Immunology (Lippincott Illustrated Reviews Series) 2nd Edition
Chapter 11: Lymphocyte Effector Functions
The innate immune system uses both humoral and cellular means to surround, phagocytize, enzymatically degrade, or otherwise kill microbial intruders (Fig. 11.1). The adaptive immune system also uses soluble (or humoral) and cellular defenses. In contrast to the innate immune system, the responses of the adaptive immune system are more narrowly targeted and directed and can be adjusted to deal with the persistence of the threat.
One arm of the adaptive immune system uses soluble molecules (fluids or “humors”), including antibodies and complement, to target and destroy invasive threats. Humoral immunity may be thought of as arrows or missiles in the immune system’s armory. Produced and secreted by plasma cells, antibodies are soluble molecules that travel throughout the body to find and bind to their targets. The binding of an antibody to a microbial epitope can inhibit or prevent microbial spread by several means: immobilization, prevention of microbial attachment to host cells, promotion of increased phagocytosis, and targeting microbes for destruction by other soluble molecules or by leukocytes such as natural killer (NK) cells and eosinophils.
The other arm of the adaptive immune system, called cell-mediated immunity, is akin to hand-to-hand combat in which leukocytes directly engage invaders or infected cells harboring the invaders. Cell-mediated adaptive immune responses are controlled and regulated by T cells. Some T cells, such as cytotoxic T lymphocytes, make direct contact with infected cells and proceed to destroy the “nest” within which the microbes are multiplying by damaging their cell membranes or inducing them to undergo apoptotic deaths. Other T cells summon and direct other leukocytes to assault and destroy the microbes or infected cells, a response called delayed (-type) hypersensitivity (DTH), which will be discussed further in Chapter 14.
Lymphocyte effector functions—an overview.
II. HUMORAL IMMUNITY
Humoral immunity is based on the actions of antibodies and complement. Although cells produce both, it is the binding of these soluble molecules that is responsible for the humoral immune responses of the adaptive immune system. One of these responses, neutralization, is directly because of the binding by antibodies, whereas opsonization, complement activation (more specifically, the classical pathway of complement activation), and antibody-dependent cell-mediated cytotoxicity involve the use of antibodies to “tag” cells or molecules for destruction by other elements of the immune system.
A. Antigen–antibody reactions
Antigen (Ag)–antibody (Ab) interactions are some of the most specific noncovalent biochemical reactions known and can be represented by the simple formula
Ag + Ab → AgAb
Although the reaction is driven to the right, favoring binding and formation of Ag–Ab complexes, notice that the process is reversible. The strength of interaction (i.e., Ag–Ab association, right arrow, over the dissociation of Ag from Ab, left arrow) is called affinity. Different immunoglobulins within an individual show a wide range of affinity. Valence refers to the number of epitope-binding sites on an immunoglobulin molecule and varies from two (monomeric forms of all isotypes) to four (secretory IgA) to ten (for pentameric IgM). The term avidity is often used to describe the collective affinity of multiple binding sites (affinity + valence) of an immunoglobulin.
The precipitin reaction is the term applied to the interaction of soluble antigen with soluble antibody that results in the formation of Ag–Ab complexes (lattices) large enough to precipitate from solution. To understand Ag–Ab reactions, you must understand the quantitative precipitin reaction.
The quantitative precipitin curve can be demonstrated by mixing and incubating varying amounts of antigen (in a constant volume) with equal and constant volumes of antiserum (containing antibodies) (Figs. 11.2 and 20.1). Precipitate formation in a series of tubes can be measured and used to describe the three distinct zones of the quantitative precipitin curve. The amount of precipitate that is formed depends on the ratio of the antigen to antibody and is also affected by the antibody’s avidity. A similar curve can be generated by keeping the antigen constant and varying the amount of antibody added.
The three zones of the quantitative precipitin curve are as follows:
• Zone of Ag excess. There is insufficient antibody to form large lattices. The antigen–antibody complexes are too small to precipitate. The net result is the formation of soluble complexes.
• Equivalence zone. Optimal precipitation occurs in this area of the curve. Large lattices can be formed, and visible precipitating complexes are formed.
• Zone of Ab excess. Not enough antigen is present to form large lattices, and the net result is formation of soluble complexes.
These principles of the quantitative precipitin curve apply to all antigen–antibody reactions and form the basis of many clinical diagnostic tests (see Chapter 20).
Precipitin curve. Formation and precipitation of large, insoluble antigen–antibody complexes occur at optimal ratios of antigen and antibody. The ration depends on the complexity of the antigen and the avidity of the antibody.
Antibodies can also bind to and cross-link cells or particles, causing an aggregate formation in the agglutination reaction. Agglutination has the effect of entrapping microbial invaders within a molecular net, inhibiting their mobility (Fig. 11.3) and rendering them more susceptible to destruction. Antibodies of the IgM and IgA isotypes are particularly adept at this because they contain 10 and 4 binding sites, respectively. However, IgG antibodies, in sufficient concentrations, can also agglutinate cells or particles. Antibodies can also agglutinate nonmicrobial cells, as is commonly demonstrated by the use of IgM antibodies for ABO typing of erythrocytes (see Chapters 17 and 20).
Agglutination. Antibodies can cross-link infectious agents (A), host cells (B), or antigen bound the surface of particles (C).
Neutralization is the binding of antibodies to microbial epitopes or soluble molecules (e.g., toxins) in a manner that inhibits the ability of these microbes or molecules to bind to host cell surfaces. Binding to host cell surfaces is a necessary step for microbes and toxins to enter and damage host cells. Antibodies generated against the microbes (or toxins) often include some that block their interaction with the host cell surface, thus preventing the microbe (or toxin) from entering the cell (Fig. 11.4). Neutralizing antibodies are usually of the IgG and IgA isotypes. It is the presence of neutralizing antibodies generated during the initial infections that provides the greatest protection against subsequent reinfection by the same organism.
Sometimes the binding of an antibody (usually of the IgG1 or IgG3 isotype) to a microbial surface is enough to “whet the appetite” of a phagocyte, making the microbe a more attractive “meal.” This process is known as opsonization. In essence, antibodies binding to microbes “tag” them for subsequent destruction by phagocytic cells. Upon binding, the antibody molecules undergo conformational changes that include the Fc region (see Fig. 6.6). Macrophages, dendritic cells, and neutrophils bear surface receptors (FcR) for the Fc portion of bound immunoglobulin. Table 11.1 presents the types and distribution of Fc receptors. FcRs on phagocytic cells recognize antigen-bound antibody molecules, tethering the “tagged” microbe to the phagocytic cell and stimulating its engulfment and destruction (Fig. 11.5). Binding and engulfment via the FcγRI receptor is facilitated by the simultaneous use of complement receptors (CR) (Fig. 11.6; also see Fig. 5.3). Thus, the roles of bound antibody and bound complement fragments such as C3b are synergistic in serving as opsonins to stimulate phagocytosis.
Neutralization. Neutralization occurs when antibodies block the structures on infectious agents or toxin molecules that are used to attach to and enter host cells.
Uptake and opsonization via Fc receptors. Fc receptors (FcR) allow attachment of epitope-bound antibodies to cells for internalization. There are multiple types of Fc receptors that are specialized for different antibody isotypes (see Table 11.1).
Synergy of Fc receptors and complement receptors for opsonization. Simultaneous use of Fc receptors (FcR) and complement receptors (CR) to tether antigens bound by both antibodies and complement fragments synergistically increases opsonization.
E. Antibody-dependent cell-mediated cytotoxicity
The “tagging” of an invasive organism can attract phagocytic cells and other cytolytic cells. FcRs on NK cells (FcγRIII) and eosinophils (FcγRI, FcεRI, and FcαRI) are IgG-, IgE-, and IgA-specific (see Table 11.1). The bound cells may be bacteria, protozoa, or even some parasitic worms. As with phagocytic cells, these receptors allow the cytolytic cells to bind invasive organisms “tagged” with IgG, IgE, or IgA antibodies, but rather than engulfment, they use cytolytic mechanisms to kill the “tagged” organisms (Fig. 11.7). This process is termed antibody-dependent cell-mediated cytotoxicity (ADCC). The cytolytic mechanisms used by NK cells and eosinophils in ADCC are similar to some of those used by cytotoxic T cells to kill the intruder.
F. Complement activation
The classical pathway of complement is activated by conformational changes that occur in the Fc portion of antibodies upon epitope binding. Antibodies (usually of the IgM and IgG isotypes) facilitate the sequential binding of the C1, C4, C2, and C3 components of the complement system (Fig. 11.8). Like the alternative and mannan-binding lectin pathways (see Figs. 5.7 and 5.10), completion of the classical complement pathway results in the production of C3b, a “sticky” fragment of C3 that readily binds to surfaces (of cells, microbes, or particles; see Fig. 20.12) as a highly effective opsonin (see Fig. 5.4), the release of small pro-inflammatory fragments such as C5a, C4a, and C3a, and the assembly of the membrane attack complex (see Figs. 5.8 and 5.9).
Antibody-dependent cell-mediated cytotoxicity (ADCC). Fc receptors on natural killer cells (A) and on eosinophils (B) allow them to attach to and destroy, by direct cellular attack, cells that have been “tagged” by antibodies. On NK cells, these are distinct from the KAR and KIR receptors used to detect stress molecules and MHC I molecules.
Classical pathway of complement activation. The classical pathway of complement activation is triggered by the binding of antibodies to antigen to form antigen–antibody (Ag–Ab) complexes that permit the subsequent binding of the C1 component.
G. Immediate hypersensitivity
Mast cells and basophils have surface receptors that bind the Fc portion of IgE molecules that have not yet bound to their epitopes. Thus, these cells acquire a set of receptor-bound immunoglobulins that function as epitope-recognizing surface receptors. When the surface IgE is cross-linked by appropriate epitopes, the mast cell/basophil is triggered to degranulate. This release of cytoplasmic granules triggers a set of events known as immediate hypersensitivities. Immediate hypersensitivity responses, including asthma and allergies, are discussed in detail in Chapter 14.
III. CELL-MEDIATED IMMUNITY
Innate and adaptive immune responses can be viewed as a form of warfare at the cellular and molecular levels against potential invasive organisms. Antibodies and complement can be effective weapons against microbes that are caught out in the open. However, microbes are not solely dependent on their numbers but also employ evasive tactics, including hiding within host cells where antibodies and complement cannot reach them.
Cell-mediated immune responses are directed to curtail microbial stealth by determining whether infectious agents are sheltered within host cells and are, thus, beyond the reach of humoral immunity. Cell-mediated responses resemble cavalry charges and hand-to-hand combat and take two basic forms: delayed (-type) hypersensitivity (DTH), mediated by CD4+ Th1 cells, and cell-mediated lysis, mediated by CD8+cytotoxic T lymphocytes (CTLs). Cell-mediated immunity is a life-or-death struggle at close quarters. In DTH, some T cells act as “scouts” and “senior officers,” identifying sites of infection, calling in reinforcements (mostly macrophages and other leukocytes), and ordering them to kill the infectious foe and/or the host cell sheltering the foe. CTLs, by contrast, engage in direct cell-to-cell combat to actively destroy their infectious opponent or the host cell in which that opponent is hiding.
A. Delayed (-type) hypersensitivity: Role of CD4+ T cells
Once activated, CD4+ Th1 cells leave the lymph nodes in which they were activated and prowl through the vasculature, body tissues, and lymphatic system, seeking host cells displaying the same pMHC II combination that originally triggered their activation, or another pMHC II so similar in structure as to be cross-reactive. If, in the course of recirculating through body tissues, a previously activated Th1 cell reencounters the appropriate pMHC class II displayed on a phagocytic cell (e.g., at the site of an infection), it binds and interacts. Access to the infectious site is facilitated by the secretion of phagocyte-derived cytokines such as IL-1, IL-8, and TNF-α that activate local vascular endothelium and promote vascular permeability. The phagocyte, as an APC, can reactivate the Th1 cell to proliferate anew and gain the ability to activate macrophages (Fig. 11.9). Thus, T cells from the adaptive immune system direct the activities of cells of the innate immune system.
In the DTH response, macrophage activation by CD4+ Th1 cells is mediated by direct contact (binding of CD40 and CD154) and by IFN-γ secreted by the T cells. Once activated, macrophages increase their phagocytic activity as well as the production and release of destructive enzymes and reactive oxygen intermediates. Activated macrophages become blind, enraged killers that attack not only infectious agents and infected cells, but also normal uninfected cells in the vicinity (see Chapter 5). They also secrete cytokines that attract other leukocytes, especially neutrophils, to the site of infection. Together, the activated macrophages and neutrophils rampage through the site of infection, damaging cells, ingesting and killing microbes, and removing cellular debris.
The DTH response can be a double-edged sword. Because activated macrophages are not antigen-specific, they injure friend and foe alike, that is, normal tissue along with infected cells. DTH responses, in fact, have two phases: a specific phase based on the Th1 T cell activity and a nonspecific phase based on the activity of the newly activated macrophages (Fig. 11.10). Reactivation of each Th1 cell is epitope-specific (e.g., a peptide derived from Leishmania) and requires stimulation by the precise pMHC II specific to its TCR. However, the macrophages that are subsequently activated by the Th1 cell are not epitope-specific and are able to destroy not only Leishmania, but also any other available microbes. Thus, a response stimulated by a single microbe can (within the context of the local infectious site) provide protection against various microbes. As long as the DTH response eliminates the threat and subsides so that proper tissue repair and healing can follow, it is an extraordinarily beneficial defense mechanism. Excessively active or chronic DTH responses often inflict permanent damage on host tissues that may impair normal function and, in some cases, may be fatal. For example, much or most of the pulmonary injury sustained in response to Mycobacterium tuberculosis is inflicted by activated macrophages that surround the bacteria to form nodules (or tubercles, from which the organism derived its name) and not by the infectious agent itself.
Delayed (-type) hypersensitivity. Activated CD4+ Th1 cells can, on subsequent reactivation through interaction with antigen-presenting cells (APC) in body tissues, secrete cytokines that activate local macrophages to engage in a nonspecific destruction of local cells and tissues.
Specific and nonspecific phases of delayed (-type) hypersensitivity. Although DTH responses are epitope-specific in their initiation because they involve binding of TCR by pMHC II, the local macrophage-mediated destruction that ensues is not limited by the triggering epitope. Activated macrophages destroy not only the infectious agents that initiated the DTH but also other microbes in the immediate vicinity.
B. Cytotoxic T lymphocytes: Role of CD8+ T cells
Only a small proportion of the cells of the body express MHC class II molecules, although all nucleated cells express MHC class I molecules. Thus, CD8+ T cells can scan nucleated cells throughout the body to see what cytoplasmically derived peptides are being presented on those MHC I molecules.
1. Target cell recognition: Like activated CD4+ T cells, activated CD8+ CTLs circulate throughout the body, “sampling” pMHC class I (pMHC I) complexes on body cells to determine whether the same pMHC I that led to its own activation can be found. If the CTL detects this same pMHC I or another pMHC I so similar in structure as to be cross-reactive, on the surface of another cell, it recognizes that it has contacted an infected cell (Fig. 11.11). CTLs bind directly to pMHC I on infected cells and destroy them.
Recognition, binding, and cytolysis by cytotoxic T lymphocytes. Cytotoxic T lymphocytes (CTLs) use their TCRs to recognize and bind specific pMHC I that are presenting appropriate cytoplasmically derived peptides (e.g., from viruses multiplying in the cytoplasm). Direct attachment to the infected cell permits the CTL to destroy the infected cell through the induction of membrane damage by perforins or through the induction of apoptosis by either granzymes or engagement of the Fas and FasL surface molecules.
2. Target cell destruction: Once attached to a cell that needs to be eliminated, CTLs can use multiple mechanisms to destroy those targeted cells (see Fig. 11.11). They release perforins and granzymes that form a complex on the membrane of the target cell, inducing the target cell to undergo apoptosis. To prevent their own death, CTLs alter their membranes in the area of contact to make themselves resistant to the perforins and granzymes being released. Finally, CTLs bear molecules (e.g., Fas ligand or FasL, also called CD178) that can engage Fas (CD95) on the surfaces of the infected cells. Fas is expressed on various body cells, and its engagement induces apoptosis. Apoptosis provides an important protective mechanism because in destroying its own DNA, the infected cells also destroy the nucleic acids of infectious organisms they carry, helping to prevent the spread of infection.
IV. IMMUNOLOGIC MEMORY
An important difference between the adaptive immune system and the innate immune system is the presence of immunologic memory. Simply put, once an infectious organism stimulates an adaptive response, subsequent encounters with that organism often produce mild or unnoticeable effects because of the rapid and enhanced action of antibodies or effector T cells. Antigen-specific cells that have been clonally expanded and have undergone some degree of activation during previous encounters with antigen (memory cells) can be rapidly mobilized in much greater numbers, thus shortening the response time to antigen. Whether generated against infectious organisms or other types of antigens, these secondary responses are typically faster and more vigorous than the primary responses stimulated by the initial exposure (Fig. 11.12).
Antibodies produced by B cells that have prolonged or repeated exposure to the same epitope may undergo an isotype switch induced by type 2 cytokines (Table 11.2) (see also Figs. 8.13 and 8.14 in Chapter 8). The availability of multiple isotypes having the same specificity permits the humoral response to initiate various mechanisms (e.g., complement activation by IgM and IgG, secretion into external body fluids by IgA, mast cell degranulation by IgE) to be directed against the same epitope. The serial reactivation of memory B cells allows the isotype switch to occur during each restimulation (Fig. 11.13). IgM is the predominant isotype seen in primary responses, whereas secondary responses include mostly IgG, with IgA and IgE also present. As the antibody isotypes change with repeated stimulation by a given antigen, the binding efficiency of the antibodies changes as well, owing to the incorporation of small mutations in the DNA encoding the variable regions of the light and heavy chains (Fig. 11.14) (also see Fig. 8.15). B cells bearing mutations that result in tighter binding of epitopes by their surface immunoglobulins are stimulated to proliferate more rapidly, whereas those binding less well do not proliferate as vigorously. As a result, the antibody response is continuously dominated by the B cells that produce the highest affinity antibodies against the epitope in question, a process known as affinity maturation (see Chapter 8).
Primary and secondary adaptive immune responses. On initial antigen encounter, both humoral and cell-mediated adaptive responses are of limited in intensity and duration (primary response). Subsequent exposures to antigen (secondary response) are characterized by increased intensity and duration. Each epitope elicits a separate response.
The development of immunologic memory can be artificially exploited through vaccination. Deliberate exposure to an infectious organism in a form that is unable to cause a full-blown disease can, thus, provide protection against a subsequent exposure to a fully virulent form of that organism. Likewise, deliberate exposure to a nontoxic form of a toxin (e.g., heat-denatured tetanus toxoid) can provide protection against future exposure to the natural form of that toxin. During the primary response, although the threat of disease is lessened by the “crippled” microbe, the body can build a defensive reservoir consisting of memory lymphocytes (both T and B) that have been expanded by proliferation and have undergone some degree of activation. Upon future exposure to that same organism, even in a virulent form, the body is armed with a large pool of reactive cells that can act more quickly and with greater vigor against the organism during a secondary response. The opportunity to develop IgG and IgA antibodies against the microbes enables an individual to neutralize the reencountered microbe, minimizing the degree of actual infection to the point where it can be eliminated with great efficiency. Clearance of infectious agents by secondary (or subsequent) responses can be so efficient that the individual is unaware of the reinfection altogether.
Isotype switch in memory B cells. Isotype switches occur during the sequential reactivations and proliferations of memory B cells that occur when they are periodically reexposed to antigen and T cell signals.
Affinity maturation in memory B cells. Somatic hypermutation occurs during the proliferation of memory B cells following reactivation. Accumulated mutations in the DNA encoding the antigen-binding regions may cause changes in the affinity of the synthesized antibody for its epitope. Mutations that cause increased affinity drive the memory cells to proliferate even more rapidly so that they represent an increased fraction of the memory B cells specific for the epitope. Thus, over time and repeated exposure, the response to a given epitope is characterized by production of antibodies with increasing affinity.
Although we think of immunologic memory primarily in the sense of enhancing the response against subsequent exposures to an infectious organism or other antigen, this is not always the case. In some cases, responses to future exposures can be diminished, a state known as tolerance. This phenomenon is important in preventing the immune system from producing superfluous (and potentially injurious) responses against harmless organisms and molecules in the environment, as well as against the body’s own cells and molecules. These important considerations are discussed in upcoming chapters.
• Humoral immunity is based on the actions of soluble antibodies and complement.
• The precipitin reaction is the interaction of soluble antigen with soluble antibody that results in the formation of Ag–Ab complexes (lattices), large enough to fall-out of solution as a visible precipitate.
• Antibodies can bind and cross-link cells or particles, causing an aggregate formation in a reaction known as agglutination.
• Neutralization is the binding of antibodies to microbial epitopes or soluble molecules (e.g., toxins) in a manner that inhibits the ability of those microbes/molecules to bind to host cell surfaces.
• Macrophages, dendritic cells, and neutrophils bear surface receptors (FcR) for the Fc portion of bound immunoglobulin. With the exception of FcRε that binds free IgE, FcRs recognize and bind only those antibodies that have already bound to their epitopes. The binding of FcRs to antibodies on microbes tethers the “tagged” microbes to the phagocytic cell and stimulates their engulfment and destruction. Bound immunoglobulin and bound complement fragments such as C3b are synergistic in serving as opsonins to stimulate phagocytosis.
• The classical pathway of complement is activated by conformational changes that occur in antibodies on epitope binding (usually of the IgM and IgG isotypes) to facilitate the sequential binding of the C1, C4, C2, and C3 components of the complement system.
• Cell-mediated responses include two basic forms: delayed (-type) hypersensitivity (DTH), mediated by CD4+ Th1 cells, and cell-mediated lysis, mediated by CD8+ cytotoxic T lymphocytes (CTLs).
• In the DTH response, macrophage activation by CD4+ Th1 cells is mediated by direct contact (binding of CD40 and CD154) and by IFN-γ secreted by the T cells. Once activated, macrophages increase their phagocytic activity as well as the production and release of destructive enzymes and reactive oxygen intermediates.
• In cell-mediated lysis, activated CD8+ CTLs search out cells that have the same pMHC I complex that stimulated their own activation or another pMHC I sufficiently similar as to be cross-reactive. Once such a cell is found, CTLs can use multiple mechanisms to destroy those targeted cells. These include lysis resulting from the infliction of membrane damage and the induction of apoptosis.
• Immunologic memory is an adaptive response. Once an infectious organism stimulates an adaptive response, the immune response to subsequent exposures is altered. Future encounters with that organism may produce mild or unnoticeable effects because of the rapid and enhanced action of antibodies or effector T cells.
11.1. Following a motor vehicle accident, a 25-year-old male requires a blood transfusion. Blood type tests done prior to the transfusion involve the use of IgM antibodies against A and B antigens on erythrocytes. A positive reaction is an aggregate formation that is known as
B. complement activation.
E. precipitin reaction.
The correct answer is A. Agglutination is the aggregation or clumping of cells or particles bound together by antibodies (usually IgM or dimeric IgA). Complement activation is initiated by the attachment of the C1 component of complement to epitope-bound antibody (IgM or IgG). Neutralization is the blocking by antibody of structures on microbes and toxins that allow them to bind to host cell surfaces. Opsonization is the increased phagocytic uptake of cells or molecules tagged by antibodies (usually IgG1). The precipitin reaction results from the assembly of large antigen–antibody complexes causing them to precipitate from solution.
11.2. The process that is synergistically enhanced by the binding of both antibodies and complement fragments such as C3b by phagocytes is known as
B. complement activation.
E. precipitin reaction.
The correct answer is D. Opsonization is the increased phagocytic uptake of cells or molecules tagged by antibodies (usually IgG1) or membrane-bound C3b or C4b. Agglutination is the aggregation or clumping of cells or particles bound together by antibodies (usually IgM or dimeric IgA). Complement activation is initiated by the attachment of the C1 component of complement to epitope-bound antibody (IgM or IgG). Neutralization is the blocking by antibody of structures on microbes and toxins that allow them to bind to host cell surfaces. The precipitin reaction results from the assembly of large antigen–antibody complexes that precipitate from solution.
11.3. The term applied to the interaction of soluble antigen with soluble antibody that results in the formation of insoluble antigen–antibody complexes is
B. complement activation.
E. precipitin reaction.
The correct answer is E. The precipitin reaction results from the assembly of large antigen–antibody complexes that precipitate from solution. Agglutination is the aggregation or clumping of cells or particles bound together by antibodies (usually IgM or dimeric IgA). Complement activation is initiated by the attachment of the C1 component of complement to epitope-bound antibody (IgM or IgG). Neutralization is the blocking by antibody of structures on microbes and toxins that allow them to bind to host cell surfaces. Opsonization is the increased phagocytic uptake of cells or molecules tagged by antibodies (usually IgG1).
11.4. The binding of antibodies to microbial epitopes or soluble molecules in a manner that inhibits the ability of these microbes/molecules to bind to host cell surfaces is termed
B. complement activation.
E. precipitin reaction.
The correct answer is C. Neutralization is the blocking by antibody of structures on microbes and toxins that allow them to bind to host cell surfaces. Agglutination is the aggregation or clumping of cells or particles bound together by antibodies (usually IgM or dimeric IgA). Complement activation is initiated by the attachment of the C1 component of complement to epitope bound antibody (IgM or IgG). Opsonization is the increased phagocytic uptake of cells or molecules tagged by antibodies (usually IgG1) or membrane-bound C3b or C4b. The precipitin reaction results from the assembly of large antigen–antibody complexes that precipitate from solution.
11.5. Which of the following antibody isotypes facilitate the sequential binding of the C1, C4, C2, and C3 components of the complement system?
A. IgA and IgD
B. IgA and IgE
C. IgA and IgM
D. IgE and IgG
E. IgG and IgM
The correct answer is E. The classical pathway of complement is initiated by the interaction of C1 (followed by C4, C2, and C3) with epitope-bound IgG or IgM. IgA, IgD, and IgE do not bind to C1.