Review of Medical Microbiology and Immunology, 13th Edition

8. Host Defenses


Principles of Host Defenses

Innate (nonspecific) immunity

Skin & Mucous Membranes

Inflammatory Response & Phagocytosis


Adaptive (Specific) Immunity

Failure of Host Defenses Predisposes to Infections


Self-Assessment Questions

Practice Questions: USMLE & Course Examinations


Host defenses are composed of two complementary, frequently interacting systems: (1) innate (nonspecific) defenses, which protect against microorganisms in general; and (2) acquired (specific) immunity, which protects against a particular microorganism. Innate defenses can be classified into three major categories: (1) physical barriers, such as intact skin and mucous membranes; (2) phagocytic cells, such as neutrophils, macrophages, and natural killer cells; and (3) proteins, such as complement, lysozyme, and interferon. Figure 8–1 shows the role of several components of the nonspecific defenses in the early response to bacterial infection. Acquired defenses are mediated by antibodies and T lymphocytes. Chapter 57 describes these host defenses in more detail.


FIGURE 8–1 Early host responses to bacterial infection.

There are two main types of host defenses against bacteria: the pyogenic response and the granulomatous response. Certain bacteria, such as Staphylococcus aureus and Streptococcus pyogenes, are defended against by the pyogenic (pus-producing) response, which consists of antibody, complement, and neutrophils. These pyogenic bacteria are often called extracellular pathogens because they do not invade cells. Other bacteria, such as Mycobacterium tuberculosis and Listeria monocytogenes, are defended against by the granulomatous response, which consists of macrophages and CD4-positive (helper) T cells. These bacteria are often called intracellular pathogens because they can invade and survive within cells.


Skin & Mucous Membranes

Intact skin is the first line of defense against many organisms. In addition to the physical barrier presented by skin, the fatty acids secreted by sebaceous glands in the skin have antibacterial and antifungal activity. The increased fatty acid production that occurs at puberty is thought to explain the increased resistance to ringworm fungal infections, which occurs at that time. The low pH of the skin (between 3 and 5), which is due to these fatty acids, also has an antimicrobial effect. Although many organisms live on or in the skin as members of the normal flora, they are harmless as long as they do not enter the body.

A second important defense is the mucous membrane of the respiratory tract, which is lined with cilia and covered with mucus. The coordinated beating of the cilia drives the mucus up to the nose and mouth, where the trapped bacteria can be expelled. This mucociliary apparatus, the ciliary elevator, can be damaged by alcohol, cigarette smoke, and viruses; the damage predisposes the host to bacterial infections. Other protective mechanisms of the respiratory tract involve alveolar macrophages, lysozyme in tears and mucus, hairs in the nose, and the cough reflex, which prevents aspiration into the lungs.

Loss of the physical barrier provided by the skin and mucous membranes predisposes to infection. Table 8–1 describes the organisms that commonly cause infections associated with the loss of these protective barriers.

TABLE 8–1 Damage to Skin and Mucous Membranes Predisposes to Infection Caused by Certain Bacteria


The nonspecific protection in the gastrointestinal tract includes hydrolytic enzymes in saliva, acid in the stomach, and various degradative enzymes and macrophages in the small intestine. The vagina of adult women is protected by the low pH generated by lactobacilli that are part of the normal flora.

Additional protection in the gastrointestinal tract and in the lower respiratory tract is provided by defensins. These are highly positively charged (cationic) peptides that create pores in the membranes of bacteria, which kills them. Neutrophils and Paneth cells in the intestinal crypts contain one type of defensin (α-defensins), whereas the respiratory tract produces different defensins called β-defensins. The mechanism by which defensins distinguish between bacterial membranes and human cell membranes is unknown.

The bacteria of the normal flora of the skin, nasopharynx, colon, and vagina occupy these ecologic niches, preventing pathogens from multiplying in these sites. The importance of the normal flora is appreciated in the occasional case when antimicrobial therapy suppresses these beneficial organisms, thereby allowing organisms such as Clostridium difficile and Candida albicans to cause diseases such as pseudomembranous colitis and vaginitis, respectively.

Inflammatory Response & Phagocytosis

The presence of foreign bodies, such as bacteria within the body, provokes a protective inflammatory response (Figure 8–2). This response is characterized by the clinical findings of redness, swelling, warmth, and pain at the site of infection. These signs are due to increased blood flow, increased capillary permeability, and the escape of fluid and cells into the tissue spaces. The increased permeability is due to several chemical mediators, of which histamine, prostaglandins, and leukotrienes are the most important. Complement components, C3a and C5a, also contribute to increased vascular permeability. Bradykinin is an important mediator of pain.


FIGURE 8–2 Inflammation. The inflammatory response can be caused by two different mechanisms. Left: Pyogenic bacteria (e.g., Staphylococcus aureus) cause inflammation via antibody- and complement-mediated mechanisms. Right: Intracellular bacteria (e.g., Mycobacterium tuberculosis) cause inflammation via cell-mediated mechanisms.

Neutrophils and macrophages, both of which are phagocytes, are an important part of the inflammatory response. Neutrophils predominate in acute pyogenic infections, whereas macrophages are more prevalent in chronic or granulomatous infections. Macrophages perform two functions: they are phagocytic and they produce two important “proinflammatory” cytokines: tumor necrosis factor (TNF) and interleukin-1 (IL-1). The synthesis of IL-1 from its inactive precursor is mediated by proteolytic enzymes (caspases) in a cytoplasmic structure called an inflammasome. The importance of the inflammatory response in limiting infection is emphasized by the ability of anti-inflammatory agents such as corticosteroids to lower resistance to infection.

Certain proteins, known collectively as the acute-phase response, are also produced early in inflammation, mainly by the liver. The best known of these are C-reactive protein and mannose-binding protein, which bind to the surface of bacteria and enhance the activation of the alternative pathway of complement (see Chapter 58). C-reactive protein was named for its ability to bind with a carbohydrate in the cell wall of Streptococcus pneumoniae (see page 123). Lipopolysaccharide (endotoxin)-binding protein is another important acute-phase protein that is produced in response to gram-negative bacteria. Interleukin-6 (IL-6) is the main inducer of the acute-phase response and is also a proinflammatory cytokine. Macrophages are the principal source of IL-6, but many other types of cells produce it as well. Gamma interferon, which activates macrophages and enhances their microbicidal action, is produced by activated helper T cells.

Neutrophils and macrophages are attracted to the site of infection by small polypeptides called chemokines (chemo tactic cyto kines). Chemokines are produced by tissue cells in the infected area, by local endothelial cells, and by resident neutrophils and macrophages. Interleukin-8 is a chemokine that attracts primarily neutrophils, whereas monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein (MIP) are attractants for macrophages and monocytes (see Chapter 58).

As part of the inflammatory response, bacteria are engulfed (phagocytized) by polymorphonuclear neutrophils (PMNs) and macrophages. PMNs make up approximately 60% of the leukocytes in the blood, and their numbers increase significantly during infection (leukocytosis). It should be noted, however, that in certain bacterial infections such as typhoid fever, a decrease in the number of leukocytes (leukopenia) is found. The increase in PMNs is due to the production of granulocyte-stimulating factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]; see Chapter 58) by macrophages soon after infection.

Note that although both PMNs and macrophages phagocytose bacteria, PMNs do not present antigen to helper T lymphocytes, whereas macrophages (and dendritic cells) do (see Chapter 58). Dendritic cells are the most important antigen-presenting cells. The phagocytic ability of dendritic cells is enhanced by the presence of receptors for mannose-binding protein.

The process of phagocytosis can be divided into three steps: migrationingestion, and killingMigration of PMNs to the infection site is due to the production of chemokines, such as interleukin-8 and complement component C5a, at that location. Adhesion of PMNs to the endothelium at the site of infection is mediated first by the interaction of the PMNs with selectin proteins on the endothelium and then by the interaction of integrin proteins called “LFA proteins,” located on the PMN surface, with intracellular adhesion molecule (ICAM) proteins on the endothelial cell surface.1

ICAM proteins on the endothelium are increased by inflammatory mediators, such as IL-1 and TNF (see Chapter 58), which are produced by macrophages in response to the presence of bacteria. The increase in the level of ICAM proteins ensures that PMNs selectively adhere to the site of infection. Increased permeability of capillaries as a result of histamine, kinins, and prostaglandins2 allows PMNs to migrate through the capillary wall to reach the bacteria. This migration is called diapedesis and takes several minutes to occur.

The bacteria are ingested by the invagination of the PMN cell membrane around the bacteria to form a vacuole (phagosome). This engulfment is enhanced by the binding of immunoglobulin G (IgG) antibodies (opsonins) to the surface of the bacteria, a process called opsonization (Figure 8–3). The C3b component of complement enhances opsonization. (The outer cell membranes of both PMNs and macrophages have receptors both for the Fc portion of IgG and for C3b.) Even in the absence of antibody, the C3b component of complement, which can be generated by the “alternative” pathway, can opsonize. This is particularly important for bacterial and fungal organisms whose polysaccharides activate the alternative pathway.


FIGURE 8–3 Opsonization. Top: An encapsulated bacterium is poorly phagocytized by a neutrophil in the absence of either immunoglobulin G (IgG) antibody or C3b. Bottom: In the presence of either IgG antibody or C3b or both, the bacterium is opsonized (i.e., it is made more easily phagocytized by the neutrophil).

At the time of engulfment, a new metabolic pathway, known as the respiratory burst, is triggered; this results in the production of two microbicidal agents, the superoxide radical and hydrogen peroxide. These highly reactive compounds (often called reactive oxygen intermediates) are synthesized by the following reactions:

O2 + e → O2

2O2 + 2H+ → H2O2 + O2

In the first reaction, molecular oxygen is reduced by an electron to form the superoxide radical, which is weakly bactericidal. In the next step, the enzyme superoxide dismutase catalyzes the formation of hydrogen peroxide from two superoxide radicals. Hydrogen peroxide is more toxic than superoxide but is not effective against catalase-producing organisms such as staphylococci.

Nitric oxide (NO) is another important microbicidal agent. It is a reactive nitrogen intermediate that is synthesized by an inducible enzyme called nitric oxide synthase in response to stimulators such as endotoxin. Overproduction of NO contributes to the hypotension seen in septic shock because it causes vasodilation of peripheral blood vessels.

The respiratory burst also results in the production of the microbicidal agent–NO. NO contains a free radical that participates in oxidative killing of ingested microbes phagocytosed by neutrophils and macrophages. Nitric oxide synthase, the enzyme that produces NO, is induced in these cells following phagocytosis.

The killing of the organism within the phagosome is a two-step process that consists of degranulation followed by production of hypochlorite ions, which are probably the most important microbicidal agents. In degranulation, the two types of granules in the cytoplasm of the neutrophil fuse with the phagosome, emptying their contents in the process. These granules are lysosomes that contain a variety of enzymes essential to the killing and degradation that occur within the phagolysosome.

(1) The larger lysosomal granules, which constitute about 15% of the total, contain the important enzyme myeloperoxidase as well as lysozyme and several other degradative enzymes. (Myeloperoxidase, which is green, makes a major contribution to the color of pus.)

(2) The smaller granules, which make up the remaining 85%, contain lactoferrin and additional degradative enzymes such as proteases, nucleases, and lipases. Lysosomal granules can empty into the extracellular space as well as into the phagosome. Outside the cell, the degradative enzymes can attack structures too large to be phagocytized, such as fungal mycelia, as well as extracellular bacteria.

The actual killing of the microorganisms occurs by a variety of mechanisms, which fall into two categories: oxygen-dependent and oxygen-independent. The most important oxygen-dependent mechanism is the production of the bactericidal molecule, hypochlorite ion, according to the following reaction:

CI + H2O2 → CIO + H2O

Myeloperoxidase catalyzes the reaction between chloride ion and hydrogen peroxide, which was produced by the respiratory burst, to produce hypochlorite ion in the presence of myeloperoxidase. Hypochlorite by itself damages cell walls but can also react with hydrogen peroxide to produce singlet oxygen, which damages cells by reacting with double bonds in the fatty acids of membrane lipids.

Rare individuals are genetically deficient in myeloperoxidase, yet their defense systems can kill bacteria, albeit more slowly. In these individuals, the respiratory burst that produces hydrogen peroxide and superoxide ion seems to be sufficient, but with two caveats: if an organism produces catalase, hydrogen peroxide will be ineffective, and if an organism produces superoxide dismutase, superoxide ion will be ineffective.

The oxygen-independent mechanisms are important under anaerobic conditions. These mechanisms involve lactoferrin, which chelates iron from the bacteria; lysozyme, which degrades peptidoglycan in the bacterial cell wall; cationic proteins, which damage bacterial membranes; and low pH.

Macrophages also migrate, engulf, and kill bacteria by using essentially the same processes as PMNs do, but there are several differences:

(1) Macrophages do not possess myeloperoxidase and so cannot make hypochlorite ion; however, they do produce hydrogen peroxide and superoxide by respiratory burst.

(2) Certain organisms such as the agents of tuberculosis, brucellosis, and toxoplasmosis are preferentially ingested by macrophages rather than PMNs and may remain viable and multiply within these cells; granulomas formed during these infections contain many of these macrophages.

(3) Macrophages secrete plasminogen activator, an enzyme that converts the proenzyme plasminogen to the active enzyme plasmin, which dissolves the fibrin clot.

Reduced Phagocytosis Predisposes to Bacterial Infections

The importance of phagocytosis as a host defense mechanism is emphasized by the observation that reduced numbers or reduced function of phagocytes predisposes to bacterial infections, especially infections caused by certain organisms (Table 8–2):

TABLE 8–2 Reduced Phagocytosis Predisposes to Infection Caused by Certain Bacteria


(1) Repeated infections occur in children who have genetic defects in their phagocytic processes. Two examples of these defects are chronic granulomatous disease, in which the phagocyte cannot kill the ingested bacteria owing to a defect in NADPH oxidase and a resultant failure to generate H2O2, and Chédiak–Higashi syndrome, in which abnormal lysosomal granules that cannot fuse with the phagosome are formed, so that even though bacteria are ingested, they survive.

(2) Frequent infections occur in neutropenic patients, especially when the PMN count drops below 500/μL as a result of immunosuppressive drugs or irradiation. These infections are frequently caused by opportunistic organisms (i.e., organisms that rarely cause disease in people with normal immune systems).

(3) Splenectomy removes an important source of both phagocytes and immunoglobulins, which predisposes to sepsis caused by three encapsulated pyogenic bacteria: S. pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. S. pneumoniae causes approximately 50% of episodes of sepsis in splenectomized patients. Patients with sickle cell anemia and other hereditary anemias can autoinfarct their spleen, resulting in a loss of splenic function and a predisposition to sepsis caused by these bacteria.

(4) People who have diabetes mellitus, especially those who have poor glucose control or episodes of ketoacidosis, have an increased number of infections and more severe infections compared with people who do not have diabetes. The main host defense defect in these patients is reduced neutrophil function, especially when acidosis occurs.

Two specific diseases highly associated with diabetes are malignant otitis externa caused by Pseudomonas aeruginosa and mucormycosis caused by molds belonging to the genera Mucor and Rhizopus. In addition, there is an increased incidence and increased severity of community-acquired pneumonia caused by bacteria such as S. pneumoniae and S. aureus and of urinary tract infections caused by organisms such as Escherichia coli and Candida albicans. Candidal vulvovaginitis is also more common in diabetic patients. Diabetic patients also have many foot infections because atherosclerosis compromises the blood supply and necrosis of tissue occurs. Skin infections, such as ulcers and cellulitis, and soft tissue infections, such as necrotizing fasciitis, are common and can extend to the underlying bone, causing osteomyelitis. S. aureus and mixed facultative anaerobic bacteria are the most common causes.


Infection causes a rise in the body temperature that is attributed to endogenous pyrogen (IL-1) released from macrophages. Fever may be a protective response because a variety of bacteria and viruses grow more slowly at elevated temperatures.


Adaptive immunity results either from exposure to the organism (active immunity) or from receipt of preformed antibody made in another host (passive immunity).

Passive adaptive immunity is a temporary protection against an organism and is acquired by receiving serum containing preformed antibodies from another person or animal. Passive immunization occurs normally in the form of immunoglobulins passed through the placenta (IgG) or breast milk (IgA) from mother to child. This protection is very important during the early days of life when the child has a reduced capacity to mount an active response.

Passive immunity has the important advantage that its protective abilities are present immediately, whereas active immunity has a delay of a few days to a few weeks, depending on whether it is a primary or secondary response. However, passive immunity has the important disadvantage that the antibody concentration decreases fairly rapidly as the proteins are degraded, and so the protection usually lasts for only a month or two. The administration of preformed antibodies can be lifesaving in certain diseases that are caused by powerful exotoxins, such as botulism and tetanus. Serum globulins, given intravenously, are a prophylactic measure in patients with hypogammaglobulinemia or bone marrow transplants. In addition, they can mitigate the symptoms of certain diseases such as hepatitis caused by hepatitis A virus, but they appear to have little effect on bacterial diseases with an invasive form of pathogenesis.

Active adaptive immunity is protection based on exposure to the organism in the form of overt disease, subclinical infection (i.e., an infection without symptoms), or a vaccine. This protection has a slower onset but longer duration than passive immunity. The primary response usually takes 7 to 10 days for the antibody to become detectable. An important advantage of active immunity is that an anamnestic (secondary) response occurs (i.e., there is a rapid response [approximately 3 days] of large amounts of antibody to an antigen that the immune system has previously encountered). Active immunity is mediated by both antibodies (immunoglobulins) and T cells:

(1) Antibodies protect against organisms by a variety of mechanisms—neutralization of toxins, lysis of bacteria in the presence of complement, opsonization of bacteria to facilitate phagocytosis, and interference with adherence of bacteria and viruses to cell surfaces. If the level of IgG drops below 400 mg/dL (normal = 1000–1500 mg/dL), the risk of pyogenic infections caused by bacteria such as staphylococci increases.

Because antibodies, especially IgG, are detectable for days to weeks after infection, they are thought not to play a major role in combating the primary infection at the initial site of infection (usually the skin or mucous membrane), but rather to protect against hematogenous dissemination of the organism to distant sites in the body and against a second infection by that organism at some future time.

(2) T cells mediate a variety of reactions, including cytotoxic destruction of virus-infected cells and bacteria, activation of macrophages, and delayed hypersensitivity. T cells, especially Th-1 cells (see Chapter 58) and macrophages, are the main host defense against mycobacteria such as Mycobacterium tuberculosis and systemic fungi such as Histoplasma and Coccidioides. T cells also help B cells to produce antibody against many, but not all, antigens.

Table 8–3 describes the essential host defense mechanisms against bacteria. These mechanisms include both humoral immunity against pyogenic bacteria and exotoxins and cell-mediated immunity against several intracellular bacteria.

TABLE 8–3 Essential Host Defense Mechanisms Against Bacteria



The frequency or severity of infections is increased when certain predisposing conditions exist. These predisposing conditions fall into two main categories: patients are immunocompromised or patients have foreign bodies such as indwelling catheters or prosthetic devices. Foreign bodies predispose because host defenses do not operate efficiently in their presence. Table 8–4 describes the predisposing conditions and the most common organisms causing infections when these predisposing conditions are present.

TABLE 8–4 Conditions That Predispose to Infections and the Organisms That Commonly Cause These Infections


Certain diseases and anatomic abnormalities also predispose to infections. For example, patients with diabetes often have S. aureus infections, perhaps for two reasons: these patients have extensive atherosclerosis, which causes relative anoxia to tissue, and they appear to have a defect in neutrophil function. Patients with sickle cell anemia often have Salmonella osteomyelitis, probably because the abnormally shaped cells occlude the small capillaries in the bone. This traps the Salmonella within the bone, increasing the risk of osteomyelitis.

Patients with certain congenital cardiac defects or rheumatic valvular damage are predisposed to endocarditis caused by viridans streptococci. Neutrophils have difficulty in penetrating the vegetations formed on the valves in endocarditis. Patients with an aortic aneurysm are prone to vascular infections caused by Salmonella species.

Patients with reduced host defenses often have a muted response to infection (e.g., a low-grade [or no] fever and a mild [or absent] inflammatory response). For this reason, a high index of suspicion regarding the presence of infection must be present when evaluating patients who are immunocompromised, especially those who are intentionally immunosuppressed, such as transplant recipients.


• Host defenses against bacterial infections include both innate and adaptive (acquired) defenses. Innate defenses are nonspecific (i.e., they are effective against many different organisms). These include physical barriers, such as intact skin and mucous membranes; cells, such as neutrophils and macrophages; and proteins, such as complement and lysozyme. Adaptive (acquired) defenses are highly specific for the organism and include antibodies and cells such as CD4-positive helper T lymphocytes and CD8-positive cytotoxic T lymphocytes.

Innate Immunity

• Intact skin and mucous membranes provide a physical barrier to infection. Loss of skin integrity (e.g., in a burn) predisposes to infection. The low pH of the skin, stomach, and vagina also protects against infection.

• The respiratory tract, a very important portal of entry for microbes, is protected by the ciliary elevator, alveolar macrophages, lysozyme, nose hairs, and the cough reflex.

• The normal flora of the skin and mucous membranes occupy receptors, which reduce the opportunity for pathogens to attach–a process called colonization resistance. Suppression of the normal flora with antibiotics predisposes to infection with certain organisms. Two important examples are the suppression of colon flora predisposing to pseudomembranous colitis caused by Clostridium difficile and the suppression of vaginal flora predisposing to vaginitis caused by Candida albicans.

• Inflammation (i.e., redness, swelling, warmth, and pain) is an important host defense. Redness, swelling, and warmth are the result of increased blood flow and increased vascular permeability, which has the effect of bringing the cells and proteins of our host defenses to the site of infection. The increased blood flow and increased vascular permeability are caused by mediators such as histamine, prostaglandins, and leukotrienes.

• The predominant phagocytic cells in inflammation are neutrophils and macrophages. Neutrophils are seen in the pyogenic inflammatory response to bacteria such as Staphylococcus aureus and Streptococcus pyogenes, whereas macrophages are seen in the granulomatous inflammatory response to bacteria such as Mycobacterium tuberculosis.

• The acute-phase response consists of proteins (e.g., C-reactive protein, mannose-binding protein, and LPS-binding protein) that enhance the host response to bacteria. Interleukin-6 is the main inducer of this response.

• Neutrophils and macrophages are attracted to the site of infection by chemokines, which are small polypeptides produced by cells at the infected site. Interleukin-8 and C5a are important chemokines for neutrophils.

• In response to most bacterial infections, there is an increase in the number of neutrophils in the blood. This increase is caused by the production of granulocyte-stimulating factors by macrophages.

• Both neutrophils and macrophages phagocytose bacteria, but macrophages (and similar cells called dendritic cells) also present antigen to CD4-positive (helper) T cells, whereas neutrophils do not. Dendritic cells are probably the most important antigen-presenting cells in the body.

• After neutrophils are attracted to the infected site by chemokines, they attach to the endothelium first using selectins on the endothelium, then by the interaction of integrins (LFA proteins) on the neutrophils with intracellular adhesion molecule (ICAM) proteins on the endothelium. The concentration of ICAM proteins is increased by cytokines released by activated macrophages, which results in neutrophils being attracted to the infected site.

• Neutrophils then migrate through the endothelium (diapedesis) and ingest the bacteria. IgG and C3b are opsonins, which enhance ingestion of the bacteria. There are receptors for the heavy chain of IgG and for C3b on the surface of the neutrophils.

• Killing of the bacteria within the neutrophil is caused by hypochlorite, hydrogen peroxide, and superoxides. Lysosomes contain various degradative enzymes and fuse with the phagosome to form a phagolysosome within which the killing occurs.

• Severe, recurrent pyogenic infections occur in those who have inadequate neutrophils. For example, people with defective neutrophils, people with fewer than 500 neutrophils/μL, and those who have had a splenectomy or who have diabetes mellitus are at increased risk for pyogenic infections.

Adaptive Immunity

• Passive immunity refers to protection based on the transfer of preformed antibody from one person (or animal) to another person. Passive immunity provides immediate but short-lived protection (lasting a few months). Examples of passive immunity include administration of antitoxin, passage of IgG from mother to fetus across the placenta, and passage of IgA from mother to newborn through breast milk.

• Active immunity refers to protection based on the formation of both antibodies and cell-mediated immunity after exposure either to the microbe itself (with or without disease) or to the antigens of the microbe in a vaccine. Active immunity provides long-term protection but is not effective for days after exposure to the microbe. In the primary response, antibody appears in 7 to 10 days, whereas in the secondary response, antibody appears in approximately 3 days.

• The main functions of antibodies are to neutralize bacterial toxins and viruses, opsonize bacteria, activate complement to form a membrane attack complex that can kill bacteria, and interfere with attachment to mucosal surfaces. IgG is the main opsonizing antibody, IgG and IgM activate complement, and IgA interferes with attachment to the mucosa.

• The main functions of cell-mediated immunity are to protect against intracellular bacteria and to kill virus-infected cells. Helper T cells (and macrophages) protect against intracellular bacteria, whereas cytotoxic T cells kill virus-infected cells.

Reduced Host Defenses

• Reduced host defenses result in an increase in the frequency and severity of infections. The main causes include various genetic immunodeficiencies, the presence of foreign bodies, and the presence of certain chronic diseases, such as diabetes mellitus and renal failure.


1. Which one of the following host defense processes is the MOST important in preventing the action of exotoxins?

(A) Binding of cytokines to exotoxin-specific receptors inhibits the attachment of exotoxins

(B) Degradation of exotoxins by the membrane attack complex of complement

(C) Lysis of exotoxins by perforins produced by cytotoxic T cells

(D) Neutralization of exotoxins by antibody prevents binding to target cell membrane

(E) Phagocytosis of exotoxins by neutrophils and subsequent destruction by hypochlorite

2. An inflammatory response in the skin is characterized by erythema (redness). Which one of the following is the most important cause of this erythema?

(A) C3b component of complement

(B) Gamma interferon

(C) Histamine

(D) Hypochlorite

(E) Superoxide

3. A 1-year-old child with repeated infections was diagnosed with chronic granulomatous disease (CGD). A defect in which one of the following is the cause of CGD?

(A) Gamma interferon receptor

(B) LFA-integrins

(C) Mannose-binding protein

(D) NADPH oxidase

(E) Nitric oxide

4. Opsonization is the process by which:

(A) bacteria are made more easily phagocytized.

(B) chemokines attract neutrophils to the site of infection.

(C) neutrophils migrate from the blood through the endothelium to reach the site of infection.

(D) the acute-phase response is induced.

(E) the alternate pathway of complement is activated.


1. (D)

2. (C)

3. (D)

4. (A)


Questions on the topics discussed in this chapter can be found in the Basic Bacteriology section of PART XIII: USMLE (National Board) Practice Questions starting on page 689. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.

1LFA proteins and ICAM proteins mediate adhesion between many types of cells. These proteins are described in more detail in Chapter 58.

2The anti-inflammatory action of aspirin is the result of its ability to inhibit cyclooxygenase, thus reducing the synthesis of prostaglandins.