Immunology

Question 1

Define monoclonal antibodies, and describe in principle how they are made

Answer 1

Antibodies derived from the progeny of a single B cell, that has been fused with a multiple myeloma tumor cell. The resultant hybrid line can grow forever in culture and makes the one specific antibody of its B cell parent

Question 2

Discuss the use of monoclonal antibodies as anti-inflammatory agents

Answer 2

Monoclonal antibodies can be engineered to have binding specificity for anti-inflammatory agents such as TNF-alpha. Once the antibodies bind the inflammatory mediators there is loss of biological activity of the inflammatory mediators.

Question 3

Compare and contrast murine, chimeric, humanized, and human monoclonal antibodies. Discuss which might have disadvantages when used in human patients, and the reason for that

Answer 3

Murine: monoclonal antibodies made from immunized mice, entirely mouse protein antibodies. Chimeric: antibody of mice and human proteins. Mouse VL and VH domains, but human C domains Humanized: only the CDRs of the V domains are from the mouse, the rest of the antibody proteins are human. Human Monoclonal: entirely human antibody proteins. Essentially these different sources of MABs constitute a progression of how much of the antibody is made of human protein and how much is mouse protein. This correlates to how quickly the body makes antibodies against them.

Question 4

Define NK cells and ADCC. Discuss the effect of Class I MHC expression levels on susceptibility of target cells to CTL and NK cells, respectively. Describe the mechanism for ADCC

Answer 4

Natural Killer (NK) cells are large granular lymphocytes (LGL) which make up 5-10% of blood lymphocytic cells. They are killers with mechanisms similar to those of CTL cells, but they do not have rearranged V(D)J genes and are not thymic derived. They have a few NK receptors which recognize molecules on the surface of “stressed” or dysregulated cells, such as virally infected cells or many tumors, which they can kill; therefore they are part of the innate immune response. They also act via Antibody-dependent cell-mediated cytotoxicity or ADCC. It is a special NK cell killing mechanism whereby antibody binds to a rogue tumor cell (for example) and the NK cells recognize the Fc portion of the IgG antibody and then attach and deliver lethal signals to the target cell to die by apoptosis. MHC Class I expression is necessitated for CTL cells to be activated, there is no MHC class expression for NK cells - they are not restricted by this mechanism.

Question 5

Describe how a monoclonal antibody against a T cell surface molecule could enhance the activity of a CTL

Answer 5

If a monoclonal antibody is 2 separate antibody chains coupled together and engineered to bind a CTL and a pathogen simultaneously, it can bring them into close proximity enhancing the ability of the CTL to destroy the pathogen. For example an antibody with one chain binding CD3 (a CTL receptor) and one chain binding CD+19 receptor of a B cell lymphoma.

Question 6

Discuss the use of modified (drugs, isotopes) monoclonal antibodies in tumor diagnosis or therapy

Answer 6

Modified monoclonal antibodies can activate compliment to lyse or phagocytose tumor cells, or invoke ADCC. Antibodies can also be tagged with poisons or a radioisotope to act as highly-targeted delivery of toxic moieties to tumor cells by binding tumor specific receptors with attached toxic molecules (diptheria toxin).

Question 7

For persons of the A blood group, give the following data: specificities of the ABO antibodies in their plasma; safe donors to that type; safe recipients of blood from that type; possible genotypes.

Answer 7

Red Cell antigens: A antigen Antibodies: anti-B Can receive blood from: A, O Can donate blood to: A, AB Possible genotypes: AA or AO

Question 8

For persons of the B blood group, give the following data: specificities of the ABO antibodies in their plasma; safe donors to that type; safe recipients of blood from that type; possible genotypes.

Answer 8

Red Cell antigens: B antigen Antibodies: anti-A Can receive blood from: B, O Can donate blood to: B, AB Possible genotypes: BB or BO

Question 9

For persons of the AB blood group, give the following data: red cell antigens; specificities of the ABO antibodies in their plasma; safe donors to that type; safe recipients of blood from that type; possible genotypes.

Answer 9

Red Cell antigens: A antigen and B antigen Antibodies: none Can receive blood from: AB, A, B, O Can donate blood to: AB Possible genotypes: AB

Question 10

For persons of the O blood group, give the following data: red cell antigens; specificities of the ABO antibodies in their plasma; safe donors to that type; safe recipients of blood from that type; possible genotypes.

Answer 10

Red Cell antigens: none Antibodies: anti-A and anti-B Can receive blood from: O Can donate blood to: A, B, AB Possible genotypes: OO

Question 11

Name the antibody class of most ABO isohemagglutinins

Answer 11

Isohemagglutinins are naturally occurring antibodies with specificity against the A and B antigens of the ABO blood group. These antibodies are typically IgM-class antibodies

Question 12

Explain the ABO antigen situation in a person of Bombay blood type, and the consequences of a transfusion of non-Bombay blood into such a patient

Answer 12

People with the Bombay phenotype lack the transferase gene that puts the final sugar on the antigen H “core”. As a result these people appear to be type O blood because they have no additional added antigenic determining sugars, when in reality they could be any blood type but simply don’t have the tools to complete the synthesis of the antigen, but if they received transfusion from any blood type other than Bombay, it could result in death because they have anti-bodies for all blood types.

Question 13

Define the crossmatch, and explain why it is important. Explain how red cells are destroyed following a mismatched transfusion, and why this may be devastating to the recipient

Answer 13

The crossmatch determines if their are antibodies in the recipient’s blood that would react with antigens on the donor’s Red Blood Cells. If there are, and you give blood there will be generalized complement-mediated hemolysis and active-complement-mediated inflammation, and free hemoglobin deposited in the kidneys leading to renal failure.

Question 14

Compare and contrast the techniques of the direct and indirect antiglobulin tests and the questions they are designed to answer.

Answer 14

Direct Test: take a patient’s RBCs, wash them, add antibody against human IgG. If the patient’s RBCs had IgG already against them the cells will agglutinate. Evaluates autoimmunity.

Indirect Test: take a donor’s RBCs, then add recipient plasma, wash, then add anti-globulin. If they agglutinate then we know there is recipient antibody against the donor RBCs.

Question 15

Define heterophile antibody, and identify a common disease in which one type is increased enough to be useful diagnostically.

Answer 15

Antibodies to one antigen that bind fortuitously to another (fancy name for cross-reactive antibodies). People with mononucleosis make an antibody, which also happens to react with sheep red blood cells, giving us a quick and presumptive test for mono.

Question 16

In Hemolytic Disease of the Newborn, explain: a. The consequences of severe hemolysis in the newborn. b. The way in which the mother becomes sensitized. c. The class of antibody to Rh(D) the mother makes. d. The consequences of sensitization to subsequent fetuses. e. The role of Rh-immune globulin.

Answer 16

a. Severe hemolysis in the newborn caused by a Rh- mother making antibodies to an Rh+ baby will cause hemolysis in the newborn as IgG cross the placenta resulting in a newborn with jaundice which is dangerous because the increased bilirubin can cross the blood-brain barrier and damage basal ganglia, resulting in cerebral palsy, or if there is severe damage, fetal death. b. The mother who is Rh- becomes sensitized when she is pregnant with her first child who is Rh+, she makes antibodies during this first pregnancy but the response mounts after birth, so no problem for the baby. However, the next pregnancy if there is a Rh+ baby she has a boosted immune response and produces more antibodies more quickly which can be detrimental to the fetus. c. IgG anti-Rh(D)+ d. subsequent fetuses are at risk (see above) e. This disease is preventable if during her first pregnancy she is given Rh-immune globulin, which is an antibody against Rh factor that combines with fetal red blood cells, opsonizing and destroying them before they have a chance to produce an immune response in the mother.

Question 17

Explain the situation in which ABO hemolytic disease of the newborn can occur.

Answer 17

Occasionally people make IgG isohemagglutins (antibodies to A and B antigens). This is especially true of Type O people, so A or B fetuses of women are at some risk of ABO hemolytic disease. There is no Rh-immune globulin to this.

Question 18

Most/least common blood type groups

Answer 18

White Black

A 42% 27%

B 9 21

AB 3 4

O 46 48

Question 19

Describe the procedure used in serum protein electrophoresis, and the underlying principles.

Answer 19

Serum protein electrophoresis uses an electrical field to separate the proteins in the blood seruminto groups of similar size, shape, and charge.

Gamma globulin (5th hump). These proteins are also called antibodies. They help prevent and fight infection. Gamma globulins bind to foreign substances, such as bacteria or viruses, causing them to be destroyed by the immune system

Question 19

Describe the procedure used in serum protein electrophoresis, and the underlying principles.

Answer 19

Serum electrophoresis is not very sensitive. It essentially tells you if you have antibodies or not, specifcally normal distribution, agammaglobulinemia, polyclonal or monoclonal. Normally, you should see a rounded lump that is ~1/2 the size of Albumin - the first hump.

Question 20

Discuss the serum protein electrophoretic pattern which would be expected if a patient: A. was normal B. had selective IgA deficiency C. had multiple myeloma D. had severe pyogenic (pus-producing) infections E. was hypogammaglobulinemic

Answer 20

A: see diagram

B: Could not pick it up b/c IgA runs together with the larger IgG band

C: large spike in the gamma zone, monoclonal

D: increase in the alpha-1 globulin, and increase in beta-gamma interzone/gamma zone b/c more antibody

E: This is easily identifiable as a “slump” or decrease in the gamma zone.

—normal image of serum electrophoresis

Question 20

Discuss single radial immunodiffusion, with regard to the types of antigens that can be quantified with it, and the way that quantization is done.

Answer 20

quantization is done by measuring/comparing the distance of the ring of precipitate from the antigenic well in the antibody agar. The farther the ring of precipitate from the well, the higher the concentration of antigen in the well.

The area and the square of the diameter of the circle at the circle’s end point are directly proportional to the quantity of antigen and are inversely proportional to the concentration of antibody.

Question 20

Describe tests that are used for determining if a patient has antibody to a soluble or particulate antigen.

Answer 20

A particulate antigen and adhering antibody will cause agglutination. If you suspect a Type III disease, put a sample of serum in the fridge and examine it after 1-7 days for a precipitate; this precipitate is called a cryoglobulin. The cryoglobulin can be mixed or monoclonal, test this via electrophoresis.

Question 20

Distinguish between direct and indirect immunofluorescence techniques.

Answer 20

Direct, immunofluorescence uses a single antibody that is chemically linked to a fluorophore. The antibody recognizes the target molecule and binds to it, and the fluorophore it carries can be detected via microscopy.

Indirect, immunofluorescence uses two antibodies; the unlabeled first (primary) antibody specifically binds the target molecule, and the secondary antibody, which carries the fluorophore, recognises the primary antibody and binds to it

Question 20

Discuss the advantages of passive agglutination (e.g., with antigen-coated latex particles) over precipitation, and outline the technique.

Answer 20

Agglutination of the beads or RBCs causes the serum to spread out within the tube.

The tighter is the reciprocal of the highest dilution that will still cause agglutination (or lowest amount of the patient’s serum/antibody that will still cause agglutination).

This test is more sensitive the larger the size of the antigen, we can modulate the antigen size by attaching the antigens to larger beads or RBCs, we also know the concentration/titer, whereas you dont with simple precipitation tests.

Question 20

Describe in principle the ELISA test. Diagram the reactions involved when the ELISA is used to measure antibody, and to measure antigen.

Answer 20

indirect immunoflourescence ELISA can meaure antibody

direct immunoflourescence ELISA can measure antigen

Question 20

Describe tests to evaluate T cell numbers and function in the lab. Describe flow cytometry.

Answer 20

T cells can be measured by counting cells with surface immunoglobulins. A flourescent molecule is coupled to a monoclonal antibody specific for CD3 to calculate all T cells, CD 4 to calculate just T helper cells, or CD 8 to calculate just CTL cells. They are counted by flow cytometry.

Flow cytometry works by pumping cells single file through an orifice and then lasers illuminate the cells causing light to emit/scatter which is collected by photomultipliers and computed. Light scatter gives information about cell size and cytoplasmic granularity, and if the cell has a flourescent tagged antibody the light emitted is quantified.

Question 20

Describe a test which can be used to evaluate T cell immunocompetence in a clinic or on the ward.

Answer 20

DTH test (Delayed-Type Hypersensitivty): use antigens that patient will have been sensitized to, place in the skin and review in 24-48 hours. Measure Th1 activity as there should be considerable macrophage infiltrate response.

Question 21

Explain the difference between “HIV-seropositive” and “AIDS”

Answer 21

HIV-seropositive: you have antibodies against HIV. AIDS: you get major opportunistic infections and/or you have an absolute CD4 count below 200.
It should be fairly obvious by this point that having antibodies against HIV does very little to actually prevent the progression of the disease– more on why below under pathogenesis info.
More to the point: HIV+ can be clinically apathological. AIDS patients are, by definition, not.
On average, at least from transfusion-acquired HIV, it’s about a 9.5-year span between infection and AIDS.
Notice also that the rise in HIV antibody takes a while– it’s about a 7-9 week span after infection to make enough antibody to be detectably infected.

Question 22

Name the virus that causes AIDS, and its classification.

Answer 22

AIDS is caused by a virus called HIV-1, for Human Immunodeficiency Virus.

HIV is a nontransforming retrovirus, that is, an RNA virus that carries no oncogene, and reproduces itself by copying its RNA into DNA by means of its own enzyme, reverse transcriptase.

Question 23

Discuss the origin of the AIDS virus and the origins of the current epidemic

Answer 23

Thought to have originated from a simian virus coming from a chimpanzee. There are available blood banks that have tested positive for HIV antibody as far back as the 1959, most likely the first innoculating event was in Zaire in the 1940s.

HIV was brought to the Caribbean in the 1960s perhaps from Cuban soldiers who had recently returned from Angola. This was then picked up by travelers in Haiti and introduced into the US. Outbreaks occurred in New York, Los Angeles and San Francisco. The virus was then spread worldwide via serum banks selling serum to other countries (or something like that).

Question 24

Identify the approximate number of HIV cases in the U.S. and in the world, and discuss the rate of change in incidence.

Answer 24

Probably about 1 million infected people in the US (about 16% of them are unaware they are infected). About 33 million infected worldwide. Incidence in the US has been falling since 1993; expanding in other places. By 2003 AIDS was the 4th leading cause of death worldwide, ahead of diarrheal diseases, tuberculosis, malaria, lung

Question 25

Discuss the pathogenesis of AIDS, including target cell types, mode of entry of the virus into a cell, mode of exit, latency versus productive infection.

Answer 25

HIV adheres to lectin on dendritic cells (DC-SIGN) and is taken up by the dendritic cell. It then uses the dendritic cell to get to the lymph node, where it gets out and infects its primary target, the T helper cells.

Entry: gp120 studs the HIV membrane and interacts with the target cell (binds CD4 receptor on Th cells); gp120 binds to Th CD4 and then opens the gp120 and gp120 binds to CCR5, this allows an enormous conformational change in gp41 opening up its extremely hydrophobic area and this “melts” itself into the Th membrane to release the viral contents into the cell

The mode of exit is one of the most irritating things about it. The infected cell will fuse with other nearby Th cells, allowing the virus to spread without moving out into the extracellular space. This makes all that lovely antibody completely useless, since antibody doesn’t get into cells and the virus never goes outside them.

Latency: partly this is the mechanism of pandemic. Because it doesn’t cause rapid death but the host is still infectious for years, it doesn’t ‘burn out’– it can build its reservoir of infected hosts over a long period of time.

Notice that HIV only has about 11 genes– the fact that it can do all this with so little is both astounding and terrible.
It may be that HIV virus is latent in resting cells and replicates productively in active cells. Really unpleasant thing: the reverse-transcribed viral genome carries with it a promoter that is activated precisely by the same transcription factor that activates IL-2 in Th1 cells. Activation of Th1 cells therefore also triggers hypertranscription of the viral genes.

Question 26

Distinguish between the roles of Th1, Tfh, and Th2 in the progression of HIV infections.

Answer 26

Tfh and Th2 seem to be preferentially activated against HIV. This is unfortunate. Not only are the B cells that the Th2 cells activate useless (antibodies don’t target HIV well, for reasons discussed above), the lack of Th1 activation means that the killer T cell response (which you’d expect to limit the extent of the infection) is weak and ineffective.
Note that this preferential Th2 stimulus seems to have something to do with how it’s presented by the dendritic cell.
Also note that there’s a problem with just stimulating Th1 cell response (thus producing lots of IL-2) due to the fact, as noted earlier, that the same factor that makes IL-2 in Th1 cells also transcribes the viral genome– so if you kick up Th1 response you also kick up HIV transcription.

Remember Th1 activates inflammation, M1 macrophages, and CTL cells. (Destruction)

Th2 activates a more parasitic response - eosinophils, M2 macrophages, IgE, etc. (Clean up/Repair)

Question 27

Discuss the types of infections seen in AIDS patients, and provide an immunological basis for this spectrum.

Answer 27

Opportunistic viral and fungal infections– mainly herpes, CMV, and hepatitis for the viruses, and Candida and Pneumocystis for the fungi. Also protozoa (mainly Toxoplasma). Intracellular bacteria such as Mycobacterium (M. tuberculosis).

Typically infections that require T cell mediated immunity (intracellular infections)

Question 28

Discuss possible reasons for which the total number of CD4 cells in AIDS patients decline.

Answer 28

Viruses bud in masse from CD4 cells tearing so many holes in the membrane that they die.
As noted, if Th1 cells start expressing IL-2 (to activate more CTL cells), the virus begins to replicate much faster as well.

Question 29

Discuss reasons for the apparent ineffectiveness of antibody in HIV infection.

Answer 29

When the virus is replicating, gp120/gp41 is made early, and it becomes inserted into the cell’s plasma membrane. This allows fusion of the infected cell to nearby uninfected CD4 cells and a syncytium forms. In this way the virus can spread without an extracellular phase and antibodies are ineffective.

Question 30

Define and discuss “elite controllers.”

Answer 30

65% of people who are infected with HIV but never develop AIDS, are HLA-B57 positive. They make more diverse CTL cells against HIV peptides

HLA-B57 infected people are “Elite Controllers” which make a very strong CTL response to the HIV virus and suppress the virus more strongly. HIV viral peptides bind into the HLA-B57 more strongly

Question 31

Describe the laboratory diagnosis of AIDS.

Answer 31

ELISA is the screening test for HIV antibodies in patient’s blood– you put some HIV+ T cells (not from your patient) in a well; you add the patient’s blood, wash it off, and look for bound antibody with immunohistologically-labeled, goat-derived anti-IgG (there’s an enzyme bound to the goat anti-IgG which can be detected by the addition of another substrate).
Cheap and sensitive (few false negatives), but not necessarily specific– get false positives. So you run a Western blot to separate the viral proteins (gp120/gp41), fix these proteins to nitrocellulose and then stain with the patient’s antibodies which must adhere to the viral proteins for a positive test.

Notice that this is technically not a diagnostic tool for AIDS– it’s a diagnostic tool for HIV. Once HIV+ people get major opportunistic infections, then it’s AIDS.

Question 32

Discuss the prospects and problems of AIDS vaccine development

Answer 32

Prospects:

bnAbs are a good prospect but only ~27%, when in reality, they need to be >80% efficacious

Challenges:

1. HIV exhibits tremendous global genetic diversity, so to vaccinate it effectively you would need to present antigen that can be targeted on all strains (potentially gp120/gp41)
2. HIV’s immense mutation capacity allows evasion of both T and B cell immunity
3. HIV goes latent in the host genome, from which it cannot be eliminated by conventional antiretroviral drugs
4. There has been no known example of spontaneous immune clearance, to use as the basis for data-driven vaccine design
5. Although bnAbs (broadly neutralizing antibody) have been found, they are rarre, only found in a subgroup, take years to evolve/develop, and are extensively hypermutated; no method exists now for induction of the Abs by immunization

Vaccines are problematic in that we need a vaccine that can preferentially stimulate Th1 cells and CTL, not just induce antibody responses.

Question 33

State the concept of the Immune Surveillance therory. Discuss whether data from immunosuppressed and immunodeficient patients support the theory.

Answer 33

Immunosurveillance Hypothesis: The immune system should be able to recognize and eliminate developing tumors based on recognition of neoantigens from the mutations of the transformation process which are present on the surface of cells.

The idea is that tumors are occurring to some extent all the time, but normally the immune system’s surveillance keeps the process under control.

Evidence: virus-associated, and some non-virus-associated, tumors increase with immune suppression. Tumor-infiltrating Lymphocytes (TILs) are found in many tumors and seem to be acting to try and keep them in check, sometimes tumors spontaneously regress - possibly the result of an immune response

T cells, NK cells, and the innate immune system seem to be most central to this process

Question 34

Describe the concept of immunoediting.

Answer 34

Elimination: Tumor is destroyed. Acute cytokines/chemokines trigger innate and adaptive immunity to target and destroy the tumor.

Equilibrium: Tumor is not destroyed but is kept in check, a constant battle between the body’s immune system and the tumor as they co-evolve. T cells infiltrate the tumor but never completely destroy it. This is tricky because the tumor is now (a) under tremendous selective pressure to adapt to avoid or inhibit the immune system, and (b) increasingly genetically unstable, meaning that it’s racking up all kinds of mutations. Eventually it’ll find a way to proliferate in a way that’s hard for the immune system to deal with, leading to the following:

Escape: Immune system is not able to destroy or contain the tumor, mainly because the tumors have hit on some mechanism to inhibit or destroy the immune cells that are trying to keep it in check. Ex: tumor sheds antigens to bind up all the antibodies/T cell MHC complexes, effectively acting as decoys so the actual tumor cells never get destroyed.

Evidence for immunoediting: woman with melanoma has it excised with no visible recurrence; 16 years later she dies and donates her kidneys; the immunosuppressed woman into which one is placed develops metastasizing melanoma, which kills her. The idea is that the melanoma had been kept in check by the donor’s immune system but proliferated in the immunoincompetent host.

Question 35

Describe tumor-associated antigens (TAA), and compare and contrast TAA from viral, mutant, and normal gene products.

Answer 35

TSA: tumor cell antigens not found on corresponding normal cells. Easier for the immune system to target.

TAA: tumor cell antigens found on corresponding normal cells; they’re just more common on tumor cells. Harder for the immune system to target (it’s ‘self’ to T cells).

• Viral tumor antigens: generally TSAs (viral antigens not found in uninfected cells).
• Mutant gene product antigens: novel gene products made by tumor cells. Also generally TSAs since normal cells don’t make them.
• Normal gene product antigens: normal gene products made to excess by tumor cells. Generally TAAs since normal cells do make them, albeit at lower quantities. Types:
  
  • Oncofetal: antigens made in fetus but not in normal adult cells.
  • Differentiation: antigens involved in, yeah, differentiation.
  • Oncospermatogonal/testis: antigens usually found only in germ cell development. Can be targeted well (since immune responses don’t generally travel into the testes).
  • Clonal: antigens only on the clone of cells that the tumor came from.

Question 36

Define carcinoembryonic antigen (CEA) and discuss its usefulness in screening for, diagnosis and follow-up of colon cancer.

Answer 36

Oncofetal antigens are made in normal fetal tissues, and are generally not found in normal adult tissues, but tumors can abnormally re-express these antigens. The most familiar is CEA, which is found in patients with colon carcinoma and other cancers. CEA can be detected in the blood.

CEA should NOT be used as a screening test because it provides too many false positives. The best use of CEA is when you have a high suspicion of colon cancer, or have since removed a colon cancer polyp to confirm complete excision as CEA levels decrease or warn of recurrence - CEA levels re-increase

Question 37

Compare and contrast the roles of CTL and NK cells in killing tumor cells, with special reference to the amount of MHC Class I expressed by the tumor.

Answer 37

Killer T cells: as you’d expect, through either Fas- or granule (perforin)-mediated induction of apoptosis. Activated in lymph nodes by dendritic cells, the standard drill. Produce IFN-gamma when bound to their target cells.
However, note that he mentions that “unmanipulated” killer T cells, even ones that recognize the TAA antigen, don’t actually kill the tumor cells very well– they expand, but don’t stop the tumor’s growth.

NK cells: Preferentially target cells which have downregulated their MHC I complexes. Tumor cells like to downregulate MHC I, because then they can hide their irregular proteins from killer T cells. NK cells catch these cells and kill them.

Question 38

Describe the nature and therapeutic use of tumor-infiltrating lymphocytes, TIL, in adoptive cellular transfer therapy.

Answer 38

Tumor-infiltrating lymphocytes are used in adoptive cellular transfer therapy. This technology utilizes cells from the patients immune system to destroy cancerous cells that cannot be surgically removed. Cells from the immune system that have potential to fight the tumor are isolated from the patient’s blood, tumor or lymph nodes. Cells directly from the tumor are called tumor infiltrating lymphocytes. These T cells are expanded in culture using cytokines such as IL-2. The patient’s immune system may then be partially destroyed to make room for the expanded anti-tumor cell clones which are then implanted into the immune depleted patient to kill the tumor.

Question 39

Summarize the Hellstrom experiments using cells from tumor-bearing and cured patients to kill tumor target cells. Indicate which patients had blocking factors. Discuss the possible nature of blocking factors.

Answer 39

Question 40

Discuss the principles underlying antibody or T cell methods that might be used as treatments of tumors.

Answer 40

According to Dr. Slansky, what she’s getting at in this LO is “the mechanisms used by T cells and antibodies that makes them effective in immunotherapies. For example, specific antibodies may kill the target cells by antibody-dependent cell-mediated cytotoxicity [NK cells–jcr], and specific CTL may be stimulated to kill the tumor using perforin, Fas, and TNF pathways when the patient is treated with specific vaccines (say antigenic peptide plus adjuvant [like the illicit help mechanism–jcr]).”

Question 41

Describe a mechanism by which BCG treatment causes tumor regression.

Answer 41

Question 42

Discuss prospects and problems concerning the use of monoclonal antibodies in the diagnosis or treatment of cancer.

Answer 42