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For Veterinarians

Immunology 101 & 102- Definitions and Terms

The following definitions are provided to help lay people and Veterinarians like me, who graduated 27 years ago and did not have a course in immunology, to understand the new principals of vaccination.

          Adjuvant

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a nonspecific stimulator of the immune system, incorporated into a vaccine to increase the immune response. Adjuvant combines with the antigen to slow the release, causing a prolonged, and stronger immune response. It also increases the immune response by causing increased inflammation

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The make-up of the adjuvant is generally a closely guarded proprietary secret of the vaccine manufacturers.  Many adjuvants are aluminum containing compounds.

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Killed vaccines (Rabies, Killed PLP) some sub-unit vaccines (FeLV) and even some MLV Vaccines (FIV) require adjuvant in order to produce an effective immune response.

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Adjuvanted vaccines are at higher risk of adverse reactions and adverse events such as vaccine associated fibrosarcomas.

Antibody

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a molecule produced by plasma cells, which interacts with it’s specific antigen, to destroy or stimulate destruction of the antigen by macrophages. Antibodies are specific for the antigen they are produced to reject.

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Antibodies are classified according to the mode of immune response they are specialized for.
Ex. IgM = early systemic, IgG= late systemic, IgA = surface, IgE = allergic.

Antigen

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a substance the body recognizes as foreign and reacts with specific antibody production to reject.
Ex. bacteria, virus, protozoa, parasite, pollen, toxin or cell.

Cellular Immunity (cell mediated immunity)

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 Immunity mediated by T lymphocytes, or an immune response where phagocytic cells play the predominate role.

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Immunity directed against a cell that is infected with a foreign organism like a virus. This is more effective then humoral immunity or antibodies, as it prevents replication of the virus. 

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Cellular immunity cannot be readily measured. It can be demonstrated by challenge studies.
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

       Challenge study – In order to assess the effectiveness
          of a vaccine,

  1. One group of animals is designated as controls and is not vaccinated.
  2. A second group of animals is vaccinated.
  3. All animals are challenged by exposure to the disease organism they were vaccinated against.
  4. The percentage of animals protected is determined. This is called the protective fraction.
bulletAlthough challenge studies cannot be done on human subjects, in Veterinary Medicine this is considered the gold standard to test the efficacy of a vaccine. Human vaccines must rely on titers to indicate efficacy.

Clades
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categories by which viruses are subdivided. Related but not identical groups. Cross protection by vaccines between viruses of different Clades is poor.        

           Humoral Immunity immunity provided by antibodies.

           Koch’s Postulates the evidence required to scientifically prove
         that an organism is the cause of a specific disease.
 
      1.  
The organism must be present every time a specific set of
          symptoms are present.

     2.
   The organism must be isolated, when the disease is
          present.

     3.
    The disease must be reproduced by infection of animals with
          the agent.
     4.
    The organism must be recovered from the diseased animal.

      *Results must be reproducible.

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Ex. Canine Corona virus has never satisfied Koch’s postulates in adult dogs, nor has it ever been demonstrated to be a cause of disease in dogs over 8 weeks of age

         Memory cells

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 B & T lymphocytes. Once programmed to produce antibodies, memory cells retain the information and persist for the life of the animal.

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Systemic memory cells can respond with antibody production, fast enough to prevent infection or prevent disease, even in the absence of an antibody titer.

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Mucosal memory cells cannot respond quickly enough to prevent infection, but respond quickly to minimize the symptoms, and hopefully provide for a lesser degree of illness.

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Memory cells cannot be readily measured. The only way to demonstrate memory cells is with a challenge study

          Temporal Association

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An event that appears related to a result, more often than would be expected by mere chance. It does not necessarily prove cause and effect.

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An example often referred to by scientists is: “ Butter keeps elephants out of the refrigerator. “ At first the correlation of these two events might appear to be a valid observation. Certainly we have butter in our refrigerators, and we have no elephants in our refrigerators. However, is butter really the cause?  With further investigation we may or may not find out that refrigerators without butter have no elephants either. And or we may find out that something else is keeping the elephants out of the refrigerator. Or we might find out that elephants are affected by the butter in such a way that they stay out of the refrigerators solely because of the butter, or in combination with another cause.

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We must be careful in drawing conclusions based on temporal associations because our conclusions may or may not be correct.

A temporal association merely implies that further investigation is warranted and may be necessary to prove cause and effect. 

bulletIf you understand this you are now thinking like a scientist, and you no longer have a personality or a life. 
bulletIf you don’t understand this, ask Dr. Seus.

          Serovars

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categories by which bacteria are subdivided or classified. Cross protection between bacteria of different serovars is poor.

          Titer

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 a measure of the quantity of antibodies. The amount of antibodies required to neutralize a measured amount of antigen, expressed as the highest dilution required for neutralization. Ex 1:10, 1:160

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A high titer is a rough correlation with immunity for some diseases.

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A negative titer does not necessarily indicate lack of immunity, as immunity is also controlled by cellular immunity, memory cells, which can respond with antibody production when needed.

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Titers do not measure or take into account memory cells or cellular immunity.

        Vaccine 

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a biologic agent containing antigens, live organisms, or killed organisms, or DNA, which will stimulate the immune system of the patient to produce antibodies, and possibly cellular immunity, as well as program memory cells to provide protection against disease. A vaccine does not provide immunity; it merely stimulates the body to produce immunity. A vaccine depends on the body’s response to provide protection.

Types of vaccines:

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Killed vaccines –(Inactivated) for safety, to prevent reversion to virulence, the organism is killed. Adjuvants are generally required to stimulate a sufficient immune response. Depending on the antigen and adjuvant, they may or may not produce cellular immunity. Duration of immunity is generally not as long as with modified live vaccines. Examples: Rabies, Leptospirosis, and Bordetella.
 

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Modified live virus vaccines –(Attenuated) the virus has been weakened or attenuated so that it should not produce the disease. MLV vaccines produce strong stimulation of the immune system because they reproduce or replicate within the host cells, providing for even more antigen.  Adjuvant is generally not needed.  Because the vaccine virus reproduces within the host cells, MLV vaccines produce cellular immunity. This immunity is directed toward future cells that become infected with the virus. This is good because it prevents any invading virus from replicating.
Duration of immunity is generally longer for MLV vaccines.
Although any vaccine can cause a fibrosarcoma, because MLV vaccines do not have adjuvant they are less likely to cause a fibrosarcoma.
 

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Subunit vaccine – a piece of DNA has been removed form the virus so it is not a whole virus vaccine. This DNA will still stimulate the immune system to provide immunity against that virus
Ex: Feline leukemia vaccine – the part of the virus that suppresses the immune system has been removed.
Most FeLV vaccines are adjuvanted. Two manufacturers, Meriel- Leukat, and Intervet Protex FeLV vaccines are non –adjuvanted.
 

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Subunit vectored vaccines – Purevac Rabies Vaccine, Muriel - a piece of rabies DNA is spliced onto a canary pox virus. The canary pox virus does not cause disease in the cat. The canary pox virus will enable the antigen to be presented to the immune system in such a way that good cellular immunity is produced without the need for an adjuvant.
This non-adjuvanted vaccine was developed because adjuvanted rabies vaccines are more likely to cause fibrosarcomas. MLV rabies vaccines were removed from the market because if administered to a FeLV infected cat they could revert to virulence and cause rabies. This vaccine cannot revert to virulence, it cannot possibly cause rabies.

Adjuvanted rabies vaccines have been incriminated in causing thousands of fibrosarcomas over the last 10 years. Only two fibrosarcomas are thought to have been caused by this new subunit vectored vaccine.
 

     


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Copyright (c) 2003. Dr. Robert L. Rogers. All rights reserved.

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Presented to Dr. Bob Rogers
for Public Education about New Vaccination Recommendations