​

​

​

​

The Immune Response

​

​

The Immune Response

​

Immunity: Ability of an organism to recognize and defend itself against specific pathogens or antigens.

Immune Response: Third line of defense. Involves production of antibodies and generation of specialized lymphocytes against specific antigens.

Antigen: Molecules from a pathogen or foreign organism that provoke a specific immune response.

​

​

The Immune System is the Third Line of Defense Against Infection

Innate or Genetic Immunity: Immunity an organism is born with.

• Genetically determined.
• May be due to lack of receptors or other molecules required for infection.
• Immunity of mice to poliovirus.

Acquired Immunity:Immunity that an organism develops during lifetime.

• Not genetically determined.
• May be acquired naturally or artificially.
• Development of immunity to measles in response to infection or vaccination.

Types of Acquired Immunity

I. Naturally Acquired Immunity: Obtained in the course of daily life.

A. Naturally Acquired Active Immunity:

• Antigens or pathogens enter body naturally.
• Body generates an immune response to antigens.
• Immunity may be lifelong (chickenpox or mumps) or temporary (influenza or intestinal infections).

B. Naturally Acquired Passive Immunity:

• Antibodies pass from mother to fetus via placenta or breast feeding (colostrum).
• No immune response to antigens.
• Immunity is usually short-lived (weeks to months).
• Protection until child’s immune system develops.

​

Types of Acquired Immunity (Continued)

​

II. Artificially Acquired Immunity: Obtained by receiving a vaccine or immune serum.

A. Artificially Acquired Active Immunity:

• Antigens are introduced in vaccines (immunization).
• Body generates an immune response to antigens.
• Immunity can be lifelong (oral polio vaccine) or temporary (tetanus toxoid).

B. Artificially Acquired Passive Immunity:

• Preformed antibodies (antiserum) are introduced into body by injection.
• Snake antivenom injection from horses or rabbits.
• Immunity is short lived (half life three weeks).
• Host immune system does not respond to antigens.

​

​

• Serum: Fluid that remains after blood has clotted and cells have been removed.
• Antiserum: Serum containing antibodies to a specific antigen(s). Obtained from injecting an animal (horse, rabbit, goat) with antigen (snake venom, botulism or diphtheria toxin).
• Serology: The study of reactions between antibodies and antigens.
• Gamma Globulins: Fraction of serum that contains most of the antibodies.
• Serum Sickness: Disease caused by multiple injections of antiserum. Immune response to foreign proteins. May cause fever, kidney problems, and joint pain. Rare today.

Duality of Immune System

I. Humoral (Antibody-Mediated) Immunity

• Involves production of antibodies against foreign antigens.
• Antibodies are produced by a subset of lymphocytes called B cells.
• B cells that are stimulated will actively secrete antibodies and are called plasma cells.
• Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells.
• Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells.
• Also cause certain reactions against transplanted tissue.

​

Antibodies are Produced by B Lymphocytes

Antibodies are Proteins that Recognize Specific Antigens

Duality of Immune System (Continued)

II. Cell Mediated Immunity

• Involves specialized set of lymphocytes called T cells that recognize foreign antigens on the surface of cells, organisms, or tissues:
• Helper T cells
• Cytotoxic T cells
• T cells regulate proliferation and activity of other cells of the immune system: B cells, macrophages, neutrophils, etc.
• Defense against:
• Bacteria and viruses that are inside host cells and are inaccessible to antibodies.
• Fungi, protozoa, and helminths
• Cancer cells
• Transplanted tissue

Antigens

• Most are proteins or large polysaccharides from a foreign organism.
• Microbes: Capsules, cell walls, toxins, viral capsids, flagella, etc.
• Nonmicrobes: Pollen , red blood cell surface molecules, serum proteins, and surface molecules from transplanted tissue.
• Lipids and nucleic acids are only antigenic when combined with proteins or polysaccharides.
• Molecular weight of 10,000 or higher.

​

​

Antigens

Epitope:

• Small part of an antigen that interacts with an antibody.
• Any given antigen may have several epitopes.
• Each epitope is recognized by a different antibody.

Epitopes: Antigen Regions that Interact with Antibodies

Antibodies

• Proteins that recognize and bind to a particular antigen with very high specificity.
• Made in response to exposure to the antigen.
• One virus or microbe may have several antigenic determinant sites, to which different antibodies may bind.
• Each antibody has at least two identical sites that bind antigen: Antigen binding sites.
• Valence of an antibody: Number of antigen binding sites. Most are bivalent.
• Belong to a group of serum proteins called immunoglobulins (Igs).

Antibody Structure

• Monomer: A flexible Y-shaped molecule with four protein chains:
• 2 identical light chains
• 2 identical heavy chains
• Variable Regions: Two sections at the end of Y’s arms. Contain the antigen binding sites (Fab). Identical on the same antibody, but vary from one antibody to another.
• Constant Regions: Stem of monomer and lower parts of Y arms.
• Fc region: Stem of monomer only. Important because they can bind to complement or cells.

�General antibody Structure

Immunoglobulin Classes

I. IgG

• Structure: Monomer
• Percentage serum antibodies: 80%
• Location: Blood, lymph, intestine
• Half-life in serum: 23 days
• Complement Fixation: Yes
• Placental Transfer: Yes
• Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.

Immunoglobulin Classes

II. IgM

• Structure: Pentamer
• Percentage serum antibodies: 5-10%
• Location: Blood, lymph, B cell surface (monomer)
• Half-life in serum: 5 days
• Complement Fixation: Yes
• Placental Transfer: No
• Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

Immunoglobulin Classes

III. IgA

• Structure: Dimer
• Percentage serum antibodies: 10-15%
• Location: Secretions (tears, saliva, intestine, milk), blood and lymph.
• Half-life in serum: 6 days
• Complement Fixation: No
• Placental Transfer: No
• Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

Immunoglobulin Classes

IV. IgD

• Structure: Monomer
• Percentage serum antibodies: 0.2%
• Location: B-cell surface, blood, and lymph
• Half-life in serum: 3 days
• Complement Fixation: No
• Placental Transfer: No
• Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

Immunoglobulin Classes

V. IgE

• Structure: Monomer
• Percentage serum antibodies: 0.002%
• Location: Bound to mast cells and basophils throughout body. Blood.
• Half-life in serum: 2 days
• Complement Fixation: No
• Placental Transfer: No
• Known Functions: Allergic reactions. Possibly lysis of worms.

How Do B Cells Produce Antibodies?

• B cells develop from stem cells in the bone marrow of adults (liver of fetuses).
• After maturation B cells migrate to lymphoid organs (lymph node or spleen).
• Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies.
• Each B cell produces antibodies that will recognize only one antigenic determinant.

​

​

Clonal Selection of B Cells is Caused by Antigenic Stimulation

monoclonal vs. polyclonal antibody preparations

​

Monoclonal Antibody: homogeneous antibody preparations produced in the laboratory. Consist of a single type of antigen binding site, produced by a single B cell clone.

​

Polyclonal antibodies: antibody preparations from immunized animals. Consist of complex mixtures of different antibodies produced by many different B cell clones

Monoclonal antibody preparation

​

Preparation containing antibodies secreted by cells of only one plasma B cell clone

The IgG fraction from blood of any vertebrate is not a convenient source of a monoclonal antibody preparation.

An individual B cell from the spleen of an animal, if separated from the other B cells, immortalized, and expanded as a clone, is a source of a monoclonal antibody preparation.

Polyclonal antibody preparation

​

Preparation containing antibodies secreted by cells of numerous different plasma B cell clones

The IgG fraction from blood of any vertebrate is a polyclonal preparation.

Example: the blood of an animal immunized with p53 from another species will contain circulating antibodies against several epitopes of p53 as well as Abs against other antigens to which the animal has been exposed.

Representative cells of the different antibody-producing clones will be found in the animal’s spleen.

Monoclonal v. polyclonal

Clinical Uses for Monoclonal Antibodies

• Very useful as diagnostic, imaging, and therapeutic reagents in clinical medicine
• Monoclonal antibodies were used primarily as in vitro diagnostic reagents
• Radiolabeled monoclonal antibodies can also be used in vivo detecting or locating
• Immunotoxins
• To compose of tumor-specific monoclonal antibodies coupled to lethal toxin
• Valuable therapeutic reagent