Vaccines: Introduction to immunity

Vaccines

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body’s immune system to recognize the agent as foreign, destroy it, and “remember” it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Introduction to immunity

The immune system refers to a collection of cells and proteins that function to protect the skin, respiratory passages, intestinal tract and other areas from foreign antigens, such as microbes (organisms such as bacteria, fungi, and parasites), viruses, cancer cells, and toxins. The immune system can be simplistically viewed as having two “lines of defense”: innate immunity and adaptive immunity. Innate immunity represents the first line of defense to an intruding pathogen. It is an antigen-independent (non-specific) defense mechanism that is used by the host immediately or within hours of encountering an antigen. The innate immune response has no immunologic memory and, therefore, it is unable to recognize or “memorize” the same pathogen should the body be exposed to it in the future. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific and, therefore, involves a lag time between exposure to the antigen and maximal response. The hallmark of adaptive immunity is the capacity for memory which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. Innate and adaptive immunity are not mutually exclusive mechanisms of host defense, but rather are complementary, with defects in either system resulting in host vulnerability.

Innate immunity

The primary function of innate immunity is the recruitment of immune cells to sites of infection and inflammation through the production of cytokines (small proteins involved in cell-cell communication). Cytokine production leads to the release of antibodies and other proteins and glycoproteins which activate the complement system, a biochemical cascade that functions to identify and opsonize (coat) foreign antigens, rendering them susceptible to phagocytosis (process by which cells engulf microbes and remove cell debris). The innate immune response also promotes clearance of dead cells or antibody complexes and removes foreign substances present in organs, tissues, blood and lymph. It can also activate the adaptive immune response through a process known as antigen presentation.

Numerous cells are involved in the innate immune response such as phagocytes (macrophages and neutrophils), dendritic cells, mast cells, basophils, eosinophils, natural killer (NK) cells and lymphocytes (T cells). Phagocytes are sub-divided into two main cell types: neutrophils and macrophages. Both of these cells share a similar function: to engulf (phagocytose) microbes. In addition to their phagocytic properties, neutrophils contain granules that, when released, assist in the elimination of pathogenic microbes. Unlike neutrophils (which are short-lived cells), macrophages are long-lived cells that not only play a role in phagocytosis, but are also involved in antigen presentation to T cells. Macrophages are named according to the tissue in which they reside. For example, macrophages present in the liver are called Kupffer cells while those present in the connective tissue are termed histiocytes.

Adaptive immunity

Adaptive immunity develops when innate immunity is ineffective in eliminating infectious agents and the infection is established. The primary functions of the adaptive immune response are the recognition of specific “non-self” antigens in the presence of “self” antigens; the generation of pathogen-specific immunologic effector pathways that eliminate specific pathogens or pathogen-infected cells; and the development of an immunologic memory that can quickly eliminate a specific pathogen should subsequent infections occur. The cells of the adaptive immune system include: T cells, which are activated through the action of antigen presenting cells (APCs), and B cells.

T cells derive from hematopoietic stem cells in bone marrow and, following migration, mature in the thymus. These cells express a unique antigen-binding receptor on their membrane, known as the T-cell receptor (TCR), and as previously mentioned, require the action of APCs (usually dendritic cells, but also macrophages, B cells, fibroblasts and epithelial cells) to recognize a specific antigen.

The surfaces of APCs express cell-surface proteins known as the major histocompatibility complex (MHC). MHC are classified as either class I (also termed human leukocyte antigen [HLA] A, B and C) which are found on all nucleated cells, or class II (also termed HLA, DP, DQ and DR) which are found on only certain cells of the immune system, including macrophages, dendritic cells and B cells. Class I MHC molecules present endogenous (intracellular) peptides while class II molecules present exogenous (extracellular) peptides. The MHC protein displays fragments of antigens (peptides) when a cell is infected with a pathogen or has phagocytosed foreign proteins.

T cells are activated when they encounter an APC that has digested an antigen and is displaying antigen fragments bound to its MHC molecules. The MHC-antigen complex activates the TCR and the T cell secretes cytokines which further control the immune response. This antigen presentation process stimulates T cells to differentiate into either cytotoxic T cells (CD8+ cells) or T-helper (Th) cells (CD4+ cells). Cytotoxic T cells are primarily involved in the destruction of cells infected by foreign agents. They are activated by the interaction of their TCR with peptide-bound MHC class I molecules. Clonal expansion of cytotoxic T cells produce effector cells which release perforin and granzyme (proteins that causes lysis of target cells) and granulysin (a substance that induces apoptosis of target cells). Upon resolution of the infection, most effector cells die and are cleared by phagocytes. However, a few of these cells are retained as memory cells that can quickly differentiate into effector cells upon subsequent encounters with the same antigen.

T helper (Th) cells play an important role in establishing and maximizing the immune response. These cells have no cytotoxic or phagocytic activity, and cannot kill infected cells or clear pathogens. However, they “mediate” the immune response by directing other cells to perform these tasks. Th cells are activated through TCR recognition of antigen bound to class II MHC molecules. Once activated, Th cells release cytokines that influence the activity of many cell types, including the APCs that activate them.

Passive Immunity

Passive immunity is the transfer of antibody produced by one human or other animal to another. Passive immunity provides protection against some infections, but this protec – tion is temporary. The antibodies will degrade during a period of weeks to months, and the recipient will no longer be protected. The most common form of passive immunity is that which an infant receives from its mother. Antibodies are trans – ported across the placenta during the last 1–2 months of pregnancy. As a result, a full-term infant will have the same antibodies as its mother. These antibodies will protect the infant from certain diseases for up to a year.

Protection is better against some diseases (e.g., measles, rubella, tetanus) than others (e.g., polio, pertussis). Many types of blood products contain antibody. Some products (e.g., washed or reconstituted red blood cells) contain a relatively small amount of antibody, and some (e.g., intravenous immune globulin and plasma products) contain a large amount.

In addition to blood products used for transfusion (e.g., whole blood, red cells, and platelets) there are three major sources of antibody used in human medicine. These are homologous pooled human antibody, homologous human hyperimmune globulin, and heterologous hyperimmune serum.

Homologous pooled human antibody is also known as immune globulin. It is produced by combining (pooling) the IgG antibody fraction from thousands of adult donors in the United States. Because it comes from many different donors, it contains antibody to many different antigens. It is used primarily for postexposure prophylaxis for hepatitis A and measles and treatment of certain congenital immuno – globulin deficiencies.

Active Immunity

Active immunity is stimulation of the immune system to produce antigen-specific humoral (antibody) and cellular immunity. Unlike passive immunity, which is temporary, active immunity usually lasts for many years, often for a lifetime.

One way to acquire active immunity is to survive infection with the disease-causing form of the organism. In general, once persons recover from infectious diseases, they will have lifelong immunity to that disease. The persistence of protection for many years after the infection is known as immunologic memory. Following exposure of the immune system to an antigen, certain cells (memory B cells) continue to circulate in the blood (and also reside in the bone marrow) for many years. Upon reexposure to the antigen, these memory cells begin to replicate and produce antibody very rapidly to reestablish protection.

Another way to produce active immunity is by vaccination. Vaccines interact with the immune system and often produce an immune response similar to that produced by the natural infection, but they do not subject the recipient to the disease and its potential complications. Many vaccines also produce immunologic memory similar to that acquired by having the natural disease.

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