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Immunology I: Basic Principles of Adaptive Immunity

and Immunization

Gusti Ayu Rai Saputri,M.Si., Apt..

Copyright © 2005 by John Wiley & Sons, Inc.

Immunology and Immunity• Immunity: refers to the ability of an organism to recognize

and defend itself against infectious agents

• Susceptibility: opposite of immunity, is the vulnerability of the host to harm by infectious agents

• Immunology: the study of adaptive immunity and how the immune system responds to specific infectious agents and toxins

• Immune system: consists of various cells, especially lymphocytes, and organs such as the thymus gland, that help provide the host with specific immunity to infectious agents

Types of Immunity• Innate immunity (genetic): exists because of genetically

determined characteristics

• All humans have immunity to many infectious agents that cause disease in pets and domestic animals

• Adaptive immunity (acquired): immunity obtained in some manner other than heredity

• Naturally acquired adaptive immunity is most often obtained by having a specific disease

• Artificially acquired adaptive immunity is obtained by receiving an antigen by injection of vaccine or immune serum

The various types of immunity: nonspecific immunity is largely innate, whereas specific immunity is acquired

Characteristics of the Immune System

• Antigen: a substance the body identifies as foreign and toward which it mounts an immune response

• Large, complex proteins can have several epitopes, or antigenic determinants (areas on the molecule to which antibodies can bind)

• Hapten: a small molecule can act as an antigen if it binds to a larger protein molecule

• Antibody: a protein produced in response to an antigen that is capable of binding specifically to the antigen

• Titer: the quantity of a substance needed to produce a given reaction

A typical antigen-antibody reaction: antibodies bind to specific chemical groups or structures, called epitopes or antigenic determinants

A typical antigen: antibody reaction: gram-negative bacterial pathogen may have several antigens, or immunogens (flagella, pili and cell wall)

Cells and Tissues of the Immune System• Specific immune responses are carried out by lymphocytes

which develop from stem cells as do other white blood cells, red blood cells, and platelets

• B lymphocytes (B cells): lymphocytes are processed and mature in tissue, referred to as bursal-equivalent tissue

• T lymphocytes ( T cells): stem cells migrate to the thymus, where they undergo differentiation into thymus-derived cells

• Natural killer cells (NK): found in tissues and circulating in blood and nonspecifically kill cancer cells and viral-infected cells

Differentiation of stem cells into B cells and T cells. This occurs in the bone marrow and thymus.

The Bursa of Fabricus

In chickens this is where B cells develop

Dual Nature of the Immune System

• Lymphocytes give rise to two major types of immune responses

1. Humoral immunity: carried out by antibodies circulating in the blood

2. Cell mediated immunity: carried out by T cells and occurs at the cellular level

Clonal selection hypothesis: One of many B cells responds to a particular antigen and begins to divide, thereby producing a large population of identical B cells (a clone)

Recognition of Self vs. Nonself

• For the immune system to respond to foreign substances, it must distinguish between host tissues and substances that are foreign to the host

• Self is normal host and nonself are foreign substances

• The clonal selection hypothesis (figure 17.5) and clonal deletion hypothesis (figure 17.6)

• This mechanism removes lymphocytes that can destroy host tissues and thereby creates tolerance for self

Clonal Delection: this process,which takes place in the bone marrow and thymus, removes those lymphocytes that have receptors for self antigens

Properties of Antibodies (Immunglobulins)

• Y-shaped protein molecules composed of four polypeptide chains – two identical light (L) chains and two identical heavy (H) chains

• Constant regions: determines the particular class that an immunoglobulin belongs to

• Variable regions: each chain have a particular shape and charge that enable the molecule to bind a particular antigen

Antibody Structure

Classes of Immunoglobulins

• Five classes of immunoglobulins have been identified in humans and other higher vertebrates

1. IgG: the main class of antibodies found in the blood accounts for as much as 20% of all plasma proteins

2. IgA: occurs in small amounts in blood and in larger amounts in body secretions (tears, milk, saliva and mucus)

3. IgM: found as a monomer on the surface of B cells and is secreted as a pentamer by plasma cells

4. IgE: has a special affinity for receptors on the plasma membranes of basophils in blood or mast cells in tissues

5. IgD: found mainly on B-cell membranes and is rarely secreted

How B Cells Build Diverse Antibodies

The Structures of the Different Classes of Antibodies

Primary and Secondary Responses• In humoral immunity the primary response to an

antigen occurs when the antigen is first recognized by host B cells

• Primary response of B cells can occur by two mechanisms:

1. B cells can be activated by binding antigen, proliferating and forming plasma cells (T-independent antigens)

2. Produces IgM antibody and no B memory cells are formed (T-dependent antigens)

• Secondary response: when an antigen recognized by memory cells enters the blood

Primary and Secondary Responses to an Antigen

Primary and Secondary Responses to an Antigen

Antibodies produced by humoral immune responses eliminate foreign agents in three ways:

1. Neutralization

2. Opsonization

3. Immune complexes

Summary of Humoral Immunity

Monoclonal Antibodies• Antibodies produced in the laboratory by a clone of

cultured cells that make one specific antibody

• Myeloma cells (malignant cells of immune system) are mixed with sensitized lymphocytes

• Lymphocytes are used because each makes a particular antibody

• Hybridoma: when two cell types are mixed in cultures, they can be made to fuse with one another to make this cell type

Production of monoclonal antibodies: only the hybridoma cells grown in culture will survive, because any unfused spleen cells cannot divide, and any unfused mouse myeloma cells cannot get the nutrients they need to grow

Cell-Mediated Immunity

• Involves the direct actions of T cells

• T cells interact directly with other cells that display foreign antigens

• Involves the differentiation and actions of different types of t cells and production of chemical mediators (cytokines)

• Cytokines: lymphokines and interleukins

The Reactions in Cell-Mediated Immunity

Cell-Mediated Immune Reaction• Involves the response of T lymphocytes

• T cells cannot be activated directly by antigens

• Macrophages that have processed an antigen secrete the lymphokine interleukin-1 (IL-1), which activates T helper cells

• T helper cells secrete interleukin-2 (IL-2) and activate delayed hypersensitivity cells and cytotoxic killer cells

• IL-1 and IL-2 cause undifferentiated cells to become natural killer cells

Types of T cells: After T cells are challenged by antigens, the cells differentiate into one of several types of functioning T cells

Summary of Cell-mediated Immunity: “CD” stands for cluster of differentiation

• Active immunization is the process of inducing active immunity

• Can be conferred by administering vaccines or toxoids

• Vaccine: a substance that contains an antigen to which the immune system responds

• Toxoid: an inactivated toxin that is no longer harmful, but retains its antigenic properties

Immunization

Recommended Immunizations

• Three vaccines that immunize against seven diseases are currently recommended in the U.S

1. DTaP vaccine: contains diphtheria toxoid, acellular pertussis (whooping cough), and tetanus toxoid

2. Poliomyelitis vaccine3. MMR vaccine contains live rubella, rubeola,

and mumps virus

Vaccination mark from inoculation with BCG vaccine: This vaccine is used in some countries to immunize against

tuberculosis

Passive Immunization

• Ready-made antibodies are introduced into an unprotected individual

• Because antibodies are found in serum, these products are often called antisera

• Established by administering a preparation such as gamma globulin, hyperimmune serum, or an antitoxin that contains large numbers of ready-made antibodies

Colorized SEM of a small T lymphocyte attacking two large tumor cells

How the Immune System Combats Viruses

How Antigens of Parasitic Protozoans Thwart the Immune System

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