Vaccinations, Transplants and Cancer

Question 1

What are vaccinations?

Answer 1

Vaccinations are defined as the deliberate induction of the adaptive immune response to a pathogen in order to prevent infectious disease.

Question 2

Why are vaccinations counter intuitive?

Answer 2

The mechanism of action is to inject someone with a version of the pathogen itself. Medical technology has advanced so greatly that it is now possible to “safely” inject an individual with a vaccine of pathogen and not cause the disease, but still be potent enough to elicit the adaptive immune response.

Question 3

Is smallpox still infecting people today? Why or why not?

Answer 3

Variola sp. was the cause of Smallpox, an infectious disease which plagued many countries from around the world. With the advance of vaccination technologies, smallpox was declared officially eradicated by the World Health Organization (WHO) in 1979. A disease that killed an estimated two million people in 1967 is now never seen. World-wide mass vaccinations programs made this feat possible.

Question 4

What were some of the earliest attempts at eradicating smallpox? What was the result?

Answer 4

The earliest documented procedures used to prevent smallpox were to have people inhale powdered smallpox scabs or scratch material from smallpox lesions into their skin. This inoculation, however, would result in the formation of the disease and now the person was contagious.

Question 5

How long has the virus variola sp. for small pox thought to be around?

Answer 5

It seemed like this virus that has been around since 10 000 BC could not be conquered.

Question 6

What was the discovery by Edward Jenner that worked as a vaccine and why did it work?

Answer 6

Edward Jenner discovered that people inoculated with material from cowpox lesions could be made immune to smallpox. The cowpox virus is from the same family as the human version of the virus which made it safer and the inoculated people were not contagious. The species variation protected people from contracting cowpox, but the virus was similar enough that the adaptive immune system would be able to eradicate smallpox if it were contracted.

Question 7

What is the current formulation of the smallpox vaccine?

Answer 7

This vaccination has been altered since the 18th century. Current formulations of the smallpox vaccine are live virus preparations of vaccinia virus, a virus that is in the same family as cowpox and Variola.

Question 8

How are “Killed or inactivated viral vaccines” made? Name an example.

Answer 8

Virus particles that have been chemically treated (formalin) or physically treated (heat or irradiation) so they can no longer replicate, and therefore not cause disease.
Example: Rabies vaccine.

Question 9

How are “Live-attenuated viral vaccines” made?

Answer 9

Live virus that is mutated so it is no longer
pathogenic to human cells (mimics a real
infection). Replication produces a more potent immune response.

Example: Measles, mumps, Sabin polio vaccine. Very rare bacterial forms.

Question 10

What are “Subunit vaccines” made from? Name an example.

Answer 10

Made from antigenic components.

Example: HBV vaccine

Question 11

What are Conjugate vaccines? Name an example.

Answer 11

Components of pathogen bound to immunogenic proteins.

Example: H. influenza vaccine.

Question 12

What are toxoids? Name some examples.

Answer 12

A vaccine made from purified toxin that has been inactivated by formalin.
Examples: 
Diphtheria toxin 
(Corynebacterium 
diphtheria) and Tetanus 
toxin (Clostridium tetani)

Question 13

What is a combination vaccine? Name an example.

Answer 13

Vaccine comprised of more than one bacteria, virus, and/or toxin that is able to prevent disease from different pathogens.
Examples:
dPT (diphtheria toxin, tetanus toxin, and killed preparations of Bordetella
pertussis).

Question 14

What are adjuvants? Name an example.

Answer 14

Substances used in vaccines that enhance adaptive immune response by creating inflammation.
Example: Aluminum hydroxide (Alum) is the only adjuvant approved for human use. It is safe but not powerful. Alum causes a delayed release of antigen.

Question 15

Why do some people who don’t get vaccinated get sick?

Answer 15

If enough of the population gets vaccinated to a particular pathogen (the “herd”) then they can help provide immunity to the unvaccinated individuals because there is no reservoir. However, if there are a large number of unvaccinated individuals, then herd immunity does not exist.

Question 16

What are some advantages (briefly touch upon) for vaccines?

Answer 16

They decrease many ill effects and even mortality from many frequently encountered pathogens.

Question 17

What is the rationale for a vaccination program?

Answer 17

A vaccine exists because the product can be created, the pathogen affects a large portion of the population, and it is cheaper to issue vaccines rather than treat the disease state. This means that vaccination programs change from province to province and country to country.

Question 18

What are some of the reasons people choose not to participate in getting vaccinated?

Answer 18

• No guarantee that the vaccine won’t cause the disease.
• Vaccines are given to “healthy” people. Unless the disease is seen, there is less importance placed on the efficiency of the vaccine.
• Afraid of the ill effects of the vaccination itself (example: potential for attenuated vaccines to revert back to becoming pathogenic).
• If an individual contracts the disease they can receive medication (if available) instead of receiving a mass vaccine

Question 19

What is a transplant?

Answer 19

Transplants are defined as the removal of cells, tissues, or organs from one person (a donor) to another (a recipient).

Question 20

What are the three criteria a transplant must meet before it can take place?

Answer 20

Must meet three criteria in order to take place:
1) the transplant must perform normal functions,
2) the health of the recipient and the transplant must be maintained, and
3) the immune system of the recipient must be prevented from attacking the transplant.
These three criteria are complex, but absolutely necessary.

Question 21

True or False, A transplant increases the risk of stimulating the immune system.

Answer 21

True! Removing cells, tissues, or organs from a source of “non-self” and placing them in “self” greatly increases the risks of stimulating the immune system.

Question 22

What are alloantigens?

Answer 22

Differences that exist in the antigen expression between members of the same species is referred to as alloantigens.

Question 23

What increases (in general) the likelihood of an organ being accepted by the recipient’s body?

Answer 23

The greater the similarity in alloantigens between donor and recipient, the greater the possibility of the cells, tissues, or organs are accepted by the recipient’s body.

Question 24

What are two potential issues that can happen if the alloantigens are too different?

Answer 24

The more likely issues such as transplant rejection and Graft-versus- Host-Reaction (GVHR) will occur.

Question 25

What is the most common type of transplant?

Answer 25

The most common type of transplant is blood.

Question 26

Can you receive a transplant of only a specific part of the blood?

Answer 26

Yes. Blood is donated as a whole and then separated into its components: packed red cells, plasma, and platelets. This allows many different people to receive treatment using the different components of one donation.

Question 27

Is there a problem with transplanting white blood cells?

Answer 27

White blood cells are immunogenic, so they are removed from the blood components as to not cause any transfusion reactions.

Question 28

What compatibility checks need to be done on blood to make sure it will not be rejected?

Answer 28

To avoid further transfusion reactions, it is important to ensure the donor and recipient are ABO and Rh compatible (example: A positive person can receive red cells that are A positive, A negative, O positive, and O negative).

Question 29

Do blood groups also need to be checked when transplanting whole organs?

Answer 29

Yes. ABO is not only important in transfusing patients with red blood cells and plasma, but also in transplanting whole organs. ABO antigens are expressed on endothelial cells of blood vessels, which means that organs must be matched for blood type as well as other antigenic similarities. If not, then the recipient may reject the transplant. Rejection would result in the violation of the crucial criteria that must exist for a transplant to occur.

Question 30

What is the intent of a bone marrow transplant? Why is this complicated?

Answer 30

The intent of transplanting bone marrow is to permanently replace an individual’s hematopoietic cells. This can be quite complicated since these cells are very immunogenic.

Question 31

During a bone marrow transplant what is done to avoid the patient’s own immune system? What is the risk during this treatment?

Answer 31

The bone marrow must come from a living donor and the recipients own bone marrow must be destroyed through myeloablative therapy (combination of cytotoxic drugs and irradiation aimed to abolish the patient’s bone marrow). This is done in an effort to terminate the patient’s own immune system response and make room for the new bone marrow. However, this also leaves the patient extremely susceptible to many dangerous and opportunistic pathogens since they lack the ability to fight off any potential invaders while they are undergoing myeloablative therapy.

Question 32

What are some obstacles that can arise with undergoing a transplant?

Answer 32

1) Supply and demand.
2) Timely, arrive quickly if from a deceased individual so it is not inflamed or ischemic.
3) Free of infections (HIV, Hepatitis, etc.)
4) Functional (not with chronic disease in that organ, e.g. kidney with renal failure)
5) ABO compatible
6) No pre-formed antibodies to organ antigens, e.g. (Antibodies to human leukocyte antigen).

Question 33

What is the problem if the transplant organ becomes inflamed and ischemic?

Answer 33

Compromises the ability of the organ to function properly.

Question 34

Why would someone have pre-formed antibodies to someone else’s human leukocyte antigens?

Answer 34

They would have had to been exposed to foreign human leukocyte antigen either through a traumatic pregnancy or birth, a previous transfusion, or a previous organ transplant.

Question 35

How long do some people wait for a compatible organ (or other) donation?

Answer 35

Often, people will wait years before they will get a compatible donation, and then the transplant will not last very long before they will need to go back on the list again.

Question 36

With all the great care being taken with transplants, does rejection still happen?

Answer 36

There are still incidences when cells, tissues, or organs are attacked by the recipient’s immune system due the transplant being recognized as non-self. There are also incidences when the transplant itself attacks the recipient by recognizing it as non-self.

Question 37

When do transplant rejections occur?

Answer 37

Transplant rejection occurs when the recipient’s immune system attacks the transplant which causes the body to reject it.

Question 38

What are the three different classifications of rejections, their mechanism of action and timeframe to occur?

Answer 38

There are three different classifications of transplant rejection based on the time it takes for rejection to occur.

1) Hyperacute Rejection: Pre-formed antibodies to antigens in transplant; Hours
2) Acute Rejection: T cells attack transplant; Days
3) Chronic Rejection: Chronic inflammation; Months or years.

Question 39

What kind of transplants experience “Graft-versus-Host Reaction” most frequently? Why?

Answer 39

Graft-versus-Host Reaction (GVHR) occurs most frequently with blood and bone marrow transplants. This is because of the presence of white blood cells in the transplant. Since white blood cells are extremely immunogenic, they will recognize recipient (“host”) tissues and organs as non-self and will attack.

Question 40

When can a patient donate their own bone marrow and what is done?

Answer 40

Autologous bone marrow transplant:
1) The patient must be healthy enough and have sufficient quantity to have their bone marrow aspirated,
2) Then the bone marrow is treated to maintain and grow healthy cells and remove abnormal cells,
3) The patient then undergoes myeloablative therapy, then their treated bone marrow is transfused back.
The benefit is that a patient will be transplanted with self, but it does not happen often that a patient is a good candidate for this type of therapy.

Question 41

What is the ‘best case scenario’ for a transplant?

Answer 41

The best case scenario would be a genetically identical transplant, which would exhibit the exact same antigens on the surface of cells. Rarely a best case and the most compatible organs are selected.

Question 42

How is the most compatible organ selected?

Answer 42

This is done through HLA typing (human leukocyte antigen) to find the most compatible matches.

Question 43

If the organ is a compatible match for transplant what are a few strategies to increase the survival of a transplant?

Answer 43

If there are slight antigenic differences that exist between the donor and the recipient, then the recipient can

1) undergo myeloablative therapy,
2) receive a xenotransplantation (transplant from another species – example: pig valve for the heart), or
3) be administered immunosuppressive medications (prevent the immune system from attacking the transplant).

Question 44

What type of immunosuppressive medication has anti-inflammatory properties?

Answer 44

Corticosteroids, like Prednisolone.

Question 45

What do cytotoxic drugs do for immunosuppressing? Name an example.

Answer 45

Cytotoxic Drugs Kill proliferating lymphocytes in recipient. Example: Cyclophosphamide.

Question 46

What type of immunosuppressive medication inhibits pathway of T cell activation?

Answer 46

Microbial Products: Inhibit pathway of T cell activation Example: Cyclosporin A (derived from Tolypocladium inflatum – fungus)

Question 47

What does Antithymocyte Globulin do?

Answer 47

Provides antibodies against human T cells. Example: Atgam

Question 48

What is cancer?

Answer 48

Cancer is defined as abnormal and invasive cellular proliferation. It is usually the result of mutations that cause uncontrolled cellular division.

Question 49

How does the immune system react to cancerous cells?

Answer 49

The immune system recognizes these cells as abnormal (or non-self) and will actually attempt to remove them from the body. Cancer cells are very similar to virally infected cells, so the immune system wants to eradicate them as invaders that are trying to cause damage to the body.

Question 50

Why do tumors sometimes occur?

Answer 50

A normal cell will undergo cell division in order to replace the “old” cells within the tissue. In order to create two identical cells, DNA replication must take place. This process occurs with great stringency; however, there is room for error. During replication errors can occur while the genetic code is being read resulting in mutations. Mutations can be corrected as there are many checkpoints found throughout the cell division cycle, but if those errors go “unfixed”, then there can be an uncontrolled population of rapidly expanding cells, referred to as tumors.

Question 51

What is the study of tumors called?

Answer 51

The study of tumors is referred to as oncology.

Question 52

What are the two different categories of tumors? Describe the characteristics of each.

Answer 52

There are two different categories of tumors: benign and malignant.

1) Benign tumors are encapsulated, localized, and limited in size. They are usually not seen to be detrimental to one’s health.
2) Malignant tumors are invasive to adjacent tissues (referred to as metastasis) and are continually increasing in size which leads to the development of the disease state cancer.

Question 53

Why do people get cancer?

Answer 53

Cancer is the result of mutations from error in reading the genetic code. One or two errors will not result in the formation of cancer. In order for a cancer to develop a cell must undergo malignant transformation, 5-6 mutations that result in uncontrolled cell division.

Question 54

How are errors in reading genetic code typically mitigated by cells?

Answer 54

Often these errors are identified by cells and they undergo apoptosis, as a mechanism to protect surrounding cells.

Question 55

What are the two classes of genes that contribute to malignant transformations?

Answer 55

1) Proto-oncogenes: Normally, proto-oncogenes contribute to controlled cell division. However, if there is a mutation in the proto-oncogene then the result in an oncogene. Oncogenes will accelerate the rate of cell division leading to the formation of cancer.
2) Tumor suppressor genes: Code for proteins that prevent unwanted proliferation of mutant cells, but if these genes themselves become mutated, then the result is unwanted proliferation of mutated cells.

Question 56

What are the characteristics of cancer?

Answer 56

Whether the cancer is the result of oncogenes or mutated tumor suppressor genes, the characteristics are still the same. The cancer cells are able to stimulate their own growth, ignore any growth inhibition signals, avoid death by apoptosis, undergo metastasis, outrun or evade the immune response, and even able to develop their own blood supply (angiogenesis).

Question 57

How can our adaptive immune system fight cancer (although hard to do)?

Answer 57

As these cancer cell divide, they begin to resemble those characteristics of a virally infected cell opposed to a normal healthy cell. They will even begin to display different antigens on their surface since they have become mutated. Antigens that are only on tumor cells and not exhibited on normal cells are referred to as tumor antigens. This allows the immune system to recognize cancer cells more readily.

Question 58

What are some of the risk factors that someone will develop cancer?

Answer 58

The chances of developing cancer are linked to genetics as well as environmental factors (such as ultraviolet light, carcinogenic chemicals, poor diet, lack of exercise, etc.). There are also infections that can increase your likelihood of developing cancer. For example, an individual infected with Hepatitis B virus is at risk of developing hepatocellular carcinoma.

Question 59

Why does it make sense that viruses can increase your likelihood of developing cancer?

Answer 59

Since viruses work by infiltrating the host genetic code in order to make the cell produce viral proteins. The virus will override the host cell and interfere with normal cell division. These types of viruses are referred to as oncogenic viruses.

Question 60

What are the first cells to act in cancer immunosurveillance?

Answer 60

The first cells to act in cancer immunosurveillance are the natural killer cells of innate immunity and CD8 cells of adaptive immunity.

Question 61

What are the two outcomes when natural killer cells or CD8 T cells encounter cancerous cells?

Answer 61

These cells are very efficient at removing cancerous cells and when the immune system encounters these there are two possible outcomes: 1) the immune response can eradicate the cancerous cells or 2) the tumor load will become so great that the immune system is overwhelmed and unable to remove the cancerous cells.

Question 62

Why can cancer overwhelm the body even though CD8 cells are efficient at removing it?

Answer 62

In the late stages of cancer there are more genetic variations due to uncontrolled cell division. Therefore, the original cancer cell that was recognized and removed is totally different then the newly mutated cancer cell. This is why cancer can quickly overwhelm the immune system even though there are efficient CD8 cells that attempt to remove it.