Chapter 17 Micro

• Edward Jenner- First Vaccine
• Robert Koch- Germ Theory of Disease
• Elie Metchnikoff- Phagocytosis (founded the first theory of immunity)
• Emil Von Behring- Diphtheria Antitoxin
• Paul Ehrlich- Theory of Immunity

• Louis Pasteur in his development of vaccination and his proposed germ theory of
• diseases exploited acquired immunity. Robert Koch’s proofs that microorganisms
• were confirmed as the caused infectious disease.

Immunology: The study of the immune system.

• Antigen: A molecule, usually a protein or
• large polysaccharides that stimulates an adaptive immune response. Antigenic
• compounds are often components of invading microbes.

Antibody: A globulin protein molecule secreted by B cells (plasma cells) that can bind to antigens.

• Humoral immunity: Immunity brought about by antibodies. The process that leads  to
• the production of antibodies starts when B cells are exposed to free, or extracellular antigens. Primary cell type:
• B cells.

• Cell-mediated immunity: Immunity that responds to intracellular antigens, such as a virus within an infected cell. Primary cell
• type: T cells.

B lymphocytes (B cells) are developed in the bone narrow and T lymphocytes (T cells) derive from the thymus.

• Antibodies bind to the epitope (antigenic
• determinant) of an antigen.

Haptens are antigens that are composed of low molecular-weight compounds and are attached to a carrier molecule. They are too small to stimulate antibody formation by itself, but when the hapten is combined with a larger carrier molecule, usually a serum protein, the hapten and its carrier together form a conjugate that can stimulate an immune response.

• Example:
• Penicillin. When penicillin combines with host proteins, the resulting combined
• molecule initiates an immune response.

An antibody is composed of four polypeptide chains two identical light chains and two identical heavy chains (light and heavy refer to the relative molecular weights) that are linked by disulfide bridges (S-S). The two sections located at the end of the Y’s arms are called variable (V) regions. An epitope is the binding site of an antigen where an antibody binds to.

The amino acid sequences of the variable regions(V), which form the two antigen-binding sites, differ from molecule to molecule.

Passive immunity: The short-term immunity that results from the introduction of antibodies from another person or animal.

Naturally acquired: Antibodies pass from mother to fetus via placenta or to infant via the mother’s milk.

Artificially acquired: Preformed antibodies in immune serum are introduced by infection.

• IgG accounts for about 80% of all antibodies in serum. IgG antibodies cross the walls of blood vessels and enter tissue fluids. They protect against circulating bacteria and viruses, neutralize bacterial toxins, trigger the complement system, and when bound to
• antigens, enhance the effectiveness of phagocytic cells. IgG antibodies protect fetus and newborn, and tend to last longer than other antibodies

IgE antibodies constitute only .0002% of the total serum antibodies. IgE molecules bind by their Fc (stem) regions to receptors on mast cells and basophils, specialized cells that participate in allergic reactions.

Isotype: the genetic variation or differences in the constant region of the heavy and light chains.

• IgG, IgD, IgE are monomers
• IgM is a pentamer
• IgA is a dimer with a secretory component

• IgG: Neutralizes toxins and viruses;
• enhances phagocytosis; protects fetus and newborn.

IgM: First antibodies produced in response to initial infection; effective against microorganisms and agglutinating antigens. 

• IgA: Localized protection on mucosal
• surfaces.

IgD: Serum function not known; Presence on B cells functions in initiation of immune response.

IgE: Allergic reactions; possibly lysis of  parasitic worms.

IgG: Blood, lymph, and intestine

IgM: Blood, lymph, B cell surface (as monomer)

• IgA: Secretions (tears, saliva, mucus,
• intestine, milk), blood, lymph.

IgD: B cell surface, blood, lymph

IgE: Bound to mast and basophil cells throughout body, and blood.

An activated B cell proliferates into large clone of cells. Some of which will differentiate into antibody-producing plasma cells. Others of the activated B cell become long-lived memory cells that are responsible for the enhanced secondary response to an antigen. This phenomenon is called clonal selection.

When a B cell is activated by its first encounter with an antigen that binds to its receptor, the cell proliferates and differentiates to generate a population of antibody-secreting plasma B cells and memory B cells.

There are 5 types of antibodies: IgG, IgM, IgA, IgD, IgE. The antibodies of the IgG class enhance phagocytosis, neutralize toxins and viruses, and also protect fetuses and newborns. The antibodies of the IgM class are especially effective against microorganisms and agglutinating antigens. They are also the first antibodies produced in response to initial infection. The antibodies of the IgA class act as localized protection on mucosal surfaces. The antibodies of the IgD class have a presence on B cell functions in initiation of immune response. Their serum function is not known. The antibodies of the IgE class are allergic reactions and are possibly lysis of parasitic worms.

This function resembles opsonization in that the target organism becomes coated with antibodies. However, the destruction of the target cell is by immune system cells that remain external to the target cell. If an organism, such as a parasitic worm, is too large for ingestion and destruction by phagocytosis, it can be attacked by immune system cells that remain external to it. The garget cell is first coated with antibodies. The cells of the immune system, such as eosinophils, macrophages, and NK cells, bind to the Fc regions of the attached antibodies. Finally, the target cell is then lysed by substances secreted by the cells of the immune system.

IgE antibodies can cause an allergic response. When an antigen such as pollen cross-links with the IgE antibodies attached to a mast cell or basophil, that cell releases histamine and other chemical mediators.

T cells go through thymic selection. This weeds out T cells that will not specifically recognize self-molecules of MHC. This is important in preventing the body from attacking its own tissues.

The basic T cell forms are T helper cells and T cytotoxic cells. Helper T cells control the immune response through the use of chemical messenger molecules called cytokines. Cytotoxic T cells (CTL) can kill intracellularly infected cells.

The recognition of antigens by a T cell requires that they be first processed by specialized antigen presenting cells. After processing, an antigenic fragment is presented on the APC surface together with a molecule of MHC. Fig 17.10: An APC encounters and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC. A receptor (TCR) on the surface of the CD4+ T helper cell (TH cell) binds to the MHC- antigen complex. If this includes a Toll-like receptor, the APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines. The cytokines cause the TH cell (which recognizes a dendritic cell that is producing costimulatory molecules) to become activated.  They proliferate and develop its effector system.

Activated B cells become antibody-producing plasma cells. Immunoglobin receptors on B cell surface recognize and attach to the antigen, which is then internalized and processed. Within the B cell a fragment of the antigen combines with MHC class II. MHC class II antigens fragment complex is displayed on B cell surface. Receptor on the T helper cell (TH) recognizes complex of MHC class II and antigen fragment and is activated- producing cytokines, which activate the B cell. The TH cell has been previously activated by an antigen displayed on dendritic cell. B cell is activated by cytokines and begins clonal expansion. Some of the progeny become antibody-producing plasma cells.

T helper cells cooperate with B cells in the production of antibodies as a part of humoral immunity and cellular immunity. Cytotoxic killing is the killing of a virus infected target cell by the cytotoxic T lymphocyte (T cytotoxic cell or CD8+ T cells). A normal cell will not trigger a response by a cytotoxic T lymphocyte, but a virus-infected cell or a cancer cell produces abnormal endogenous antigens. The abnormal antigen is presented on the cell surface in associated with MHC class I molecules. CD8+ T cells with receptors for the antigen are transformed into cytotoxic T lymphocytes (CTL). The CTL induces destruction of the virus infected cell by apoptosis.

A small protein released from human cells that regulates the immune response; directly or indirectly may induce fever, pain, or T cell proliferation.

The exposed person’s serum contains no detectable antibodies for 4-7 days. The IgM appears first in response to the initial exposure. IgG follows and provides longer term immunity. The second exposure to the same antigen stimulated the memory cells (formed from the initial exposure) to rapidly produce a large amount of antibody. The antibodies produced in response to this second exposure are mostly IgG.

Vaccines are introduced into the body as antigens that contain killed or inactivated living microorganisms or inactivated bacterial toxins. Immunity can be acquired this way because the body has been exposed to the foreign substance. The body produces antibodies and specialized lymphocytes to prepare the body for future infections. Vaccines are designed to stimulate an artificial adaptive immune response without the risk of infection. Vaccines are weakened, genetically modified, or simply antigenic parts of an organisms that will cause limited damage to the host.

Innate immune responses involve the natural transfer of antibodies from mother to her infant. Antibodies in a pregnant woman cross the placenta to her fetus called the transplacental transfer. The antibodies can also be passed through mother’s milk. During active transfer, antigens enter the body naturally and the body induces antibodies and specialized lymphocytes. Adaptive immune responses are antigens introduced to the body through vaccines and can also be introduced by injections of preformed antibodies in immune serum.