Vaccination and Disorders of the Immune System

1
Vaccination and Disorders of the Immune System

• The second half of Disorders of the Immune System
  will be combined with Diagnosing Infection due to
  the large amount of material.

2
Types of Vaccines

• Attenuated whole-agent weakened form of microbe
  or virus due to mutations acquired during
  long-term culture in the lab.
• Pasteur saw this happen while working with Fowl
  Cholera in the lab. The longer he kept a
  particular culture in the lab and re-grew it, the
  less virulent it became. Essentially, organisms
  will not hang onto genes, or extra genetic
  material that they dont need. So if they dont
  need virulence genes to live, they wont use them
  because it is costly from a metabolic standpoint.
• Lifelong immunity is more likely to occur from
  this form of vaccine because it replicates just
  like a typical infecting organism would until the
  immune system takes over.
• There is a chance that an organism could mutate
  back into an infectious form.
• Ex. of vaccines that are attenuated whole-agents
  are Polio, measles, mumps, rubella.

3

• Inactivated whole-agent microbes that have been
  killed or viruses that have been inactivated
  chemically or physically (heat).
• Less risk of infection because the organism is
  not able to replicate.
• Ex. Pertussis, Influenza vaccines.
• Toxiods inactivated toxins.
• Require a series of injections for full immunity,
  followed by boosters every few years to remain
  sufficiently immune.
• Ex. Tetanus

4

• Subunit vaccines use anitgenic fragments of a
  microorganism that best stimulate an immune
  response.
• Recombinant The gene that makes a protein on
  the outside of an pathogen is inserted into an
  avirulent organism. This avirulent organism then
  makes the protein and the body makes antibodies
  to that protein without ever coming into contact
  with the actual pathogen.
• Acellular Virulent cells are lysed and the
  virulent proteins are retained for the vaccine.
• Ex. Hepatitis B

5

• Conjugated developed to deal with poor immune
  response in children under the age of 15-24
  months.
• Infants under the age of 15-24 months dont have
  a well developed immune system. As a result the
  immune system doesnt respong well to antigens
  that use T cells to make antibodies.
• To trick the immune system into recognizing the
  antigen a chain of polysaccharides is combined
  with the antigenic protein. The presence of the
  polysaccharides activates the immune response.
• Ex. Haemophilus influenzae

6

• Nucleic-Acid plasmids of naked DNA injected
  into muscle produce protein which in turn causes
  an immune response.
• This form of vaccine is still being researched.
• Problems As soon as the DNA is degraded, the
  vaccine is done. More research needs to be done
  to figure out how to prolong the life of the DNA
  to give the immune system sufficient time to
  respond.
• No human vaccines yet available.

7

• One way to improve their effectiveness is through
  the use of adjuvants.
• Adjuvant chemicals added to increase the immune
  response to a vaccine.

8

• Before the discovery of AIDS it was thought that
  all the vaccines that were ever going to be
  developed had already been done. With the
  advances in technology and our increased
  understanding of Molecular biology, more vaccines
  are currently being developed and tested.
  Vaccines for at least 75 diseases are currently
  being developed.
• The newest vaccine that is currently undergoing
  clinical trials is for a strain of Genital Warts
  that can cause Cervical Cancer.

9

• Now the challenge is in educating the general
  public about the importance of keeping their
  vaccinations current as well as having their
  children vaccinate on time.
• Many parents have never seen most of the
  childhood illness that we are vaccinating
  against. They often feel that since that disease
  is rarely seen, there is no need to have their
  children vaccinated.
• Other people are worried that their child might
  get the disease from the vaccine, however
  statistics show that the chances of getting the
  disease are greater when the child is not
  vaccinated at all.

10

• There is also increasing evidence that Autism is
  not a result of the MMR vaccine.
• Rather there seems to be a genetic component to
  the disease as well as a microbial component.
• A researcher here in Austin has found evidence of
  intestinal cell changes consistent with microbial
  infection in children with Autism. Further
  research is being conducted to better understand
  the disease.

11
Disorders of Immune System

• Hypersensitivity Reactions
• Aka. Allergy
• Occurs in individuals who have had previous
  exposure to an antigen, sensitization. This
  means that they have been sensitized to the
  antigen and have made antibodies to that antigen.
• Once sensitized, on subsequent exposures, the
  immune system reacts to that antigen in a
  damaging manner.
• See Fig. 16.3 for a great summary of this
  process.

12
4 Types of hypersensitivity

• 1. Atopy and Anaphylactic Reactions
• Allergens are foreign particles in the body, such
  as pollen that the body suddenly reacts to with
  an immune response. It usually does so by making
  IgE antibodies.
• The allergens, antigens, combine with IgE
  antibodies, causing a large histamine release.
  These chemicals are responsible for the visible
  symptoms such as sneezing, coughing, itchy eyes,
  difficulty in breathing, etc.
• Fewer allergies are seen in developing countries
  where parasite infection is frequent. IgEs
  appear to play a role in defending against
  parasite infection. In countries where parasite
  exposure and infection is rare, allergies are
  more frequent. So in other words, we have
  allergies because the IgEs need a job.

13

• Atopic reactions are localized reactions seen in
  seasonal allergies. Anaphylactic reactions are
  systemic, such as those seen with food allergies.
• Localized
• Usually associated with antigens that are
  ingested or inhaled.
• Symptoms are teary eyes, congestion, coughing,
  and sneezing.
• Treatment (Rx)
• 1. An antihistamine which competes for histamine
  receptor sites. Antihistamines block histamine
  from binding to their target cells. Thus
  preventing the symptoms caused by histamine.
• 2. Avoidance of the allergen. Not easily done
  with seasonal allergies.
• 3. Train the immune system to make IgG
  antibodies to the allergen instead of IgE
  antibodies. The IgG antibodies do not cause
  histamine response.

14

• Systemic
• Injected antigens, such as insect stings, are
  most likely to cause this type of allergic
  response.
• Some foods, such as peanut allergies, can also
  cause this response. (Most food allergies are
  not allergies, they are an intolerance. This is
  referring to items that cause gastrointestinal
  responses, such as gas or bloating or cramping.)
• The release of chemicals caused by systemic
  allergens cause a drop in blood pressure (shock)
  and difficulty in breathing.
• This can be fatal within minutes.
• Rx self-administered epinephrine injection.

15

• 2. Cytotoxic Rxns
• Blood transfusions with the wrong blood type are
  an example of this type of hypersensitivity.
• ABO, Rh factors are proteins that are found on
  the outside of Red Blood Cells.
• Lets use the Rh factor as an example. Some
  cells have the Rh protein on their outside
  membranes and some do not.
• If a person normally does not have the Rh factor
  on the outside of the cell then the body
  recognizes only RBCs without Rh as self.
  Anything different is foreign and an antibody
  response will follow.

16

• The Rh factor only becomes a concern after a
  person is sensitized to the Rh protein.
• So when an Rh negative mom is pregnant with an Rh
  positive fetus for the first time no harm comes
  to the baby because mom doesnt have any
  antibodies to the Rh factor in the fetuss blood.
• The second time Rh negative mom gets pregnant
  with a Rh positive fetus the antibodies are
  present and destroy the fetuss RBCs.
• The purpose of the RhoGAM shot is to prevent the
  mothers immune system from making antibodies the
  first time by removing the fetal RBCs from the
  mothers blood.

17

• 3. Immune Complex Rxn
• Occurs when certain ratio of antigen to antibody
  exists
• Usually slightly more antigen than antibody.
• The antibody works to clump the antigen together
  so that it can be easily phagocytosed and removed
  from the body.
• Some small immune complexes form that escape
  phagocytosis.
• The immune complexes circulate in the blood until
  they are deposited in blood vessel walls.
• All of a sudden the blood vessel wall has an
  unfamiliar protein group attached to it and the
  body mounts an immune response to get rid of it.
• Complement and other inflammatory cells are
  activated that cause damage to surrounding
  tissues as they try to remove the deposited
  immune complex.

18

• 4. Cell-Mediated Rxns The classic example of
  cell-metiated reactions is poison iv/oak.
• This reaction is caused mainly by T cells.
• It is a delayed reaction that is not apparent for
  a day or more.
• The oil/antigen binds to the proteins on the host
  cells causing the cell to look different to the
  body. (No longer self.)
• Upon the first exposure the antigen is presented
  to the T cells.
• A memory cell made.
• Upon reexposure, T cells are activated.
• T cells release chemicals to activate the
  inflammatory response.
• Active macrophages are brought to the site and
  tissue damage occurs in the area where the
  oil/antigen is bound to the host cell.