Learned Self-Defense
The specific (adaptive) immune system is divided into two components, the humoral immune system and the cellular immune system. These systems differ from the innate immune system in that your body learns to identify specific pathogens and to take steps to protect itself from those specific pathogens.
The Humoral Immune System
The humoral immune system relies on B cells that lead to the creation of antibody-producing plasma cells. As antibodies are produced, they link pathogens together into larger and larger masses, which prevents their dispersal throughout the body and provides a larger target for phagocytic cells. Additionally, antibodies opsonize pathogens for more rapid removal by WBCs.
Antibodies
When B lymphocytes are activated by their reciprocal pathogen, they begin to rapidly divide and clone themselves into either plasma cells (active antibody-producing cell) or memory B cells. Memory B cells are inactive and held in reserve for a subsequent exposure to the same antigen later in life.
Antibodies (also called immunoglobulins, abbreviated Ig) are proteins consisting of four amino acid polymers linked together via disulfide bonds between adjacent cysteine amino acids. For a general idea of the shape of an antibody, imagine a person standing with arms upward and legs together, making their body into the shape of a Y. If you split the body into right and left halves, you would have created the two heavy chains that make up an antibody. Two additional chains, the light chains, are smaller proteins attached to the arms only.
Just as you use your hands to grasp, the antibody has various regions that grasp (bind to) specific antigens. These regions are highly adaptable and changeable when needed, enabling an antibody to protect the body against an almost infinite array of antigens.
The remainder of the antibody, which would be the torso and legs, is a constant fragment. These portions are constant in the sense that when antibodies of the same isotype (genetic family) have regions that differ, the constant fragments are identical. These constant fragments, regardless of variable region or isotype, function as an opsonin for phagocytic cells.
Isotypes
While the variable regions of antibodies are specific for their antigen, the constant fragments are the same from antibody to antibody of the same isotype. The genes for the constant fragment are subdivided into different isotypes that can be used to build an antibody at certain developmental stages or for specific responses. These isotypes are arranged on the chromosome in the order they may be used. The first isotypes used are on the upstream or 5' portion of the chromosome, while the last isotype will be on the far 3' end (recall how in DNA replication, 3' or 3 prime and 5' or 5 prime indicate various points on the molecule).
The change from one isotype to another results in the splicing out of the upstream genes, meaning once you pass an isotype on the chromosome, that gene is eliminated and no longer available to be switched to later in the life of that cell or its clones.
The IgM isotype (class M immunoglobulin) is the first to be expressed on naïve B cells. This constant fragment directs five IgM antibody monomers to link together via their constant chains (the heavy chains that make up the constant fragment of the antibody), making a large pentameric molecule that is capable of binding ten antigens at a time (just as you have two hands, a single antibody has two variable regions, and can bind two antigens).
The next isotype to be expressed is the IgD isotype. This is the predominant antibody found in the circulating plasma. It is also the protein predominantly responsible for the humoral immunity. Like the IgD, IgG antibodies are monomeric in structure. These are the only antibodies that can cross the placenta during pregnancy and provide a passive immunity to the developing fetus. However, these isotypes can also cross the placenta and lead to destructive effects, including hemolytic disease of the newborn.
The next isotype is the IgA isotype, which is a dimeric antibody consisting of two monomers joined via the constant fragment. These antibodies are particularly resistant to degradation and can be found in many mucous secretions including tears, saliva, and breast milk.
The final isotype is the IgE type. This type is capable of eliciting some of the most powerful immune responses of the body. These monomeric antibodies are often linked to the surface of mast cells via an IgE constant fragment receptor. If an antigen is present, this may result in two adjacent antibodies binding simultaneously and bringing the two receptors close enough together to trigger a cellular response.
In this way, mast cells are signaled to degranulate or rapidly secrete their inflammatory cytokines. When enough of these mast cells release their chemical mediators in a mass explosion, it can trigger a severe to dangerous allergic response and send someone into anaphylactic shock.
Primary Immune Response
Upon initial exposure of the body to a particular antigen, B lymphocytes, granulocytes, and macrophages stimulate a primary immune response. The leukocytes phagocytose (consume by the process of phagocytosis, or engulfing) material and signal with cytokines, and the B lymphocytes begin to divide. When an antigen binds to the B cell receptor (which is also the antibody that a B cell will produce), the cell begins to clone itself into more B cells.
Over the course of approximately 2 weeks, the individual suffers from the symptoms of the disease as the entire immune system fights to remove the pathogen and prevent further damage. This is the natural primary immune response. However, although a few IgG antibodies result, the principal product of this response is a vast number of memory B cells. These remain in the body and remain viable for possibly the entire lifetime of the individual. With these in place, when the same antigen is encountered again, there is a much faster and more robust response.
Adapting the immune system through vaccines
Vaccines are the clinical way individuals are given the opportunity to mount an immune response, build up their memory cells, and prevent the disease. In many cases, the pathogen introduced artificially is either already dead or unable to reproduce, leading to the activation of the immune cells and not the detrimental effects of a living pathogen.
Secondary Immune Response
The purpose of the primary immune response is to create more of the specific B cells and memory cells to quickly remove the pathogen before it can cause harm. While the primary response takes days or even weeks, a subsequent exposure to the pathogen results in a mass production of IgG antibodies that flood the circulation in a matter of hours. In this manner, the pathogen is eliminated and the individual suffers no symptoms.
The Cellular Immune System
The second component of the specific (adaptive) immune system involves the T lymphocytes and requires physical contact between cells. It is therefore named cellular immunity. There are four types of T lymphocytes. Each has specific receptors capable of binding to a reciprocal receptor on cells of the body. Much like the activation of B cells leads to the production of memory B cells, stimulation of T cells leads to the formation of memory T cells.
T Lymphocytes
The first T lymphocyte to consider is the helper T cell. These cells are filled with cytokines and are responsible for the chemical stimulation and activation of the immune system. This is true chiefly of T lymphocytes and to a lesser degree B cells and leukocytes. While histologically indistinguishable from any other T cell, helper T cells display a receptor on their surface called CD4, a glycoprotein that will be used along with the complementary receptor on antigen-presenting cells to become activated when a pathogen is present. Therefore, helper T cells are often referred to as CD4 positive T cells.
Cytotoxic T cells express a different CD receptor on their surface, called CD8, which has a complementary receptor on all cells in the body except for RBCs. In this way, if any cell becomes virally infected or tumorigenic, the CD8 receptor recognizes this foreign material and activates a response. When activated, the cytotoxic T cell attacks the problematic cells with a barrage of cytokines, which potentially signal the cell to undergo apoptosis (cell death).
Regulatory T cells are also produced during an immune response. While these cells do not directly attach to pathogenic cells, or signal increases in the immune system, they do play a vital role in homeostasis.
An immune response is a form of a positive feedback loop: activated immune cells activate more immune cells. To halt this chain reaction, regulatory T cells divide until a threshold mass of cells are produced, at which time they bind to the helper and cytotoxic T cells and signal them to undergo apoptosis and stop their action. These cells, however, do not affect the memory T cells that are held in reserve.
Major Histocompatibility Complex Antigens
The complementary receptors for the CD proteins on T cells are the major histocompatibility complex (MHC) antigens. The pairings of these molecules are MHC class I, which is on every cell in the body except RBCs, and is the binding partner for the CD8 of cytotoxic T cells. If the cell is normal and healthy, the cytotoxic T cell is not activated. However, if a viral or tumor marker is displayed along with the MHCI, that leads to T cell activation and cellular destruction.
For the CD4 receptor of helper T cells, the reciprocal protein is the MHC class II that is present on antigen-presenting cells, such as macrophages and dendritic cells. These phagocytic cells destroy the pathogen, display specific antigens on their MHCII molecule, and present them to T cells in order to find the exact match for the pathogen and activate the appropriate response.