What happens when Antibodies work against you?

Allergic Reactions

The Fc portion of IgE binds to the surface of mast cells and basophils

 When the allergen cross-links the Fab portions  of the mast cell-bound IgE, this triggers histamine  release by the mast cell, a process called degranulation, and the synthesis of other inflammatory mediators such as arachadonic acid, leukotrienes,  prostaglandins, and cytokines that contribute to inflammation (these act as chemoattractants). These agents cause the early phase of allergic reactions that appears within minutes after exposure to the antigen.

Autoimmune Disease

 

Mechanism: Either IgG or IgM is made against normal self antigens as a result of a failure in immune tolerance , or a foreign antigen resembling some molecule on the surface of host cells enters the body and IgG or IgM made against that antigen then cross reacts with the host cell surface. The binding of these antibodies to the surface of host cells then leads to:

a. opsonization  of the host cells whereby phagocytes stick to host cells by way of IgG,  and discharge their lysosomes  and ;

b. activation of the classical complement pathway causing MAC lysis  of the cells

c. ADCC  destruction of the host cells whereby NK cells  attach to the Fc portion  of the antibodies. The NK cell then release pore-forming proteins called perforins and proteolytic enzymes called granzymes. Granzymes pass through the pores and activate the enzymes that lead to apoptosis of the infected cell by means of destruction of its structural cytoskeleton proteins and by chromosomal degradation.

Multiple Sclerosis

Characteristics:

• female (45 years old) (ration of women:men = 10:1)
• Notice spatial awareness problems
• Behavioral changes
• Flare ups

Observations:

• Higher levels of Ab to the myelin basic protein during flare up

• Myelin BP (insulation around nerve cells)

• Nerve cells become exposed

• Eventual destruction of the nerve cell

What are correlations?

• Usually seen in small families
• Development of childhood diseases early in life
• (Turned out that this was not a reason for MS)
• Distemper in dogs?
• Environment (moving from high incidence to low decreases chances)

Disease Response

Involves T and B cells

B cell and T cell are autoreactive

So what is going on?

• There is evidence that APC's are defective and that they make  an excess of cytokines
• This leads to the activation of Tc cells

Myasthemia Gravis

Ab made to the nerve endings

Nerve endings used Acetylcholine to signal muscles

• Ab comes in and blocks the ability of AC to bind to the muscle receptor
• Therefore the muscle cannot function

Immune Complex

Ex Rheumatoid Arthritis

• Synovial fluid around joints have IgG to the cartilage (normal)

• In RA there is a production of IgM that reacts with IgG (Fc) along with compliment

• Tissue damage

Mechanism: This is caused when soluble antigen-antibody (IgG or IgM) complexes, which are normally removed by macrophages in the spleen and liver, form in large amounts and overwhelm the body . These small complexes lodge in the capillaries, pass between the endothelial cells of blood vessels - especially those in the skin, joints, and kidneys - and become trapped on the surrounding basement membrane  beneath these cells . The antigen/antibody complexes then activate the classical complement pathway  . This may cause:

Lupus (10:1) (younger age 15-40)

Characteristics:

• Flaring redness on cheeks, forehead

Full Blown:

•  Make Ab to multiple epitopes on foods (beef, cheese) as well as RBC's single and double stranded DNA
• Lupus identified by the ability to make Ab to DS DNA
• No answer as to why this happens
• Cause of Lupus not known

Type I Diabetes

5% of diabetes

95% Type II (not AI disease as B cells are making insulin rather just non response to insulin made)

Type I = destruction of  beta cells in the pancreas

Normal:

Beta cells express low levels of class I but not classII

In Type I, beta cells do express type II MHC

Beta cells are attacked self antibodies

The Mouse in Science:
Cancer Research

Mice have been used in cancer research since 1894. Initially, mice were used for same-species tumor transplantations and drug treatment studies. In 1921, inbred strains that were predisposed to getting tumors were started and disseminated among cancer researchers. Many more strains of mice were originated beginning in 1929 with the founding of the Jackson Laboratory in Bar Harbor, Maine, now the largest supplier of mice.

In 1962, the discovery of a mutant mouse with low immunity led to human tumor transplantations, a valuable breakthrough for cancer research. A further breakthrough in the late 1980s led to transgenic mice, those whose genes have been altered to produce a desired characteristic. Oncogenes, or genes that cause cancer, could then be studied in greater detail.

Life in the Laboratory.
Mice adapt well to laboratory housing and can be housed socially or individually. Significant numbers can be housed in relatively little space because of their small body size. They possess a surprising genetic similarity to humans. These features, combined with a rapid rate of reproduction, make mice the mammal of choice for fine-tuned genetic manipulation. Mice with many different special features have been bred or created, including some described here.

Inbred Strains.
The inbreeding of mice predisposed to developing cancer has led to a variety of specialized strains. In 1921, Leonell Strong established many inbred strains that frequently and spontaneously developed cancer. Serving as a virtually unlimited source of many types of tumors, these inbred mice have made it possible to study the growth and general characteristics of tumors.

Nude Mice.
The nude mouse is a major breakthrough for cancer research because it allows human tumors to be studied in another animal. The nude mouse, a hairless mutant discovered in 1962, is immunodeficient, and thus does not reject tumor transplantations from other species. It lacks a thymus, which is essential for the production of T-cells, lymphocytes that are essential to the immune system. iBy transplanting an actual human tumor into a nude mouse, the tumor can be studied in a whole animal system.

Before discovery of the nude mouse, human tumors were grafted and grown in immune-privileged sites, such as the anterior chamber of the eye, the brain and the cheek pouch. These locations are inconvenient, and the tumors are eventually rejected. The recessive nu gene, which is responsible for the lack of a thymus in nude mice, has since been introduced into many types of inbred strains of mice with other immunodeficiencies.

SCID Mice.
In 1983, mice with severe combined immune deficiency (SCID) were discovered. SCID mice are even more immunodeficient than nude mice. Tumors from other species are easily transplanted into SCID mice and will grow without being rejected. For certain specific tumors, SCID mice show improved transplantability over nude mice. In addition, SCID mice are ideal for the growth of hybridomas in vivo to produce a continuous supply of antibody (Ab). Sometimes referred to as a reagent, Ab is necessary for a wide range of diagnostic, clinical and experimental procedures.

Transgenic Mice.
In the late 1980s the methodology for engineering transgenic mice made it possible to create mice to address specific questions and problems. Transgenic mice result from genetically altered embryos: a gene or combination of genes is microinjected into developing oocytes. The genetic alteration affects the germ plasm, and subsequently can be transmitted to progeny. Through selective breeding, it then is possible to maintain a strain of mice consisting of individuals with particular traits of interest.

A specific trait, such as a predisposition to develop a particular type of tumor, can be introduced into a mouse strain by injecting into the embryo an oncogene, a gene that causes cancer. Transgenic mice permit the study of cancer in specific tissues, including initial tumor development.

Uses.
The purpose of cancer research is to understand tumor initiation and growth. This information helps researchers develop treatments, and eventually cures, for cancer.

	Blood Groups, Blood Typing and Blood Transfusions       The discovery of blood groups     Experiments with blood transfusions, the transfer of blood or blood components into a person's blood stream, have been carried out for hundreds of years. Many patients have died and it was not until 1901, when the Austrian Karl Landsteiner discovered human blood groups, that blood transfusions became safer. Mixing blood from two individuals can lead to blood clumping or agglutination. The clumped red cells can crack and cause toxic reactions. This can have fatal consequences. Karl Landsteiner discovered that blood clumping was an immunological reaction which occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. Karl Landsteiner's work made it possible to determine blood types and thus paved the way for blood transfusions to be carried out safely. For this discovery he was awarded the Nobel Prize in Physiology or Medicine in 1930.           What is blood made up of?     An adult human has about 4–6 liters of blood circulating in the body. Among other things, blood transports oxygen to various parts of the body. Blood consists of several types of cells floating around in a fluid called plasma. The red blood cells contain hemoglobin, a protein that binds oxygen. Red blood cells transport oxygen to, and remove carbon dioxide from, the body tissues. The white blood cells fight infection. The platelets help the blood to clot, if you get a wound for example. The plasma contains salts and various kinds of proteins.           What are the different blood groups?     The differences in human blood are due to the presence or absence of certain protein molecules called antigens and antibodies. The antigens are located on the surface of the red blood cells and the antibodies are in the blood plasma. Individuals have different types and combinations of these molecules. The blood group you belong to depends on what you have inherited from your parents. There are more than 20 genetically determined blood group systems known today, but the AB0 and Rh systems are the most important ones used for blood transfusions. Not all blood groups are compatible with each other. Mixing incompatible blood groups leads to blood clumping or agglutination, which is dangerous for individuals. Nobel Laureate Karl Landsteiner was involved in the discovery of both the AB0 and Rh blood groups.           AB0 blood grouping system       According to the AB0 blood typing system there are four different kinds of blood types: A, B, AB or 0 (null).       Blood group A If you belong to the blood group A, you have A antigens on the surface of your red blood cells and B antibodies in your blood plasma.         Blood group B If you belong to the blood group B, you have B antigens on the surface of your red blood cells and A antibodies in your blood plasma.         Blood group AB If you belong to the blood group AB, you have both A and B antigens on the surface of your red blood cells and no A or B antibodies at all in your blood plasma.         Blood group 0 If you belong to the blood group 0 (null), you have neither A or B antigens on the surface of your red blood cells but you have both A and B antibodies in your blood plasma.           Rh factor blood grouping system     Many people also have a so called Rh factor on the red blood cell's surface. This is also an antigen and those who have it are called Rh+. Those who haven't are called Rh-. A person with Rh- blood does not have Rh antibodies naturally in the blood plasma (as one can have A or B antibodies, for instance). But a person with Rh- blood can develop Rh antibodies in the blood plasma if he or she receives blood from a person with Rh+ blood, whose Rh antigens can trigger the production of Rh antibodies. A person with Rh+ blood can receive blood from a person with Rh- blood without any problems.           Blood group notation       According to above blood grouping systems, you can belong to either of following 8 blood groups: A Rh+ B Rh+ AB Rh+ 0 Rh+ A Rh- B Rh- AB Rh- 0 Rh- Do you know which blood group you belong to?                   Blood typing – how do you find out to which blood group someone belongs?     A person with A+ blood receives B+ blood. The B antibodies (yellow) in the A+ blood attack the foreign red blood cells by binding to them. The B antibodies in the A+ blood bind the antigens in the B+ blood and agglutination occurs. This is dangerous because the agglutinated red blood cells break after a while and their contents leak out and become toxic.     1. You mix the blood with three different reagents including either of the three different antibodies, A, B or Rh antibodies. 2. Then you take a look at what has happened. In which mixtures has agglutination occurred? The agglutination indicates that the blood has reacted with a certain antibody and therefore is not compatible with blood containing that kind of antibody. If the blood does not agglutinate, it indicates that the blood does not have the antigens binding the special antibody in the reagent. 3. If you know which antigens are in the person's blood, it's easy to figure out which blood group he or she belongs to!     What is happening when the blood clumps or agglutinates? For a blood transfusion to be successful, AB0 and Rh blood groups must be compatible between the donor blood and the patient blood. If they are not, the red blood cells from the donated blood will clump or agglutinate. The agglutinated red cells can clog blood vessels and stop the circulation of the blood to various parts of the body. The agglutinated red blood cells also crack and its contents leak out in the body. The red blood cells contain hemoglobin which becomes toxic when outside the cell. This can have fatal consequences for the patient. The A antigen and the A antibodies can bind to each other in the same way that the B antigens can bind to the B antibodies. This is what would happen if, for instance, a B blood person receives blood from an A blood person. The red blood cells will be linked together, like bunches of grapes, by the antibodies. As mentioned earlier, this clumping could lead to death.           Blood transfusions – who can receive blood from whom?   People with blood group 0 are called "universal donors" and people with blood group AB are called "universal receivers."     Of course you can always give A blood to persons with blood group A, B blood to a person with blood group B and so on. But in some cases you can receive blood with another type of blood group, or donate blood to a person with another kind of blood group. The transfusion will work if a person who is going to receive blood has a blood group that doesn't have any antibodies against the donor blood's antigens. But if a person who is going to receive blood has antibodies matching the donor blood's antigens, the red blood cells in the donated blood will clump. Blood Group Antigens Antibodies Can give blood to Can receive blood from AB A and B None AB AB, A, B, 0 A A B A and AB A and 0 B B A B and AB B and 0 0 None A and B AB, A, B, 0 0

Blood Group (Rh) Incompatibility

Rh incompatibility occurs when the mother's blood type is Rh negative and her fetus's blood type is Rh positive. An alternative name is Rh disease. Rh is an abbreviation for Rhesus.

What Is It?

Everyone is born with a certain blood type that is either Rh positive or Rh negative. Rh-positive blood is more common than Rh-negative blood. About 85% of Caucasians are Rh positive, while the percentage is even higher for African-Americans, Asians, and American Indians. If you are Rh positive, or if both you and the baby's father are Rh negative, there is no reason to worry about Rh incompatibility. However, if you are Rh negative and the baby's father is Rh positive, then your baby may inherit the father's blood type, creating incompatibility between you and the fetus.

With Rh incompatibility, if some of the fetal blood gets into your blood stream, your body will produce antibodies. These antibodies could pass back through the placenta and harm the developing baby's red blood cells, causing very mild to very serious anemia in the fetus. Your first baby is usually safe, because fetal and maternal blood usually do not mix until delivery. If your second baby is also Rh positive, there's a risk that your antibodies will attack her blood cells and cause problems.

How Do I Know I Have It?

Organ transplants and rejection

All your body cells have markers on their surface that signal to your lymphocytes and make sure that they are not attacked by your own immune system. They are called the tissue-type markers. Before a patient receives a donated organ, such as a kidney, great care is taken to match the donor's and recipient's tissues-type markers so that they are as similar as possible. They are usually quite close in family members and only ever a perfect match in genetically identical twins. Even a slight mis-match could mean that the organ was attacked by the recipient's immune system and rejected. To try and prevent transplant rejection, recipients will also take medicines to reduce the efficiency of their immune system. These medicines are called immunosuppressants. They reduce the chances of the donated organ being attacked by the recipient's immune system but they also increase the likelihood of them catching infectious diseases. A balance needs to be maintained where there immune system does not reject the transplant while the recipient is not harmed by dangerous infections.