3. Lymphocyte proliferation (fig. 15.4): Clones of responder cells and memory cells are derived from B cells and T cells.

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1 Chapter 15 Adaptive, Specific Immunity and Immunization* *Lecture notes are to be used as a study guide only and do not represent the comprehensive information you will need to know for the exams. Specific Immunity Review The elements of acquired specific immunity are exhibited in five stages (fig. 15.1): 1. Lymphocytes originate in hematopoietic tissue and diverge into two distinct types: B cells and T cells. B lymphocytes mature in bone marrow & T lymphocytes mature in the thymus. 2. Macrophages detect invading foreign antigens and phagocytose them. Antigens are then presented to B and T lymphocytes that recognize the antigen and initiate the specific immune response. (fig 15.1 & fig. 15.9) 3. Lymphocyte proliferation (fig. 15.4): Clones of responder cells and memory cells are derived from B cells and T cells. 4. Activated B cells become plasma cells that produce and secrete large quantities of antibodies. A subpopulation of B cells become memory cells. The memory cells serve as early responders should an immune challenge from the same antigen be presented again. (This is naturally acquired immunity.) See fig 15.9B for events in B-cell activation 5. Activated T-cells differentiate into one of four subtypes (fig 15.14; table 15.2): a. helper cells (TH CD4 cells) - These cells assist in initiating nearly all immune cells reactions. They are corner-stone cells that if absent will result in a person having a severely compromised immune system (e.g. AIDS). b. suppressor cells (TS) that suppress T cells and B cells and regulate immune reactions. c. cytotoxic killer cells (TC) that destroy specific target cells (fig ). These cells smell their targets and release enzymes to destroy the antigen containing cell. Cytotoxic T cells are also very important in removing cancer cells Specific Immunity: The Adaptive Line of Defense Immunology is the study of the immune system. The immune system is a collection of structures that fight infection should invading organisms penetrate the first two lines of defense. Immune system organs include the lymph nodes, tonsils, thymus gland, spleen, and Peyer s patch in the intestines. Humans have an adaptive, or acquired immunity which is responsible for long term protection, also called the Third Line of Defense. The body must have immunocompetence, the ability to recognize a wide variety of foreign substances. 1

2 Antigens are substances that can stimulate a response by B and T cells. Nonspecific resistance has been discussed with the first two lines of defense. Specific resistance involves the production of antibodies. Antibodies bind to antigenic determinants on invading elements. Adaptive immunity has specificity and memory. Antibodies are produced against a specific antigen, and the immune system has the ability to remember when the body is confronted with the antigen again. Normally, a person's cells and circulating biochemicals do not stimulate an immune response because they are interpreted as "self (fig. 14.3). If, however, the body does begin to produce antibodies against certain cells or tissues, it is referred to as autoimmune disease (see chapter 16 if you are interested in autoimmune disease) Lymphocyte Maturation and The Nature of Antigens Characteristics of Antigens and Immunogens Antigens are foreign, non-self substances capable of potentially provoking the production of antibodies. This property is known as antigenicity. Antigens can be proteins, flagella, toxins, or some other component of a bacterium or virus. Antigens are large, complex molecules that are not normally present in the body (fig. 15.7). An immunogen is an antigen that does induce a specific immune response when introduced to the body. Effects of Molecular Shape and Size on Antigenicity A substance must be of a certain size to catch the attention of the immune system. An epitope is just a portion of the antigen molecule. The area of activity on the antigen which stimulates the immune system is called an antigenic determinant. Foreign substances that are too small to illicit an immune response is called haptens (fig. 15.8) Cooperation in Immune Reactions to Antigens B-Cell Responses Products of B Lymphocytes: Antibody Structure and Functions Antibodies or Immunoglobulins (Ig) are large glycoprotein molecules that serve as the specific receptors of B cells and as proteins of specific defense. Antibodies combine with antigens forming an antigen-antibody complex that inactivates the antigens via several methods. Antibodies are found in blood serum, mucous, 2

3 tears, saliva, and breast milk. Some antibodies are produced in response to the introduction of antigen, while others are products prior to antigen presence. (figs & 15.6 & fig ) An Ig is made up of four polypeptides: a pair of identical heavy chains and a pair of identical light chains. A pocket formed between heavy and light chains comprises the antigen binding site; these sites are highly variable (fig & fig ). Some Antibody Functions (fig ) (a) neutralization (b) opsonization (c) complement fixation (d) agglutination There are 5 classes of immunoglobulins (table 15.3): IgG, IgA, IgM, IgD, IgE. IgG - are the most prevalent antibodies circulating throughout tissues and blood and function in neutralization, opsonization, agglutination, and complement fixation. IgGs can cross the placenta. IgA - are the secreted antibodies found in breast milk, mucous, saliva, and tears. IgM produced as first response to antigens; can fix complement proteins IgD are receptors on B lymphocytes IgE function against helminth infections and in allergic responses. Monitoring Antibody Production over Time: Primary and Secondary Responses to Antigens It is possible to monitor the level of antibody production in serum overtime, called a titer (fig ). When a person is first (1 st ) exposed to an immunogen, the person produces a primary response. When the immune system is exposed again to the same immunogen later in time, a secondary response is produced. The secondary response is also called an anamnestic response. Monoclonal Antibodies: Useful Products from Cancer Cells Monoclonal antibodies originate from a single clone and have a specific antigen. This has been useful for treating certain diseases and therapy. See 15.1 MAKING CONNECTIONS Of Mice and MABs? 3

4 15.5 A Classification Scheme for Specific, Acquired Immunities A. Innate (natural) immunity is inborn; independent of previous exposure; depends on phagocytic cells, nonspecific antimicrobial substances and metabolic changes (i.e. the first and second lines of defense). B. Acquired immunity is gained as the result of exposure to microbes or another foreign substance; depends on the production or acquisition of antibodies or specialized immune cells (specific immunity). Figure Acquired means the person has somehow come in contact with the antigen or has received the antibodies. Artificial means it was given by injection. Active means the person received the antigens which in turn stimulated their immune system. Passive means the person received the antibodies, which provides only short-term protection. Natural active immunity The person has had the actual disease and now has an immunity to that specific disease (measles or chickenpox as a child provides lasting immunity). Natural passive immunity The person has received antibodies by some natural process. Antibodies are small enough to cross the placental barrier and can be supplied to a nursing infant. The antibodies are secreted in mothers' milk. Artificial passive immunity The person receives antibodies during an outbreak of the disease, such as gamma globulin during a hepatitis epidemic, or Rh- mothers receiving Rhogam after the birth of an Rh+ child (fig ). Artificial active immunity The person receives a preparation of antigens that have been inactivated so they will cause the production of antibodies, not the disease. This usually confers long-term immunity (two exceptions: diphtheria and tetanus). These preparations are called vaccines. 4

5 15.6 Immunization: Methods of Manipulating Immunity for Therapeutic Purposes Immunization refers to the process where a person is given preformed antibodies (passive immunization) or suspensions of killed pathogens or their antigens (active immunization). Vaccination refers specifically to inducing active immunity through artificial means. (Note: we will discuss specific vaccines like the flu vaccine and the new HPV vaccine when we cover those pathogens later in the semester). Vaccines are made from: (see fig for strategies in vaccine design) (a) killed bacterial suspensions (b) killed viruses (c) living attenuated organisms that have been made incapable of causing the disease. Attenuation is any process that substantially lessens or negates the virulence of viruses or bacteria, but still allows them to stimulate the immune system to produce antibodies. (d) inactivated toxins, or toxoid vaccines (e.g. diphtheria and tetanus) (e) purified subunits of bacteria or viruses (subunit vaccines) Table 15.5 lists currently approved vaccines. Vaccination is recommended for all typical childhood infectious diseases for which a vaccine is available and for people in certain high-risk circumstances. Table 15.6 lists the recommended childhood and adolescent immunization schedule. Table 15.6 lists the recommended adult immunization schedule. Herd immunity individuals in a population that have received their vaccines make it difficult to harbor infectious agents, thus reducing the communicable transmission of the infectious agent. With so many in the population with the vaccine, it is unlikely that an individual who has not received their vaccines will unlikely acquire the infectious agent. Hazards of vaccination: No treatment is ever without its own side-effects. However, that certain diseases are prevented by vaccinations far outweighs the risk of the possible complications. Remember, the single best way to treat viral infections is prevention. Common mild complications: 1. Local reactions at the injection site 2. Fever 3. Allergic reactions (some to the vaccine agent and some to the medium it is suspended in). Rare severe side effects: 1. encephalitis (measles vaccine, 1 case in 220,000) 2. back-mutation to a virulent strain (polio vaccine) 5

6 3. neurotoxicity (pertussis and swine flu vaccine) Note: To date, no link has been confirmed between the MMR vaccine and autism in children. FYI: Information on vaccines changes fairly regularly, so for the most complete, up to date information, always check the excellent website operated by the Center for Disease Control (CDC): Take the adult immunization quiz to see if you are missing a potentially important vaccine! 6