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 don’t need. So if they don’t need virulence genes to live, they won’t 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 don’t have a well developed immune system. As a result the immune system doesn’t 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. • Let’s 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 doesn’t have any antibodies to the Rh factor in the fetus’s blood. • The second time Rh negative mom gets pregnant with a Rh positive fetus the antibodies are present and destroy the fetus’s RBCs. • The purpose of the RhoGAM shot is to prevent the mother’s immune system from making antibodies the first time by removing the fetal RBCs from the mother’s 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.