Immunity – Humans are Exposed with Microbes

Humans are exposed to microbes that contain a vast array of allergenic substances, threatening normal homeostasis. Therefore, the immune system is important to defend the body from pathogens. It eliminates pathological microbes and toxic or allergenic proteins, but it must avoid responses that cause excessive damage to self-tissues or potentially eliminate beneficial commensal microbes. A general feature of the immune system is that its mechanisms rely on detecting structural features of the pathogen or toxin that mark it as distinct from host cells.

Host-toxin discrimination is essential to allow the host to eliminate the threat while keeping its own tissues from damage. The immune system, which is comprised of specialized cells, tissues, proteins, and organs, defends people against germs and microorganisms every day. In most cases, the immune system develops immunity, helping people stay healthy by being able to resist specific diseases. However, sometimes problems with the immune system can lead to illness and infection.

All of these specialized cells and parts of the immune system are needed for body protection against disease, a safeguard commonly referred to as immunity. There are four types of immunity. The first type is Innate (Natural) immunity, which includes natural resistance components such as intact skin, salivary enzymes, and neutrophils, natural killer cells, and acts as the first response against infection. An individual has this from birth, prior to exposure to any pathogen or antigen. The second type is Adaptive (Acquired) Immunity, which is developed after an infection or through the passive transfer of antibodies from a pregnant mother to a fetus or vaccination. The third type, Active immunity, comes from exposing the body to an antigen, generating an adaptive immune response. This can take days or even weeks to develop but may be long-lasting. For instance, recovery from the Hepatitis-A virus can give a natural active immune response that usually leads to lifelong protection. In a similar manner, receiving two doses of the Hepatitis-A vaccine generates an acquired active immune response, leading to long-lasting defense. The fourth type is Passive immunity, a process of administering IgG antibodies to protect against infection. It provides immediate, though short-lived, protection for several weeks to three or four months at most. This often occurs during pregnancy, with the transfer of maternal tetanus antibody (mainly IgG) across the placenta providing passive immunity to a newborn for several weeks or months until the antibody is degraded and lost.

The immune system mechanism employs many potent effectors that have the ability to destroy a broad range of microbial cells and clear numerous toxic and allergenic substances. Therefore, this immune response can avoid releasing these destructive mechanisms against the host’s own tissues. The ability of the immune response to avoid damaging self-tissues is referred to as self-tolerance. Because the failure of self-tolerance underlies the broad class of autoimmune diseases, this process has been extensively studied. It is now clear that mechanisms to avoid reactions against self-antigens are expressed in many parts of both the innate and adaptive immune responses. An important aspect of the T-cell arm of the immune system is its ability to recognize host cells infected by viruses, intracellular bacteria, or other parasites. T cells have gradually developed a mechanism that recognizes foreign antigens together with self-antigens as a molecular complex.

This requirement for T cells to recognize both self-structures and foreign antigens makes the need for these cells to maintain self-tolerance particularly crucial. The first set of responses constitutes the innate immune response. The innate response includes soluble proteins and bioactive small molecules, such as complement proteins, defensins, and ficolins or those released from activated cells. It includes cytokines that act as regulators of other cells' functions, chemokines that attract inflammatory leukocytes, lipid mediators of inflammation, reactive free radicals, and bioactive amines and enzymes that also contribute to tissue inflammation. As the recognition molecules used by the innate system are expressed broadly on a large number of cells, this system is poised to act rapidly after an invading pathogen or toxin is encountered, thus constituting the initial host response. In cellular elements of the immune response, an intact immune response includes contributions from many subsets of leukocytes. The different leukocyte subsets can be discriminated morphologically by a combination of conventional histological stains, and by the analysis of the spectrum of glycoprotein differentiation antigens displayed on their cell membranes.

The second set of responses is the adaptive immune response. Because the adaptive system is composed of small numbers of cells with specificity for an individual pathogen, toxin, or allergen, the responding cells must proliferate after detecting the antigen in order to attain an effective response against the microbe or the toxin. Thus, the adaptive response generally expresses itself temporally after the innate response in host defense. A key feature of the adaptive response is that it produces long-lived cells that persist in an apparently dormant state but can re-express effector functions rapidly after another encounter with their specific antigen. This provides the adaptive response with the ability to manifest immune memory, permitting it to contribute prominently to a more effective host response against specific pathogens or toxins when they are encountered a second time, even decades after the initial sensitizing encounter.

When antigens (foreign substances that invade the body) are detected, several types of cells work together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies, which are specialized proteins that lock onto specific antigens. Once produced, these antibodies stay in a person's body so that if his or her immune system encounters that antigen again, the antibodies are already there to do their job. So, if someone gets sick with a certain disease, like chickenpox, that person usually won't get sick from it again. This is also how immunizations prevent certain diseases. An immunization introduces the body to an antigen in a way that doesn't make someone sick but does allow the body to produce antibodies that will then protect the person from future attack by the germ or substance that produces that particular disease. Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That's the job of the T cells, which are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed.

Cell death is a loss of plasma membrane integrity and it can be classified according to its morphological appearance, enzymological criteria, functional aspects, or immunological characteristics. Necrosis is best defined by light or electron microscopic detection of cell and organelle swelling or rupture of surface membranes with spillage of intracellular contents (Richard S, 2009). If the infection is severe, the infected cells will eventually die, resulting in increased inflammation which can cause a delay in the healing process. Accumulating evidence indicates that necrosis is more ordered than was originally thought. When cells die from necrosis, damage-associated molecular-pattern (DAMP) molecules, such as high-mobility group protein, enter the circulation and activate innate immune cells. Apoptosis (programmed death) occurs when infected cells die to prevent further damage to the body and assist in the healing process. Most chemotherapeutic agents induce apoptosis in tumor cells. The tyrosine kinase inhibitor imatinib (Gleevec) kills chronic myeloid leukemia cells by up-regulating the proapoptotic BCL2 family members. In multicellular organisms, cells that are no longer needed or are a threat to the organism are destroyed by a tightly regulated cell suicide process known as programmed cell death, or apoptosis.

Apoptosis is mediated by an enzyme called caspases, which trigger cell death by cleaving specific proteins in the cytoplasm and nucleus. Caspases exist in all cells as inactive precursors, or procaspases, which are usually activated by cleavage by other caspases, thus producing a proteolytic caspase cascade. The activation process is initiated by either extracellular or intracellular death signals, which then cause intracellular adaptor molecules to aggregate and activate procaspases. Caspase activation is regulated by members of the Bcl-2 and IAP protein families. Cells that die as a result of acute injury will swell and burst, spilling their contents all over their neighbors. This process, called cell necrosis, triggers a potentially damaging inflammatory response. Meanwhile, a cell that undergoes apoptosis dies neatly, without damaging its neighbors. The cell condenses and shrinks. The cytoskeleton collapses, the nuclear envelope disassembles, and the nuclear DNA breaks up into fragments. Most importantly, the cell surface is altered, displaying properties that cause the dying cell to be rapidly phagocytosed, either by a neighboring cell or by a macrophage. Excess macrophages die to ensure all remnants of the pathogen and antigen are rid for the better healing process.

The immune system uses many different mechanisms to combat infection caused by microbes. These mechanisms work together and have evolved into a fully integrated immune response. This response draws elements from many effector systems in order to adapt a response to the specific invading pathogen. Abnormal regulation of the various effector mechanisms can lead to chronic or acute tissue damage. Understanding the relationships between the different immune effector pathways will permit improved immunomodulatory therapeutics, development of improved vaccines, and avoidance of unintended tissue injury, thus further expediting the healing process."

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