NK cells. Double stranded rna FIGURE 17-1 Leading infectious disease killers. Data collected and (dsRNA) produced during the viral life cycle can induce the compiled by the World Health Organization in 2000 for deaths in expression of IFN-a and IFN-B by the infected cell. Macro- 1998 HIV-infected individuals who died of TB are included among phages, monocytes, and fibroblasts also are capable of AIDS deaths thesizing these cytokines, but the mechanisms that induce the production of type I interferons in these cells are not completely understood. IFN-a and IFN-B can induce an example, some United States troops returned from the Per- antiviral response or resistance to viral replication by bind sian Gulf with leishmaniasis; cholera cases have recently ing to the iFN a/B receptor. Once bound, IFN-a and IFN increased worldwide, with more than 100,000 cases reported activate the JAK-STAT pathway, which in turn induces the in KwaZulu-Natal, South Africa, during the summer of 2001; transcription of several genes. One of these genes encodes an TABLE 1 Mechanisms of humoral and cell-mediated immune responses to virus Response type Effector molecule or cel Activity Humoral Antibody(especially, secretory IgA) Blocks binding of virus to host cells, thus preventing infection or reinfection IgM, and IgA antibody Blocks fusion of viral envelope with host-cells plasma membrane Enhances phagocytosis of viral particles Complement activated by igG or Mediates opsonization by C3b and lysis IgM antibody f enveloped viral particles by membrane- IFN-y secreted by tH or Tc cells Has direct antiviral activity Cytotoxic T lymphocytes(CTLs Kill virus-infected self-cells NK cells and macrophages Kill virus-infected cells by antibody- dependent cell-mediated cytotoxicity(ADCC)example, some United States troops returned from the Per￾sian Gulf with leishmaniasis; cholera cases have recently increased worldwide, with more than 100,000 cases reported in KwaZulu-Natal, South Africa, during the summer of 2001; and a new drug-resistant strain of Mycobacterium tuberculo￾sis is spreading at an alarming rate in the United States. In this chapter, the concepts described in earlier chapters, antigenicity (Chapter 3) and immune effector mechanisms (Chapters 12–16), as well as vaccine development (which will be considered in Chapter 18) are applied to selected infec￾tious diseases caused by viruses, bacteria, protozoa, and helminths—the four main types of pathogens. Viral Infections A number of specific immune effector mechanisms, together with nonspecific defense mechanisms, are called into play to eliminate an infecting virus (Table 17-1). At the same time, the virus acts to subvert one or more of these mechanisms to prolong its own survival. The outcome of the infection de￾pends on how effectively the host’s defensive mechanisms resist the offensive tactics of the virus. The innate immune response to viral infection is primar￾ily through the induction of type I interferons (IFN- and IFN-) and the activation of NK cells. Double stranded RNA (dsRNA) produced during the viral life cycle can induce the expression of IFN- and IFN- by the infected cell. Macro￾phages, monocytes, and fibroblasts also are capable of syn￾thesizing these cytokines, but the mechanisms that induce the production of type I interferons in these cells are not completely understood. IFN- and IFN- can induce an antiviral response or resistance to viral replication by bind￾ing to the IFN / receptor. Once bound, IFN- and IFN- activate the JAK-STAT pathway, which in turn induces the transcription of several genes. One of these genes encodes an 390 PART IV The Immune System in Health and Disease Deaths in millions 4.0 3.0 2.5 2.0 1.5 1.0 0.5 0 Acute respiratory infections (including pneumonia and influenza) AIDS Malaria Measles Diarrheal TB diseases 3.5 2.3 Over age five 1.1 0.9 1.5 2.2 Under age five FIGURE 17-1 Leading infectious disease killers. Data collected and compiled by the World Health Organization in 2000 for deaths in 1998. HIV-infected individuals who died of TB are included among AIDS deaths. TABLE 17-1 Mechanisms of humoral and cell-mediated immune responses to viruses Response type Effector molecule or cell Activity Humoral Antibody (especially, secretory IgA) Blocks binding of virus to host cells, thus preventing infection or reinfection IgG, IgM, and IgA antibody Blocks fusion of viral envelope with host-cells plasma membrane IgG and IgM antibody Enhances phagocytosis of viral particles (opsonization) IgM antibody Agglutinates viral particles Complement activated by IgG or Mediates opsonization by C3b and lysis IgM antibody of enveloped viral particles by membrane￾attack complex Cell-mediated IFN- secreted by TH or TC cells Has direct antiviral activity Cytotoxic T lymphocytes (CTLs) Kill virus-infected self-cells NK cells and macrophages Kill virus-infected cells by antibody￾dependent cell-mediated cytotoxicity (ADCC)