Chapter 18

18Natural Defensesagainst Disease

18 Natural Defenses against Disease

• Animal Defense Systems

• Nonspecific Defenses

• Specific Defenses: The Immune System

• B Cells: The Humoral Immune Response

• T Cells: The Cellular Immune Response

• The Genetic Basis of Antibody Diversity

• Disorders of the Immune System

18 Animal Defense Systems

• Animal defense systems are based on the distinction between self and nonself.

• There are two general types of defense mechanisms:

Nonspecific defenses, or innate defenses, are inherited mechanisms that protect the body from many different pathogens.

Specific defenses are adaptive mechanisms that protect against specific targets.


• Components of the defense system are distributed throughout the body.

• Lymphoid tissues (thymus, bone marrow, spleen, lymph nodes) are essential parts of the defense system.

• Blood plasma suspends red and white blood cells and platelets.

• Red blood cells are found in the closed circulatory system.

• White blood cells and platelets are found in the closed circulatory system and in the lymphatic system.


• Lymph consists of fluids that accumulate outside of the closed circulatory system in the lymphatic system.

• The lymphatic system is a branching system of tiny capillaries connecting larger vessels.

• These lymph ducts eventually lead to a large lymph duct that connects to a major vein near the heart.

• At sites along lymph vessels are small, roundish lymph nodes.

• Lymph nodes contain a variety of white blood cells.

Figure 18.1 The Human Lymphatic system


• White blood cells are important in defense.

• All blood cells originate from stem cells in the bone marrow.

• White blood cells (leukocytes) are clear and have a nucleus and organelles.

• Red blood cells are smaller and lose their nuclei before they become functional.

• White blood cells can leave the circulatory system.

• The number of white blood cells sometimes rises in response to invading pathogens.


• There are two main groups of white blood cells: phagocytes and lymphocytes.

• Phagocytes engulf and digest foreign materials.

• Lymphocytes are most abundant. There are two types: B and T cells.

• T cells migrate from the circulation to the thymus, where they mature.

• B cells circulate and also collect in lymph vessels, and make antibodies.

Figure 18.2 Blood Cells (Part 1)




• Four groups of proteins play key roles in defending against disease:

Antibodies, secreted by B cells, bind specifically to certain substances.

T cell receptors are cell surface receptors that bind nonself substances on the surface of other cells.

Major histocompatibility complex (MHC) proteins are exposed outside cells of mammals. These proteins help to distinguish self from nonself.

Cytokines are soluble signal proteins released by T cells. They bind and alter the behavior of their target cells.

18 Nonspecific Defenses

• The skin acts as a physical barrier to pathogens.

• Bacteria and fungi on the surface of the body (normal flora) compete for space and nutrients against pathogens.

• Tears, nasal mucus, and saliva contain the enzyme lysozyme that attacks the cell walls of many bacteria.

• Mucus and cilia in the respiratory system trap pathogens and remove them.

• Ingested pathogens can be destroyed by the hydrochloric acid and proteases in the stomach.

• In the small intestine, bile salts kill some pathogens.


• Vertebrate blood contains about 20 antimicrobial complement proteins.

• Complement proteins provide three types of defenses:

They attach to microbes, helping phagocytes recognize and destroy them.

They activate the inflammation response and attract phagocytes to the site of infection.

They lyse invading cells.


• Interferons are produced by cells that are infected by a virus.

• All interferons are glycoproteins consisting of about 160 amino acids.

• They increase resistance of neighboring cells to infections by the same or other viruses.

• Each vertebrate species produces at least three different interferons.


• Phagocytes ingest pathogens. There are several types of phagocytes:

Neutrophils attack pathogens in infected tissue.

Monocytes mature into macrophages. They live longer and consume larger numbers of pathogens than do neutrophils. Some roam and others are stationary in lymph nodes and lymphoid tissue.

Eosinophils kill parasites, such as worms, that have been coated with antibodies.

Dendritic cells have highly folded plasma membranes that can capture invading pathogens.


• Natural killer cells are a class of nonphagocytic white blood cells

• They can initiate the lysis of virus-infected cells and some tumor cells.


• The inflammation response is used in dealing with infection or tissue damage.

• Mast cells and white blood cells called basophils release histamine, which triggers inflammation.

• Histamine causes capillaries to become leaky, allowing plasma and phagocytes to escape into the tissue.

• Complement proteins and other chemical signals attract phagocytes. Neutrophils arrive first, then monocytes (which become macrophages).


• The macrophages engulf invaders and debris and are responsible for most of the healing.

• They produce several cytokines, which may signal the brain to produce a fever.

• Pus, composed of dead cells and leaked fluid, may accumulate.

Figure 18.4 Interactions of Cells and Chemical Signals in Inflammation (Part 1)

Figure 18.4 Interactions of Cells and Chemical Signals in Inflammation (Part 2)

18 Specific Defenses: The Immune System

• Four characteristics of the immune system: 1. Specificity: Antigens are organisms or

molecules that are specifically recognized by T cell receptors and antibodies.

The sites on antigens that the immune system recognizes are the antigenic determinants (or epitopes).

Each antigen typically has several different antigenic determinants.

The host creates T cells and/or antibodies that are specific to the antigenic determinants.

Figure 18.6 Each Antibody Matches an Antigenic Determinant


2. Diversity:

It is estimated that the human immune system can distinguish and respond to 10 million different antigenic determinants.

3. Distinguishing self from nonself:

Each normal cell in the body bears a tremendous number of antigenic determinants. It is crucial that the immune system leave these alone.

4. Immunological memory:

Once exposed to a pathogen, the immune system remembers it and mounts future responses much more rapidly.


• The immune system has two responses against invaders: The humoral immune response and the cellular immune response.

• The two responses operate in concert and share mechanisms.


• The humoral immune response involves antibodies that recognize antigenic determinants by shape and composition.

• Some antibodies are soluble proteins that travel free in blood and lymph. Others are integral membrane proteins on B cells.

• When a pathogen invades the body, it may be detected by and bound by a B cell whose membrane antibody fits one of its potential antigenic determinants.

• This binding activates the B cell, which makes multiple soluble copies of an antibody with the same specificity as its membrane antibody.


• The cellular immune response is able to detect antigens that reside within cells.

• It destroys virus-infected or mutated cells.

• Its main component consists of T cells.

• T cells have T cell receptors that can recognize and bind specific antigenic determinants.


• Several questions arise that are fundamental to understanding the immune system.

How does the enormous diversity of B cells and T cells arise?

How do B and T cells specific to antigens proliferate?

Why don’t antibodies and T cells attack and destroy our own bodies?

How can the memory of postexposure be explained?


• Clonal selection explains much of this.

• The healthy body contains a great variety of B cells and T cells, each of which is specific for only one antigen.

• Normally, the number of any given type of B cell present is relatively low.

• When a B cell binds an antigen, the B cell divides and differentiates into plasma cells (which produce antibodies) and memory cells.

• Thus, the antigen “selects” and activates a particular antibody-producing cell.

Figure 18.7 Clonal Selection in B Cells


• An activated lymphocyte (B cell or T cell) produces two types of daughter cells: effector and memory cells.

• Effector B cells, called plasma cells, produce antibodies.

• Effector T cells release cytokines.

• Memory cells live longer and retain the ability to divide quickly to produce more effector and more memory cells.


• When the body encounters an antigen for the first time, a primary immune response is activated.

• When the antigen appears again, a secondary immune response occurs. This response is much more rapid, because of immunological memory.

Figure 18.8 Immunological Memory


• Artificial immunity is acquired by the introduction of antigenic determinants into the body.

• Vaccination is inoculation with whole pathogens that have been modified so they cannot cause disease.

• Immunization is inoculation with antigenic proteins, pathogen fragments, or other molecular antigens.

• Immunization and vaccination initiate a primary immune response that generates memory cells without making the person ill.


• Antigens used for immunization or vaccination must be processed so that they will provoke an immune response but not cause disease. There are three principle ways to do this:

Attenuation involves reducing the toxicity of the antigenic molecule or organism.

Biotechnology can produce antigenic fragments that activate lymphocytes but do not have the harmful part of the protein toxin.

DNA vaccines are being developed that will introduce a gene encoding an antigen into the body.


• The body is tolerant of its own molecules, even those that would cause an immune response in other individuals of the same species.

• Failure to do so results in autoimmune disease.

• This self tolerance is based on two mechanisms: clonal deletion and clonal anergy.


• Immunological tolerance is a poorly understood but clearly observable phenomenon.

• Exposing a fetus to an antigen before birth provides later tolerance to the antigen.

• Continued exposure is necessary to maintain the tolerance.

• Some individuals experience the opposite effect; they lose tolerance to themselves, which results in autoimmune disease.

18 Disorders of the Immune System

• HIV (human immunodeficiency virus), which leads to AIDS (acquired immune deficiency syndrome), causes a depletion of TH cells.

• It can be transmitted through blood or by exposure of broken skin or an open wound to the body fluids of an infected person.

Figure 18.21 The Course of an HIV Infection


• HIV uses RNA as its genetic molecule.

• The core of the virus contains two identical molecules of RNA and the enzymes reverse transcriptase, integrase, and a protease.

• The envelope is derived from the plasma membrane of the cell in which the virus grew.

• The virus enters the cell via cell membrane proteins on TH cells.


• Once in the cell, reverse transcriptase makes a DNA copy (cDNA) of the viral RNA, and cellular DNA polymerase makes the complementary strand.

• Reverse transcriptase is error prone; this elevates the mutation rate and adds to the adaptability of the virus.

• The cDNA integrates into the host DNA.

Chapter 18

Technology

red blood cells

infected cells

invading cells

stem cells

tumor cells

target cells

cells of mammals

white blood cells leukocytes