16-2 Adaptive Immunity - introductory concepts
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- Know that adaptive immunity involves humoral immunity and cell-mediated immunity.
- Describe the role of dendritic cells in the immune system.
- Understand that the immune system is specific, it remembers a previous exposure to an antigen, and it tolerates the presence of its own macromolecular components.
- Describe the actions of B lymphocytes when exposed to antigen.
In contrast to the innate immune system, the adaptive immune system's initial response to a pathogen is weak or non-existent, but as the host has time to respond, this system becomes quite vigorous. To respond to a pathogen, the adaptive immune system must learn to recognize it. The mental picture to have in your mind is that of the body taking bits and pieces of the pathogen (its antigens) and presenting them to certain cells of the adaptive immune system. Those cells that can react with the antigen then marshal a bilateral response with one set of cells producing antibodies (humoral immunity) and the other set activating a group of cells to attack the pathogen (cell-mediated immunity). In this part, we will describe the cells that are involved in the processing and response to antigens, followed by the next section when we will put it all together and look at the reaction of the entire immune system to two different types of pathogens.
In addition to their role in innate immunity, phagocytic cells also play a critical role in adaptive immunity. Macrophages and monocytes take a portion of the debris left over from the digestion of a pathogen and provide that as antigens to the adaptive immune system. This ability is not only present in macrophages but B-lymphocytes and dendritic cells as well. These cells are collectively referred to as antigen presenting cells. One of the more important cell types capable of antigen presentation are dendritic cells.
Most tissues of the body contain a cell type with long tendrils that wrap around and between neighboring cells. Because these branch-like projections are so similar to the intricate dendrites of nerve cells, these immune system components are called dendritic cells. There are four populations of dendritic cells named for their origin or location. Dendritic cells, Figure 16.1, are found in skin, mucous membranes, bloodstream, lymph and all solid organs of the body except the brain, the eyes and testes.
Figure 16.1. A Dendritic Cell. Dendritic cells are found in most tissues of the body, projecting their branches throughout the immediate area, they serve to monitor foreign antigens that may exist. If an antigen if found, it is taken up by the dendritic cell and presented to the immune system.
These cells play at least three roles in the body.
- Dendritic cells in various tissues play a pivotal role in activating the immune system. Due to their placement throughout the body and their projections snaking through tissues, they are among the first cells to be exposed to invading pathogens. During the response to a parasite they take up antigens from it and present these to the immune system.
- Dendritic cells located in the thymus help to educate immature T cells by exposing them to various antigens (see below).
- Dendritic cells maintain the stimulation of B cells so that they continue to synthesize antibodies. Dendritic cells located in various lymphoid tissues carry out this role.
Dendritic cells are the only cells that can activate a naive T-cell and are the most potent antigen-presenting cells in the body.
Lymphocytes Make Antibodies and Regulate the Immune System
Lymphocytes are the other major type of white blood cells important in the immune system, and they work in concert with phagocytic cells to combat infections. However, the role lymphocytes play in fighting infections is very different than that played by phagocytes. Lymphocytes, with the help of antigen-presenting cells, are part of what is called the adaptive immune system. This system has three important features that all depend on lymphocytes.
- Specificity. B cells/antibodies or T cells react specifically with the antigen that activated them and they generally do not react with any other antigens with a different stucture. These reactions are as specific as the binding of substrate to the active site of an enzyme; in fact, antigen-antibody reactions share many features with enzyme-substrate binding.
- Memory. The immune system remembers an antigen after exposure to it. During the first immunological response to an antigen, lymphocytes capable of responding to that antigen (due to their specific membrane receptors) increase in number and remain present after the antigen is removed. During a second challenge by the same antigen, the immune response of this larger population of lymphocytes produces more antibodies and activates T cells faster, resulting in the swift removal of the entity producing the offending antigen. This type of response is referred to as a memory or secondary response.
- Tolerance. A healthy mammal does not react to its own macromolecular components, all of which are potentially antigenic. The animal is said to be tolerant of its self-antigens. The body achieves this tolerance by eliminating lymphocytes that react to self.
Cytokines and Chemokines
In many cases, the cells in the immune system need to communicate with other cells. When a cell is infected with a virus, it acts to notify its neighbors. When a tissue is damaged by bacterial invasion or physical injury, the surrounding tissue must be informed to begin the repair process. When cells are differentiating in the bone marrow, modulation of gene expression dictates the final cell type. In all of these cases, this communication takes place in the form of small proteins called cytokines and chemokines.
Cytokines are a group of small (less than 30 kDa) soluble proteins that regulate cellular function. Cytokines made by lymphocytes are called lymphokines. Table 16.1 lists some of the more important cytokines that play a role in the immune response. T helper cells, macrophages and monocytes produce many of these cytokines. Some of the most important cytokines are those that communicate between leukocytes and these are given the designation interleukins.
Table 16.1. Important Cytokines and Chemokines in the Immune Response
|Cytokine or Chemokine||Producing cell||Target cell||Effect|
|Interleukin-1 (IL-1)||Macrophages, monocytes and B cells||T cells, B cells||Acts as a growth regulator of T cells and B cells. Induces other cells such as hepatocytes to produce proteins relevant to host defense Serves as an endogenous pyrogen, which produces fever.|
|Interleukin-2 (IL-2)||T cells||T cells||Stimulates the proliferation of T cells and activates natural killer cells.|
|Interleukin-3 (IL-3)||Stem cells, Mast cells||Regulates the proliferation of stem cells and the differentiation of mast cells.|
|Interleukin-4 (IL-4)||TH2||B cells||B cell proliferation and enhanced antibody synthesis.|
|Interleukin-5 (IL-5)||TH2||B cells||B cell differentiation and IgA synthesis|
|Interleukin-6 (IL-6)||TH2, monocytes, macrophages||B cells, plasma cells, stem cells||B cell differentiation and antibody production. T cell activation, growth and differentiation. Has a major role in the mediation of the inflammatory and immune responses initiated by infection or injury.|
|CXCL-8||Many host cells||T cells, neutrophils, macrophages||Chemoattractant for neutrophils|
|α-Interferon (IFN-α)||Leucocytes, tissue cells||Tissue cells||Inhibition of viruses|
|γ-Interferon (IFN-γ)||T cells||Tissue cells, macrophages, natural killer cells||Inhibition of protein synthesis in virally infected cells. Activation of macrophages and natural killer cells. Stimulates IL-1, IL-2 and antibody production.|
|Tumor Necrosis Factor-α (TNF-α)||T cells||Tissue cells (tumors)||Kills cells, including tumor cells|
|Tumor Necrosis Factor-β (TNF-β)||T cells||Tissue cells (tumors)||Kills cells, including tumor cells|
|Colony Stimulating Factors (CSF)||TH1, macrophages||Phagocytes||Causes phagocytic white cells of all types to differentiate and divide.|
|Macrophage chemoattractant and activating factor (MCAF)||Monocytes, macrophages, fibroblasts (connective tissue cells) and keratinocytes (skin cells)||Macrophages, T cells||Attract and activate macrophages and T cells.|
|B cell growth factors||T cells||B cells||Multiplication of B cells|
A large number of signal molecules are manufactured by various tissues of the body. The cytokines and chemokines listed here are important in various parts of the immune response.
Another important group of signal proteins in immunity are the chemokines. Chemokines are a set of small molecular weight proteins (8-12 kDa) that serve as chemoattractants to phagocytes and T cells. Damage to cellular tissue from bacterial invasion, viral infection or physical injury causes the secretion of chemokines. Since many parts of the body are susceptible to this type of damage, it is not surprising that a large assortment of cell types, including lymphocytes, are capable of synthesizing chemokines. Their production attracts T cells and phagocytes to the area of damage stimulating an inflammatory and immune response.
- Adaptive immunity involves humoral immunity and cell-mediated immunity.
- Dendritic cells ingest foreign antigens in the body and present them to the immune cells. They are also important in educating immature T cells and help to maintain the stimulation of B cells so that they continue to make antibodies.
- The immune system has three important properties: It is specific, it remembers a previous exposure to an antigen, and it tolerates the presence of its own macromolecular components.
- Cells of the immune system (and other cells of the body) communicate by the secretion of small (< 30 kDa) proteins called cytokines. Chemokines are 8-12 kDa proteins that serve as chemoattractants to phagocytes and T cells.