18.1 Overview of Specific Adaptive Immunity
- 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).
18.2 Major Histocompatibility Complexes and Antigen-Presenting Cells
- Major histocompatibility complex (MHC) is a collection of genes coding for glycoprotein molecules expressed on the surface of all nucleated cells.
- MHC I molecules are expressed on all nucleated cells and are essential for presentation of normal “self” antigens. Cells that become infected by intracellular pathogens can present foreign antigens on MHC I as well, marking the infected cell for destruction.
- MHC II molecules are expressed only on the surface of antigen-presenting cells (macrophages, dendritic cells, and B cells). Antigen presentation with MHC II is essential for the activation of T cells.
- Antigen-presenting cells (APCs) primarily ingest pathogens by phagocytosis, destroy them in the phagolysosomes, process the protein antigens, and select the most antigenic/immunodominant epitopes with MHC II for presentation to T cells.
- Cross-presentation is a mechanism of antigen presentation and T-cell activation used by dendritic cells not directly infected by the pathogen; it involves phagocytosis of the pathogen but presentation on MHC I rather than MHC II.
18.3 T Lymphocytes and Cellular Immunity
- Immature T lymphocytes are produced in the red bone marrow and travel to the thymus for maturation.
- Thymic selection is a three-step process of negative and positive selection that determines which T cells will mature and exit the thymus into the peripheral bloodstream.
- Central tolerance involves negative selection of self-reactive T cells in the thymus, and peripheral tolerance involves anergy and regulatory T cells that prevent self-reactive immune responses and autoimmunity.
- The TCR is similar in structure to immunoglobulins, but less complex. Millions of unique epitope-binding TCRs are encoded through a process of genetic rearrangement of V, D, and J gene segments.
- T cells can be divided into three classes—helper T cells, cytotoxic T cells, and regulatory T cells—based on their expression of CD4 or CD8, the MHC molecules with which they interact for activation, and their respective functions.
- Activated helper T cells differentiate into TH1, TH2, TH17, or memory T cell subtypes. Differentiation is directed by the specific cytokines to which they are exposed. TH1, TH2, and TH17 perform different functions related to stimulation of adaptive and innate immune defenses. Memory T cells are long-lived cells that can respond quickly to secondary exposures.
- Once activated, cytotoxic T cells target and kill cells infected with intracellular pathogens. Killing requires recognition of specific pathogen epitopes presented on the cell surface using MHC I molecules. Killing is mediated by perforin and granzymes that induce apoptosis.
- Superantigens are bacterial or viral proteins that cause a nonspecific activation of helper T cells, leading to an excessive release of cytokines (cytokine storm) and a systemic, potentially fatal inflammatory response.
18.4 B Lymphocytes and Humoral Immunity
- B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells.
- B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity.
- Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens.
- T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells.
- T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated TH2 cells, and plasma cells that produce different classes of antibodies as a result of class switching. Memory B cells are also produced.
- Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen.
- Adaptive immunity can be divided into four distinct classifications: natural active immunity, natural passive immunity, artificial passive immunity, and artificial active immunity.
- Artificial active immunity is the foundation for vaccination and vaccine development. Vaccination programs not only confer artificial immunity on individuals, but also foster herd immunity in populations.
- Variolation against smallpox originated in the 10th century in China, but the procedure was risky because it could cause the disease it was intended to prevent. Modern vaccination was developed by Edward Jenner, who developed the practice of inoculating patients with infectious materials from cowpox lesions to prevent smallpox.
- Live attenuated vaccines and inactivated vaccines contain whole pathogens that are weak, killed, or inactivated. Subunit vaccines, toxoid vaccines, and conjugate vaccines contain acellular components with antigens that stimulate an immune response.