Week 12

Question 1

Which cells function to destroy body cells that harbor foreign molecules? What specific cells do they target and how do they destroy them?

Answer 1

Cytotoxic or Killer T Lymphocytes, also called CD8+ cytotoxic T lymphocytes. They usually target foreign molecules originating from invading microorganisms or transplants, but can also target malignant self cells (cancer) or some self cells it just doesn’t recognize (eyes, testes). They kill by cell-mediated destruction and must make actual physical contact with the victim. During this membrane-membrane contact they secrete Perforins to open a pore and Granzymes to activate caspases and apoptosis.

Question 2

What is the bacteria that causes tuberculosis and how is it tested for?

Answer 2

Mycobacterium tuberculosis. Injections of these bacteria or their products under the skin will produce inflammation after a few days. This Delayed Hypersensitivity Reaction is cell-mediated (T cells).

Tuberculine Tine Test uses little tines to inject in the skin. Mantoux test or Purified protein derivative (PPD) test injects with a needle right into the skin making a bubble. Hardness of the area indicates positive result for exposure to tuberculosis at some point in life - NOT that they actively are infected. Result will be positive for the rest of life after exposure.

Question 3

Which cells function to enhance immune response and how?

Answer 3

Helper T lymphocytes (identified by CD4) improve both B lymphocyte function and cytotoxic T lymphocyte response. They secrete lymphokines (a type of cytokine) such as interleukins which aid immune response.

Question 4

Which cells function as a brake on immune response and how? *What would over/under activity of these cells cause?

Answer 4

Regulatory T lymphocytes (Treg) inhibit cytotoxic T cells and B cells. The gene *FOXP3 is required for their development. They are activated by antigens and respond by secreting anti-inflammatory cytokines (like TGFB) and deplete factors that would cause immune response. Sometimes they will promote destruction by releasing granzymes and perforins.
Autoimmune diseases occur due to decreased Treg numbers or function (FOXP3 mutation). Overactivity could cause increased viral or cancer disease

Question 5

Describe four common lymphokines

Answer 5

Interleukin-1: secreted by macrophages in response to toll-like receptor activation, this molecule activates T cell system and has other effects like promoting fever
Interleukin-2: produced by helper T lymphocytes and is important for development of helper, cytotoxic, and regulatory T cells
Interleukin-4: required for proliferation and development of B cells
Interleukin-5: has central role in eosinophil differentiation, proliferation, and activation

Question 6

How do T cells recognize antigens? how is this different from B cells?

Answer 6

B cells recognize antigen proteins or carbohydrates, T cells only recognize proteins. T cells do not make antibodies and do not have surface antibodies to recognize antigens. They have antigen receptors that serve the same function, but they can’t bind FREE antigens. Antigen-Presenting Cells (chiefly dendritic cells, also macrophages and B cells) must present the antigen to T cells. These APCs are concentrated at skin, intestinal mucosa, and lungs. Once they recognize antigens and engulf them, they move them to their surface ((w/ histocompatibility)) and migrate through lymphatic vessels, secreting chemokines to attract T cells. When the correct T cell encounters its antigen, it divides to produce effector T cells and memory T cells.

Question 7

Describe the function of histocompatibility antigens and what complication they can cause. What other name do these have?

Answer 7

All tissue cells (except RBCs) are marked with a characteristic combination of histocompatibility antigens to identify self from non-self. These are what cause transplant rejection, the greater the variance between donor and recipient the greater chance of rejection. Therefore “tissue type” is usually matched somewhat before transplant. White blood cells are used for this purpose, so histocompatibility antigens are also called Human Leukocyte antigens (HLAs). All of these antigens are encoded by genes called the Major Histocompatibility Complex (MHC) on chromosome 6.

Question 8

*Explain what molecules are necessary to activate T lymphocytes. Which molecules activate which specific type of T lymphocyte??

Answer 8

Along with the antigen, these molecules MUST be presented on the Antigen presenting cell for activation of the lymphocyte

Class-1 Major Histocompatibility Complex molecules (present on ALL body cells except RBCs) which binds to coreceptor CD8 on Cytotoxic T lymphocyte receptors.

Class-2 MHC molecules (present only on antigen presenting cells, which also have class-1 MHC) which binds to coreceptor CD4 on Helper T lymphocyte receptors.

Question 9

*How are T lymphocytes destroyed after clearing infection? How is this same system used to protect vulnerable cells in the eye and testes?

Answer 9

T cells increase production of a receptor called FAS during infection, and after a few days the T cells produced FAS ligand. Binding of FAS to FAS ligand causes apoptosis.
Immunologically privileged sites (brain, anterior chamber of the eye, testicular tubules) can be recognized and killed by T cells, so they secrete FAS ligand to trigger apoptosis of any T cells that enter the area. Sertoli cells do this to protect sperm (along with tight junctions to form a barrier) and interior eye is coated with FAS ligand (along with secreting anti-inflammatory cytokines)

Bad news is that tumor cells can use FAS ligand too

Question 10

Describe T lymphocyte response to a virus from start to finish

Answer 10

Antigen presenting cells have PRRs that detect and cause engulfing of the virus. They migrate to secondary lymphatic organs and present the viral antigens w/ MHC class-2 molecules to Helper T cells. Helper T cells then activate to Effective helper cells which stimulate B cells (start making antibodies = long term humoral immunity, basis of vaccines!) and proliferation of Cytotoxic T cells via interleukin-2. Cytotoxic T cells travel the body and destroy infected cells presenting the antigen and class-1 MHC.

Question 11

*describe the cause of SCID and what they did to that one kid who had it

Answer 11

Severe combined immunodeficiency disease (SCID) or Bubble Boy disease is when children lack both B cells (antibody-mediated immunity) and T cells (cell-mediated immunity). Their white blood cells lack an enzyme called adenosine deaminase and they can’t fight any infections.
David Vetter lived for 12 years in a germ-free plastic bubble and died when an injection of bone marrow from his sister contained the mononucleosis virus (Epstein-Barr virus) which caused David to develop a B cell lymphoma (cancer) and die.

Question 12

What were two of the first vaccines created and how?

Answer 12

1. Edward Jenner (1796) found that cowpox (vaccinia virus) infection made people immune to subsequent smallpox infections. Cowpox is a less virulent form of smallpox and conferred “cross-reactive immunity”
2. Louis Pasteur (1800s) isolated the bacteria that cause anthrax and heated them until they lost virulence, but they retained antigenicity. This altered bacteria was injected in sheep and they could then survive lethal anthrax injections later

Question 13

Describe the 4 types of acquired immunity

Answer 13

1. Naturally acquired active immunity: exposure by normal contact and infection, producing antibodies and specialized T cells in response. Long lasting immunity
2. Naturally acquired passive immunity: natural transfer of humoral antibodies from mother to fetus, either transplacental transfer (IgG) or in colostrum/milk (IgA). Lasts a few months
3. Artificially acquired active immunity: vaccines administered to promote antibody production. Long lasting
4. Artificially acquired passive immunity: transfer of humoral antibodies from one person to another. Antivenin against rattlesnake venom or gamma globulin injections that generally increase humoral immunity before traveling to foreign countries. Short lived

Question 14

Describe the two types of responses to a pathogen (first and second time)

Answer 14

First exposure produces a primary response after a latent period of 5-10 days. This sluggish response may not be sufficient to protect the person against disease. Antibody concentration plateaus in a few days and declines after some weeks.
Second exposure the the same antigen produces a rapid secondary response. Maximum antibody levels are reached in <2 hours and maintained a longer time. Usually this prevents disease development.

Question 15

Explain clonal selection theory

Answer 15

How the immune system “learns”: Each B lymphocyte inherits ability to produce one particular antibody and T cells inherit ability to respond to particular antigens. So, some cells can respond to a pathogen even if a person has never been exposed before! Such exposure causes the lymphocytes to divide many times to make a large identical population, some memory some plasma cells, called a CLONE. A clone founded by a B cell becomes a germinal center where the B cell with the best antigen affinity is made by somatic hypermutation and many divisions. The high affinity antibodies created target the antigen more effectively during secondary exposure. Also, memory T cells live long and are the most abundant lymphocyte in adults (numbers decline with age though), they quickly develop ability to kill pathogens upon re-exposure.

Question 16

Define active immunity. how does vaccination work to cause this?

Answer 16

long lasting immunity acquired through production of antibodies in response to antigens. The development of a secondary response provides active immunity because it overcomes the sluggish primary response that may allow disease development. Vaccine immunization does exactly this by inducing the primary response via attenuated/destroyed pathogens so that the secondary response will develop for future exposures.
(The word vaccine comes from “vaccinia virus” or vacca meaning cow, remember the cowpox story!)

Question 17

What were the two polio vaccines?

Answer 17

Sabin vaccine used living viruses with attenuated virulence. It was “infectious” since its living and spreads to other kids, so that was good. Unfortunately it caused paralysis in a small number of patients…

Salk vaccine uses killed viruses inactivated with formaldehyde. This does not cause paralysis and is the most used vaccine in the US

Question 18

What are the three ways vaccines are produced

Answer 18

1. Live viruses with attenuated virulence (like Sabin polio vaccine and vaccinations agains measles and mumps)
2. Killed viruses that do not cause any disease (like Salk polio vaccine)
3. Recombinant viral proteins produced via genetic engineering (like Hepatitis B and HIV vaccines)

Question 19

What is an adjuvant?

Answer 19

Adjuvants boost immune response when delivered with vaccine agents. Generally they are PAMPs (pathogen associated molecular patters) that activate the PRRs (pattern recognition receptors) on dendritic cells which then secrete interleukins that enhance B and T cell response. Remember that PAMPs are an innate immune system activator, so this pathway demonstrates the cooperation of the innate and adaptive immune responses!

Question 20

How does the immune system learn to recognize Self? When would it not recognize self?

Answer 20

During the first month of postnatal life, immunological competence is established to tolerate self-antigens while not tolerating non-self antigens. Tolerance requires continuous exposure while the immune system is weak (during fetal/early postnatal life) and works by two mechanisms: Clonal Deletion is when lymphocytes that recognize self-antigens are destroyed, and Clonal Anergy is when lymphocytes that recognize self-antigens are prevented from becoming activated.
However, some antigens are normally hidden from the blood such as thyroglobulin (thyroid gland) and lens protein (eye) so exposure of these results in production of Autoantibodies (antibodies made against self-antigens) and Autoreactive T cells (killer T cells that attack self-antigens)

Question 21

Describe the steps of prenatal development up until implantation. What are the two main stages?

Answer 21

Embryo stage: from zygote to 8 weeks. Zygote starts to divide (cleavage) after 30-36 hours at an accelerated rate. The third cleavage (50-60 hours after fertilization) produces the 8-cell ball called the Morula, which enters the uterus 3 days post ovulation. It remains unattached to the uterine wall for 2 more days until it becomes hollow Blastocyst. The two parts of the blastocyst are the inner cell mass (fetus) and chorion/trophoblast cells (placenta). On day 6 it implants in uterine wall which the inner cell mass positioned against the endometrium - this is *Nidation (implantation).

Fetus stage: from 8 weeks through parturition (birth)

Question 22

If fertilization occurs, what prevents menstruation?

Answer 22

The blastocyst secretes Human Chorionic Gonadotropin (hCG) from trophoblast cells of the chorion. This hormone is identical to LH in effects and maintains the corpus luteum, thus secretion of estradiol and progesterone is maintained and menstruation prevented. hCG is only required for the first 5-6 weeks until the placenta develops and becomes the hormone-secreting gland

Question 23

Between days 7-12 the blastocyst becomes completely embedded in endometrium. What layers develop in the chorion and the inner cell mass?

Answer 23

The chorion develops an Inner Cytotrophoblast layer and an Outer Syncytiotrophoblast layer. The inner cell mass develops the Ectoderm (future nervous system and skin) and Endoderm (future gut), the mesoderm forms later. The amniotic cavity separates the chorion and embryo.

Question 24

What structure forms to access maternal blood for the fetus? Why isn’t it attacked by maternal immune system

Answer 24

The syncytiotrophoblast invades endometrium and secretes protein digesting enzymes that create blood filled protections (villi) the grow and produce leafy structures called Chorion Frondosum. This only occurs on the side of the chorion facing the uterine wall. The other side loses villi and bulges in a smooth appearance.
The placenta is an immunologically privileged site that protects the foreign fetus from immune attack. It works by peripheral generation of regulatory T cells specific for paternal antigens and FAS ligand. (Pregnant uterus also contains unique natural killer cells that remodel spiral arteries for adequate perfusion of placenta with blood.)

Question 25

How is the placenta and the amniotic sac are formed

Answer 25

Two tissues, the chorion frondosum (fetal) and decidua basalis (maternal), together form the placenta (=cake). They undergo the Decidual reaction to grow and accumulate glycogen. Cytotrophoblast cells remodel spiral arteries of the endometrium to flow maternal blood to the placenta.
Immediately beneath the chorionic membrane is the amnion which envelops the entire embryo (=amniotic sac!). Isotonic amniotic fluid fills the sac

Question 26

How can a fetus’s health be assessed and tested for genetic defects? How can structural abnormalities by detected?

Answer 26

Amniocentesis: aspiration of the amniotic fluid which is filled with fetal cells. Usually performed about week 16 of pregnancy, when enough fluid is present to avoid damaging fetus. The cells extracted can have chromosomes examined to detect diseases like Down syndrome or Tay-Sachs disease.

Ultrasound: detects major structural abnormalities that are not predictable by genetic analysis by reflecting sound-wave vibrations from tissues w/ different densities. Also allows detection of a heartbeat weeks before it can be heard via stethoscope.

Question 27

Two types of immune tolerance and how they work

Answer 27

Central tolerance: mechanisms that occur in the thymus (for T cells) and bone marrow (for B cells). Both work by apoptosis and removal of auto reactive T cells (clonal deletion) as well as suppression by Treg cells (clonal anergy)

Peripheral tolerance: involves lymphocytes outside of the thymus and bone marrow. Works by complex mechanisms producing clonal anergy. This is needed because as lymphocytes divide, the randomly generate new antigen receptors to respond to pathogens, but it also creates self-antigen receptors throughout life. It is important to suppress these Forbidden Clones with Treg cells to prevent autoimmune disease

Question 28

Describe why and how antibodies are passed from mother to fetus.

Answer 28

The fetus is not immunologically competent until a month after birth so that it won’t reject its mother. Mother gives Passive Immunity to the fetus by transplacental trafficking of IgG antibodies while in uterus and then by breast feeding after birth (IgA antibodies). Colostrum is the first milk and is especially rich. The passive immunity conferred to the child will fade after a few months as the antibodies are destroyed, by then the child should have their own immune responses functioning.

Question 29

How is passive immunization used clinically? give three examples

Answer 29

People affected by toxins can be injected with antiserum (serum containing antibodies) or antitoxin specific to the toxin to sequester and remove the threat. Immunization is not long lasting, so future exposures will require more antitoxin treatment! Snake venom is an example where antivenin is administered after a bite. RhoGAM is another antiserum used to prevent hemolytic disease of the newborn. Intravenous Immunoglobulin from pooled plasma samples provides great IgG diversity to patients with immunodeficiency diseases, autoimmune conditions, or compromised immune systems (cancer).

Question 30

What are monoclonal antibodies? how are they made and what are they used for?

Answer 30

Normal immune response makes polyclonal antibodies first where some have great specificity and some are poor. Monoclonal antibodies are purified, highly specific, antibody populations.

A clone is made by extracting a single B cell with high specificity for the antigen then fusing it with a cancerous myeloma cell to make an immortal Hybridoma to produce the antibodies. They can then detect or target the antigen. Uses include pregnancy tests and cancer treatments (trastuzumab/herceptin for HER2 receptor in breast cancer, bevacizumab/avastin for VEGF in colorectal, lung, kidney, and brain cancer)

Question 31

Name the types of innate lymphoid cells and what they do

Answer 31

Innate lymphoid cells (ILCs) are lymphocytes used in the innate system. They don’t have antigen receptors and don’t respond specifically to antigens like adaptive lymphocytes.

1. Noncytotoxic innate helper lymphoid cells: like helper T cells. they produce lymphokines to help with immunity and allergy. Prominent in mucosal barriers
2. Natural killer (NK) cells: like cytotoxic T cells. They INHERIT receptors to target cancerous cells and intracellularly infected cells. They release cytokines and contain granzymes and perforin so they can destroy targets by cell-cell contact, however they do it without prior exposure to the antigens!

Question 32

How are NK cells activated and what do they do after activation? what are NKT cells

Answer 32

Natural Killer cells must be activated by interferon-a, interferon-b, and other cytokines first. Then they release interferon-gamma to activate macrophages and cells of the adaptive immune system. Therefore NK cells are a “first line” of defense in innate immunity. They also produce memory cells similarly to adaptive T cells, so they blur the boundary of innate vs adaptive.
Natural killer T cells/ NKT cells similarly have both innate and adaptive characteristics and respond to lipid antigens

Question 33

there are 3 categories of immune caused diseases. describe 1) Autoimmune diseases.
What causes this disease? what group are they most common in?

Answer 33

Autoimmune diseases: caused by failure of immune system to recognize and tolerate self-antigens. Autoreative T cells activate and produce autoantibodies, causing inflammation and organ damage. 2/3rds of people with autoimmune disease are women (women have more efficient immune system). There are 6 reasons why self tolerance may fail (see next card for that)

Question 34

What are the 6 reasons self-tolerance fails and autoimmune disease results? give an example of a disease for each one

Answer 34

1. An antigen that does not normally circulate in blood becomes exposed: thyroglobulin protein exposure causes Hashimoto’s thyroiditis (thyroid destruction) and exposure of eye lens from damage causes sympathetic ophthalmia
2. A foreign happen combines with a tolerated self-antigen: drug induced thrombocytopenia caused by aspirin, penicillin, etc
3. Antibodies are produced against other antibodies: rheumatoid arthritis caused by IgM attacking IgG
4. Antibodies produced against foreign antigens cross-react with self: Rheumatic Fever and Glomerulonephritis caused by *Streptococcus pyogenes infection
5. Self antigens are presented to helper T lymphocytes w/ class-2 MHC: Graves disease caused by thyroid cells producing class-2 MHC molecules = Thyroid-Stimulating Antibodies overstimulate gland. Type I diabetes caused by pancreatic beta cells producing class-2 MHC molecules = destroy insulin producing cells.
6. Inadequate activity of regulatory T lymphocytes: low FOXP3 expression = low suppression of auto reactive T cells

Question 35

there are 3 categories of immune caused diseases. describe 2) Immune Complex Disease
What causes this disease? What are three examples of such diseases?

Answer 35

Immune complex disease: antigen-antibody combinations FREE in the blood activate complement proteins and cause inflammation. Large numbers of complexes formed prolong inflammation and disperse to cause widespread damage.
Hepatitis B results from viral antigens/antibody complexes causing periarteritis (artery inflammation).
Rheumatoid arthritis (see other card)
Systemic Lupus Erythrematosis (see other card)

Question 36

Describe Rheumatic arthritis cause, symptoms, and how to diagnose.

Answer 36

Rheumatoid arthritis (an immune complex disease) results from helper T cells infiltrating synovial membranes and secreting inflammatory cytokines = B cells produce Rheumatoid Factors, IgM antibodies that bind IgG antibodies = complex activates complement = inflammation and joint damage. Joints are affected symmetrically on the body and systemic symptoms (fatigue, anorexia, weakness) occur. Other modifications targeted by antibodies in this disease include conversion of arginine to citrulline, which is tested in Cyclic Citrullinated Peptide (CPP) assay to diagnose rheumatoid arthritis.

Question 37

Describe SLE cause, symptoms, treatment and how to diagnose

Answer 37

Systemic Lupus Erythematosus (SLE) occurs mostly in women of childbearing years and is caused by autoantibodies that target their own nuclear constituents. An Antinuclear antibodies (ANA) test is used to diagnose. Cells that die release nuclear products, so immune system is always exposed to such antigens, but for some reason SLE loses immune tolerance. Binding of autoantibodies to nuclear antigens promotes complement and inflammation, damaging organs like kidneys (glomerulonephritis is inflammation of kidney capillaries). Causes of SLE may be genetic or environmental, ultraviolet light (sunlight) exposure and infections may trigger.
Treatments include antimalarial drugs (inhibit toll-like receptors) and anti-inflammatory/immunosuppressive drugs

Question 38

there are 3 categories of immune caused diseases. describe 3) Allergy
What causes this disease? *What are the two major forms?

Answer 38

Allergy or Hypersensitivity refers to abnormal immune response to antigens (allergens). *Two major forms are:

1. Immediate hypersensitivity: due to abnormal B cell response to allergen producing response in seconds-minutes
2. Delayed hypersensitivity: due to abnormal T cell response producing symptoms between 24-72 hours after exposure

Question 39

What is RU-486 used for (3 possible effects)? what drug is used together with it?

Answer 39

RU-486 or Mifepristone (Mifeprex) is a synthetic steroid that works as a progesterone receptor antagonist to block progesterone action. Through this effect, it promotes abortion in early pregnancy, and so has been called the “abortion pill” for pregnancies of 49 days or less. Mifepristone is used together with a prostaglandin such as misoprostol (Cytotec, causes contractions VIDEO!) to cause abortion, but it can be used by itself in low doses as an emergency contraceptive (probably by preventing ovulation) after unprotected sex. Because of this, it has also been called the morning after pill. Additonally, mifepristone has anti-glucocorticoid as well as anti-progesterone actions, and may be used in the treatment of Cushing’s syndrome.

Question 40

How do pregnancy tests work? what do they test for specifically and where is it produced? What can cause a false negative?

Answer 40

Pregnancy tests use monoclonal antibodies against the beta subunit of human Chorionic Gonadotropin. Because hCG is produced not by the mother but by the trophoblast embryonic cells, the test should normally be negative if the woman is not pregnant, unless she took exogenous hCG to treat infertility. False negative results occur when the test is performed too early, because hCG does not reach detectable levels until implantation, which may not occur until as late as day 12. Considering that sperm may survive in a woman’s reproductive tract for up to five days, a pregnancy test may be falsely negative for more than two weeks following intercourse. Tests are accurate when taken a week after missing menstruation

Question 41

What tests exist to asses fetal genetic health? three options

Answer 41

Amniocentesis: aspiration of fluid containing fetal cells from the amniotic sac, usually performed when about 14 to 20 weeks pregnant with at-risk fetus. Samples can be analyzed by microscopic observation of the chromosomes (karyotyping), and by biochemical analysis of DNA using chromosomal microarrays. This allows the detection of abnormal numbers of chromosomes, as in Down’s syndrome (trisomy 21) and Turner’s syndrome (single X). Certain genetic disorders may be detected, including sickle-cell disease, Tay-Sach’s disease, cystic fibrosis, and muscular dystrophy.
Chorionic villus sampling (CVS), which provides larger numbers of fetal cells, can be performed as early as 10 to 12 weeks of pregnancy.
DNA analysis of the mother’s blood (placental cells undergo apoptosis and release their DNA in her blood) can be used to noninvasively test fetal DNA.

Question 42

What causes AIDS and how is it treated?

Answer 42

Acquired immune deficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV), which infects and destroys helper T cells, particularly in the gastrointestinal mucosa where 30% of helper T cells reside. This results in decreased immunological function and greater susceptibility to infections and cancer.
HIV (a retrovirus) carries its genetic code as RNA and its enzyme reverse transcriptase is needed to transcribe this viral RNA into DNA for viral replication. Antiretroviral therapy (ART) involves drugs that inhibit this enzyme. Two different reverse transcriptase inhibitors with an inhibitor of protease produce a drug “cocktail” that can suppress HIV replication indefinitely, a good treatment but not a cure. When the ART drugs are stopped, the virus reappears.

Question 43

What additional developments (besides ART) gives hope in fighting HIV/AIDS?

Answer 43

1) early and continual treatment with the ART drugs can lower the risk of infecting a sexual partner by 96%
2) vaginal gels with antiretroviral drugs reduce transmission of HIV to women
3) male circumcision significantly reduces the risk that a man will be infected with HIV
4) methods to stimulate passive immunity have shown some promise. Injecting broadly neutralizing antibodies or genes for these antibodies within a virus vector
5) possible vaccines for stimulating active immunity against HIV. Developing vaccines has been difficult because crucial epitopes are hidden in the virus and because of a high mutation rate of the HIV antigens. Newly designed antigens contain many different epitopes

Question 44

What is sepsis, what causes it, and how do we treat?

Answer 44

Sepsis is life-threatening organ dysfunction caused by an abnormal immune response to infection, even after the infection has been cleared. Symptoms include high fever, a rapid pulse and respiratory rate, hypotension (septic shock danger of inadequate perfusion!), hypoxemia, oliguria (low urine output) and acidosis due to lactic acid. Sepsis is usually triggered by a bacterial infection, and is treated with antibiotics and intravenous fluids.
Endotoxin/bacterial lipopolysaccharide (LPS) on Gram-negative bacteria is the most powerful instigator of sepsis. It triggers innate immunity (through toll-like receptors) and massive amounts of LPS stimulate the widespread release of inflammatory cytokines.

Question 45

What do glucocorticoid drugs do and how?

Answer 45

Glucocorticoid drugs (hydrocortisone/cortisol, cortisone, prednisone, prednisolone, dexamethasone) are used to suppress the immune system for the treatment of various inflammatory conditions, autoimmune diseases, and allergy. They inhibit lymphocytes and phagocytic cells but enhance the cytokines secreted from TH2 cells (not TH1), promoting a shift from cell-mediated to humoral immunity.
The immunosuppressive effects of glucocorticoids result from suppression of pro-inflammatory cytokines IL-1 and other interleukins, gamma interferon, and TNFα. Microglia in the brain release these cytokines to stimulate the hypothalamus to secrete CRH, which stimulates the anterior pituitary to secrete ACTH and then the adrenals to secrete cortisol (glucocorticoid hormone). See the negative feedback loop?

Question 46

Describe how a patients T cells could be used to treat their cancer. Two therapies

Answer 46

Adoptive cell transfer therapies for cancer involve harvesting a patient’s T cells and using them to combat the cancer. A melanoma generates T cells that are specific for the cancer’s antigens. These can be harvested and proliferated in vitro by IL-2, and then put back into the tumor. To prevent these anti-tumor T cells from being suppressed by Treg cells, the patient’s immune system has previously been repressed by radiation or chemotherapy. This tumor-infiltrating lymphocyte (TIL) therapy has treated melanoma only.
Chimeric antigen receptor (CAR) therapy involves T cells removed from a patient and engineered to produce chimeric receptors with an activating portion and an antigen-binding portion (against CD19 on B cells). CAR therapy has treated B cell diseases like pediatric acute lymphoblastic leukemia

Question 47

Tumors often evade immune attack by activating “checkpoint” receptors on T cells. What is the anti-cancer therapy that blocks this action and how does it work?

Answer 47

Tumors often evade immune attack by activating so-called “checkpoint” receptors on T cells, which normally inhibit T cell function to promote self-tolerance and prevent autoimmunity. Immune Checkpoint Blockade involves the administration of antibodies that block the inhibitory checkpoint receptors on cytotoxic T cells. Blocking inhibitory checkpoint receptors unleashes the T cells’ ability to attack the tumor, significantly improving the treatment of several types of cancer, including advanced melanoma and non-small-cell lung cancer.

Question 48

What vaccines are available for cancers and what new vaccines are in development? Describe what these vaccines target

Answer 48

Scientists are developing vaccines against unique tumor antigens. Sometimes these antigens are produced by viral DNA due to infection by specific viruses. Examples include cervical cancer caused by the human papillomavirus (HPV), and hepatocellular carcinoma produced by the human hepatitis B virus (HBV). More often, the antigens are neoantigens (new antigens) produced by mutated DNA in the tumor, which produces many differently mutated cells as the tumor grows. Also, some tumor antigens are normal cellular products that are produced abnormally (such as carcinoembryonic antigen, which is not normally produced by adult cells). Such tumor-associated antigens can be used to develop vaccines that will hopefully help in the therapy of cancer.