CONCEPT MAP: THE GENERATION OF BIOCHEMICAL ENERGY
29.4 Plasma Proteins, White Blood Cells,
An antigen is any molecule or portion of a molecule recognized by the body as a foreign invader. An antigen might be a molecule never seen before by the body or a molecular segment recognized as an invader (for example, a protein on the sur- face of a bacterium or virus). Antigens can also be small molecules, known as hap- tens, that are only recognized as antigens after they have bonded to carrier proteins.
Haptens include some antibiotics, environmental pollutants, and allergens from plants and animals.
The recognition of an antigen can initiate three different responses. The first, the inflammatory response, is a non-specific, localized response to a given antigen.
Antigen A substance foreign to the body that triggers the immune response.
Inflammatory response A nonspe- cific defense mechanism triggered by antigens or tissue damage.
The two remaining types of immune response (cell-mediated response and antibody- mediated response) do depend on recognition of specific invaders (such as viruses, bacteria, toxic substances, or infected cells; Figure 29.7). At the molecular level, the invading antigen is detected by an interaction very much like that between an enzyme and its substrate. Noncovalent attraction allows a spatial fit between the antigen and a defender that is specific to that antigen. The cell-mediated immune response depends on white blood cells known as T cells. The antibody-mediated immune response depends on antibodies (or immunoglobulins) produced by the white blood cells known as B cells.
Both inf lammation and the immune responses require normal numbers of white blood cells to be effective (5 to 10 million white blood cells per milliliter).
If the white blood cell count falls below 1000 per milliliter of blood, any infection can be life- threatening. The devastating results of white blood cell destruction in AIDS is an example of this condition (see Chemistry in Action: Viruses and AIDS on p. 794).
Inflammatory Response
Cell damage due to infection or injury initiates inflammation, a nonspecific defense mechanism that produces swelling, redness, warmth, and pain. For example, the swollen, painful, red bump that develops around a splinter in your finger is an inf lammation (generally known as a wheal-and-f lare reaction). Chemical messengers released at the injured site direct the inflammatory response. One such messenger is histamine, which is synthesized from the amino acid histidine and is stored in cells throughout the body. Histamine release is also triggered by an allergic response.
O− Histidine
Histidine decarboxylase
C O
CH2CH NH3+
Histamine
CH2CH2 NH3+ + CO2 HN
N HN
N Antibody (immunoglobulin)
Glycoprotein molecule that identifies antigens.
Immune response Defense mecha- nism of the immune system dependent on the recognition of specific antigens, including viruses, bacteria, toxic sub- stances, and infected cells; either cell- mediated or antibody-mediated.
Inflammation Result of the inflam- matory response; includes swelling, redness, warmth, and pain.
Antigens
B cells activated Phagocytes
activated
T cells activated CELL–MEDIATED IMMUNITY
ANTIBODY–MEDIATED IMMUNITY Communication
and feedback SPECIFIC
DEFENSES (Immune response)
Direct physical and chemical
attack
Attack by antibodies
▶Figure 29.7 The immune response.
The attack on antigens occurs by cell-mediated and antibody-mediated immune responses.
S E C T I O N 2 9 . 4 Plasma Proteins, White Blood Cells, and Immunity 881 Histamine sets off dilation of capillaries and increases the permeability of capillary
walls. The resulting increased blood flow into the damaged area reddens and warms the skin, and swelling occurs as plasma carrying blood-clotting factors and defensive proteins enters the intercellular space. At the same time, white blood cells cross capil- lary walls to attack invaders.
Bacteria or other antigens at the inflammation site are destroyed by white blood cells known as phagocytes, which engulf invading cells and destroy them by enzyme- catalyzed hydrolysis reactions. Phagocytes also emit chemical messengers that help to direct the inflammatory response. An inflammation caused by a wound will heal com- pletely only after all infectious agents have been removed, with dead cells and other debris absorbed into the lymph system.
Cell-Mediated Immune Response
The cell-mediated immune response is under the control of several kinds of T lympho- cytes, or T cells. The cell-mediated immune response principally guards against abnor- mal cells and bacteria or viruses entering the normal cells; it also guards against the invasion of some cancer cells and causes the rejection of transplanted organs.
A complex series of events begins when a T cell recognizes an antigenic cell. The result of these events is production of cytotoxic, or killer, T cells that can destroy the invader (for example, by releasing a toxic protein that kills the antigenic in- vaded perforating cell membranes) and helper T cells, which enhance the body’s defenses against the invader. Thousands of memory T cells are also produced; they remain on guard and will immediately generate the appropriate killer T cells if the same pathogen reappears.
◀White blood cells. (left) A lymphocyte phagocytizing a yeast cell. (right) A lymphocyte reaches out to snare several E. coli bacteria.
Antibody-Mediated Immune Response
The white blood cells known as B lymphocytes or B cells, with the assistance of T cells, are responsible for the antibody-mediated immune response. Unlike T cells, which identify only antigenic cells, B cells identify antigens adrift in body fluids. A B cell is activated when it first binds to an antigen and then encounters a helper T cell that recognizes the same antigen. This activation can take place anywhere in the body, but it often occurs in lymph nodes, tonsils, or the spleen, which have large concentrations of lymphocytes.
Once activated, B cells divide to form plasma cells that secrete antibodies specific to the antigen. The antibodies are immunoglobulins. The body contains up to 10,000 different immunoglobulins at any given time, and we have the capacity to make more than 100 million others. The immunoglobulins are glycoproteins composed of two
“heavy” polypeptide chains and two “light” polypeptide chains joined by disulfide bonds, as shown in Figure 29.8. The variable regions are sequences of amino acids that will bind a specific antigen. Once synthesized, antibodies spread out to find their antigens.
Formation of an antigen–antibody complex (Figure 29.9) inactivates the antigen by one of several methods. The complex may, for example, attract phagocytes, or it may block the mechanism by which the invader connects with a target cell.
Light chain
Heavy chain
(a)
Constant region in different
types of immunoglobulins Variable regions for binding antigen
Disulfide bond
(b)
▶ Figure 29.8
Structure of an immunoglobulin, which is an antibody.
(a) The regions of an immunoglobulin.
The disulfide bridges that hold the chains together are shown in orange.
(b) Molecular model of an immu- noglobulin; the heavy chains are gray and blue and both light chains are red.
Antigenic determinant sites
Antigenic determinant sites
Antigen
(a) (b)
Antibodies Antigen
Antibody
▶ Figure 29.9
Antigen–antibody complexes.
(a) Antigens bind to antigenic- determinant sites on the surface of, for example, a bacterium. (b) Because each antibody has two binding sites, the interaction of many antigens and antibodies creates a large immune complex.
Activated B-cell division also yields memory cells that remain on guard and quickly produce more plasma cells if the same antigen reappears. The long-lived B and T memory cells are responsible for long-term immunity to diseases after the first ill- ness or after a vaccination.
Several classes of immunoglobulins have been identified. Immunoglobulin G anti- bodies (known as gamma globulins), for example, protect against viruses and bacteria.
Allergies and asthma are caused by an oversupply of immunoglobulin E. Numerous dis- orders result from the mistaken identification of normal body constituents as foreign and the overproduction of antibodies to combat them. These autoimmune diseases include attack on connective tissue at joints in rheumatoid arthritis, attack on pancre- atic islet cells in some forms of diabetes mellitus, and a generalized attack on nucleic acids and blood components in systemic lupus erythematosus.