Antigens and Antibodies

Immunodeficiency

Immunodeficiency occurs when the immune system cannot appropriately respond to infections.

Immunodeficiency

Failures, insufficiencies, or delays at any level of the immune response can allow pathogens or tumor cells to gain a foothold to replicate or proliferate to high enough levels that the immune system becomes overwhelmed, leading to immunodeficiency; it may be acquired or inherited. Immunodeficiency can be acquired as a result of infection with certain pathogens (such as HIV), chemical exposure (including certain medical treatments), malnutrition, or, possibly, by extreme stress. For instance, radiation exposure can destroy populations of lymphocytes, elevating an individual's susceptibility to infections and cancer. Dozens of genetic disorders result in immunodeficiencies, including Severe Combined Immunodeficiency (SCID), bare lymphocyte syndrome, and MHC II deficiencies. Rarely, primary immunodeficiencies that are present from birth may occur. Neutropenia is one form in which the immune system produces a below-average number of neutrophils, the body's most abundant phagocytes. As a result, bacterial infections may go unrestricted in the blood, causing serious complications.

HIV/AIDS

Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/AIDS), is a disease of the human immune system caused by infection with human immunodeficiency virus (HIV). During the initial infection, a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the illness progresses, it interferes more and more with the immune system. The person has a high probability of becoming infected, including from opportunistic infections and tumors that do not usually affect people who have working immune systems.

After the virus enters the body, there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood. This response is accompanied by a marked drop in the number of circulating CD4+ T cells, cells that are or will become helper T cells. The acute viremia, or spreading of the virus, is almost invariably associated with activation of CD8+ T cells (which kill HIV-infected cells) and, subsequently, with antibody production. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts recover.

Ultimately, HIV causes AIDS by depleting CD4+ T cells (helper T cells). This weakens the immune system, allowing opportunistic infections. T cells are essential to the immune response; without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by cytotoxic T cells accounts for CD4+ T cell depletion, although apoptosis (programmed cell death) may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.

Antibody Functions

Antibodies, part of the humoral immune response, are involved in pathogen detection and neutralization.

Antibody Functions

Differentiated plasma cells are crucial players in the humoral immunity response. The antibodies they secrete are particularly significant against extracellular pathogens and toxins. Once secreted, antibodies circulate freely and act independently of plasma cells. Sometimes, antibodies can be transferred from one individual to another. For instance, a person who has recently produced a successful immune response against a particular disease agent can donate blood to a non-immune recipient, confering temporary immunity through antibodies in the donor's blood serum. This phenomenon, called passive immunity, also occurs naturally during breastfeeding, which makes breastfed infants highly resistant to infections during the first few months of life.

Antibodies coat extracellular pathogens and neutralize them by blocking key sites on the pathogen that enhance their infectivity, such as receptors that "dock" pathogens on host cells. Antibody neutralization can prevent pathogens from entering and infecting host cells, as opposed to the cytotoxic T-cell-mediated approach of killing cells that are already infected to prevent progression of an established infection. The neutralized antibody-coated pathogens can then be filtered by the spleen and eliminated in urine or feces.

Antibodies also mark pathogens for destruction by phagocytic cells, such as macrophages or neutrophils, because they are highly attracted to macromolecules complexed with antibodies. Phagocytic enhancement by antibodies is called opsonization. In another process, complement fixation, IgM and IgG in serum bind to antigens, providing docking sites onto which sequential complement proteins can bind. The combination of antibodies and complement enhances opsonization even further, promoting rapid clearing of pathogens.

Affinity, avidity, and cross reactivity

Not all antibodies bind with the same strength, specificity, and stability. In fact, antibodies exhibit different affinities (attraction) depending on the molecular complementarity between antigen and antibody molecules. An antibody with a higher affinity for a particular antigen would bind more strongly and stably. It would be expected to present a more challenging defense against the pathogen corresponding to the specific antigen.

The term avidity describes binding by antibody classes that are secreted as joined, multivalent structures (such as IgM and IgA). Although avidity measures the strength of binding, just as affinity does, the avidity is not simply the sum of the affinities of the antibodies in a multimeric structure. The avidity depends on the number of identical binding sites on the antigen being detected, as well as other physical and chemical factors. Typically, multimeric antibodies, such as pentameric IgM, are classified as having lower affinity than monomeric antibodies, but high avidity. Essentially, the fact that multimeric antibodies can bind many antigens simultaneously balances their slightly-lower-binding strength for each antibody/antigen interaction.

Antibodies secreted after binding to one epitope on an antigen may exhibit cross reactivity for the same or similar epitopes on different antigens. Cross reactivity occurs when an antibody binds not to the antigen that elicited its synthesis and secretion, but to a different antigen. Because an epitope corresponds to such a small region (the surface area of about four to six amino acids), it is possible for different macromolecules to exhibit the same molecular identities and orientations over short regions.

Cross reactivity can be beneficial if an individual develops immunity to several related pathogens despite having been exposed to or vaccinated against only one of them. For instance, antibody cross reactivity may occur against the similar surface structures of various Gram-negative bacteria. Conversely, antibodies raised against pathogenic molecular components that resemble self molecules may incorrectly mark host cells for destruction, causing autoimmune damage. Patients who develop systemic lupus erythematosus (SLE) commonly exhibit antibodies that react with their own DNA. These antibodies may have been initially raised against the nucleic acid of microorganisms, but later cross-reacted with self-antigens. This phenomenon is also called molecular mimicry.