Thursday, February 28, 2008

Vaccines

If nothing else watch this very short video on how different vaccines are made.

Naturally Acquired Immunity is that immunity acquired upon exposure to a specific pathogen or foreign antigen.

Artificially Acquired Immunity is that immunity obtained via vaccination with a killed or live attenuated pathogen.

Vaccine is a preparation of killed or live attenuated pathogen or of specially derived pathogen antigenic determinants that is used to induce an immune response that protects an individual to a subsequent exposure to that pathogen.

Vaccination (immunization) is a means of inducing artifically acquired immunity. The goal of vaccination is to induce antibody or cell-mediated immune responses against a pathogen, without simultaneously inducing disease.



Edward Jenner was the army surgeon who is generally credited with advancing the art of "vaccination". On May 14, 1776, Jenner purposely exposed James Phipps with cowpox virus obtained from dairymaid Sarah Nelmes. Phipps became immune to smallpox as evidenced by survival of several purposeful attempts to infect him with the virus. Benjamin Jesty claims to have done the same thing 20 years prior to Jenner. Actually, the Chinese probably were vaccinating against smallpox hundreds of years before either of these men were born.

After the introduction of the smallpox vaccine in 1778 additional vaccines were introduced such as Rabies 1885, Plague 1897, Diptheria 1923, Pertussis 1926, Tuberculosis and Tetanus 1927 and Yellow fever 1935.

TYPES OF VACCINES

Inactivated Vaccines (killed) are vaccines consisting of an inactivated whole pathogen. Because the pathogen is dead these vaccines are considered very safe. However, they usually require several booster doses of the vaccine to induce sufficient immunity. An example of an inactivated vaccine is the Salk Polio vaccine and the Influenza vaccine.

Live, Attenuated Vaccines are vaccines that are made from a live pathogen that has been weakened so it cannot cause disease. These vaccines actually result in a mild infection, thus inducing a very strong protective immune response. A disadvantage of these vaccines is that they typically cannot be given to immunosuppressed individuals. An example of a live, attenuated vaccine is the oral Sabin Polio vaccine and the smallpox vaccine.

Toxoid Vaccine is a vaccine that is made from an inactivated toxin. Many infectious bacteria produce a toxin that is the cause of disease. Toxoid vaccines are made by treating the toxin chemically or with heat to inactivate it. Examples of toxoid vaccines are Diptheria and Tetanus vaccines.

SECOND GENERATION VACCINES

These vaccines are the result of recombinant DNA techology.

Subunit Vaccines are vaccines developed from well defined antigenic fragments of a pathogen.

Recombinant subunit vaccine are obtained using recombinant DNA techniques. Yeast cells are transfected with DNA which encodes an antigenic determinant of a pathogen. The yeast cells are grown in culture and the recombinant vaccine antigen is purified from the yeast cell culture. An example of this type of vaccine is the Hepatitis B vaccine.

Recombinant vector vaccines are made by inserting pathogen genes that encode protective antigens into a virus that does not cause disease (such as the vaccinia virus) but can express the pathogen genes. Although clinical trials are being done using these vaccines, there are no currently approved recombinant vector vaccines.

Conjugate Vaccine is a vaccine that is specially designed to induce immunity in babies who have an immature immune system. These vaccines consist of a polysaccharide (bacterial surface coat antigen) which is combined with an immunogenic protein that can be recognized by the baby's immune system. An example of this type of vaccine is the Haemophilus influenzae type b (Hib) vaccine.

FUTURE VACCINES

DNA Vaccines are made of a modified form of the pathogens DNA. When this DNA is injected into an individual, the pathogen DNA enters the cells which leads to the expression of the genes in the DNA (pathogen antigens). You can read more about DNA vaccines here.

Edible Vaccines are vaccines in which the pathgen antigens are expressed in edible plants such as potatoes and tomatoes. Read more about edible vaccines here.

VACCINE SIDE EFFECTS

Vaccination can result in side effects. These are typically local side effects including pain, redness, swelling, itching or a small lump at the site of injection.

However, occasionally systemic side effects can occur. These might include headache, fever, muscle aches or rashes. Very occasionally severe side effects might occur such as anaphylaxis shock.

Immunity - Lymphocytes






Lymphocytes: these are the cells that are responsible for specific immune responses. There are two distinct classes of lymphocytes:

B lymphocytes: are the cells that produce antibodies. The specific antigen receptors on B cells are membrane-bound forms of antibodies. Antibody producing B cells are called plasma cells.

T lymphocytes: do not produce antibody molecules. They produce a wide variety of molecules called cytokines that mediate immune resistance and have the capacity to directly kill other cells. There are at least three main types of T cells:

Helper T lymphocytes: (CD4+) participate in th activation and development of B lymphocytes, the activation of macrophages and the inflammatory response. They recognize foreign antigens presented by cells displaying MHC Class II molecules. You can see an animation of how this works here.






Helper T lymphocytes can be further divided into TH1 and TH2 lymphocytes.



Pathways to TH1 and TH2 lymphocyte differentiation can be seen here.

TH1 and TH2 lymphocytes are differentiated by the cytokines that they secrete. Cytokines are small protein hormones that mediate and regulate immune responses and inflammation. Learn more about cytokines here, here and here.



Cytotoxic T lymphocytes: (CD8+) are the cells that have the capacity to kill virus-infected cells, tumor cells and allografts. They can also mediated other forms of cell-mediated immunity. They recognize foreign antigens presented by cells displaying MHC Class I molecules.



Regulatory T lymphocytes: (FoxP3+) are T cells that act to suppress or regulate the activation of the immune system. These cells are probably important in preventing the expression of autoimmune diseases. These cells are a relatively recent discovery and it is not yet known exactly how they work in many cases.



Lymphocytes can also be differentiated based on the surface proteins they express called clusters of differentiation.





Here is a pretty good representation of the overall immune response to a viral infection obtained from a U. of Texas website.

Down the left side of the picture:

1) A host cell becomes infected with a virus.
2) The cell processes and presents viral antigen epitopes bound to MHC Class I molecules to the antigen receptor on a CD8+ cytotoxic T cell.
3) Activated effector viral antigen-specific CD8+ cytotoxic T cell recognizes a virally infected cell and kills it.
4) After viral pathogen is cleared some CD8+ viral specific cytotoxic T cells become memory cells.

Down the right side of the picture:

1) Lysed virally infected cell releases viral particles.
2) Viral particles are engulfed by activated macrophages, processed and presented, bound to MHC Class II molecules, to the CD4+ helper T cells.
3) CD4+ helper T cell becomes activated, proliferates, differentiates and secretes cytokines to help B cells become antibody producing plasma cells and CD8+ cytotoxic cells to become better killers.
4) Later in the response, viral specific B lymphocytes become very potent antigen presenting cells due to their antigen receptors.
5) As virus is cleared, CD4+ T cells and B cells become either die or become memory cells.

Immunity - Overview


Immune is from the latin immunitas refering to freedom from taxes or the exemption from service. We use the word to mean protection from disease, usually infectious disease.

Immunity is mediated by the immune system, a network of organs, tissues, cells and molecules. A brief introduction to the immune system can be found here.

The immune response is the collective and integrated response of the immune system to the introduction of a foreign antigen into the body.

NATURAL (INNATE) AND ACQUIRED (SPECIFIC) IMMUNITY

Natural or innate immunity are the barriers and mechanisms that mediate nonspecific resistance or defense in the body. Skin, mucous membranes, phagocytic cells and various molecules mediate innate immunity.

Acquired or specific immunity are those immune responses that are specific for distinct antigens and can increase in magnitude and capabilities with every exposure to the same antigen. An animation of specific immunity in action can be seen here.

Active Immunity is the type of specific immunity that is induced when an individual is exposed to an infectious agent or foreign antigen. This is the immunity that is generated in response to vaccination.

Passive Immunity is that immunity that can be transferred using cells or serum obtained from an immune individual. This is a means of rapidly inducing resistance to an individual.

The adaptive immune system is often classified into:

Humoral immunity which is mediated by antibodies. Go here to learn how lymphocytes make antibodies. Watch this animation on an allergic reaction that is mediated by IgE antibodies.

Cell-Mediated immunity which is mediated by T lymphocytes.

The immune response has several important features:

Specificity: immune response is specific for the antigen that induced the immune response.

Diversity: the number of antigen that can be recognized by the immune system is estimated to be 10,000,000,000.

Memory: exposure of the immune system to an antigen results in enhanced capacity to produce more antibodies or T cells to subsequent exposure to the same antigen.

Tolerance: individuals typically do not make immune responses to their own tissues. This is because the immune system is capable of discriminating self from non-self.

Self-limitation: immune responses normally decline after a period of time. This usually correlates with elimination of the antigen that originally induced the immune response.

Learn more about the immune system here and here.