18.1 Overview of specific adaptive immunity  (Page 5/9)

Antigen-antibody interactions

Different classes of antibody play important roles in the body’s defense against pathogens. These functions include neutralization of pathogens, opsonization for phagocytosis, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity. For most of these functions, antibodies also provide an important link between adaptive specific immunity and innate nonspecific immunity.

Neutralization involves the binding of certain antibodies (IgG, IgM, or IgA) to epitopes on the surface of pathogens or toxins, preventing their attachment to cells. For example, Secretory IgA can bind to specific pathogens and block initial attachment to intestinal mucosal cells. Similarly, specific antibodies can bind to certain toxins, blocking them from attaching to target cells and thus neutralizing their toxic effects. Viruses can be neutralized and prevented from infecting a cell by the same mechanism ( [link] ).

As described in Chemical Defenses , opsonization is the coating of a pathogen with molecules, such as complement factors, C-reactive protein , and serum amyloid A , to assist in phagocyte binding to facilitate phagocytosis . IgG antibodies also serve as excellent opsonins, binding their Fab sites to specific epitopes on the surface of pathogens. Phagocytic cells such as macrophages , dendritic cells , and neutrophils have receptors on their surfaces that recognize and bind to the Fc portion of the IgG molecules; thus, IgG helps such phagocytes attach to and engulf the pathogens they have bound ( [link] ).

Agglutination or aggregation involves the cross-linking of pathogens by antibodies to create large aggregates ( [link] ). IgG has two Fab antigen-binding sites , which can bind to two separate pathogen cells, clumping them together. When multiple IgG antibodies are involved, large aggregates can develop; these aggregates are easier for the kidneys and spleen to filter from the blood and easier for phagocytes to ingest for destruction. The pentameric structure of IgM provides ten Fab binding sites per molecule, making it the most efficient antibody for agglutination.

Another important function of antibodies is activation of the complement cascade . As discussed in the previous chapter, the complement system is an important component of the innate defenses, promoting the inflammatory response, recruiting phagocytes to site of infection, enhancing phagocytosis by opsonization, and killing gram-negative bacterial pathogens with the membrane attack complex (MAC) . Complement activation can occur through three different pathways (see [link] ), but the most efficient is the classical pathway , which requires the initial binding of IgG or IgM antibodies to the surface of a pathogen cell, allowing for recruitment and activation of the C1 complex .

Yet another important function of antibodies is antibody-dependent cell-mediated cytotoxicity (ADCC) , which enhances killing of pathogens that are too large to be phagocytosed. This process is best characterized for natural killer cells ( NK cells ), as shown in [link] , but it can also involve macrophages and eosinophils . ADCC occurs when the Fab region of an IgG antibody binds to a large pathogen; Fc receptors on effector cells (e.g., NK cells) then bind to the Fc region of the antibody, bringing them into close proximity with the target pathogen. The effector cell then secretes powerful cytotoxins (e.g., perforin and granzymes ) that kill the pathogen.

Key concepts and summary

• Adaptive immunity is an acquired defense against foreign pathogens that is characterized by specificity and memory. The first exposure to an antigen stimulates a primary response , and subsequent exposures stimulate a faster and strong secondary response.
• Adaptive immunity is a dual system involving humoral immunity (antibodies produced by B cells) and cellular immunity (T cells directed against intracellular pathogens).
• Antigens , also called immunogens , are molecules that activate adaptive immunity. A single antigen possesses smaller epitopes , each capable of inducing a specific adaptive immune response.
• An antigen’s ability to stimulate an immune response depends on several factors, including its molecular class, molecular complexity, and size.
• Antibodies ( immunoglobulins ) are Y-shaped glycoproteins with two Fab sites for binding antigens and an Fc portion involved in complement activation and opsonization.
• The five classes of antibody are IgM , IgG , IgA , IgE , and IgD , each differing in size, arrangement, location within the body, and function. The five primary functions of antibodies are neutralization, opsonization, agglutination, complement activation, and antibody-dependent cell-mediated cytotoxicity (ADCC).

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