Getting Started With Immunology

Question: Although we have not yet covered the components of the innate immune system,
think about how organisms can defend against microbes. Which of the functions, below, might
be important mechanisms involved in innate immune defense? (select all that apply)

Answer:
 Physical and chemical barriers, such as the epithelial linings of the skin and gut.
 Anti-microbial proteins at epithelial surfaces and in the blood. Correct
 Immune cells that can phagocytose (ingest) and kill microbes.

Innate Immunity and Inflammation

Question: For each of the immune cells listed below, indicate whether they are a tissue-resident
sentinel cell or a circulating leukocyte. Please note that "circulating leukocytes" refer to white
cells that are found in the cardiovascular (blood) circulation.

Answer:
Monocyte - circulating leukocyte
Macrophage - tissue resident sentinel cell
Neutrophil - circulating leukocyte
Dendritic Cell - tissue resident sentinel cell
Mast Cell - tissue resident sentinel cell

Question: A ____________ is a cell that uses innate immune receptors to recognize and
phagocytose microbes; these cells have a short life span within tissue and often rapidly die by
apoptosis.

Answer: Neutrophil

Question: A ____________ is a cell that uses innate immune receptors to recognize and
phagocytose microbes. It also will phagocytose and digest apoptotic cells.

Answer: Macrophage

Question: Which of the cells below is a tissue-resident cell that releases histamine upon
recognition of a microbe with innate immune receptors?

Answer: Mast Cell

Question: Mast cells, dendritic cells, and tissue-resident macrophages all release pro-
inflammatory ____________ when their innate immune receptors recognize microbes.

Answer: Cytokines

Question: Of the cells listed below, which is the first line of defense against the diverse microbial
world?

Answer: Epithelial Cells

Question: Pro-inflammatory cytokines and mediators bind to receptors on ____________ cells,

which respond by undergoing changes that will promote the recruitment of circulating
leukocytes from the blood into the tissue.
Answer: Endothelial Cells

Question: What are the primary features of endothelial cells that contribute to an innate
immune response in tissue? (select two answers)

Answer:
 They increase the expression of adhesion molecules on their luminal side.
 They express receptors that bind to and recognize cytokines.

Question: Which of the statements below best describes high affinity interactions between a
neutrophil and endothelial cell?

Answer: ICAM-1 on endothelial cells binds to LFA-1 on leukocytes to mediate stable arrest.

Question: The ____________ is one type of circulating leukocyte that binds to adhesion
molecules on endothelial cells and recruited into tissue as part of the innate immune response.

Answer: Neutrophil

Question: What are the primary differences between neutrophils and macrophages in the
context of inflammation? (select two answers)

Answer:
 Neutrophils only phagocytose microbes; macrophages ingest microbes and apoptotic cells.
 Neutrophils rapidly undergo apoptosis in tissue, macrophages do not.

Question: Which of the following is NOT a major component of pus?

Answer: Red Blood Cells

Question: The patient mentioned that she takes an over-the-counter medication called Benadryl
® (diphenhydramine). Diphenhydramine is an antihistamine (a drug that blocks the action of
histamine). The patient takes this medication to treat what aspects of her disease?

Answer: Itch

Question: Which of the following is NOT a true statement about psoriasis risk factors?

Answer: Females are more likely than males to develop psoriasis.

Question: The biologics that target TNFα block its interaction with TNFα receptors. How might
these drugs work to prevent psoriasis? (select two answers)

Answer:
 They prevent the expression of adhesion molecules on the surface of endothelial cells; this
prevents leukocytes from migrating into inflamed tissue.
 They prevent TNFα from acting directly on skin cells; this blocks the overgrowth of cells in
the skin.

Question: There is another biologic drug that has been used to treat psoriasis. It prevents
leukocytes from gaining access to the tissue by blocking one of the adhesion interactions that
occurs when leukocytes arrest and enter tissue. Specifically, it blocks the high affinity adhesion
molecule mentioned in this lesson that is expressed on leukocytes. What is the name of the
molecule blocked by this treatment?
 Answer: LFA-1

Question: Each sentence below describes a step of inflammation. Indicate the order in which
these steps occur by choosing the corresponding number, beginning with 1. Note that not every
step shown in the interactive is listed here.

Answer:
Description Order
Tissue-resident sentinel cells secrete cytokines and inflammatory mediators. 2
Migration of neutrophils into inflamed tissue. 7
Low-affinity interactions between neutrophils and endothelial cells. 5
Expression of adhesion molecules increases on endothelial cells. 4
Receptors on endothelial cells are bound by pro-inflammatory molecules. 3
High-affinity interactions lead to stable arrest. 6
Neutrophils kill microbes by phagocytosis and destruction in lysosomes. 8
Innate receptors on tissue-resident sentinel cells recognize microbes. 1

Question: “Nothing was formerly more striking in surgical experience than the difference in the
behavior of injuries according to whether the skin was implicated or not.” This quote highlights
the critical role of what component of the innate immune system in defense against microbes?

Answer: Epithelial Barriers

Question: Which of the cells below are tissue resident sentinel cells? (select two answers)

Answer:
 Dendritic Cells
 Mast Cells

Question: Which of the cells below are circulating blood cells that will enter tissue in response to
inflammation? (select two answers)

Answer:
 Neutrophils
 Monocytes

Question: For each of the immune functions listed below, select the immune cell type that best
matches that function. Note that some cells may match more than one description, and some
cells may not be used at all.

Answer:
Function Immune Cell
Releases histamine when activated Mast Cell
Most abundant leukocyte Neutrophil
Phagocyte that rapidly dies after ingesting microbes Neutrophil
Phagocyte that cleans up apoptotic cells Macrophage

Question: When a monocyte moves into the tissues, it changes rapidly and becomes a
____________ .

Answer: Macrophage
Question: Leukocyte adhesion deficiency (LAD) is a genetic defect that leads to recurrent
infections in the tissue and severe problems with wound healing. LAD patients also develop
severe gingivitis (infections and inflammation of the gums). In LAD, leukocyte migration into
tissues is severely impaired. All of these problems can be traced back to a genetic defect. Of the
genetic defects listed below, which is the most likely cause of LAD?

Answer: A mutation that introduces a stop codon into a gene that encodes part of the LFA-1
molecule (leading to a truncated protein).

Microbial Recognition and Responses in Innate Immunity

Question: Our cells activate an immune response by recognizing molecules that are specifically
expressed by pathogens and not expressed by our own cells. Below is a list of different molecules
found in living organisms. Which of these molecules might be recognized as non-self?

Answer: Proteins

Question: The molecules that bind to receptors on cells and activate the antiviral state are type I
____________.

Answer: Interferon

Question: Imagine an epithelial cell that is infected with a virus and has activated the antiviral
state. Which of the following statements does NOT describe a likely mechanism used by this cell
to reduce the spread of the virus?

Answer: The cell increases expression of adhesion molecules to recruit neutrophils to the site of
infection.

Question: The type of sentinel cell that helps induce the antiviral state is called a ____________.

Answer: pDC or Plasmacytoid Dendritic Cell

Question: How does our innate immune system distinguish microbes from ourselves?

Answer: We inherit genes encoding innate immune receptors that recognize molecules common
on many microbes but not found on mammalian cells.

Question: The innate immune system recognizes certain molecules found in groups of microbes
but not found in vertebrate cells. These molecules are called ____________ .

Answer: PAMP or Pathogen Associated Molecular Pattern

Question: The main type of pattern recognition receptor is called a ____________ receptor.

Answer: TL or toll-like

Question: The cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFα) are produced
by sentinel cells in response to extracellular bacteria. They are important for initiating
inflammation and the formation of pus. Tissue-resident sentinel cells express pattern recognition
receptors that are essential for initiating IL-1 and TNFα signaling. What is the likely localization of
these pattern recognition receptors within or on sentinel cells?

Answer: The Cell Membrane

Question: Several different molecules, or classes of molecules, are listed below. Which is the
most important PAMP for viral recognition?

Answer: Nucleic Acids

Question: Plasmacytoid dendritic cells (pDCs) efficiently produce type I interferons. Which of the
statements below best describes the first events that activate type I interferon signaling in pDCs?

Answer: Viral molecules bind to PRRs expressed on the endosomal membrane.

Question: Which sequence of events best describes pro-inflammatory signaling in response to

bacteria?

Answer: Bacterial PAMPs bind to TLRs. TLR signaling triggers the degradation of an inhibitor,
which releases NF-kB. NF-kB enters the nucleus and activates transcription of TNFα and IL-1.

Question: Which sequence of events best describes signaling in response to viruses that leads to
the production of antiviral cytokines?

Answer: Viral PAMPs bind to TLRs. TLR signaling leads to phosphorylation of a transcription
factor. The transcription factor enters the nucleus activates transcription of type I IFNs.

Question: Which complement protein fragments can activate inflammation? (select two answers)

Answer:
 C3a
 C5a

Question: The first event in complement that is activated by all pathways, regardless of the exact
activation trigger, is the cleavage of the ____________ protein.

Answer: C3

Question: Which of the statements below best describes the alternative pathway of complement?

Answer: C3 is spontaneously cleaved and remains activated upon interaction with the microbial
surface.

Question: Which of the statements below best describes the classical pathway of complement?

Answer: Antibodies bound to a microbe recruit C1q, which activates a series of events that lead
to C3 cleavage.

Question: Lectins are a diverse group of proteins found in our bodies. What statement below
most accurately describes the lectins that activate complement?

Answer: Lectins bind to sugars that are commonly expressed by microbes.

Question: Which of the following antimicrobial functions is NOT activated by the complement
system?

Answer: The Antiviral State

Question: Of the statements below, what is NOT a shared feature of IgM and immune lectins?

Answer: Both recognize only microbial carbohydrates (sugars).

Question: All of the signs and symptoms listed below are associated with hepatitis C infection.
What was this patient’s chief complaint when he was first diagnosed with HCV?

Answer: Fatigue

Question: The patient was treated more than once with a particular cytokine in an attempt to
clear his HCV infection and control the progression of his liver disease. What is the name of that
cytokine?

Answer: Interferon

Question: Which of the molecules below are most likely to be important in the innate immune
response to infection with HCV? (select two answers)

Answer:
 PRRs that recognize nucleic acids
 Type I interferons

Question: Like many viruses, the HCV genome has genes for comparatively few proteins, and
mostly utilizes host cell proteins to replicate and spread. One of the proteins produced by HCV is
called NS3/4A. NS3/4A is a protease (a protein that enzymatically cleaves other proteins). Which
of the conclusions below are consistent with these results? (select two answers)

Answer:
 NS3/4A cleaves and inactivates a protein required for pattern recognition receptor signaling.
 NS3/4A decreases innate immune signaling.

Question: Imagine a continuation of the experiment described above. How might NS3/4A
expression impact Sendai virus replication, as measured by the amount of virus produced by the
different cells?

Answer: Cells expressing NS3/4A will produce more Sendai virus than cells that do not express
NS3/4A.

Question: Several different cells and molecules are listed below. Which are primarily
components of the innate immune system? (select all that apply)

Answer:
 Complement Proteins
 Toll-like Receptors
 Macrophages
 Dendritic Cells
 Mast Cells

Question: When a healthy individual is first exposed to a particular type of infectious microbe,
the adaptive immune system generates

Answer: A delayed response to very specific microbial antigens.

Question: oll-like receptors for bacterial PAMPs are found on/in the cell’s ____________.
Answer: Membrane

Question: There are a few different proteins that act as inhibitors of NF-kB. There is a very rare
genetic disease in which one of these proteins, IkBα, is mutated. The mutation substantially
alters the stability of the IkBα protein. In patients with this disease, IkBα protein expression does
not change in response to stimuli that cause IkBα degradation in healthy individuals. Consider
the biological role of NF-kB inhibitors. What are the most likely symptoms of this genetic defect?

Answer: Immunodeficiency with a susceptibility to bacterial infections.

Question: The complement pathway initiated by host proteins that bind to microbial sugars is
called the ____________ pathway.

Answer: Lectin

Question: ssRNA (single-stranded RNA) and dsDNA (double-stranded DNA) are present in
mammalian cells. Why don’t our plasmacytoid dendritic cells activate an innate immune
response against these self nucleic acids that are necessary for normal cellular function?

Answer: The TLRs that recognize ssRNA and dsDNA are sequestered in endosomes.

Question: How can the antiviral state be propagated in the absence of immune cells?

Answer: Type I IFNs are produced by infected epithelial cells; this induces anti-viral biochemical
changes in the same cell and adjacent cells.

Question: A child presents with recurrent bacterial infections. Of the genetic defects described
below, what is the most likely cause of her disease?

Answer: A mutation in the C3 gene that renders the C3 protein nonfunctional.

Question: ____________ is the process by which something that is not otherwise recognized as a
pathogen is coated with proteins that make it more recognizable to the immune system.

Answer: Opsonization

Antibodies - Structure and Function

Question: Later in the course, you will learn about a process used by the immune system to
generate a diverse set of antibodies. Yet antibodies themselves can also cause disease. Some
ways that an antibody might cause disease are listed below. Which of these options do you think
would lead to disease? (select one answer)

Answer:
 Antibodies could clump together with self proteins, making complexes that interfere with
organ function.
 Antibodies could bind to self cells, activating an immune response that kills those cells.
 Antibodies could bind to self proteins, blocking the normal function of the proteins.

Question: What differentiates adaptive immunity from innate immunity? (select two answers)

Answer:
 Adaptive immunity is a response to a specific pathogen whereas innate immunity is a
response to a pathogen-associated pattern.
 The adaptive immune response is more vigorous on repeated exposure to the same
pathogen.

Question: Which of the cells below is a type of lymphocyte?

Answer: B Cell

Question: What is the term for a molecule recognized by the adaptive immune system as foreign?

Answer: Antigen

Question: Which of these statements most accurately describes humoral immunity?

Answer: Immune functions mediated mostly by B cell-derived antibodies that act outside of cells.

Question: ____________ refers to the process of antibodies binding to microbes, thereby

preventing them from interacting with receptors on cells and infecting the cells.

Answer: Neutralization

Question: The process of ____________ refers to antibodies coating a pathogen to make it more
palatable to be eaten by phagocytes.

Answer: Opsonization

Question: Antibody-dependent cellular cytotoxicity involves:

Answer: Natural killer cells recognizing antibodies bound to virus-related proteins on the
infected cell surface.

Question: The protein complex recruited by antibodies that mediates the direct killing of
microbes is part of the ____________ system.

Answer: Complement

Question: For each of the indicated regions on the immunoglobulin (antibody) shown below,
select the appropriate label.

Label Region
A Variable Region
B Fab
C Fc
D Heavy Chain
E Light Chain
Question: The __________ portion of the antibody is the part that is bound to complement or is
recognized by the receptors on phagocytes or on natural killer cells.

Answer: Fc

Question: What are the isotypes (classes) of antibodies that require J chains for their function?
(select two answers)

Answer:
 IgA
 IgM

Question: Consider the structure of a single antigen binding site on an antibody. How many
individual loops of the light chain of the antibody contribute to the formation of the antigen
binding site?

Answer: 3

Question: Consider the structure of a single antigen binding site on an antibody. How many
individual loops of the heavy chain of the antibody contribute to the formation of the antigen
binding site?

Answer: 3

Question: In this lesson we will revisit some of the concepts covered in an earlier lesson about
antibodies. To review, select the antibody class that best matches each of the descriptions listed
below.

Answer:

Question: All examples of antibody-mediated damage to non-infected cells require antibody

recognition of self antigens.

Answer: False

Question: IgM is a potent activator of the complement system. A person with a particular blood
type may have pre-formed IgM antibodies against other blood types. Blood type matching
ensures that patients do not suffer an “immediate” intravascular transfusion reaction. If a
patient receives a transfusion of a different blood type, and they have IgM against this blood
type, what outcomes are most likely? (select two answers)

Answer:
 IgM binds to transfused blood cells and recruits complement, leading to lysis of the cells.
 Complement proteins activate a cascade of inflammation.

Question: A delayed transfusion reaction can result from the coating of transfused cells with IgG,
which recruits macrophages. This process of coating a cell with Ig is referred to as ____________.

Answer: Opsonization

Question: In an example of inflammation-mediated antibody damage to cells, Ig binds to self

antigen on epithelial cells → complement binds Ig and is activated → pro inflammatory
fragments of complement proteins are produced → the fragments bind to vessel walls →
neutrophils move out of vessels → neutrophils bind to ____________ via receptors →
neutrophils are triggered to release granules that damage cells.

Answer: Ig Fc Portion

Question: On occasion, leukemia or lymphoma is discovered in abnormal results of routine blood

tests. For example, above-normal white blood cell counts (leukocytosis) can be caused by
immune cancers. Other immune cancers are diagnosed by abnormally high levels of antibodies in
the blood. The antibody is usually of just one type, indicating that a single cell is dividing
uncontrollably and secreting this antibody. What type of immune cell is the likely source of this
antibody?

Answer: B Cell

Question: In the past few decades, antibodies have emerged as powerful therapeutic agents.
They have been used to treat certain immune cancers. In 1997, rituximab was approved for the
treatment of some lymphomas. Rituximab is a monoclonal antibody, which means that it is a
single antibody that can recognize one antigen. With modern laboratory techniques, it is possible
to purify large quantities of monoclonal antibodies in a sterile laboratory environment.
Monoclonal antibodies are administered to patients by injection or infusion. Which of the
mechanisms of action, below, does NOT contribute to the depletion of B lymphocytes in
rituximab therapy?

Answer: Neutralization of CD20, which blocks its normal function in B cells.

Question: One of your colleagues has a new idea for a B cell lymphoma therapy. He would like to
create a smaller version of an antibody that recognizes CD20. In particular, he wants to create a
single-chain variable fragment (scFv) antibody. You tell your colleague not to waste his time. You
are almost certain that an scFv therapy will not work to treat lymphoma. Why is this?

Answer: scFv lack the full Fc region, which is necessary for the immune functions of the antibody.

Question: The majority of the symptoms of tetanus infection are caused by the tetanus toxins,
chiefly tetanospasmin. Tetanospasmin is one of the deadliest toxins known; even very small
doses (nanograms) can be lethal. It targets the nerves, causing severe muscle spasms. The
tetanus vaccine consists of inactivated tetanus toxin; the vaccine is highly effective for
preventing tetanus. Inoculation with the tetanus vaccine leads to the production of protective
antibodies. How do these antibodies prevent tetanus?
Answer: Neutralization

Question: Streptococcus pneumoniae is an extracellular bacterium that is a leading cause of

bacterial pneumonia and meningitis, particularly in children and the elderly. Fortunately, most
cases of S. pneumoniae can be prevented with a vaccine that contains components of the
bacterial capsule. The vaccine is known to lead to the production of antibodies that recognize
intact bacteria. What are the most likely mechanisms activated by these antibodies that result in
protection against S. pneumoniae infection? (select two answers)

Answer:
 Opsonization and Phagocytosis
 Complement Fixation

Question: There is strong interest in developing a vaccine that would prevent human
immunodeficiency virus (HIV) infection or substantially reduce viral loads in a person with HIV.
HIV infects immune cells by binding to a receptor called CD4 on the surface of those cells.
Laboratory studies have identified rare antibodies that bind to intact HIV viral particles and
effectively control the virus in certain individuals. Structural studies revealed that some of these
antibodies bind to a protein on the surface of HIV at the same location where this protein binds
to CD4. What is the most likely mechanism of action of these antibodies?

Answer: Neutralization

Question: How many distinct peptide chains are found in a single molecule of IgG?

Answer: 4

Question: How many distinct binding sites are found in a single molecule of IgG?

Answer: 2

Question: Which of the following antibodies is protected from proteases that are commonly
found in the gut?

Answer: IgA

Question: Neutrophils, NK cells, and macrophages all have receptors for the
__________________ portion of the antibody, and use this to recognize antigens that are coated
with antibodies.

Answer: Fc

Question: Antibodies can cause disease by:

Answer: All of the Above

 A combination of complement fixation and opsonization, leading to frustrated phagocytosis
and inflammation-mediated damage.
 Forming complexes in the circulation that can deposit in vessel walls and potentially trigger
further immune activation.
 Recognizing antigens that are part of our own cells, leading to opsonization and destruction
by phagocytes.
 Recognizing antigens that are part of our own cells, leading to complement activation
Question: Which of the following is an example of an autoimmune disease caused by antibodies
that interfere with the function of a self protein?

Answer: Antibodies bind to receptors for a neurotransmitter, leading to paralysis.

Lymphocyte Development and Diversity

Question: Which of the following is an accurate statement about antibody recognition of antigen?

Answer: Antibodies can recognize any class of molecule outside of cells.

Question: The adaptive immune system is responsible for coordinating a specific response to
microbes, in contrast to the innate immune system, which provides a rapid, but generalized,
response. Which of the following is NOT a challenge that the adaptive immune system must
overcome to mount a specific response to a microbe?

Answer: Lymphocyte receptors are not sufficiently diverse to recognize all possible microbes.

Question: Clonal selection describes the interaction between microbial antigen and its specific
lymphocyte receptor, while clonal ____________ describes the proliferation of the lymphocyte
in response to the antigen-receptor interaction.

Answer: Expansion

Question: Which of the cells, below, arise from the common lymphoid progenitor (CLP)? (Select
two answers.)

Answer:
 NK Cells
 B Cells

Question: A cell that can undergo self-renewal and differentiate into any of the cells of the blood
is called a hematopoietic ____________. (answer is two words)

Answer: Stem Cell

Question: Neutrophils, eosinophils, and basophils are all examples of ____________, which are
cells that have many granules in their cytoplasm.

Answer: Granulocytes

Question: Consider the anatomical locations of blood cell development. The earliest stages of
HSC differentiation occur in the ____________. (answer is two words)

Answer: Bone Marrow

Question: At a certain stage in B cell development, the developing B cells move to lymphoid
tissues. This occurs at which stage of differentiation?

Answer: Immature B Cell

Question: At which stage of development do B cells first express immunoglobulin (Ig) heavy
chains?
Answer: Pre B Cell

Question: At the pro-T cell stage, differentiating T cells migrate to the ____________, the site of
all subsequent stages of T cell development.

Answer: Thymus

Question: What structure binds to the T cell receptor?

Answer: A Peptide bound to an MHC Protein

Question: Cytotoxic T cells (CTLs) are a subset of T cells that express the molecule CD8 on their
cell surface and contain granules filled with proteins that can cause death to infected cells. In the
right circumstances, when they bind to antigen they will release these granule contents as a
“lethal payload.” The granule contents induce apoptosis in the cell that displays the antigen.
What type of pathogen cannot be controlled by CTLs?

Answer: Bacteria that replicate outside of cells.

Question: In a previous lesson, you learned about antibody structure. Which portion of the
antibody light chain protein contains the antigen binding site?

Answer: The N-terminus, which contains the variable region.

Question: In human cells, there are approximately 45 V segments, 23 D segments, and 6 J

segments in the Ig heavy chain gene region. How many possible heavy chain proteins can be
created from these different segments, simply due to combinatorial diversity?

Answer: 6210

Question: The immunoglobulin light chain does not have a D segment. In humans, there are two
different possible light chain proteins, termed kappa and lambda. Assume that there are 35 V
segments and 5 J segments in the human kappa light chain region, and there are 30 V segments
and 4 J segments in the human lambda light chain region. How many possible light chain genes
can be created from these different segments, simply due to combinatorial diversity?

Answer: 295

Question: Using the numbers calculated above, approximately how many possible
immunoglobulin genes can be generated by combinatorial diversity alone?

Answer: 1.8 × 10^6

Question: It is estimated that there are between 10^11 to 10^12 different possible antibodies.
The possibilities from combinatorial diversity are substantially lower than this number.
Additional variation in antibodies comes from a type of diversity caused by variability in the
sequences that join the gene segments. This is called ____________ diversity.

Answer: Junctional

Question: Usually there are only a small number of individual cells that represent each T cell or B
cell clone in the body. Which of the conditions below is generally required for the expansion of
antigen-specific lymphocytes such that hundreds of thousands (or more) of copies of a single
clone are found in the body?

Answer: Exposure to an antigen with high affinity for the antigen receptor.

Question: Let’s begin with a review question. You studied some psoriasis treatments in an earlier
lesson. Which immune molecule is a direct target of current psoriasis therapies?

Answer: TNFα

Question: Of the different psoriasis therapies we have discussed so far, which is likely to have
the lowest risk of increasing susceptibility to infections?

Answer: Narrowband UVB

Question: Many new immune therapies that target cytokines (such as some of the TNFα
inhibitors used to treat psoriasis) are actually monoclonal antibodies. Think back to the lesson on
antibody functions. What is the mechanism of action of these antibodies?

Answer: Neutralization

Question: It is possible to use molecular genetic techniques to characterize the T cells found in
psoriasis plaques and compare them to the T cells found in healthy skin. In healthy skin, T cells
have a wide diversity of T cell receptors. In other words, there are many different T cell clones
found in healthy tissue. In psoriasis plaques, there are fewer T cell clones, but often there are a
large number of T cells representing only a small number of clones (this is called oligoclonal
expansion). There are usually many more T cells in total found in psoriasis plaques relative to
healthy skin.

Answer: Specific T cells react with a large number of antigens in psoriasis.

Question: Which of the following are components of an adaptive immune response to pathogen?
(Select two answers.)

Answer:
 Clonal selection by specific antigen
 Clonal expansion

Question: A researcher suspects that a certain leukocyte population plays a role in a particular
disease. She studies mice with a genetic defect that leads to the development of the disease in
young mice. She decides to test her hypothesis by surgically removing the thymus from newborn
mice, then observing these mice for disease progression. What leukocyte population does she
suspect contributes to the development of the disease?

Answer: T Cells

Question: Which of the cells below are granulocytes? (Select two answers.)

Answer:
 Eosinophils
 Neutrophils

Question: Which of the following cells would fail to develop due to a genetic defect in the
enzymes involved in V(D)J recombination? (Select two answers.)
Answer:
 T Cells
 B Cells

Question: What would be the most common symptom in humans with the genetic defect
described above?

Answer: High susceptibility to infections

Question: Which of the following would be a logical approach to curing SCID?

Answer: transplantation of bone marrow from a normal donor

Question: Which of these statements accurately describes the differences between B cells and T
cells?

Answer: B cell receptors can recognize virtually any antigen, T cell receptors only recognize
peptides displayed on MHC molecules.

Question: Which of the following does NOT contribute to the diversity of different antibodies?

Answer: Millions of different antibody genes are inherited from each parent.

T Cell Activation by Antigens

Question: We have not covered MHC molecules in much detail up to this point in the course.
Before we begin, which of the following antigens might be broken down into peptides and
displayed on MHC molecules?

Answer: A protein from a virus that is infecting an epithelial cell.

Question: A mature T lymphocyte that has never been exposed to antigen is called a
____________ T cell.

Answer: Naive

Question: What is the name of the T cell co-receptor expressed by helper T cells?

Answer: CD4

Question: Which of the following statements best describe the functions of dendritic cells (DCs)
in infected tissue? (select two answers)

Answer:
 They ingest microbial proteins from the environment and break them into peptides.
 They recognize microbes with innate pattern recognition receptors.

Question: When they are activated, DCs increase the expression of MHC class I and MHC class II
molecules. What is the function of these molecules?

Answer: MHC molecules display peptide antigen to T cells.

Question: When they are activated, dendritic cells increase expression of CCR7. What is the
function of this molecule?

Answer: CCR7 helps DCs to migrate to the lymph node.

Question: Imagine that a person is exposed to an infectious microbe for the first time. They
develop a robust innate immune response; an adaptive response is likely to follow. Where is it
LEAST likely that antigen-specific naive T cells will be activated?

Answer: in the tissue at the site of infection

Question: An activated dendritic cell (DC) migrates to a site where it can present antigen to naive
T cells. What route is the DC most likely to follow?

Answer: The DC migrates through lymphatic vessels to the lymph node.

Question: How does a naive T cell migrate to a lymph node?

Answer: The T cell migrates through blood vessels and enters the lymph node at high endothelial
venules (HEV).

Question: DCs and naive T cells both express a chemokine receptor called ____________ that
helps them to interact in the same area of lymph nodes.

Answer: CCR7

Question: Which of the following statements best describe the activation of a naive T cell?
(select two answers)

Answer:
 The T cell receptor binds to a peptide-MHC complex on a DC. The binding event initiates T
cell receptor signaling.
 Costimulatory molecules on the DC bind to costimulatory receptors on the T cell. This
initiates costimulatory signaling in the T cell.

Question: Which of the following is a costimulatory molecule that is up-regulated on the surface
of activated DCs?

Answer: B7-1

Question: The primary costimulatory receptor expressed by virtually all naive T cells is called
________.

Answer: CD28

Question: Imagine that a DC encounters some fragments of a dead microbe. The DC is able to
take up the fragments and present microbial peptides on MHC molecules on its surface. However,
the microbial fragments do not initiate an innate immune response in the DC or in other tissue-
resident sentinel cells (perhaps because it does not express PAMPs that are recognized by PRRs
in this organism). What is the most likely outcome?

Answer: The DC will not migrate to the lymph node and will not activate naive T cells.
Question: What are the most likely outcomes when a T cell is exposed to signal 1 (T cell receptor
signaling) in the absence of signal 2 (costimulatory receptor signaling)? (select two answers)

Answer:
 The T cell undergoes apoptosis.
 The T cell becomes anergic.

Question: Many of the peptides displayed on MHC molecules are self peptides; some of these
peptide-MHC complexes are recognized by self-reactive T cells. If a DC becomes activated (for
example when TLRs on the DC recognize bacterial PAMPs), this DC will continue to display some
self peptides. What prevents self-reactive T cells from becoming activated under these
circumstances?

Answer: Self reactive T cells will already have undergone apoptosis or become anergic.

Question: Peptides broken down in lysosomes are presented on MHC class I molecules, while
peptides broken down in proteasomes are presented on MHC class II molecules.

Answer: False

Question: CD8+ T cells recognize peptide-MHC class I complexes, while CD4+ T cells recognize
peptide-MHC class II complexes.

Answer: True

Question: What is the primary mechanism that acts to down-regulate activation of T cells in
lymph nodes?

Answer: T cells upregulate CTLA-4; CTLA-4 binds to B7 molecules with high affinity, which blocks
signal 2 by preventing B7-CD28 interaction.

Question: What mechanism limits activation of T cells in the tissue?

Answer: T cells upregulate PD-1; when PD-1 is bound by its ligand the T cells become exhausted.

Question: Let’s begin with a review question. You studied hepatitis C therapies earlier in the
course. Which immune molecule is used to treat hepatitis C infection?

Answer: Type I Interferon

Question: Which of the following statements is LEAST supported by the finding of an association
between specific MHC variants and spontaneous clearance of HCV?

Answer: An innate immune response, mediated by APCs that express MHC molecules, is
sufficient to clear acute HCV infection.

Question: Patients with chronic HCV generally have effector T cells that are specific for HCV, yet
for some reason these T cells do not clear the infection. Many chronic HCV patients have T cells
that express high levels of PD-1. The molecule PD-L1 is expressed on hepatocytes. How might
these factors contribute to a failure to clear HCV in chronic infection?

Answer: PD-1:PD-L1 interactions induce T cell exhaustion.

Question: Which of the following cells is LEAST likely to display peptides on MHC class I
molecules?

Answer: A Red Blood Cell

Question: Peptides displayed on MHC class I molecules are:

Answer: Degraded in proteasomes and recognized by CD8+ T cells.

Question: How do peptides reach the correct subcellular compartment to bind to MHC class I
molecules?

Answer: They are transported into the ER by TAP.

Question: Which of the following cells is LEAST likely to display peptides on MHC class II
molecules?

Answer: A liver cell (hepatocyte)

Question: Peptides displayed on MHC class II molecules are:

Answer: Derived from proteins that are degraded in lysosomes and recognized by CD4+ T cells.

Question: What step in the formation of an MHC-peptide complex is shared by the MHC class I
and class II pathways?

Answer: The MHC molecules are synthesized in the endoplasmic reticulum.

Question: Think about the function of MHC class I vs. MHC class II. Which MHC molecule is more
likely to bind to a peptide derived from a pyogenic (obligate extracellular) bacterium?

Answer: MH Class II

Question: Below is a list of molecules expressed on immune cells. For each of the molecules,
indicate whether it is expressed on dendritic cells, helper T cells, or neither cell type.

Answer:
Molecule Expressed on
B7-2 Dendritic Cell
CD28 Helper T Cell
CD4 Helper T Cell
CD8 Neither
CTLA-4 Helper T Cell
MHC Dendritic Cell
PD-1 Helper T Cell

Question: Which of the molecules, below, is required for both naive T cells and activated
dendritic cells (DCs) to migrate to the lymph node?

Answer: CCR7

Question: A T cell in the lymph node recognizes a peptide-MHC complex and T cell receptor
signaling begins. The T cell enters a state of anergy. How might this have happened? (select two
answers)
Answer:
 CTLA-4 on the T cell binds to B7 with high affinity, blocking CD28 signaling.
 The antigen presenting cell does not express any costimulatory molecules.

Question: The table below contains different features of antigen presentation. For each entry,
select the appropriate description of the pathways by which peptides degraded by proteasomes
and lysosomes are presented on MHC molecules.

Answer:
Peptides degraded by Peptides degraded by
proteasomes lysosomes
Peptides presented on... MHC Class I MHC Class II
MHC expressed on... Nucleated cells Professional APCs only
Peptides presented to... CD8⁺ T cells CD4⁺ T cells

Question: Think about the function of MHC class I vs. MHC class II. Which MHC molecule is more
likely to display a peptide derived from a virus that has infected an epithelial cell?

Answer: MHC Class I

Question: In the example above, an epithelial cell is infected with a virus. If the organism has
never been exposed to the virus before, it has no effector T cells specific for viral antigens. How
do naive CD8+ T cells become activated in this situation?

Answer: DCs will take up viral antigens in the infected tissue and present it on MHC class I, they
will then migrate to the lymph node and present to naive T cells.

Question: A rare genetic disease arises from mutations in subunits of TAP (TAP1 or TAP2).
Individuals with this disease are susceptible to recurrent infections. What effects would you
expect from this mutation?

Answer: MHC class I molecules will not be loaded with peptides, so CD8+ T cells cannot be
activated.

T Cell-Dependent B Cell Responses

Question: Similarly, B cell receptor signaling alone is not sufficient to activate B cells.
B cells require assistance from helper T cells to become activated by monovalent
protein antigens and gain certain immune functions. What changes do you suspect
will occur to B cells when they are activated by protein antigen and receive T cell
help? (select all that apply)

Answer:
 They will generate memory cells that can respond to a subsequent exposure to
antigen.
 Their immunoglobulin genes will be mutated in a way that alters antigen affinity.
 The isotype of their immunoglobulin (Ig) genes will change.
 They will proliferate and expand.
 They will secrete antibodies.
Question: B cells primarily present antigen to:

Answer: CD4+ T cells.

Question: What are the primary antigen presenting cells that are necessary to
initiate collaboration between T and B cells in the lymph node? (select two answers)

Answer:
 Dendritic Cells
 B Cells

Question: When B cell receptors are bound by antigen, signals are generated in the B
cell so that it will express a certain molecule that promotes migration to the T cell
zone of lymph nodes. What is the name of this molecule?

Answer: CCR7

Question: If a B cell receptor is specific for a protein antigen, how does the B cell
present peptides derived from that protein antigen on MHC class II molecules?

Answer: B cells take up protein antigens that bind to their B cell receptor by
receptor-mediated endocytosis. These antigens are processed into peptides inside
the cell and displayed on MHC class II.

Question: What surface molecule interactions are required for T cells to provide help
to B cells? (select two answers)

Answer:
 T cell receptors interact with peptide-MHC class II complexes
 CD40L interacts with CD40

Question: In this lesson we will revisit some of the concepts covered in an earlier
lesson about antibodies. To review, select the antibody class that best matches each
of the descriptions listed below.

Answer:
Question: Of the changes that might occur to antibodies listed below, which are
most likely to result from the germinal center reaction? (select two answers)

Answer:
 Class switching from IgM to IgG
 Antibody affinity increases

Question: The chemokine receptor ____________ is up-regulated by CD40 signaling

in B cells and T cell receptor signaling in T cells. Expression of this chemokine
receptor promotes the migration of both cells into the B cell follicle.

Answer: CXCR5

Question: Of the cells listed below, which is LEAST likely to be found inside germinal
centers?

Answer: Naive T Cells

Question: The germinal center reaction generates new cell types from antigen
specific B cells that have gained certain functions. What are these cells? (select two
answers)

Answer:
 Long-lived plasma cells
 Memory B Cells

Question: What are the signals provided by TFH cells that promote germinal center-
specific changes to B cells? (select two answers)

Answer:
 Cytokines
 CD40L

Question: In response to TFH signals, B cells undergo high rates of mutation in the

Answer: Variable regions of Ig heavy and light chain genes.

Question: In germinal centers, follicular dendritic cells (FDCs) display protein

antigens that bind to B cell receptors of B cells. How does this contribute to the
germinal center reaction?

Answer: B cells that express immunoglobulin receptors with high affinity for those
antigens can bind the antigens, and they are rescued from apoptosis.

Question: B cells that express immunoglobulin receptors with high affinity for those
antigens can bind the antigens, and they are rescued from apoptosis.
Answer: IgM

Question: What antibody isotypes most efficiently neutralize protein function?

(select two answers)

Answer:
 IgA
 IgG

Question: Class switch recombination occurs in the:

Answer: Constant region of Ig heavy chain genes.

Question: How does class switching impact the affinity of B cell receptors for antigen?

Answer: Affinity remains the same

Question: What antibody isotype is most likely to activate mast cells?

Answer: IgE

Question: Let’s begin by taking a step back and considering leukemia and lymphoma
in general. We learned that an important way to classify cancers is to consider the
cell of origin. Leukemias and lymphomas are cancers that arise from:

Answer: Hematopoietic (blood) cells, or the cells that give rise to mature blood cells.

Question: In a particular type of immune cell cancer, patients often have high levels
of circulating antibodies of the IgG or IgA isotype. Based on this information, what is
the likely cell of origin?

Answer: A plasma cell that has been through the germinal center reaction.

Question: In most cases of multiple myeloma, the excess antibodies found in the
blood all share an identical protein sequence (thus they have the same structure).
Consider such a case where all of the antibodies are identical and think about the
cell(s) of origin. How many different B cell clones gave rise to this immune cancer?

Answer: 1

Question: What process changes the nucleotide sequence of the genes encoding a B
cell receptor antigen binding site during an immune response to protein antigen?

Answer: Somatic Hypermutation

Question: Activated T cells up-regulate the expression of certain molecules that are
necessary for migration toward B cell follicles in the lymph node and necessary to
provide signals to activate B cells. What are the names of these molecules? (select
two answers)

Answer:
 CXCR5
 CD40L

Question: The changes to the antigen binding sites of B cell receptors in the germinal
center reaction are achieved by mutation of the:

Answer: Variable regions of Ig genes, combined with selection for high affinity
receptors.

Question: What are possible consequences of class switching from IgM to another
isotype? (select two answers)

Answer:
 A loss of complement activating function
 A gain of ADCC activating function

Question: You have learned that different antibody isotypes activate distinct
immune mechanisms. For example, IgE activates mast cells, while IgG activates ADCC.
The heavy chain isotypes differ structurally in the constant regions. These structural
differences lead to functional differences. What is NOT one of the structural or
functional differences between different antibody isotypes?

Answer: Different isotypes have different antigen affinities.

Helper T Cells

Question: You have already learned that naive T cells are typically activated in the
lymph node. Upon activation, they proliferate and gain effector functions, becoming
effector T cells. In this lesson, we’ll begin to discuss the effector functions of helper T
cells, which arise from activated naive CD4+ T cells. For a moment, let’s consider
both CD4+ and CD8+ T lymphocytes. Which of the functions given below is NOT a
major effector function of T cells?

Answer: Direct killing of extracellular microbes.

Question: Helper T cells can perform their effector functions in multiple different
locations. What immune function is likely to be activated by helper T cells in
secondary lymphoid organs?

Answer: The Germinal Center Reaction

Question: Which of the statements below best describes the migration of effector T
cells to sites of infection in the tissue?

Answer: T cells migrate via blood circulation into the tissue following a pathway
similar to acute inflammation.

Question: The different Th subsets perform different functions. For each of the types
of pathogens shown below, select the Th subset that coordinates an immune
response to that pathogen.

Answer:

Question: Which cytokines that are secreted by Th2 cells function to increase gut
mucus production and gut motility? (select two answers)

Answer:
 IL-13
 IL-4

Question: What are the two main factors produced by Th1 cells that function to
enhance phagocytic and antimicrobial activity of macrophages? (select two answers)

Answer:
 CD40L
 IFN-γ

Question: ______________ are the primary cell type activated by IL-5. When
activated, these cells release the contents of their cytoplasmic granules. The granule
contents are very toxic to helminths (parasitic worms).

Answer: Eosinophil

Question: There are many examples of the adaptive immune system activating cells
and components of the innate immune system. Which of the Th-associated cytokines,
below, activates the migration of neutrophils and monocytes into tissue, thereby
contributing to inflammation?

Answer: IL-17

Question: Cells of the innate immune system encounter a particular pathogen.

Innate cells release a certain set of cytokines, and antigen-specific naive CD4+ cells
are activated. These naive T cells proliferate and differentiate into cells that secrete
IFN-γ. Which of the pathogens listed below is most likely to cause this response?

Answer: Mycobacterium tuberculosis (an intracellular bacterium)

Question: A researcher studies Crohn’s disease. She has access to a ‘mouse model’
of Crohn’s disease. As they mature, the mice develop an inflammatory condition that
strongly resembles this disease. Before the mice mature and develop the disease,
she injects some of the mice with a neutralizing antibody that targets interferon-γ
(anti-IFN-γ). Assuming that the causes of this disease are similar in mice and humans,
what effect would you expect this treatment to have on the severity of the disease?

Answer: The disease will be lease severe.

Question: Allergic conditions are most associated with which Th subset?

Answer: Th2 Cells

Question: Let’s begin with a review question. All of the following drugs have been
used to treat psoriasis at some point in time. Which of these drugs is a biologic
therapy that binds to and blocks an adhesion molecule expressed on leukocytes?

Answer: Anti-LFA-1

Question: Dr. Merola discussed four different biologic therapies for psoriasis with
the patient. Which of these therapies does NOT block TNFα?

Answer: Secukinumab

Question: The correct answer to the question above is a monoclonal antibody. What
molecule does this antibody target?

Answer: IL-17

Question: What is the name of the cytokine produced by Th17 cells that acts directly
on skin cells, leading to epithelial hyperproliferation and the formation of plaques?

Answer: IL-22
Question: What is the name of the cytokine that drives the differentiation of Th17
cells and is the molecular target of ustekinumab?

Answer: IL-23

Question: We have seen that many different drugs that suppress immune function
increase the risk of infection. In a large clinical trial, patients treated with
secukinumab had increased incidence of infection with a particular microbe relative
to patients treated with etanercept. Based on your knowledge of helper T cell
biology, can you deduce which microbe patients were susceptible to?

Answer: Candida albicans (a fungus)

Question: Hyper-IgM syndrome is a rare genetic disease caused by a loss-of-function

mutation in the gene that codes for the CD40L protein. What are the two most likely
direct effects of CD40L deficiency?

Answer:
 Reduced phagocytic function of macrophages. Correct
 A failure of the germinal center reaction.

Question: Which Th subsets are most associated with chronic inflammatory diseases?

Answer: Th1 and Th17 Cells

Question: Which cytokine is a potent activator of eosinophils?

Answer: IL-5

Question: Which cytokine contributes to the development of sarcoidosis?

Answer: IFN-γ

Question: Tuberculosis (TB) is caused by Mycobacterium tuberculosis. A weakened

form of Mycobacterium bovis is the primary component of the main vaccine for TB;
this vaccine is called BCG. A healthy person vaccinated with BCG will develop a
robust adaptive immune response to the vaccine and is immune to subsequent TB
exposure. However, the M. bovis bacteria in the BCG vaccine are living bacteria.
Though M. bovis is not highly pathogenic in humans it can proliferate and cause
disease. In a very small number of individuals, BCG vaccination leads to M. bovis
infection. Which of the following genetic defects is most likely to predispose an
individual to infection with the bacteria in the BCG vaccine?

Answer: IFN-γ receptor deficiency

Question: Currently, one of the most exciting areas of growth in cancer therapeutics
is checkpoint blockade. Antibodies that block the interaction of PD-1 with PD-L1
have been successfully used to treat advanced melanoma and certain types of lung
cancer. There are possible immune side effects directly related to the mechanism of
action of these drugs. Which is the most likely side effect?

Answer: Autoimmunity

Question: An individual develops bacterial pneumonia (a bacterial infection of the

lungs). What Th subset is LEAST likely to play an important role in the response to
this infection?

Answer: Th2

Cytotoxic T Cells

Question: When appropriately activated, a naive CD8+ T cell will become an effector
T cell called a cytotoxic T lymphocyte (CTL). CTLs can enter infected tissue where
they target and kill infected cells. Do you think that these effector CTLs require
costimulatory signals to kill target cells?

Answer: No

Question: CTLs can kill cells infected with viruses or intracellular bacteria. They also
can kill cancerous cells. How might an infected or cancerous cell evade immune
control by CTLs?

Answer: Decreased expression of MHC class I molecules.

Question: If an individual is infected with a virus that primarily infects epithelial cells,
how might a dendritic cell display viral peptides to naive CD8+ T cells?

Answer: A DC internalizes viral particles and fragments by endocytosis. Viral proteins

are broken into peptides in proteasomes and displayed to CD8+ T cells on MHC class
I molecules.

Question: Naive CD4+ and CD8+ T cells require costimulation (signal 2). Usually the
costimulatory ligand is a B7 molecule that is expressed on the surface of an activated
DC. These B7 molecules bind to a molecule called ____________ expressed on the
surface of T cells.

Answer: CD28

Question: Naive T cells are initially activated in

Answer: Secondary Lymphoid Organs

Question: What are two consequences of naive CD8+ T cell activation?

Answer:
 Synthesis of perforin and granzymes
 Clonal expansion

Question: Which of the statements below best describe some effector functions of
CTLs? (select two answers)

Answer:
 Direct killing of infected cells.
 Release of IFN-γ.

Question: When activated, CTLs release ____________, a protein that perturbs

membrane integrity. The perturbation in membrane integrity leads to the entry of
granzymes into the target cell cytosol.

Answer: Perforin

Question: When granzymes enter target cells, they activate a cell-intrinsic

programmed cell death pathway known as

Answer: Apoptosis

Question: The process of ____________ describes the massive reduction in the

number of antigen-specific effector lymphocytes after an infection is cleared. Most
of these lymphocytes undergo apoptosis.

Answer: Contraction

Question: CD4+ and CD8+ T cells are critical players in an effective response to the
intracellular bacterium Mycobacterium tuberculosis. The most widely-used vaccine
for M. tuberculosis (BCG) is composed of live bacteria from the Mycobacterium
genus that elicit an immune response but rarely cause disease. Individuals
vaccinated with BCG develop a T cell response to the bacteria in the vaccine. In an
individual with no prior exposure to Mycobacterium, what type of T cells would first
be activated in the immune response to the BCG vaccine?

Answer: Naive T Cells

Question: Suppose an individual is vaccinated with BCG and develops protective

immunity. A few years later, this individual is exposed to M. tuberculosis. What type
of T cells would be activated against the tuberculosis pathogen?

Answer: Memory T Cells

Question: CD28 binds to B7 molecules, but ____________ binds to B7 with higher
affinity. This binding blocks the interaction of CD28 with B7 that is necessary for
costimulatory signaling.

Answer: CTLA-4

Question: High expression of ____________ by tumor cells could render that tumor
resistant to T cell immunity.

Answer: PD-L1

Question: Recall that this patient has been treated with antiviral therapy and HCV is
no longer detectable in his blood. Consider the patient’s physical exam in light of this
treatment history. Dr. Dienstag conducted a physical exam to look for signs of liver
damage. What can we conclude from the physical exam?

Answer: The patient has abnormal exam findings and he may have liver scarring or
damage.

Question: Which of the following immune cells are likely to be involved in the
immune response to HCV? (select all that apply)

Answer:
 Cytotoxic T Lymphocytes
 Helper T Lymphocytes
 B Lymphocytes
 Dendritic Cells

Question: Which of the following immune cells would be most likely to directly kill
liver cells infected with HCV?

Answer: Cytotoxic T Lymphocytes

Question: Many individuals infected with hepatitis C will fail to clear the virus in the
acute phase of infection and progress to chronic infection. Which factors are most
likely to contribute to this failure to clear hepatitis C infection? (select two answers)

Answer:
 Cytotoxic T lymphocyte exhaustion
 A high rate of viral mutation

Question: What cells cannot be killed by CTLs?

Answer: Red Blood Cells

Question: You have neutralizing antibodies that target each of the following
molecules. Blockade of which molecule is LEAST likely to elicit an anti-tumor immune
response?

Answer: CD40

Question: Proteases called ____________ are found in the cytotoxic granules of CTLs.
When released, they activate programmed cell death in target cells.

Answer: Granzymes

Question: Which of the following events would NOT contribute to the killing of an
epithelial cell by a CTL?

Answer: The epithelial cell expresses B7-2.

Question: Which of the effector cells listed below are major cellular sources of IFN-γ?
(select two answers)

Answer:
 Th1
 CTL

Failures of the Immune System

Question: Which primary immunodeficiency mainly impacts B cell development

without affecting T cells?

Answer: X-linked agammaglobulinemia (XLA)

Question: Individuals with X-linked agammaglobulinemia (XLA) are more susceptible

to some kinds of pathogens than others. What pathogen do you think an XLA patient
would be LEAST susceptible to?

Answer: Mycobacterium tuberculosis (an intracellular bacterium)

Question: The number of B lymphocytes and T lymphocytes in the blood is an

important component of the clinical diagnosis of primary immunodeficiencies. Which
disorder would be most likely to lead to low blood counts of T cells and B cells?

Answer: RAG type SCID

Question: Which of these factors does NOT contribute to the generation of self-
reactive T cells?
Answer: Millions of different inherited T cell receptor genes.

Question: Which of the following is a mechanism of peripheral tolerance that

controls self-reactive effector B cells AND self-reactive effector T cells?

Answer: Regulatory T Cell Suppression

Question: What is the main difference between central tolerance in the thymus and
in the bone marrow?

Answer: Clonal deletion of T cells occurs in the thymus, while receptor editing of B
cells occurs in the bone marrow.

Question: How do antibodies contribute to glomerulonephritis in lupus?

Answer: Antibodies form immune complexes, which cause inflammation that

damages kidney vessels.

Question: How do antibodies contribute to myasthenia gravis?

Answer: Antibodies neutralize a key molecule involved in neuron function.

Question: Monozygotic (identical) twins are approximately 50% concordant for type
1 diabetes (T1D). This means that if one twin has T1D, there is about a 50% chance
that the other twin will also have the disease. T1D is not a common disease. This
suggests that ____________.

Answer: T1D risk is determined partially by genetic factors and partially by

environmental factors.

Question: What distinguishes allergy from autoimmunity?

Answer: Allergy is a response to environmental antigens; autoimmunity is a

response to self antigens.

Question: Some “type 2” T follicular helper cells secrete IL-4 and IL-13. In response, B
cells initiate class switching that favors the ___________ isotype, which plays a
particularly important role in allergy.

Answer: IgE

Question: In addition to the cytokine IL-4, what signal do helper T cells provide to B
cells that would favor B cell receptor affinity maturation and isotype switching?

Answer: CD40L
Question: What molecule that is released by mast cells contributes to the formation
of the wheal and flare reactions we observed in this patient’s skin tests?

Answer: Histamine

Question: Researchers have found that the level of microbes (specifically bacteria)
were higher in Amish households than Hutterite households. They sought
immunologic evidence for differences in bacterial exposure between the populations.
Which of the following observations of immune function would be most directly
supportive of the idea that the Amish children were exposed to more bacteria than
the Hutterite children?

Answer: Amish children have a higher proportion of neutrophils out of all blood
leukocytes than Hutterite children. Correct

Question: Which of the following statements best describes the relationship

between environmental factors and allergy risk, based upon this summary of the
hygiene hypothesis?

Answer: Available evidence supports the concept that exposure to some microbes
protects against allergy.

Question: A monoclonal antibody that binds to IgE is used as a drug to treat allergies.
This anti-IgE drug directly interferes with a process that leads to activation of
____________.

Answer: Mast Cells

Question: The therapeutic antibody that targets IgE probably binds to what portion
of the IgE antibodies that contribute to allergies?

Answer: Fc

Question: Which primary immunodeficiency would be most effectively treated by

transfusions of IgG extracted from the blood of healthy adults?

Answer: XLA

Question: Plasmapheresis is a procedure that involves removing blood from a

patient, fractionating it and discarding some fraction, then returning the blood to the
patient. For example, this can be done to remove immunoglobulins from the blood
but return leukocytes and red blood cells. Which of the autoimmune or
inflammatory diseases below might be most effectively treated with plasmapheresis
to remove immunoglobulins? (Select two answers.)

Answer:
 Myasthenia Gravis
 Lupus

Question: Human immunodeficiency virus (HIV) is a virus that primarily infects CD4+
T cells. As HIV infection progresses, CD4+ T cell counts drop precipitously. To which
of the following diseases would a patient with HIV have increased susceptibility?
(Select all that apply.)

Answer:
 Mycobacterium tuberculosis (an intracellular bacterium)
 Streptococcus pneumoniae (an extracellular bacterium)
 Pneumocystis jirovecii (a fungus)
 Herpes simplex viruses

Question: What immune mediator, below, is most typically associated with allergy?

Answer: IL-4

Question: All of the genetic defects described below exist at very low frequency in
the human population. Which loss-of-function mutation would be most likely to lead
to autoimmune disease? Assume each mutation causes a complete loss of function
of the associated gene.

Answer: Disruption of the FOXP3 gene which is necessary for Treg development.

Question: Anaphylaxis is an acute allergic response. What aspects of allergic

anaphylaxis are the most immediately life-threatening? (Select two answers.)

Answer:
 Low Blood Pressure
 Airway Constriction

Question: In this lesson, we discussed mechanisms of central and peripheral

tolerance for T cells. Imagine a self-reactive T cell that has not undergone clonal
deletion in the thymus (that is to say, it has escaped central tolerance). If it
encounters self antigen in the absence of an infection or inflammation, what will
happen to this self-reactive T cell? (Select two answers.)

Answer:
 The T cell undergoes apoptosis.
 The T cell becomes anergic.

Immunology-Based Therapy of Diseases

Question: Transplantation involves the transfer of tissues or organs from one person
to another person. Some transplantation procedures can involve the transfer of
tissue between different sites on the same individual’s body. Consider the case of
the transplantation of a liver from one person to an unrelated recipient who has liver
failure. Although any two humans are more than 99% genetically identical, they do
have genetic differences that might lead to a reaction in which the recipient’s
immune system attacks the donor tissue. This is called transplant rejection.
Although we have not yet covered the immunologic basis of transplant rejection,
consider what you have learned about the immune system so far in this course.
What scenario, below, is most likely to cause transplant rejection?

Answer: Antigen receptors on recipient T cells will bind to peptide-MHC complexes

in donor tissue and initiate an adaptive response that causes transplant rejection.

Question: Given what you have learned about the genetic loci that are most
important for transplant compatibility, it is likely that ____________ are the primary
mediators of transplant rejection.

Answer: T Lymphocytes

Question: A burn victim receives a skin transplant. Theoretically, his medical team
could choose from several different donors, but the choice of donor is obvious in this
case. Who is the donor?

Answer: The Patient

Question: Which immune mechanisms or processes are most commonly associated

with transfusion reactions? (select two answers)

Answer:
 Complement Activation
 Opsonization

Question: The antigens of the ABO blood groups are:

Answer: Carbohydrates

Question: Recall that HSC transplantation is colloquially known as a “bone marrow

transplant”. Assume that HLA matching is not performed in any of these scenarios.
Given this information alone, predict the order of the likelihood of transplant
rejection for these scenarios. Note that in all cases below, answers are ordered from
lowest risk of transplant rejection (left) to greatest risk of rejection (right).

Answer: Self = Identical Twin < Parent < Cousin

Question: You have learned about many different kinds of immune diseases in this
course. The therapies given to patients to prevent transplant rejection are most
similar to therapies used to treat

Answer: Autoimmune Diseases

Question: A man with blood type A is in a car accident and has a large amount of
internal bleeding. He needs an emergency red blood cell (RBC) transfusion. RBCs of
which blood types, below, can be safely transfused? Note that for the purposes of
this exercise, we are not considering the Rh factor, which is commonly denoted with
a positive or negative after the blood type. (select all that apply)

Answer:
 A
 O

Question: In 2015, there was a major outbreak of disease caused by Ebola virus that
caused a public health emergency in West Africa. The outbreak was eventually
controlled with public health measures (isolation and treatment of infected
individuals and careful follow-up with other individuals with whom infected
individuals had been in contact). Some individuals with severe disease were treated
with blood or serum transfusions from Ebola survivors. What form of therapy was
this, and how does it work?

Answer: Passive immunotherapy; protection is mediated by antibodies transferred

from the survivors.

Question: Which of the methods of immune therapy that have been covered so far
in this course involve the transfer of new genetic material into an individual’s cells?
(select two answers)

Answer:
 Vectored Immunoprophylaxis
 CAR T Cells

Question: To date, the most common clinical use of CAR T cell therapy has been for
the treatment of patients with B cell leukemias. To review what you have learned
about B cell malignancies in this course, select this link. Which antigen is the most
likely target of these CAR T cells?

Answer: CD19 (a cell surface antigen on most B cells)

Question: Which of the therapies listed below involves administration of antibodies

to activate T cells?

Answer: Checkpoint Blockade

Question: Like many medical specialties, oncology is increasingly moving towards

personalization of therapy. Which of the therapies that we have discussed in this
course so far require the most personalization of therapy based on a cancer patient’s
genotype?
Answer: Vaccination with cancer neoantigens.

Question: Dr. Flaherty and his patient discussed different treatments for melanoma.
What therapy pre-dates checkpoint blockade but gives us a hint that melanoma
could be controlled by the immune system?

Answer: Cytokines

Question: Before checkpoint blockade therapy was ever used for cancer therapy,
what line of evidence most strongly suggested that these therapies might be
successful for patients with melanoma?

Answer: Many melanoma patients have pre-existing T cells that are specific for
antigens expressed by melanoma cells.

Question: The patient was treated with an antibody that blocks PD-L1. Where is this
molecule expressed, and how might it function in the treatment of melanoma?

Answer: PD-L1 is expressed by immune cells, such as DCs, and non-immune cells,
including many cancer cells. Blocking PD-L1 prevents its interaction with PD-1
expressed by T cells, thus relieving a negative regulator of T cell function.

Question: You are studying transplant rejection in a wild and genetically diverse
population of mice. You have captured some of the mice for laboratory studies. You
have four mice from a family. Mouse 1, mouse 2, and mouse 3 are littermates, thus
they all share the same mother and father. Mouse 4 is the father of the other three
mice. You transplant a small patch of skin from mouse 2 (the donor) onto mouse 1
(the recipient). There is a delayed inflammatory response and two weeks later the
skin is necrotic due to transplant rejection. You decide to attempt another transplant.
Which follow-up transplant is LEAST likely to be rejected?

Answer: Skin from Mouse 4

Question: Now consider the same scenario as the question above.

Which follow-up transplant is MOST likely to be rapidly rejected?

Answer: Skin from Mouse 2

Question: A woman with type O blood type requires emergency surgery. The surgical
team wants to have blood ready for a transfusion if it is needed during the
procedure. What blood types are safe to transfuse?

Answer: O

Question: Consider a man with end-stage renal disease who has recently received a
kidney transplant. He recovers normally but months later there are indications that
he has developed a complication related to the transplant. Which of the possible
conditions listed below is LEAST likely to happen as a result of his transplant or the
treatment he received along with the transplant?

Answer: Myasthenia Gravis (a systemic autoimmune disease)

Question: Which of the circumstances below most accurately describes conditions

that are likely to permit a robust anti-tumor adaptive immune response?

Answer: A tumor with high expression of proteins that have mutations in sequences
encoding HLA-binding peptides.

Question: Which of the therapies listed below involves the use of antibodies that
bind to an infectious agent?

Answer: Vectored Immunoprophylaxis