Roitt's Essential Immunology

Table of Contents
Innate immunity ................................................................................................................................... 2
Specific Immunity ............................................................................................................................... 11
Immunoglobulin .................................................................................................................................. 22
Membrane receptor for antigen........................................................................................................ 31
Antigen specific recognition .............................................................................................................. 42
Anatomy of immune system ............................................................................................................. 53
Lymphoctic Activation ........................................................................................................................ 65
Innate immunity

Which of the following does NOT protect body surfaces?

A Skin

B Mucus

C Gastric acid

D Salivary amylase

E Gut microflora

The correct answer is D. The enzyme splits starch and is of importance for digestion
but not for protection. Intact skin prevents entry of microorganisms. Damage, as in
burns, causes vulnerability to infection. Mucus lining the mucosal surfaces of the
body tends to inhibit direct attachment of infectious microorganisms to the mucosal
surface. Gastric acid provides a hostile environment to many microorganisms. Gut
microflora produce antibiotic substances, colicins, which can kill other bacteria

Pattern recognition receptors (PRR) include which of the following?

A Lipopolysaccharide (LPS)

B Pathogen-associated molecular patterns (PAMPs)

C Lipoteichoic acid

D Lectin-like molecules

E Unmethylated CpG sequences

The correct answer is D. Many PRR are lectin-like in that they recognize exposed
microbial sugars. Gram-negative bacteria produce LPS, the biologically active lipid A
moiety of which is recognized by LPS-binding protein (LBP); the LBP-LPS complex is
captured by the CD14 scavenger molecule on phagocytic cells which then become
activated through Toll-like receptor-4 (TLR4). PAMPs are recognized by the pattern
recognition receptors. Lipoteichoic acid is produced by Gram-positive bacteria and
acts as a PAMP. Unmethylated guanosine-cytosine dinucleotide sequences in
bacterial DNA are an example of a PAMP linked to intracellular infection.

Which of the following does the mononuclear phagocyte system NOT

include?
 A Monocytes

B Kupffer cells

C Kidney mesangial cells

D Lymph node medullary macrophages

E Endothelial cells

The correct answer is E. Endothelial cells are not essentially phagocytic although
they do contribute by the production of mediators of the inflammatory process,
particularly acute inflammation, and were previously lumped together with the
mononuclear phagocyte system in what was known as the reticuloendothelial system
(RES). Monocytes circulate in the blood, being derived from hematopoietic myeloid
stem cells. Monocytes settle to become phagocytic Kupffer cells in the liver. The
mononuclear phagocytes that form the mesangium in the glomeruli are part of this
system. Macrophages lining the medullary sinuses are part of the mononuclear
phagocyte system.

A polymorphonuclear neutrophil (PMN):

A Is a bone marrow stem cell

B Is closely similar to a mast cell

C Contains microbicidal cytoplasmic granules

D Is not a professional phagocytic cell

E Has granules that stain with eosin

The correct answer is C. The granules contain a wide spectrum of microbicidal

agents. The bone marrow hematopoietic stem cell is the precursor of the formed
elements of the blood which include the PMN. The granular polymorphonuclear cell
which stains with basic dyes (i.e., the basophil) is similar to a mast cell. The major
professional phagocytic cells are the neutrophils and the macrophages. The word
neutrophil implies that the granules stain neither with acid nor basic dyes. The
eosinophil has granules that stain with the acid dye eosin and is important in
defense against parasitic infections.
Which of the following is NOT produced following activation of the NADPH
oxidase microbicidal pathway?

A O2−

B O2

C H2O2

D NO

E OH

The correct answer is D. NO is produced following the induction of nitric oxide

synthase. O2− is the superoxide anion obtained by addition of an electron to
molecular oxygen by the cytochrome b558 oxidase system. Oxygen is utilized as a
substrate to which cytochrome b558 transfers an electron from NADPH. Hydrogen
peroxide is generated from O2− and, although not as active as the free radicals, is
more stable and therefore diffuses further. The hydroxyl radical is one of the most
reactive free radicals known and is formed by the reduction of H2O2, for example
following its reaction with Fe2+.

Neutrophil defensins are:

A Anti-toxins

B Oxygen-dependent

C Enzymes

D Glycolipids

E Peptide antibiotics

The correct answer is E. The defensins are peptide antibiotics present in the
granules in extremely high concentration. Anti-toxins are usually antibodies. The
defensins are part of the oxygen-independent defensive system of the neutrophil.
There are enzymes within the neutrophil granules, some of which participate in the
production of reactive intermediates and some of which help the digestion of killed
microorganisms, but the defensins do not have enzymic activity. Neutrophils possess
various cell surface glycolipids, but these are not defensins.

The Toll-like receptor 9 (TLR9) pattern recognition receptor recognizes:

 A CpG motifs

B Bacterial lipopeptides

C Lipoteichoic acid

D Gram-negative LPS

E dsRNA

The correct answer is A. TLR9 recognition of these microbial dinucleotide sequences

leads to activation of the NFκB transcription factor. It is the TLRI/TLR2 heterodimer
that recognizes bacterial lipopeptides. Lipoteichoic acid is recognized by the
TLR2/TLR6 heterodimer. Following its ligation by LPS-binding protein, the LPS from
Gram-negative bacteria is recognized by TLR4 in a CD14-dependent process. The
presence of double-stranded RNA is a marker of viral infection and is detected by
TLR3.

Complement component C3 is cleaved by:

A C3b

B C3bBb

C Factor B

D Factor D

E Factor H

The correct answer is B. C3bBb is the C3 convertase enzyme generated in the

alternative complement pathway and is responsible for splitting off the small peptide
C3a, leaving C3b as a residue. C3b is an opsonizing agent that assists phagocytosis
and also contributes to some of the cleavage enzymes. Factor B is cleaved by factor
D and then contributes the resulting Bb fragment to the alternative pathway C3
convertase (see learning response B). Factor D splits factor B to form Bb. Factor H
combines with C3b making it vulnerable to cleavage by factor I. It displaces factor
Bb from the convertase so leading to its destabilization

The membrane attack complex consists of:

A OH
 B Colicins

C C3bBb3b

D C5b,6,7,8,9

E Properdin

The correct answer is D. These terminal components form a complex that inserts
into the membrane to form a transmembrane ion channel which leads to lysis of the
cell. The hydroxyl radical is a reactive oxygen intermediate. The colicins are
antibiotics produced by the gut microflora. C3bBb3b is the convertase that splits
component C5 to give C5a and C5b. Properdin is a component of the alternative
pathway which stabilizes the C3bBb C3 convertase.

Which of the following statements is TRUE of C3b?

A C3b is chemotactic for neutrophils

B C3b is an anaphylatoxin

C C3b opsonizes bacteria

D C3b directly injures bacteria

E C3b is the inactive form of C3

The correct answer is C. Bacteria coated with C3b adhere to C3b receptors on
professional phagocytic cells. C5a, not C3b, is chemotactic for neutrophils. C3a and
C5a, small peptides split off from the parent C3 and C5 molecules, are
anaphylatoxins that trigger mast cell degranulation. There is no evidence that C3b
directly injures bacteria. The inactive form of C3 is obtained by splitting the C3b to
form iC3b, C3d, and C3dg.

Acute inflammation characteristically involves:

A Constriction of arterioles

B Capillary endothelial cell enlargement

C Influx of macrophages

D Influx of mast cells

 E Influx of neutrophils

The correct answer is E. Neutrophils are chemotactically attracted to the site of

inflammation by C5a and mast cell chemotactic factors such as leukotriene B4. The
arterioles dilate rather than constrict. The endothelial cells separate and make the
basement membrane accessible to the neutrophils. Macrophages are in the minority
in acute inflammation. Mast cells, unlike basophils, do not migrate to a significant
extent but their degranulation mediates acute inflammatory reactions.

Which of the following statements is TRUE of lysozyme?

A Lysozyme is a cytoplasmic organelle

B Lysozyme activates complement

C Lysozyme is a proteolytic enzyme

D Lysozyme splits peptidoglycan

E Lysozyme is released by mast cells

The correct answer is D. Lysozyme splits the peptidoglycan of bacterial cell walls.
Lysozyme is a protein present in extracellular fluids and in certain granules of
professional phagocytic cells. Although complement activation involves an enzyme
cascade, lysozyme has no role in this process. Lysozyme is an enzyme, but its
activity is not proteolytic. Lysozyme is not present in mast cells.

Which of the following is NOT an acute phase protein?

A Serum amyloid P component

B Chondroitin sulfate

C C-reactive protein

D Mannose-binding lectin

E Fibrinogen

The correct answer is B. Chondroitin sulfate is a cell matrix component. Serum

amyloid P component is an acute phase reactant whose concentration increases
dramatically on infection. C-reactive protein is an acute phase reactant which binds
to certain bacterial polysaccharides and activates the first component of
complement. Mannose-binding lectin is a major acute phase protein which binds to
mannose on bacteria, fixes complement, and facilitates adherence to macrophages.
Fibrinogen shows a moderate increase in concentration on infection.

Which of the following statements is TRUE of interferons?

A Interferons are found only in mammalian species

B Interferons are divided into five main families

C Interferons induce enzyme synthesis in the target cell

D Interferons only affect infected cells

E Interferons are specific for individual viruses

The correct answer is C. Derepression of genes in the target cell result in the
synthesis of a protein kinase and an endonuclease. Interferons are present in birds,
reptiles, and fishes as well as higher animals. There are three main families of
interferons: α, β, and γ. In fact, the interferons render cells unable to support viral
replication, thereby establishing a cordon sanitaire around the site of a virus
infection so restraining its spread. Interferons were first recognized by the
phenomenon of viral interference in which an animal infected with one virus resists
superinfection by a second unrelated virus.

Natural killer (NK) cells do NOT:

A Respond to interferon

B Contain perforin

C Contain tumor necrosis factor (TNF)

D Kill only by damaging the target cell outer membrane

E Contain serine proteases

The correct answer is D. Perforin inserts into the target cell membrane thereby
facilitating entry of TNF and granzymes into the target cell. Their activity is
stimulated by interferon. They contain perforin, which is released on contact with a
target, inserts itself into the target cell membrane, and creates a pore through which
granzymes are transferred into the target cell. TNF produced by NK cells contributes
to the killer function. NK cells contain a number of serine proteases of the granzyme
family, one of which, granzyme B, can split procaspase 8 and thereby activate
apoptosis in the target cell

Eosinophils do NOT:

A Stain with basic dyes

B Contain a major basic protein

C Contain peroxidase

D Give a respiratory burst on activation

E Have C3b receptors

The correct answer is A. They do stain with acidic dyes. The secreted basic protein
damages helminth membranes. The peroxidase contributes to the generation of
reactive oxygen intermediates. There is a respiratory burst involving the concomitant
generation of active oxygen metabolites. The C3b receptors bind opsonized
pathogens, including microorganisms and larger parasites such as helminths.

Polymorphonuclear neutrophils attack bacteria:

A Exclusively by oxygen-dependent mechanisms

B Exclusively by oxygen-independent mechanisms

C By phagocytosis

D By secreting complement

E By secreting interferon

The correct answer is C. The ability to ingest bacteria and kill them is a major
feature of these professional phagocytic cells. Loss of neutrophils renders the host
very susceptible to overwhelming infection. The production of reactive oxygen
intermediates is not the only mechanism of attack. The oxygen-independent
mechanisms such as lysozyme, defensins, and so on are not the only mechanisms of
attack. Macrophages but not neutrophils secrete a number of complement
components. Interferon is active against viruses.

Which of the following is a complement component that is strongly

chemotactic for neutrophils?
 A C9

B C5a

C C3

D C3b

E C5b

The correct answer is B. C5a is a powerful chemotactic agent and also an

anaphylatoxin. C9 is the terminal complement component which forms part of the
membrane attack complex. C3 has no direct biological action but is split to give C3a
and C3b when the complement system is activated. C3b opsonizes microorganisms
for adherence to phagocytic cells. C5b initiates formation of the membrane attack
complex.

Acute inflammation can be initiated by:

A Mast cell activation

B Influx of neutrophils

C An increase in vascular permeability

D C3

E Lysozyme

The correct answer is A. Activation of mast cells releases chemotactic factors for
neutrophils and also vasoactive mediators such as histamine. The influx of
neutrophils represents part of the acute inflammatory response itself. The increase
in vascular permeability is an essential feature of the acute inflammatory response
itself. C3 has no biological activity before being cleaved. Lysozyme is not a part of
the acute inflammatory process although it may be released from neutrophils, and
also participate in intracellular killing within the neutrophils following phagocytosis

The NLRP3 inflammasome leads to the release of:

A IL-8

B IL-1β

C TNF
 D Interferon-α

E Platelet activating factor (PAF)

The correct answer is B. The NLRP3 inflammasome converts pro-IL-β to active IL-1β.
IL-8 leads to the release of IL-18. Although the NLRP3 inflammasome is involved in
the generation of pro-inflammatory cytokines, the pro-inflammatory cytokine TNF is
not one of them. Interferon-α is not generated by the NLRP3 inflammasome. PAF is
not generated by the NLRP3 inflammasome.

Specific Immunity

The NLRP3 inflammasome leads to the release of:

A IL-8

B IL-1β

C TNF

D Interferon-α

E Platelet activating factor (PAF)

The correct answer is B. The NLRP3 inflammasome converts pro-IL-β to active IL-1β.
IL-8 leads to the release of IL-18. Although the NLRP3 inflammasome is involved in
the generation of pro-inflammatory cytokines, the pro-inflammatory cytokine TNF is
not one of them. Interferon-α is not generated by the NLRP3 inflammasome. PAF is
not generated by the NLRP3 inflammasome

Several of the complement components are:

A Glycolipids

B Cell surface molecules of lymphocytes

C Precursors of enzymes

D Hormones

E Antibodies
The correct answer is C. Upon splitting, individual components form enzymatically
active complexes that act in a sequential proteolytic cascade. The complement
components are all proteins or glycoproteins. Although they may become deposited
on the cell surface following activation, they are normally present in soluble form in
blood and tissue fluids. Note, however, that several receptors for complement
components are present as cell surface molecules on lymphocytes and other cell
types. The complement components are produced by several different cell types and
do not function as hormones. Antibodies are the specific recognition molecules that
bind antigen.

The classical and alternative pathways meet at complement component:

A C4

B C4b

C Factor D

D C5

E C3

The correct answer is E. Each pathway of complement activation produces a C3

convertase, either C4b2b (classical and lectin pathways) or C3bBb (alternative
pathway), which cleaves C3 into C3a and C3b. C4 is only found in the classical and
lectin pathways. Note that the complement components are numbered in the order
they were first identified rather than the order in which they act. C4b is produced by
cleavage of C4 by C1qrs or MBL/MASP1/2 and forms part of the classical and the
lectin pathways of complement activation. Factor D is found in the alternative
pathway and cleaves factor B in the C3bB complex to produce C3bBb, the alternative
pathway C3 convertase. C5 is one of the later complement components which upon
being split by C5 convertase forms the anaphylatoxin C5a and may go on to form
the membrane attack complex containing complement components C5b, C6, C7, C8,
and C9.

Clonal selection occurs when antigen is encountered by:

A Neutrophils

B Mast cells
 C T-cells

D Basophils

E Eosinophils

The correct answer is C. Both T- and B-cells possess antigen-specific receptors and
clones of these lymphocytes will be selected to proliferative when specific antigen is
encountered. Neutrophils can phagocytose and destroy antigens, but are not clonally
selected. Mast cells sensitized with IgE will release inflammatory mediators if the IgE
is cross-linked by multivalent antigen, but this is not referred to as clonal selection.
Basophils are the blood-borne equivalent of the tissue mast cell and are not clonally
selected by antigen. Eosinophils can release inflammatory mediators and kill by
extracellular cytotoxic mechanisms, but do not possess the antigen-specific receptors
required of cells that undergo clonal selection.

Which of the following statements is TRUE of plasma cells?

A Plasma cells have a thin layer of cytoplasm

B Plasma cells are derived from T-cells

C Plasma cells develop into B-cells

D Plasma cells secrete large amounts of IFNγ

E Plasma cells have a high RNA content

The correct answer is E. Plasma cells secrete large amounts of antibody and
therefore require considerable amounts of mRNA to make this protein. Resting B-
cells have only a thin layer of cytoplasm, but plasma cells possess a large amount of
cytoplasm. It is B-cells that give rise to plasma cells. B-cells develop into plasma cells
that are terminally differentiated and therefore are not able to further develop into
any other cell type or to revert to being B-cells. IFNγ is a cytokine that is
characteristically a product of Th1 cells and natural killer (NK) cells.

Specific antibodies are readily detectable in serum following primary

contact with antigen after:

A 10 min

B 1h
 C 5–7 days

D 3–5 weeks

E Only following a second contact with antigen

The correct answer is C. 5 days or more are required for B-cell proliferation,
maturation, and the secretion of a large enough amount of antibody for it to be
readily detected systemically. Following antigen selection, the B-lymphocyte requires
time to proliferate in order to expand up the clone of cells, some of which then
differentiate into antibody- secreting plasma cells. By 3–5 weeks, the level of specific
antibody is declining. While a greater amount of antibody is produced following the
second contact with antigen, appreciable amounts are produced following primary
contact.

A single plasma cell secretes:

A Antibody of a single specificity related to that on the surface of the parent B-

cell

B Antibody of two antigen specificities

C The antigen it recognizes

D Many different types of antibody

E Lysozyme

The correct answer is A. A single plasma cell secretes millions of molecules of

antibody but they are all identical and will be related to the single specificity of
antibody used as the antigen receptor on the B-lymphocyte from which the plasma
cell was derived. A plasma cell secretes antibody of a single specificity. Although
antibodies have two antigen binding arms, they both have identical specificity. It
secretes the antibody which recognizes the antigen. A plasma cell secretes antibody
of a single specificity. Lysozyme is an antimicrobial enzyme that is produced by
phagocytic cells, not plasma cells.

Immunological memory can be transferred experimentally by:

A Antibody

B Complement
 C Phagocytes

D Lymphocytes

E Serum

The correct answer is D. Adoptive transfer experiments helped establish that

immunological memory, one of the hallmarks of the adaptive immune response, is a
property of the small lymphocyte. Experimental situations in which antibody, or
antibody-containing serum, is transferred from one experimental animal to another
is referred to as passive transfer of immunity, but it does not confer immunological
memory. Experimentally, complement components may be transfered to, for
example complement-deficient strains of mice, in order to help confirm the role of
that component. However, this does not transfer acquired immune responsiveness.
Adoptive transfer can be used to transfer immunological memory to a naive recipient
but phagocytic cells are not the cell type responsible for the enhanced immune
response which occurs on the second encounter with specific antigen. Experimental
situations in which antibody-containing serum is transferred from one experimental
animal to another is referred to as passive transfer, but it does not confer
immunological memory.

What is the main reason an experimental animal treated with X-rays can
act as a living test tube for lymphocyte transfer experiments?

A It is microbiologically sterile

B Complement components will be inactivated

C The host lymphocytes are destroyed or unable to divide

D Only non-dividing cells are affected

E The requirement for T-cell help is overcome

The correct answer is C. Lymphocytes are highly sensitive to radiation and if the
host's lymphocytes are destroyed or unable to divide following treatment with X-
rays, then any immune response observed following lymphocyte transfer will be of
donor, not recipient, origin. Although X-irradiation can be used to kill microorganisms
this is not the reason it is used in lymphocyte transfer experiments, which utilize a
comparatively low level of irradiation. The doses of irradiation used are too low to
cause any substantial damage to complement. It is dividing cells that are affected by
irradiation. X-irradiation does not overcome a requirement for T-cell help and
therefore for an antibody response to a T-cell-dependent antigen to occur in the
recipient, both T- and B-lymphocytes must be transferred.

What is immunological unresponsiveness to self-antigens called?

A Tolerance

B Tolerogen

C Memory

D Acquired immunity

E Antibody-dependent cellular cytotoxicity (ADCC)

The correct answer is A. Tolerance is a specific immunological non-responsiveness.

While tolerance can be induced to any antigen, the mechanism is thought to have
evolved as a means of preventing the maturation of self-reactive lymphocytes. A
tolerogen is an antigen capable of inducing a state of tolerance. Most antigens are
capable of acting as tolerogens. Whether the outcome of an initial encounter with
antigen results in an immune response or tolerance depends on several criteria
including the amount of antigen (very high or very low doses are often tolerogenic),
route of administration, and the form in which the antigen is given (e.g., monomeric
or polymeric). Memory is the phenomenon whereby the immune system is able to
recall a previous encounter with a given antigen and thus mount a secondary
immune response. The term recall antigen is sometimes used to denote common
antigens capable of eliciting strong secondary immune responses (e.g., tetanus
toxoid, Candida). The term acquired immunity is used to differentiate the adaptive
immune system from the innate immune system, and refers to the fact that the
immune system acquires a large range of specificities based on antigen receptor
gene rearrangement followed by exposure of lymphocytes to a broad range of
environmental antigens. ADCC is a mechanism for killing target cells coated with
antibody, but instead of a complement-mediated or phagocytic attack, Fc receptor-
bearing cells such as monocytes and NK cells recognize the antibody-coated target
cells and then kill the target by delivering a ‘lethal hit’.

Edward Jenner vaccinated against smallpox using:

A Killed smallpox virus

B A recombinant protein derived from smallpox

 C An unrelated virus

D Toxoid

E Cowpox

The correct answer is E. The smooth unblemished skin of milkmaids gave Jenner the
idea of using cowpox. The cowpox virus is non-virulent in humans but shares
antigens with the related smallpox virus and is therefore able to elicit protection
against subsequent infection with smallpox. Note, however, that killed organisms are
used in some present day vaccines against other infectious agents (e.g., influenza,
cholera, and inactivated poliomyelitis (Salk) vaccines). The term recombinant protein
is used to refer to a molecule produced using recombinant DNA technology, not
available 200 years ago. An unrelated virus would be unlikely to share antigens with
smallpox and therefore would be of no use as a vaccine for this disease. Toxoids are
chemically modified non-pathogenic bacterial toxins which can be used as vaccines
against the harmful effects of the corresponding bacteria by eliciting antibodies that
neutralize the toxin (e.g., diptheria toxoid, tetanus toxoid).

Protective antibodies against infectious agents are often:

A Autoantibodies

B Neutralizing

C Toxoids

D Natural killer (NK)

E Non-specific

The correct answer is B. They protect by neutralizing a function of the pathogen

such as the harmful part of a toxin or a viral coat protein which binds to a cell-
surface viral receptor on the host cells. Autoantibodies are antibodies against ‘self’
molecules. Toxoids are chemically modified non-pathogenic bacterial toxins which
can be used as vaccines against the harmful effects of the corresponding bacteria by
eliciting antibodies that neutralize the toxin. NK is a type of lymphoid cell that is
able to kill certain target cells such as tumor cells and some virally infected cells,
whereas antibodies are molecules. All antibodies, irrespective of the type of
antigen they recognize, are defined by and have their protective action through their
specificity for that antigen.

Intracellular parasites within macrophages are killed more readily in the

presence of:

A Antibody

B Kinins

C Properdin

D IFNγ

E Anaphylatoxin

The correct answer is D. IFNγ activates microbicidal mechanisms within the

macrophage, thereby leading to the death of intracellular parasites. Generally
speaking, antibodies do not readily enter the cytoplasm of cells and therefore
intracellular parasites are inaccessible to antibodies. Fc receptor-mediated
internalization of antibody does occur, but the antibody is confined within
endocytotic vesicles and would not be able to attack intracellular parasites. Kinins
are vasoactive peptides that are produced following tissue injury. Properdin binds to
and stabilizes C3bBb in the alternative pathway of complement activation. The
anaphylatoxins are molecules such as the complement components C3a and C5a,
which trigger mast cell degranulation.

T-cell surface receptors for antigen partly recognize:

A Cytokines

B Major histocompatibility complex (MHC)

C ADCC

D Antibody

E IL-2

The correct answer is B. T-cells recognize processed antigen plus the MHC molecules
which act as a marker to inform the T-cell that it is in contact with another cell.
Cytokines are molecules that mediate communication between cells. They are not
recognized by the T-cell surface receptors for antigen, but note that T-cells possess
other receptors (cytokine receptors) that specifically recognize individual cytokines.
ADCC is a mechanism of cell killing. Antibody acts as the B-cell surface receptor for
antigen. IL-2 is a cytokine that can be recognized by activated T-cells, but they
detect the presence of IL-2 using a cytokine receptor, not their specific antigen
receptor.

An immune response against grass pollen often involves:

A Pathogen-associated molecular patterns (PAMPs)

B Breakdown of self-tolerance

C A hypersensitivity reaction

D Reaction against MHC

E Persistent infection by the pollen

The correct answer is C. Hypersensitivity to otherwise innocuous antigens can lead

to tissue damage. PAMPs are repetitive structures widely expressed on infectious
microorganisms and recognized by the pattern recognition receptors (PRR).
Breakdown of self-tolerance can lead to the development of autoimmune diseases
such as multiple sclerosis and type I diabetes. Immunopathological reactions occur
during transplant rejection in which MHC antigens on the donor graft are the target
of an immune response. Grass pollen is not an infectious agent, a term used to
describe organisms that invade the host and are capable of replication (e.g.,
bacteria, viruses, nematode worms).

Why are secondary antibody responses better?

A They provide defense against unrelated antigens

B The antibody can be made by both T- and B-cells

C Complement-fixing antibodies are made

D They do not require T-cell help

E They are stronger and faster

The correct answer is E. Upon the second encounter with the same antigen, the
response occurs much faster, the amount of antibody made is much greater, and the
response lasts longer. This forms the basis for vaccination, using a harmless form of
the infectious agent for the immunization. Both primary and secondary immune
responses are specific for the antigen that elicits the response. A secondary immune
response only occurs if the same antigen is encountered as that which produced the
primary immune response. The only cells in the body that are capable of producing
antibody are B-cells, and their fully differentiated progeny referred to as plasma
cells. The antibodies produced in both the primary and secondary immune responses
can be efficient at complement fixation. Secondary immune responses require T-cells
which provide help, mainly in the form of cytokines, in order for the B-cells to make
antibody. In fact, antigens that provoke antibody responses in the absence of T-cells
(T-independent antigens) are unable to elicit a secondary type of immune response
but rather stimulate a primary type of immune response no matter how many times
they are encountered.

Which cell type produces antibodies?

A Macrophages

B T-lymphocytes

C NK

D Plasma cells

E Eosinophils

The correct answer is D. B-lymphocytes have antibody on their cell surface that acts
as an antigen receptor. Upon activation they differentiate into plasma cells which
secrete large amounts of antibody. Macrophages are phagocytic cells which are able
to bind the Fc portion of antibodies but do not produce antibodies themselves. T-
lymphocytes form part of the adaptive immune response and are usually required to
help in antibody production, but do not themselves produce antibody. NK cells are
able to directly lyse target cells in the absence of antibody. Eosinophils release
inflammatory mediators and are able to mediate extracellular killing of parasites.

What is the single best defining description of the classical pathway of

complement activation?

A It acts as a cascade

B It produces a C5 convertase

C In generates the membrane attack complex (MAC)

 D It results in the splitting of C3 into C3a and C3b

E It utilizes complement component C1r

The correct answer is E. C1q, C1r and C1s are unique to the classical pathway. In
the lectin pathway the components mannose-binding lectin (MBL) and the MBL-
associated serine proteases MASP-1 and -2 are homologous to these three
components. Although the classical pathway is based on an enzymatic cascade, so
are the alternative and lectin pathways of complement activation, and indeed certain
other systems in the body such as the clotting system. The classical pathway does
produce a C5 convertase (C4b2a3b), but so does the alternative pathway
(C3bBb3b). Activation of any one of the three complement pathways, not just the
classical pathway, can result in the formation of the membrane attack complex.
Activation of any one of the three pathways (classical, lectin, or alternative) results
in the generation of a C3 convertase that cleaves C3 into C3a and C3b.

What is the single best defining feature of a lymphocyte?

A A type of leukocyte

B A cell that is specialized to produce cytokines

C Present in the circulation

D Antigen-specific

E Able to undergo cell proliferation

The correct answer is D. While many cells can recognize antigens using pattern-
recognition receptors, lymphocytes are the only cell type to possess antigen-specific
receptors (B- and T-cell receptors) that can exquisitely distinguish between closely
related antigens. Lymphocytes are a type of leukocyte (white blood cell) but so are
neutrophils, eosinophils, basophils, monocytes, and NK cells. Lymphocytes are a
particularly rich source of cytokines, but many other cell types produce cytokines
and there are certain cytokines that are not produced in significant amount by
lymphocytes (e.g., IL-1β and IL-7). Lymphocytes are present in both the circulation
and tissues, as are neutrophils, eosinophils, and NK cells. Lymphocytes undergo
clonal proliferation upon encounter with antigen, but proliferation per se is not a
defining feature of a lymphocyte.
What is the characteristic that best defines the acquired immune
response?

A It exhibits immunological memory

B It involves leukocytes

C It involves cell proliferation

D The cells involved recognize pathogens

E It is not present at birth

The correct answer is A. High specificity for antigen and immunological memory are
the two defining characteristics of the acquired (adaptive) immune response. Innate
responses also involve leukocytes. Although proliferation is required in order to
generate sufficient numbers of antigen-specific cells to mediate the acquired
response, cell proliferation is not the best defining characteristic of the acquired
immune response. The cells of the innate response also recognize pathogens, using
pattern recognition receptors. At the time of birth, acquired immunity is not well
developed, although some protection will be afforded by maternal antibodies.
However, this is not the best defining characteristic in the list.

Immunoglobulin

The basic immunoglobulin (Ig) unit is composed of:

A Two identical heavy and two identical light chains

B Two identical heavy and two different light chains

C Two different heavy and two identical light chains

D Two different heavy and two different light chains

E Non-covalently bound polypeptide chains

The correct answer is A. Once a given light (or heavy) chain has been successfully
rearranged, the other light (or heavy) chain gene loci remain unrearranged. Thus,
only one light and one heavy chain is expressed, a phenomenon known as allelic
exclusion. The heavy and light chains are linked by interchain disulfide bonds.
A fragment antigen binding (Fab) fragment:

A Is produced by pepsin treatment

B Is produced by separation of heavy and light chains

C Binds antigen

D Lacks light chains

E Has no interchain disulfide bonds

The correct answer is C. Pepsin treatment produces the divalent F(ab′)2 through
splitting C-terminal to the disulfide bond linking the two heavy chains, whereas
papain treatment is required to generate Fab fragments by splitting the hinge region
N-terminal to the inter-chain disulfide bond. The Fab fragment produced by papain
splitting the hinge region N-terminal to the inter-heavy chain disulfide bond includes
the light chain and only a portion of the heavy chain. The Fab consists of a light
chain and the VH and CH1 domains of the heavy chain. The disulfide bonds linking
the light and part of the heavy chain are present.

The complementarity determining regions (CDRs):

A Are restricted to light chains

B Are in the constant part of the Ig molecule

C Bind to Fc receptors

D Are concerned in antigen recognition

E Occur at the C-terminal end of the Ig peptide chains

The correct answer is D. Three CDRs in the heavy and three in the light chain may
all be concerned in forming the antigen recognition structure. Both the three CDRs in
the variable part of the light chain and the three CDRs in the variable part of the
heavy chain contribute to antigen binding in most antibodies. They are in the
variable regions rather than the constant part of the Ig molecule. Being in the
variable regions, they cannot bind to Fc receptors as these recognize the constant
region of the heavy chain (except of course if an antibody is specifically raised
against an Fc receptor, i.e., an anti-FcR). They occur at the N-terminal region and
not the C-terminal end of the Ig peptide chains.
Which of the following gene clusters do NOT contribute to antigen
binding?

A VL

B CL

C VH

D D

E J

The correct answer is B. The constant region genes encoding the constant region of
the light chain do not bear antigen binding CDRs. VL gene products are involved in
antigen binding. VH gene products bind antigen. The D segments contribute through
recombination with V and J segments to form antigen binding variable regions. The J
segments contribute through recombination with V and D segments to form antigen
binding variable regions.

Recombination of V, D, and J Ig gene segments:

A Only occurs in mature B-cells

B Only occurs in light chains

C Involves heptamer-spacer-heptamer flanking sequences

D Does not occur until the mRNA stage

E Is effected by recombinase enzymes

The correct answer is E. The RAG-1 and RAG-2 encoded recombinase enzymes are
critically involved in the gene rearrangement process. Recombination occurs in
developing immature B-cells. The light chain gene complex does not contain D gene
segments. It involves heptamer-spacer-nonamer flanking sequences. It involves
recombination of DNA gene segments.

Ig idiotypes are found:

A In the constant region of the heavy chain

 B In the constant region of the light chain

C In the hinge region

D In the variable region of both heavy and light chains

E Only in the light chain

The correct answer is D. Idiotypes are the collection of epitopes on the variable
region of an immunoglobulin that are recognized by a collection of antibodies
directed against them (an anti-idiotypic serum). The constant region of the heavy
chain determines the isotype (class) of antibody. The constant region of the light
chain determines whether it is a κ or λ light chain. The hinge region confers
molecular flexibility on the immunoglobulin molecule but this is not where the
idiotypes are located. Idiotypes are present on both the heavy and light chains of
immunoglobulins.

With reference to the variable Ig domain, which of the following

statements is FALSE?

A It mediates the secondary consequences of antigen recognition

B It has anti-parallel beta-pleated sheet structures

C It uses beta-turn loops to bind antigen

D It has an extra long beta-turn relative to constant region domains

E It has a typical Ig fold with an intra-chain disulfide bond

The correct answer is A. The variable domains recognize antigen and secondary
consequences of this are mediated by the Fc region composed of the C-terminal
segments of the heavy chains. The other statements are true.

Which of the following statements does NOT apply to IgG?

A Appears early in the primary immune response

B Neutralizes bacterial toxins

C Can fix complement

D Crosses the human placenta

 E Opsonizes bacteria

The correct answer is A. IgM is the class that appears early following the first
encounter with a specific antigen.

The low affinity FcγRII IgG receptor:

A Has a glycosyl phosphatidylinositol (GPI) anchor

B Binds monomeric IgE

C Avidly binds monomeric IgG

D Binds aggregated IgG

E Is not present on macrophages

The correct answer is D. Although IgG has a low intrinsic affinity for the FcγRII,
aggregated IgG binds in a multivalent fashion and gains by the bonus effect of this
multivalent binding. Most of the Fcγ receptors are anchored into the cell membrane
by a hydrophobic transmembrane segment, although the low affinity FcγRIIIb IgG
receptor has a GPI anchor. The receptor does not cross-react with IgE. Because of
its low affinity, the binding of the monomer is very weak. All three isoforms
(FcγRIIa, FcγRIIb, and FcγRIIc) are present on macrophages.

IgA in seromucus secretions:

A Has no J-chain

B Has no secretory piece

C Is dimeric

D Cannot bind to neutrophils

E Activates the classical complement pathway

The correct answer is C. The molecule dimerizes within the plasma cell so that the
four Fab regions are identical and the multivalency assists binding to polymeric
bacterial and other antigens. The secretory piece is that part of the poly-Ig receptor
bound to the dimeric IgA which remains after cleavage following transport across
the glandular epithelial cell. Neutrophils have Fcα receptors. There is no evidence
that IgA can activate the classical pathway of complement activation, nor is there
any evidence that an intact complement system exists at the mucosal surface or in
seromucus secretions

Which of the following statements is TRUE of IgM?

A IgM is usually of high intrinsic affinity

B IgM is most commonly tetrameric

C IgM has the same number of constant domains as IgG

D IgM is a weak bacterial agglutinator

E IgM is the main class of the natural antibodies

The correct answer is E. The natural antibodies, which include many anti-bacterial
antibodies, arise largely without external antigenic stimulation. In the mouse they
are made by the CD5+ B1 subset. IgM is usually of low affinity but because of its
many valencies (i.e., combining sites for antigen) it is of a high avidity for a
polymeric antigen. The majority of circulating IgM is pentameric. The IgG heavy
chain has three constant domains whereas IgM has four. It is a strong bacterial
agglutinator because of its multivalency.

Which of the following statements is TRUE of IgD?

A IgD is pentameric

B IgD is resistant to proteolytic degradation

C IgD is present mainly as a surface receptor on B-cells

D IgD is present with unusual frequency in myelomas

E IgD is abundant in milk

The correct answer is C. Naive B-cells coexpress surface IgM and IgD of the same
antigen specificity. IgD is monomeric. It is highly susceptible to proteolysis. It very
rarely occurs as a myeloma protein. IgA is abundant in milk.

Which of the following statements is TRUE of IgE?

A IgE is abundant in saliva

 B IgE binds strongly to mast cells

C IgE cannot bind to macrophages

D IgE activates the complement cascade

E IgE has an insignificant role in worm infestations

The correct answer is B. The Fcϵ receptor on mast cells, FcϵRI, binds IgE very
strongly and cross-linking by antigen leads to mast cell activation and initiation of an
inflammatory response. IgE is at a very low concentration in the body fluids. IgA is
predominant in saliva. The FcϵRIIb isoform of the low affinity FcϵRII (CD23) is
present on several different cell types including macrophages. IgE antibodies have
an important role in defense against worm infection.

Which of the following Fc receptors has the highest affinity?

A CD64

B FcγRII

C CD16

D FcϵRI

E CD23

The correct answer is D. The high affinity IgE receptor on mast cells and basophils
has a very high affinity of 1010M−1. CD64 is FcγRI which has a relatively high affinity
of 107−108M−1, but it is not the highest affinity receptor out of the five listed here.
There are various isoforms of FcγRII (CD32) but they all have a relatively low affinity
of <107M−1. CD16 is FcγRIII which has a variant with relatively high affinity for IgG3
(FcγRIIIa, 107M−1) and a low affinity variant (FcγRIIIb, <107M−1). CD23 is the low
affinity (<107M−1) FcϵRII.

Cleavage of IgG by papain produces:

A Divalent antigen binding fragments

B Isolated light chains

C Isolated heavy chains

D F(ab′)2
 E Fab

The correct answer is E. Papain splits the hinge sequences above the inter-heavy
chain disulfide bond and produces a monovalent antigen binding fragment consisting
of light chain and part of the heavy chain containing the VH and CH1 domains.
Monovalent antigen binding fragments are produced. Light chains can be separated
from heavy chains by reduction of the interchain disulfide bonds. Heavy chains can
be separated from light chains by reduction of the interchain disulfide bonds. The
divalent antigen binding fragment, F(ab′)2 is produced by cleavage of IgG with
pepsin and there is loss of the Fc region.

A given myeloma protein:

A Has a homogeneous amino acid structure

B Has diverse variable polypeptide segments

C Has a constant heavy chain but both κ and λ light chains

D Is produced by different plasma cell clones

E Does not behave as an antibody

The correct answer is A. A given myeloma protein is the product of a single clone of
cancer cells all producing an immunoglobulin with identical polypeptide structure and
therefore the same variable regions. Constant heavy chain is associated with either κ
or λ light chains but never both. The myeloma protein is a product of a single
plasma cell clone that has proliferated in an uncontrolled manner. It is an
immunoglobulin and as such can function as an antibody although usually the
antigen will not have been identified as it could be any of the vast number of
possible antigens.

Next question

What is the approximate number of D segment genes in the

immunoglobulin heavy chain gene locus?

A 40

B 23

C 9
 D 6

E 1

The correct answer is B. Note that D regions are only found in the heavy chain; the
light chain gene loci lack D segments. The approximate number of immunoglobulin
heavy chain V genes is 40. There are 9 genes encoding immunoglobulin heavy chain
constant regions which specify the class and subclass of antibody: IgG1-4, IgA1-2,
IgM, IgD, IgE. There are 6 immunoglobulin heavy chain J genes. Multiple D genes
are present. Different D genes are used by different B-cells, contributing to the
generation of antibody diversity.

RAG-1 and RAG-2 enzymes mediate the recombination of:

A VDJ to CH

B H to L

C CDR1 to CDR2

D V to D

E VJ to Cλ

The correct answer is D. Random recombination of V, D, and J gene segments

greatly increases the number of variable region structures and hence specificities for
antigen. The joining of VDJ to a constant region in the heavy chain takes place by
splicing at the mRNA level. The joining of the heavy and light chains occurs by
disulfide linking of the polypeptide chains. CDR1 and CDR2 are both encoded within
the V gene segment and therefore do not undergo recombination relative to each
other. The joining of VJ to a κ or λ light chain constant region takes place by splicing
at the mRNA level

A given Ig isotype is:

A A heavy chain variant encoded by allelic genes

B A light chain constant region encoded by allelic genes

C Present in all normal individuals

D A collection of hypervariable region epitopes recognized by an anti-idiotype

 E Monoclonal

The correct answer is C. Isotypes are the immunoglobulin classes and subclasses
expressed in all normal individuals. The polymorphic forms in statements A and B
are termed allotypes and, being genetically controlled, are not present in each
individual. Statement D is the definition of an idiotype. Any given immunoglobulin
constant region isotype is connected to a whole variety of different variable regions
and therefore to that extent is extensively polyclonal.

The Fab region of an Ig is responsible for:

A C1q fixation

B Binding to antigen

C Binding to Fc receptors

D Binding to macrophages

E The ability of Ig to cross the human placenta

The correct answer is B. Fab is the abbreviation for fragment antigen binding. C1q
fixation is a role of the Fc region. Note that the Cγ1 domain in the Fab region of IgG
is able to bind complement component C4b, but that the generation of C4b is
dependent upon prior activation of the classical pathway. The Fab is distinct from
the Fc and does not bind to the Fc receptors. The binding to macrophages occurs
through the Fc region. The ability of Ig to cross the human placenta is mediated by
binding of IgG to the FcRn receptor on the placenta.

Membrane receptor for antigen

What is the first immunoglobulin heavy chain class to be expressed on the

surface of a newly produced B-cell?

A IgA

B IgD
 C IgE

D IgG

E IgM

The correct answer is E. IgM is the first immunoglobulin class to be expressed on the
surface of the developing B-cells, shortly followed by IgD. Early mature B-cells co-
express IgM and IgD antibodies of identical antigen specificity. IgA and IgE are
found later on in the immune response following class switching and are particularly
associated with mucosal immunity. Although IgD is found on the membrane early on
in the development of B-cells, it is not the first immunoglobulin to be expressed. IgG
is found later on in the immune response following class switching and is the major
immunoglobulin class in serum and in the tissues.

A B-cell is able to make cell-surface and secreted versions of antibody

using:

A Different gene pools

B Differential splicing

C Different heavy chain class but the same light chain

D Different light chain class but the same heavy chain

E F(ab′)2 fragments

The correct answer is B. Differential (alternative) splicing of a primary RNA transcript

can produce antibody either with or without exons encoding a hydrophobic
transmembrane sequence which leads to retention of antibody in the cell surface
membrane. The gene pools used for the cell-surface and secreted antibodies are
identical. In a given B-cell, heavy chains of different classes (e.g., IgM and IgD) can
combine with the same light chain, although not in a single antibody molecule.
However, the heavy chain class does not determine whether the antibody will be
cell-surface associated or secreted. In a given B-cell the antibody heavy chains are
always associated with the same light chains. Note that during early B-cell
development if the antibody produced reacts against “self,” the B-cell may be able to
express a different light chain and be given the opportunity of avoiding tolerance
induction mechanisms if the new heavy : light combination no longer reacts with
self, a phenomenon referred to as receptor editing. F(ab′)2 fragments lack the
transmembrane sequence (and all but one of the heavy chain constant region
domains) of the antibody but are produced artificially in the laboratory by digestion
with the proteolytic enzyme pepsin and do not occur naturally in vivo.

What does the cytoplasmic region of cell surface IgM consists of?

A A single H chain constant region domain

B A light chain

C 110–120 amino acids

D Three amino acids

E Carbohydrate

The correct answer is D. This is too short to directly transmit a signal into the cell
following antigen binding, a function carried out by the Ig-α and Ig-β accessory
molecules. An IgM heavy chain possesses four constant region domains, but these
all lie extracellularly. The light chains are disulfide-bonded to the transmembrane
heavy chains but are not themselves directly held in the membrane and therefore do
not possess any cytoplasmic regions. 110–120 amino acids is the size of an
immunoglobulin domain. IgM is glycosylated but only on the extracellular part of the
molecule

What is the percentage of human peripheral blood T-cells bearing a γδ T-

cell receptor?

A 30–80%

B 1–5%

C 100%

D 0%

E Only present during mycobacterial infections

The correct answer is B. Although they constitute a minority of the peripheral blood
T-cells in humans, γδ T-cells are more heavily represented in intestinal epithelium
and in skin. However, 30–80% would be correct for the percentage of peripheral
blood γδ T-cells in ruminants.Human peripheral blood T-cells comprise both αβ and
γδ subsets. γδ T-cells are present in human peripheral blood. Although many γδ T-
cells recognize mycobacterial antigens, they are normally present irrespective of
mycobacterial infection.
The T-cell receptor genes were originally identified using:

A A monoclonal anti-idiotype

B The polymerase chain reaction (PCR)

C A liver DNA gene library

D In situ hybridization

E Subtractive hybridization

The correct answer is E. Given that the vast majority of the mRNA in B-cells encodes
molecules also expressed in T-cells, subtractive hybridization was used as a step in
the initial identification of the T-cell receptor. This technique removed from a T-cell
polysomal mRNA preparation all of the mRNA molecules also present in B-cells,
leaving a T-cell specific series of clones, some of which hybridized to DNA which was
rearranged only in mature T-cells. A monoclonal anti-idiotype was used to identify
clonally restricted receptors on the surface of T-lymphocytes, but not to identify the
genes encoding these molecules. In fact, the PCR technique as used today was first
described in 1985, 1 year after the first reports of the cloning of T-cell receptor
genes. Although a liver DNA gene library would contain all the T-cell receptor genes
in a given individual, these would be in the germ line (unrearranged) configuration
and would not be expressed as mRNA. The original discovery of the T-cell receptor
genes relied on identifying genes which were rearranged in T-cells. In
situ hybridization can be used to identify genes expressed in individual cells, but was
not utilized in the discovery of the T-cell receptor genes.

A chromosome on which T-cell receptor α chain gene rearrangement has

occurred lacks which of the following gene segments?

A Joining (J)

B Diversity (D)

C Variable (V)

D Constant (C)

E T-cell receptor (TCR) β chain

The correct answer is B. The TCR α chain genes do not possess D gene segments,
although the δ chain genes do. However, because the δ chain locus is found entirely
within the α chain locus and is located between the V α and the J α gene segments,
any α chain gene rearrangements lead to the loss of the δ chain gene segments,
including all of the Dδ segments. The J α gene segment to which a V α gene
segment has rearranged, together with all the J α gene segments 3′ of that to which
the rearrangement occurred, will be present. The V α gene segment which has
rearranged, together with all the remaining 5′ V α gene segments, will be present.
The C δ gene which lies within the TCR α chain gene locus will be lost but the single
C α gene will still be present. The TCR α and β chain genes are encoded on separate
chromosomes

Using only random VDJ recombination, from 40 V, 23 D, and 6 J gene

segments, what are the number of possible variable regions of an antigen
receptor molecule?

A 40

B 69

C 5520

D 1.1 × 106

E 1.3 × 109

The correct answer is C. 40 × 23 × 6 = 5520. The use of geometric random

recombination enables a much larger number of different molecules to be produced
than would otherwise be possible. The variable region of the protein is encoded by
three separate gene segments, V, D, and J, not solely by one of the V (variable)
gene segments. Random combination gives more than the arithmetical summation
of the individual gene segments. If this were not the case there would be little point
in employing the complex VDJ recombination strategy used by the antigen receptor
genes. 1.1 × 106 is much greater than would be produced solely by random
recombination of the specified number of genes, but purely by combining 5520
heavy chains with 200 different possible κ light chains would produce this number of
different immunoglobulin molecules. The addition of λ light chains would make this
number even greater. 1.3 × 109 is an estimated potential diversity of heavy chain–κ
light chain combinations based not solely on random VDJ (for heavy chain) and VJ
(for light chain), but also on additional mechanisms that are used to create diversity.
The use of λ light chains further increases diversity.
N-region insertion is associated with the expression of:

A Terminal deoxynucleotidyl transferase.

B NK cell antigen receptors

C The immunoproteasome

D Lysozyme

E Heat shock proteins

The correct answer is A. This enzyme mediates the insertion of nucleotides at the N-
region of the D and J gene segments. Conventional NK cells do not express
receptors that are encoded following rearrangement of gene segments, and
therefore there is no opportunity for N-region insertion to occur. The
immunoproteasome is an enzyme complex involved in the processing of cytosolic
protein antigens into short peptides for subsequent presentation by MHC class I
molecules to CD8+ T-cells. Lysozyme is an enzyme with antimicrobial activity due to
its ability to digest bacterial cell wall peptidoglycan. Evolutionarily highly conserved
molecules involved in chaperone functions, heat shock proteins are not involved in
N-region insertion.

Which of the following statements is TRUE of receptor editing?

A Has been described for antibody but not TCR

B Is associated with reexpression of RAG-1 in germinal centers

C Can involve V genes which are 3′ of the initially selected V gene

D Involves the S (switch) sequences

E For B-cells only occurs in bone marrow

The correct answer is B. Following immunoglobulin gene rearrangement in the bone

marrow, B-cells switch off expression of RAG-1 and RAG-2. However, mature B-cells
in germinal centers can reexpress both RAG-1 and RAG-2, thereby permitting
receptor editing. Receptor editing has been described for both antibody and TCR
genes. V(D)J rearrangement will have deleted all of the V genes 3′ of the one that
was selected to recombine with a D segment (for the heavy chain) or a J segment
(for the light chain). S sequences are associated with each of the immunoglobulin
heavy chain constant region genes (except C δ) and are involved in class switching.
The term receptor editing is used to refer to the replacement of an already
rearranged V gene with a new V gene. While the initial rearrangement of the
immunoglobulin genes only occurs in the bone marrow, receptor editing can occur
elsewhere in locations such as the germinal centers in lymph nodes.

Somatic hypermutation of V genes:

A Is confined to the hypervariable regions

B Involves heavy but not light chain immunoglobulin V genes

C Does not occur in IgM antibodies

D Can decrease the affinity of an antibody

E Is commonly seen for both antibody and TCR

The correct answer is D. Although somatic hypermutation is thought to be aimed at

increasing the overall affinity of the antibody response, some mutations will result in
clones bearing a surface antigen receptor of decreased affinity. However, clonal
selection will result in the preferential stimulation of any higher affinity mutants, with
antigen thereby driving the affinity maturation of the response. Somatic
hypermutation can also occur in the framework regions of V genes. It occurs in both
the heavy and light chain V genes. While somatic hypermutation occurs at a higher
frequency following class switching to isotypes such as IgG and IgA, it is seen in IgM
antibodies. Somatic hypermutation is not a feature of the TCR, probably because if
the mutation mechanism were allowed to operate for the TCR autoreactive clones
might be generated which react with self MHC molecules irrespective of the peptide
they are holding

NK cells lack receptors with:

A Specificity for MHC class II molecules

B Specificity for MHC class I molecules

C C-type lectin domains

D Immunoglobulin-like domains

E Specificity for the Fc region of IgG

The correct answer is A. NK cells do not bear receptors with specificity for MHC class
II, only class I. NK cells have inhibitory receptors for MHC class I molecules, thereby
preventing them killing normal cells which usually express MHC class I. Cells that
lack MHC class I because they are malignant or infected are not able to engage the
inhibitory NK receptors and are therefore killed. Examples of both activating and
inhibitory NK receptors can be found among the C-type lectin domain receptors on
NK cells. Examples of both activating and inhibitory NK receptors can be found
among the killer immunoglobulin-like receptors (KIRs) on NK cells. NK cells utilize
Fcγ receptors to mediate antibody-dependent cellular cytotoxicity of IgG-coated
target cells.

The Ly49A receptor on NK cells does NOT:

A Exist as a dimer

B Possess an α-helix in its structure

C Recruit phosphatases

D ITAMS

E ITIMS

The correct answer is D. LY49A is an inhibitory receptor and therefore does not
possess immmunoreceptor tyrosine-based activation motifs. It is normally present as
a homodimer. An α-helix connects the C-type lectin domain to the transmembrane
segment. This inhibitory receptor antagonizes NK cell activation by recruiting
phosphatases such as SHP-1. Being an inhibitory receptor, LY49A possesses
immmunoreceptor tyrosine-based inhibitory motifs (ITIMS).

What does the MHC class I heavy chain consists of?

A β2-microglobulin

B Three Ig-type domains

C A truncated MHC class II heavy chain

D Three globular domains

E Two globular domains

The correct answer is D. They consist of one membrane-proximal immunoglobulin-
type domain and two membrane-distal domains which form a grooved structure
comprising two extended α-helices lying on top of a β-pleated sheet floor which can
bind peptides generated by cytoplasmic protein processing. β2-microglobulin
constitutes the MHC class I light chain which is noncovalently linked to the
transmembrane heavy (α) chain. There is only one immunoglobulin-type domain in
the MHC class I heavy chain. The class I and II molecules are encoded by different
genes. Each of the two chains of the MHC class II molecule comprises an
immunoglobulin-type domain and a membrane distal domain. The membrane-distal
domains together form a grooved structure comprising two extended α-helices lying
on top of a β-pleated sheet floor.

What is the molecular weight of MHC class II β chain?

A 28–29 kDa

B 34 kDa

C 43–44 kDa

D 11–12 kDa

E 24–25 kDa

The correct answer is A. Like the α chain, the β chain is a transmembrane

glycoprotein with two extracellular globular domains. 34 kDa is the size of the MHC
class II α chain. The MHC class I α chain, weighing in at 43–44 kDa, is the largest of
the chains of the classical MHC molecules. 11–12 kDa is the molecular weight of β2-
microglobulin, a single immunoglobulin-type domain molecule encoded outside the
MHC and which, lacking a transmembrane region, associates noncovalently with the
MHC class I α chain. 24–25 kDa is the molecular weight of an immunoglobulin light
chain.

Where are the MHC class II region genes in the mouse located?

A On a different chromosome to the class I region genes

B On a different arm, but on the same chromosome as the class I region genes

C On chromosome 6

D Adjacent to a class I gene

 E In the HLA locus

The correct answer is D. The MHC class II genes in mouse, H-2 A and H-2E, are
located in between a class I gene, H-2K, and the MHC class III genes. All the MHC
genes lie adjacent to each other, located on the same chromosome. The MHC genes
in humans are on chromosome 6 but in the mouse are on chromosome 17. The MHC
in mouse is termed H-2; HLA is the human MHC.

What do MHC class III genes encode?

A Complement component C3

B Tumor necrosis factor

C IL-2

D β2-microglobulin

E HLA-DQ

The correct answer is B. Both TNF (TNFα) and lymphotoxin (TNFβ) are encoded
within the MHC class III region. Complement components C2, C4, and factor B are
encoded within this region. IL-2 is not encoded within any part of the MHC. β2-
microglobulin forms part of the structure of the MHC class I molecule, but is
encoded outside of the MHC. HLA-DQ is one of the MHC class II molecules in
humans

Extensive allelic polymorphism is found in MHC:

A DRβ

B DRα

C β2-microglobulin

D Class I α3 domain

E Class II β2 domain

The correct answer is A. Class I HLA-A, -B, and -C molecules are highly polymorphic,
so are the class II molecule DRβ, DPβ, and DQβ chains. DRα is not polymorphic,
although the DPα and DQα chains are, albeit to a lesser extent than the β chains. β2-
microglobulin is not polymorphic. The α1 and α2 domains of MHC class I molecules
are highly polymorphic and form the peptide-binding cleft of the molecule. The
β1 domain of MHC class II molecules is polymorphic and, together with the
polymorphic α1 domain of the α chain forms the peptide-binding cleft of the
molecule

Expression of MHC genes is:

A Codominant

B Dominant for maternal genes

C Dominant for paternal genes

D Dependent on thymic selection

E Totally dependent on the antigenic exposure of the individual

The correct answer is A. The MHC molecules encoded by both parental genes are
expressed. Thymic selection is for T-cells expressing T-cell receptors that can
recognize foreign peptides presented by self MHC molecules. The expression of MHC
genes is not directly regulated by the antigenic exposure of the individual, although
cytokines released by T-cells responding to foreign antigen may cause
an upregulation of MHC gene expression.

What are the molecules mediating signal transduction following antigen

binding to cell surface immunoglobulin on a B-cell called?

A Ig Fc

B Ig-α and Ig-β

C MHC

D CD4

E CD8

The correct answer is B. Ig-α and Ig-β possess C-terminal cytoplasmic regions which
become phosphorylated upon cross-linking of membrane immunoglobulin, leading to
a rapid mobilization of intracellular calcium. The Fc part of a cell surface antibody
molecule contains a short cytoplasmic tail but this is not responsible for signal
transduction. MHC molecules are specialized for the presentation of antigenic
peptides to the TCR. CD4 molecules are found on a subpopulation of T-cells, but not
on B-cells, and they recognize MHC class II molecules. CD8 molecules are found on
a subpopulation of T-cells, but not on B-cells, and they recognize MHC class I
molecules.

The TCR for antigen is:

A Derived from the immunoglobulin gene pool by alternative splicing

B A tetramer

C A homodimer

D A heterodimer

E A single chain molecule

The correct answer is D. There are two versions of the TCR, both of which are
heterodimers consisting of an α chain and a β chain, or a γ chain and a δ chain. The
immunoglobulin and TCR molecules are encoded by entirely separate gene pools.
Unlike immunoglobulin molecules, which are tetramers made up of two identical
heavy chains and two identical light chains. TCR molecules are dimers but the chains
are not identical. Although a number of T-cell surface molecules are single chain
structures (e.g., Thy-1 and CD4), the TCR is not

Antigen specific recognition

A hapten is best defined as being:

A An epitope

B A paratope

C A small chemical grouping that reacts with preformed antibodies

D A carrier

E An immunogen

The correct answer is C. The chemical grouping reacts with preformed antibodies
including that on the specific B-cell surface but cannot induce an antibody response.
An epitope is that region of an antigen that is in contact with a combining site of a
single antibody. A paratope is that part of the antibody surface which is in contact
with the antigen. A carrier is a protein moiety bearing T-cell epitopes which can act
to provide T-cell help for B-cell antibody responses, including those to an attached
chemical grouping (hapten). A hapten cannot stimulate an immune response even
though it can react with preformed antibodies. To induce antibody formation it
needs to be linked to a carrier. The hapten–carrier conjugate would then be termed
an immunogen (i.e., a molecule capable of generating an immune response).

A discontinuous antigen epitope is:

A Presented by MHC molecules

B Usually concave

C Representative of only a minority of B-cell epitopes

D Produced by a continuous linear peptide sequence

E Produced by amino acid residues on non-adjacent polypeptide sequences

The correct answer is E. Residues that may be far apart on the linear sequence of a
protein may be brought close together in space by the protein folding. Denaturation
of the protein will tend to result in a loss of binding power for antibody. MHC
molecules present continuous linear peptides to the T-cell receptor. Concave regions
of the antigen surface bind water strongly and are usually very poorly immunogenic.
Epitopes are usually present on the protruding parts of the antigen surface. The
majority of protein B-cell epitopes are discontinuous. The discontinuous epitope is
produced by non-adjacent amino acid residues brought together by the folding of
peptide chains. Part of the epitope might have a contribution from two or three
adjacent amino acid residues

Binding of antigen to antibody:

A Is usually unaffected by molecular rigidity

B Is unaffected by the presence or absence of water molecules

C Involves covalent bonding

D Is optimized by spatial complementarity

E Is usually unaffected by pH

The correct answer is D. Spatial complementarity is vital for strong binding of

antigen to antibody so that the otherwise non-specific intermolecular forces which
depend reciprocally on distance apart, can become stronger. Antigen and antibody
very rarely match as exactly complementary structures. Flexibility therefore allows
residues to come together to give strong binding energy. The exclusion of water
molecules is essential for the development of a hydrophobic bond between antigen
and antibody. The high dielectric constant of water greatly reduces the Coulombic
attraction of opposite charges on antigen and antibody if water molecules intervene
between two charges. Van der Waals forces only become great when antigen and
antibody are in close electron cloud apposition and this is unlikely if water molecules
intervene. Where positive or negative charges are not balanced by an opposite
charge on the ligand, water molecules lower the free energy of the system and can
be found interspersed between antigen and antibody. The antigen–antibody bonds
are entirely reversible, which would not be the case if there were covalent bonding
such as occurs in disulphide bonds for example. A change in pH either adds or
subtracts hydrogen ions from antigen and antibody, depending on the direction of
the pH change, and this will cause a conformational alteration in the protein folding
and also make both proteins bear similar charges. This leads to a lowering of
affinity.

Next question

The intermolecular forces that contribute to the interaction between

antibody and antigen:

A Are all electrostatic

B Are all van der Waals

C Are all hydrophobic

D Are all hydrogen bonds

E Rely on a combination of the above

The correct answer is E. Antibody–antigen interactions depend upon a combination

of intermolecular forces, all of which are non-covalent. Electrostatic interactions
between opposite charges do contribute, but other forces are also involved. Van der
Waals forces representing interaction between electron clouds on antigen and
antibody do contribute to binding and are very strong at small intermolecular
distances. However, other forces are also involved. Hydrophobic bonding between
groups of antigen and antibody, which do not hydrogen bond with water,
contributes to antigen–antibody binding. However, other forces are also involved.
Hydrogens bonds involving the formation of reversible hydrogen bridges between
hydrophilic groups do contribute, but other forces are also involved.

Which of the following statements is NOT TRUE of affinity?

A A measure of the strength of the binding of antigen to antibody

B The equilibrium constant of the Ag/Ab complex

C Avidity

D Related to the free energy change of the Ag/Ab interaction

E Related to specificity

The correct answer is C. This statement is untrue because avidity refers to the
functional “affinity” of the interaction between a (at least) divalent antibody and a
multivalent antigen. In such cases, the avidity is much greater than the intrinsic
affinity of the binding of one antigen-binding site to one epitope because of the
bonus effect of multivalency. The other statements are true. Affinity measures the
strength of binding of an epitope on the antigen to the antigen-binding site on the
antibody. Affinity is the equilibrium constant of the formation of the antigen–
antibody complex. The relationship is δ G = −RT1nKa, where δ G is the free energy
change, R the universal gas constant, T absolute temperature, 1n the natural
logarithm, and Ka the affinity constant. The ability of antibody to discriminate
between two antigens is related to the relative affinity for each of the antigens.

What is the structure recognized by the αβ T-cell receptor on the cell

surface of an antigen-presenting cell?

A Native protein antigen plus major histocompatibility complex (MHC) molecule

B Processed (peptide) antigen plus MHC

C Processed peptide antigen

D Native antigen

E MHC alone

The correct answer is B. The peptide in the MHC groove is derived from intracellular
proteins, either endogenous or exogenously derived. The native protein antigen does
not combine with the MHC. The T-cell recognizes processed not native antigen. The
peptide antigen by itself without the MHC would not be held on the cell surface.
Native antigen is normally recognized extracellularly by antibody. The expression of
MHC on a cell surface is antigen (peptide) dependent. The antigen can be either self
or foreign

The processing of cytosolic protein involves:

A Transport into late endosomes

B Proteasome-mediated cleavage

C Displacement of invariant chain

D Displacement of β2-microglobulin

E Binding to the MHC class II groove

The correct answer is B. The cytosolic proteins are cleaved to small peptides in the
(immuno)proteasome complex before they are transported by the TAP-1/2
molecules into the endoplasmic reticulum. Exogenously derived proteins are
processed within endocytic vesicles and become acidic late endosomes before fusion
with MHC class II derived from the endoplasmic reticulum. Fusion with late
endosomes leads to DM-catalyzed displacement of the invariant chain CLIP from its
union with the nascent MHC class II molecules. Thereafter, appropriate peptides
within the fused vacuoles combine with the MHC class II groove. The processed
cytosolic proteins give rise to peptides which reinforce the stability of the β2-
microglobulin–class I heavy chain complex. The cytosolic protein after processing
binds to the MHC class I groove within the endoplasmic reticulum before transport to
the surface.

Which of the following statements does NOT apply to the

immunoproteasome?

A It is generated in response to IFNγ stimulation

B It contains the β-1i subunit

C It contains the β-5i subunit

D Very few of the peptides generated are 8–10 residues in length

It contains a 19s regulator

The correct answer is D. The immunoproteasome is specialized to produce a greater
proportion of peptides of this length which is optimal for insertion into the MHC class
I groove. IFNγ increases production of immunoproteasome-associated catalytic
subunits which replace homologous catalytic subunits in the housekeeping
proteasome. β-1i and β-5i replace the β1 subunit of the housekeeping proteasome
during the generation of the immunoproteasome. Both the housekeeping
proteasome and the immunoproteasome contain a 19s regulator to which proteins
bind following their ubiquitination.

Antigen processing for presentation by MHC class II molecules

involves:

A DM

B ERp57

C TAP1 and TAP2

D Calnexin

E Proteasomal-mediated cleavage

The correct answer is A. The MHC-related dimeric molecule DM catalyzes the

removal of CLIP from the MHC class II binding groove and keeps the groove open so
that peptides generated in the endosome can be incorporated. ERp57 isomerizes
MHC class I disulfide bonds to ensure the correct conformation of MHC in the
endoplasmic reticulum. The TAP1 and TAP2 transporters are employed in the
translocation of peptides from the cytosol into the endoplasmic reticulum prior to the
incorporation of the peptides into MHC class I molecules. Calnexin acts as a
molecular chaperone for the MHC class I heavy chain prior to its assocation with
β2 microglobulin together with peptide derived from endogenous antigen. Cleavage
of proteins by the proteasome, and especially the immunoproteasome, provides a
source of peptides for presentation by MHC class I

The processed peptide binding to the MHC class I groove:

A Is usually more than 11 amino acids long

B Hangs over the ends of the groove

 C Usually binds to the groove through two anchor residues

D Is mainly recognized by the CDR2 of the T-cell receptor chains

E Is mostly derived from exogenous protein taken in by endocytosis

The correct answer is C. Each polymorphic MHC class I molecule usually has two,
although sometimes there are three, major pockets associated with the groove
which bind strongly to side chains on the processed peptide. The processed peptide
fitting to the class I groove is usually 8–10 amino acids long. The peptide sits within
the MHC class I groove and if it is slightly long, it kinks up in the middle. The CDR2
is mainly concerned in recognition of the MHC α helices. Peptide is recognized mainly
by the CDR3 regions. CDR1 makes contacts with the MHC α helices, as well as some
contacts with the peptide. The exogenous proteins are degraded and usually finish
up in the MHC class II groove. Processed cytosolic proteins are usually bound finally
to the MHC class I groove. Note, however, that “cross-presentation” also occurs at a
significant rate.

TCR recognition of peptide-MHC class II depends on:

A Covalent binding

B Very high affinity interactions

C CDR-mediated binding

D A minimum of two peptides occupying the binding groove of each MHC

molecule

E The presence of β2 microglobulin

The correct answer is C. As with antibody molecules, it is the CDRs that are primarily
involved in the recognition process. Binding of the TCR to the peptide-MHC, like
binding of antibody to antigen, is reversible and based upon non-covalent
interactions. The interaction is of fairly low affinity with a Ka of around 104−107 M−1.
Sufficiently high affinity to enable activation of the T-cell arises primarily because of
the multiple interactions occurring which also involve various adhesion molecule
pairs such as LFA-1–ICAM-1 and CD2–LFA-3. Only one peptide at a time can occupy
the groove of a single MHC molecule as there is simply not enough room to
accommodate more than one. β2 microglobulin is mandatory for cell surface
expression of peptide-MHC class I, but is not a component of MHC class II.
Cross-presentation of exogenous antigen to αβ T-cells does NOT require
the involvement of:

A Peptide-MHC recognition by the T-cell receptor

B Antigen-processing

C MHC class I

D MHC class II

E An antigen-presenting cell

The correct answer is D. Exogenous antigen is conventionally presented by MHC

class II, but if being cross-presented on MHC class I then MHC class II is not
required. All T-cells bearing an αβ T-cell receptor recognize peptide-MHC,
irrespective of whether the antigen is exogenously or endogenously derived,
conventionally presented or cross-presented. All T-cells bearing an αβ T-cell receptor
recognize processed antigen presented by MHC molecules. Endogenous antigen is
conventionally presented by MHC class I; therefore if exogenous antigen is being
presented by class I this is referred to as cross-presentation. Some type of cell must
by definition be cross-presenting the antigen. Dendritic cells, and to a lesser extent
macrophages, are adept at cross-presenting exogenous antigen.

An example of a “non-classical” MHC molecule is:

A H-2A

B HLA-C

C H-2L

D H-2E

E H-2M

The correct answer is E. H-2M are non-classical MHC molecules in mice. H-2M3, for
example, is known to present bacterial N-formylated peptides to CD8+ T-cells
bearing an αβ receptor. H-2A and H-2E are mouse classical MHC class II molecules.
HLA-C is a human classical MHC class I molecule. H-2L is a mouse classical MHC
class I molecule.

Which of the following statements is TRUE of CD1?

 A CD1 is encoded in the MHC region

B CD1 structurally is most similar to MHC class II molecules

C CD1 can present antigens to γδ, but not αβ T-cells

D CD1 can present lipid antigens

E CD1 is encoded by a single gene

The correct answer is D. CD1 molecules are specialized for the presentation of lipid
and glycolipid microbial antigens. CD1 is encoded on chromosome 1 in humans and
chromosome 3 in mice, whereas the MHC genes are present on chromosomes 6 and
17 in human and mouse, respectively. Structurally, CD1 is most similar to MHC class
I. Indeed, CD1 incorporates β2 microglobulin into its structure just like the classical
MHC class I molecules. Clonally diverse γδ and αβ T-cell populations can recognize
antigens presented by CD1. CD1 is a family of molecules (CD1a-e) each encoded by
a separate gene.

Next question

Which of the following statements is TRUE of iNKT cells?

A iNKT cells bear diverse TCRα chains

B iNKT cells have a limited TCRβ chain repertoire

C iNKT cells comprise 2–3% of T-cells in the mouse liver

D Following stimulation, iNKT cells secrete IFNγ but not IL-4

E iNKT cells are restricted by classical MHC molecules

The correct answer is B. Although not invariant like the TCRα chain of iNKT cells, the
TCRβ chain repertoire is greatly limited compared with that of conventional T-cells.
iNKT cells bear an invariant α chain, V α 14–J α 18 in mouse and V α 24–J α 18 in
humans, with no N-region modifications. They recognize lipid antigens such as α
galactosylceramide presented by CD1d. iNKT cells are a major component of the T-
cell compartment in mice, accounting for approximately 30% of T-cells in the liver
and up to 2.5% of T-cells in the secondary lymphoid tissues. Note that iNKT cells
(unlike NKT cells with diverse receptors) are present at a much lower frequency in
humans. Both iNKT cells and NKT cells rapidly secrete IL-4 and IFNγ following
stimulation and therefore can be involved in the stimulation of many cell types,
including dendritic cells, NK cells, and B-cells. iNKT cells recognize lipid antigens
presented by CD1d.

Which of the following statements is TRUE of superantigens?

A Superantigens do not cause pathology

B Superantigens are not mitogenic for T-cells

C Superantigens bind to MHC class III

D Superantigens bind to all members of a given V β TCR family

E Superantigens have to be processed before recognition by the T-cell

The correct answer is D. Superantigens recognize the common structures in a given

V β TCR family and bind to all of them, cross-linking the T-cell to the MHC class II on
an antigen-presenting cell. This is a powerful stimulus. The pyogenic toxin
superantigen family can cause food poisoning, fever, vomiting, and diarrhea.
Superantigens are very powerfully mitogenic for T-cells bearing certain V β families
and therefore cause their proliferation. Superantigens bind to MHC class II non-
polymorphic sites. They combine with the V β TCR in their native state and do not
require processing.

αβ T-cells recognizing MHC plus processed peptide can:

A Themselves produce antibody to directly eliminate extracellular organisms

B Release histamine

C Develop into γδ T-cells

D Directly kill viruses

E Recognize an intracellular infection

The correct answer is E. T-cells deal directly cell to cell with an infected cell, either
through cytotoxicity or by release of appropriate cytokines such as the macrophage
activating IFNγ. In order to recognize an intracellular infection, it uses the code,
MHC = cell, processed peptide = infectious agent within the cell. Extracellular
organisms are eliminated by antibody but this is produced by B-cells, although they
usually require help from T-cells in order to do so. T-cells do not release histamine,
this is a property of activated mast cells. αβ and γδ T-cells are two separate
populations which do not convert into the other type. The T-cell does not recognize
a virus directly. It sees peptide derived from intracellular virus associated with MHC
and can kill the virally infected cell before the virus has had time to replicate
significantly.

Which of the following statements is TRUE about an epitope?

A An epitope is the area on an antigen that contacts antibody

B An epitope is the area on an antibody that contacts antigen

C An epitope requires both antigen-binding arms of the antibody molecule for its
recognition

D An epitope is usually composed of a linear sequence of amino acids

E An epitope is usually associated with a concave region of the antigen

The correct answer is A. It refers to a single antibody not a polyclonal antiserum.

The area on an antibody that contacts antigen is the antigen-binding site, sometimes
referred to as the paratope. It contacts the epitope on the antigen. Both arms of the
antibody molecule recognize identical epitopes, but a single Fab arm–epitope
interaction is sufficient for the antibody to bind to the antigen. Note, however, that
multivalent interactions will lead to much stronger binding because of the “bonus”
effect. Most antibodies directed to a protein antigen react with a discontinuous
determinant in which the residues that contact antibody are present on different
segments of the peptide chain brought close together in space by the protein
folding. Concave regions contain water that is difficult to displace and consequently
these regions are poorly immunogenic unlike the convex regions.

The single best unique description of the interaction of the αβ T-cell

receptor with peptide-MHC is that it:

A Involves non-covalent forces

B Results in T-cell activation

C Requires the peptide to be presented by MHC class I

D Involves CDR (complementarity-determining region) binding to both peptide

and MHC
 E Is of relatively low affinity compared with antibody binding to native antigen

The correct answer is D. Generally speaking, CDR1 and CDR2 bind to the MHC
component whereas CDR3 binds to the peptide. Non-covalent forces are also
involved in other types of antigen binding such as the binding of antibody to native
antigen and of γδ TCR to, for example, glycolipids presented by CD1. It results in T-
cell activation in the presence of costimulation, but so does the binding of γδ TCR to
their ligands. Peptides can also be presented to αβ TCR by MHC class II. It is of
relatively low affinity compared with antibody binding to native antigen, but so are
many other receptor–ligand interactions

What is the single best definition of the most common form of antigen
recognized by the T-cell receptor (TCR)?

A Native protein

B Cleaved

C A short peptide

D Linear

E Accessible

The correct answer is C. The most common type of antigen recognized by the TCR is
a short peptide derived by intracellular cleavage of a protein. Most TCRs recognize
protein antigens that have been processed. It is a cleaved (processed) antigen, but
this is not the single best description in the list. Although the form of antigen sitting
in the MHC groove is a linear stretch of amino acids, some antibodies are also
capable of recognizing “linear” (continuous) epitopes. Almost by definition, all
antigens need to become accessible in order for them to be detected by the immune
system

Anatomy of immune system

Which of the following statements is the best example of a primary

lymphoid organ?

A Lymph nodes

B Spleen
 C Peyer's patch

D Tonsil

E Thymus

The correct answer is E. T-cells are derived from bone marrow hematopoietic stem
cells and differentiate into immunocompetent cells in the thymus. The lymph nodes
occur at the junctions of the lymphatic vessels and essentially filter off and respond
to foreign material draining from the tissues. They form part of the secondary
lymphoid tissue. The spleen monitors the blood and removes effete red and white
cells as well as responding to blood-borne antigens. The spleen forms part of the
secondary lymphoid tissue, although in the fetus it acts as a primary lymphoid
organ. The Peyer's patches are unencapsulated mucosa-associated lymphoid tissues
(MALT) in the small intestine. Antigen enters across specialized epithelial cells and
stimulates cells committed to IgA and IgE synthesis. The tonsils, together with the
adenoids and associated lymph nodes, form the Waldeyer's ring of lymphoid tissue.

The thoracic duct:

A Enters the spleen

B Directly drains the lymph nodes

C Forms an interface between the lymph and blood

D Transports T-cells from the bone marrow to the thymus

E Is a part of the lamina propria

The correct answer is C. The lymphatics and associated lymph nodes form a network
draining the viscera and the more superficial body structures before returning to the
blood by way of the thoracic duct. The spleen is a highly vascularized secondary
lymphoid organ into which blood enters via the splenic artery. It is a very effective
blood filter, removing effete red and white blood cells and responding actively to
blood-borne antigens. The efferent lymphatics drain the lymph nodes. Lymphocytes
that are destined to become T-cells pass from the bone marrow to the thymus via
blood vessels. This process is controlled by “homing” adhesion molecules. The
lamina propria is unencapsulated lymphoid tissue underlying the gut wall.

When antigen reaches a lymph node in a primed animal:

 A There is an increase in the output of cells in the efferent lymphatics over the
following 24 h

B There is a decrease in the output of cells in the efferent lymphatics over the
following 24 h

C There is an immediate output of activated blast cells

D It is transported to the spleen

E It is all immediately destroyed by macrophages

The correct answer is B. Antigen-reactive cells are depleted from the circulating pool
of lymphocytes within 24 h of antigen first localizing in the lymph nodes or spleen,
and there is a dramatic fall in the output of cells in the efferent lymphatics. There is
no increase in the output of cells in the efferent lymphatics over the 24 h following
the arrival of antigen at a lymph node in a primed animal. A peak of activated blast
cell output occurs at around 80 h following the arrival of antigen at a lymph node.
Generally, tissue-derived antigens are dealt with by the draining lymph nodes while
blood-borne antigens elicit immune responses in the spleen. Although macrophages
are able to degrade phagocytosed antigen very efficiently, at least a proportion of
the antigen remains for long periods of time as immune complexes on the surface of
follicular dendritic cells.

What are the specialized cell type involved in the entry of lymphocytes
into lymph nodes called?

A M-cells

B Mesangial cells

C Periarteriolar lymphoid sheaths (PALS)

D High-walled endothelium of the postcapillary venules (HEV) cells

E Selectins

The correct answer is D. The HEV cells in lymph nodes express vascular addressins
which are recognized by homing receptors on lymphocytes passing through the
afferent lymphatics and which mediate entry of the lymphocytes into the lymph
nodes. Antigen is largely excluded from entering the body by the mucosal epithelial
cells which have tight junctions and a protective mucus layer. However, specialized
antigen-transporting M-cells interspersed between the gut columnar epithelium pass
antigen from the gut to the underlying antigen-presenting cells. Mesangial cells are
the phagocytic macrophages of the kidney. PALS is a tissue, not a cell. These PALS
in the spleen consist predominantly of T-cells which surround the splenic arterioles.
Selectins are a family of molecules, not cells. L-selectin is involved in entry of
lymphocytes into lymph nodes and is the lymphocyte homing receptor which
recognizes the HEV addressin molecule.

The very late antigen (VLA) molecules are:

A Homotrimers

B Homodimers

C Single chain molecules

D Heterodimers with a common β chain

E Heterodimers with a common α chain

The correct answer is D. The α chain is specific for each VLA molecule (e.g., VLA-1 is
an α1β1 molecule while VLA-6 is an α6β1 molecule). These VLA are members of the
integrin family of adhesion molecules, but are not homotrimers or homodimers, nor
are they single chain molecules. They possess α chains but these are specific for
each VLA molecule.

Next question

On entering a germinal center, the primary B-blasts grow exponentially to

form which cell type in the dark zone?

A Secondary B-blasts

B Centrocytes

C Centroblasts

D Memory B-cells

E Plasma cells

The correct answer is C. Centroblasts are found in the dark zone and are highly
mitotic cells with no surface IgD and very little surface IgM. Secondary B-blasts are
found in the apical light zone and are derived from centrocytes. Centrocytes are
found in the basal light zone, are formed from centroblasts, are non-cycling, and
begin to upregulate their expression of surface immunoglobulin. At this stage there
is very extensive apoptotic cell death giving rise to DNA fragments which are visible
as tingible bodies within the macrophages—the final resting place of the dead cells.
Memory B-cells are formed from secondary B-cell blasts and either take up residence
in the mantle zone or join the recirculating B-cell pool. Plasma cells are formed from
the secondary B-cell blasts and, being specialized for the secretion of large amounts
of antibody, have a well-defined endoplasmic reticulum, prominent Golgi apparatus,
and cytoplasmic immunoglobulin. They migrate to the medullary cords which project
between the medullary sinuses.

The tingible bodies inside germinal center macrophages are:

A DNA fragments

B Phagocytosed foreign antigen

C A sign of macrophage apoptosis

D Bacterial cell wall components resistant to degradation

E VLA molecules

The correct answer is A. There is very extensive apoptotic cell death amongst light
zone centrocytes and the resultant DNA fragments are visible as “tingible bodies”
within the macrophages which have phagocytosed the apoptotic lymphocytes.
Germinal center macrophages do phagocytose external antigen, but this is not the
origin of the tingible bodies. They are not a sign of macrophage apoptosis. Bacterial
cell walls are not the source of the tingible bodies. VLA molecules are widely
distributed integrins involved in adhesion to ligands such as laminin, collagen, and
fibronectin.

The paracortical area of a lymph node comprises mainly:

A Follicular dendritic cells

B Plasma cells

C Macrophages

D B-cells
 E T-cells

The correct answer is E. T-cells are mainly found in the paracortical (thymus-
dependent) area of lymph nodes, and in nodes taken from children with selective T-
cell deficiency the paracortical region is virtually devoid of lymphocytes. Follicular
dendritic cells are found in primary and secondary follicles of lymph nodes, and in
the germinal centers they form a tight network of cells with elongated cytoplasmic
processes. The plasma cells are mainly found in the medullary cords that project
between the medullary sinuses, a site distinct from that at which antigen triggering
has occured. This may prevent the generation of high local concentrations of
antibody within the germinal center to avoid neutralization of the antigen on the
follicular dendritic cells. Macrophages are scattered throughout the lymph nodes but
are found especially in the medullary sinuses and in the basal light zone of the
germinal centers. B-cells are mostly located in the outer cortex.

In a lymph node, the antigen pneumococcus polysaccharide SIII leads to:

A Lymphocyte proliferation in the paracortex

B Periarteriolar lymphoid sheath (PALS) development

C Development of cellular hypersensitivity

D Proliferation in cortical lymphoid follicles

E The absence of germinal centers

The correct answer is D. Stimulation of antibody-formation by this thymus-

independent antigen leads to proliferation in this location with development of
germinal centers while the paracortical region remains inactive, reflecting the
inability to develop cellular hypersensitivity to the polysaccharide. Pneumococcus
polysaccharide SIII is a thymus-independent antigen, so the paracortex, being
mainly a T-cell area, is not significantly involved. The PALS is found in the spleen,
not in the lymph node. Pneumococcus polysaccharide SIII is a thymus-independent
antigen and therefore cellular (T-cell) hypersensitivity does not ensue. Germinal
centers are produced during the response to both T-dependent and T-independent
antigens.

Which of the following lymphoid tissues is unencapsulated?

A Thymus
 B Lymph node

C Spleen

D Tonsil

E MALT

The correct answer is E. The respiratory, intestinal, and genitourinary tracts are
guarded immunologically by subepithelial accumulations of lymphoid tissues which
are not constrained by a connective tissue capsule. These may occur as diffuse
collections of lymphocytes, plasma cells, and phagocytes throughout the body and
the lamina propria of the intestinal wall, or as more clearly organized tissue with
well-formed follicles as found in the Peyer's patches. The thymus is encapsulated by
a layer of connective tissue. The lymph nodes are encapsulated by a layer of
connective tissue. The spleen is encapsulated by a layer of connective tissue. The
tonsils are encapsulated by a layer of connective tissue.

Expression of a CD8 α-α homodimer is characteristic of:

A Intraepithelial lymphocytes

B Follicular dendritic cells

C Eosinophils

D Classical cytotoxic T-lymphocytes

E Classical helper T-lymphocytes

The correct answer is A. CD8 α-α homodimers are almost exclusively found on
intraepithelial lymphocytes and appear to restrict these cells to recognition of certain
non-classical MHC molecules such as T-lymphocytes in mice. Follicular dendritic cells
do not express any form of the CD8 molecule. Eosinophils do not express any form
of CD8. Classical cytotoxic T-cells express a CD8 α-β heterodimer, not a CD8 α-α
homodimer. Classical helper T-cells express CD4, not CD8.

Which of the following functions are macrophages unable to carry out?

A Pinocytosis

B Phagocytosis
 C Antigen processing

D Activation of naive T-cells

E Antigen presentation to activated cells

The correct answer is D. Macrophages have an impressive range of functions but

appear unable to prime naive T-cells. This is carried out by interdigitating dendritic
cells. Macrophages are extremely efficient at pinocytosis. Antigens are readily
phagocytosed by macrophages, especially if first opsonized by coating with antibody
and/or complement. Antigens taken up by macrophages are broken down in the
endosomes and phagolysosomes and can then be presented to T-cells as processed
peptide associated with MHC class II which is expressed on the macrophage
following activation by bacterial components such as lipopolysacchride (LPS).
Macrophages function as general antigen-presenting cells for primed lymphocytes.

When Langerhans' cells differentiate into fully mature dendritic cells (DCs)
they:

A Downregulate CD1 expression

B Increase their endocytic activity

C Increase expression of B7.1

D Decrease expression of B7.2

E Become resistant to infection by HIV-1

The correct answer is C. A large number of molecules involved in antigen

presentation and costimulation are upregulated if the DCs become full mature,
including B7.1 (CD80), B7.2 (CD86), MHC class II, CD1, CD40, ICAM-1, and ICAM-2.
Dendritic cells that remain in an “immature” state therefore lack costimulatory
molecules and such DCs are thought to be involved in the maintenance of peripheral
tolerance by inducing anergy in T-cells. As the DCs become fully mature, they
increase their expression of the CD1 antigen-presenting molecule. The Langerhans'
cells are very actively endocytic but this activity is downregulated if they differentiate
into fully mature DCs. Expression of the B7.2 costimulatory molecule, which engages
CD28 on the T-cell, is increased when Langerhans' cells differentiate into fully
mature DCs. DCs express CD4 and the chemokine receptors CCR5 and CXCR4. HIV
utilizes these molecules as cell surface receptors to gain entry to the cell and
therefore the DCs are susceptible to infection by this virus.

Langerhans' cells are found in:

A Lymph

B Lymph nodes

C Periarteriolar lymphoid sheaths (PALS)

D Skin

E Mantle zone

The correct answer is D. Langerhans' cells in the skin pick up and process antigen,
then travel as veiled cells in the lymph before becoming interdigitating dendritic cells
in the paracortical T-cell zone of the draining lymph node, where they are potent
stimulators of T-cell responses. However, the veiled cells found in lymph are derived
from Langerhans' cells. Langerhans' cells migrate to lymph nodes where they
become interdigitating dendritic cells which initiate T-cell responses. The PALS are T-
cell areas of the spleen. The mantle zone of B-lymphocytes surrounds the germinal
center which together form a secondary follicle.

Which of the following statements is TRUE of lymphocytes?

A Lymphocytes enter the tissues and remain there for the rest of their life

B When mature, lymphocytes are only found in secondary lymphoid organs

C Lymphocytes recirculate between blood and lymphoid tissues

D Lymphocytes are only educated in the thymus

E When present in the lymph, lymphocytes are called veiled cells

The correct answer is C. Lymphocyte recirculation between the blood and lymphoid
tissues is guided by specialized homing receptors on the surface of high walled
endothelium of the postcapillary venules. They then re-enter the bloodstream via the
thoracic duct. However, blood monocytes differentiate into macrophages upon
entering the tissues and are thought to remain there for the rest of their life, as do
granulocytes which enter the tissues from the circulation although they have a very
short life compared to macrophages. Mature lymphocytes are also found in the
primary lymphoid organs. In fact, the bone marrow is a major site of antibody
production by fully differentiated plasma cells. Although T-lymphocytes are educated
in the thymus, B-lymphocyte education occurs in the bone marrow. The veiled cells
in the lymph are derived from skin Langerhans' cells which are in the process of
carrying antigen to the local lymph nodes where, as interdigitating dendritic cells
they settle down in the paracortical T-cell zone where they stimulate naive T-cells.

Which of the following statements is TRUE of follicular dendritic cells?

A Follicular dendritic cells can bind immune complexes

B Follicular dendritic cells are small round cells

C Follicular dendritic cells retain antigen for up to 24 h

D Follicular dendritic cells possess Fc receptors but lack C3b receptors

E Follicular dendritic cells are not found in germinal centers

The correct answer is A. Secondary antibody responses can be boosted by quite

small amounts of immunogen which complex with circulating antibody and fix C3 so
that they localize very effectively on the surface of follicular dendritic cells within the
germinal centers of secondary follicles. Follicular dendritic cells have very elongated
processes which can make contact with numerous lymphocytes. Antigen can be
detected on the surface of follicular dendritic cells for long periods of time and
provide a sustained source of antigenic stimulation for the generation and
maintenance of memory B-cells. Follicular dendritic cells possess surface receptors
for IgG Fc and for C3b. Germinal centers possess a meshwork of follicular dendritic
cells which expand B-cell blasts produced by secondary antigen challenge, and direct
their differentiation into memory cells and antibody-secreting plasma cells.

The spleen is largely involved with the response to antigens which are in
the:

A Tissues

B Blood

C Gut

D Lungs

E Urogenital tract
The correct answer is B. The spleen can be thought of as a filter sampling the blood
for effete red cells and for foreign antigens. Draining lymph nodes at the junctions of
lymphatic vessels deal with antigens derived from the tissues. The mucosa-
associated lymphoid tissues (MALT) are concerned with responding to antigens in
the gut, largely by mounting IgA or IgE responses. The bronchus-associated
lymphoid tissue (BALT) provides protective IgA responses against antigen entering
the airways. The MALT produce protective IgA responses in the urogenital tract.

Which of the following statements is the single best description of the

location where adaptive immune responses arise?

A Secondary lymphoid tissue

B Spleen

C Lymph node

D MALT

E Germinal centers

The correct answer is E. Germinal centers develop in secondary lymphoid tissues

(MALT, lymph nodes, spleen) when antigen initiates an adaptive immune response.
Adaptive responses do develop in secondary lymphoid tissues, but this is not the
single most precise description from those provided. Although adaptive responses
can develop in the spleen, this answer excludes other locations where such
responses are also initiated. Although adaptive responses can develop in lymph
nodes, this answer excludes other locations where such responses are initiated.
Adaptive responses against many pathogens are initiated in the MALT, but it is not
the only location where such responses can arise.

Next question

Which of the following statements is the single best defining characteristic

of a follicular dendritic cell (FDC)?

A FDC is present in germinal centers

B FDC possesses long “dendrite-like” processes

C FDC expresses Fcγ receptors

 D FDC functions to present antigen to B-cells

E FDC lacks expression of MHC class II

The correct answer is D. These cells, which possess both Fcγ receptors and
complement receptors, bind immune complexes and thereby multivalently present
native antigen to the B-cell receptors on B-cells. While it is not obligatory for B-cells
to have the antigen presented to them in this way they are activated more efficiently
when it is, particularly in the case of soluble antigens. FDCs are characteristically
present in germinal centers, but this is not the single best defining feature of these
cells as many other cell types are also present in germinal centers. FDC possesses
long “dendrite-like” processes, but so do interdigitating dendritic cells which
functionally are quite different from FDC. FDCs express receptors for the Fc region of
IgG, but so do many other cell types including macrophages, neutrophils, B-cells,
and NK cells. FDC lacks expression of MHC class II, but then so do the vast majority
of cells in the body. Indeed, MHC class II is usually only expressed on dendritic cells,
macrophages, B-cells, activated human T-cells, and thymic epithelium.

What is the single cell type most characteristically associated with the
mucosa-associated lymphoid tissue (MALT)?

A M-cell (microfold cell)

B Dendritic cell

C T-cell

D B-lymphocyte

E Mast cell

The correct answer is A. These antigen-sampling cells are interspersed amongst the
epithelium overlying the Peyer's patches. Dendritic cells are present scattered
throughout the tissues of the body. T-cells develop in the thymus and then migrate
to the secondary lymphoid tissues including not only the MALT but also the lymph
nodes and spleen. B-cells become fully mature within the bone marrow and then
migrate to the secondary lymphoid tissues including not only the MALT, but also the
lymph nodes and spleen. Mast cells are present not only in the mucosal tissues, but
also in connective tissue.
Lymphoctic Activation

What is CD8 a marker of?

A B-cells

B Helper T-cells

C Cytotoxic T-cells

D An activated macrophage

E A neutrophil precursor

The correct answer is C. CD8 + T-cell receptor on the cytotoxic T-cell recognize the
MHC class I + peptide on the target cell surface. B-cells bear surface markers such
as CD19 and surface Ig antigen receptor. Helper T-cells bear CD4 as well as the
CD3/T-cell receptor. Activated macrophages exhibit increased expression of a
number of cell surface molecules including MHC class II, Fc receptors for IgG, and
the CR3 complement receptor. CD8 is not found on any type of polymorph.

Which of the following statements is TRUE of CD4?

A CD4 is essentially an intracellular glycoprotein

B CD4 is heterodimeric

C CD4 binds processed peptide in its outer groove

D CD4 binds to MHC class II on antigen-presenting cells

E CD4 is highly polymorphic

The correct answer is D. The CD4 binds to constant regions on the MHC class II.
CD4 is a cell surface molecule and has a single polypeptide chain. Processed peptide
is held in the outer groove of an MHC molecule. While, as with any other molecule,
occasional polymorphisms will be found amongst the population, CD4 is not a highly
polymorphic molecule.

Which of the following is characteristic of B- but not T-cells?

A Class I MHC

B CD3
 C Measles virus receptor

D Polyclonal activation by concanavalin A (ConA)

E Transmembrane surface immunoglobulin

The correct answer is E. B-cells express transmembrane surface immunoglobulin of a

specificity created by that cell's particular immunoglobulin gene recombinations. A
totally different gene set encodes the T-cell receptor for antigen. Class I MHC is
present on both B- and T-cells. CD3 is present only on T-cells. Measles virus receptor
is a feature of T-cells. T-cells but not B-cells are polyclonally activated by ConA.

Next question

When a resting naive T-cell engages its specific MHC–peptide complex

displayed on the surface of a fibroblast, it:

A Undergoes blast cell formation

B Produces IL-2

C Moves from G0 to G1 of the cell cycle

D Becomes anergic

E Secretes IL-1

The correct answer is D. In the absence of costimulator, a cell becomes anergic and
incapable of subsequent response to the specific antigen. The naive T-cell receptor
recognizes the MHC–peptide complex but in the absence of a costimulator such as
B7 on the antigen-presenting cell, the T-cell does not proliferate and generate blast
cells. However, an already activated T-cell would proliferate and generate blast cells
and IL-2 in the absence of the costimulator. In the absence of costimulator, the cell
is not activated. In the absence of costimulator, a cell becomes anergic and
incapable of subsequent response to the specific antigen. Even if stimulated by a
dendritic cell capable of activating naive T-cells, IL-1 would not be secreted by the
T-cells as this cytokine is not a T-cell product, being mainly produced by
macrophages and dendritic cells.

What is the T-cell ligand binding B7 on a professional antigen-presenting

cell?
 A CD28

B CD2

C LFA-1

D ICAM-1

E VCAM-1

The correct answer is A. An alternative ligand for B7, present on activated T-cells, is
CTLA-4. The ligand for CD2 is LFA-3. The ligands for LFA-1 are ICAM-1 and ICAM-2.
The ligand for ICAM-1 is LFA-1. The ligand for VCAM-1 is VLA-4.

Which of the following statements is TRUE of Sos (Son of sevenless)?

A Sos itself directly activates Raf

B Sos is recruited to non-phosphorylated LAT

C Sos is a guanine nucleotide exchange factor

D Sos is a GTPase-activating protein

E Sos is phosphorylated by Mek

The correct answer is C. Sos is a guanine nucleotide exchange factor (GEF) which
promotes the conversion of Ras-GDP to Ras-GTP. Raf is activated by Ras-GTP.
Phosphorylation of LAT is required for the recruitment of the GRB2–Sos complex.
GTPase-activating proteins can increase the intrinsic GTPase activity of Ras. Mek is a
MAP kinase which phosphorylates downstream MAP kinases such as ERK.

Protein tyrosine kinase activity following T-cell stimulation:

A Phosphorylates and thereby activates phospholipase Cγ1

B Is an inherent property of the T-cell receptor α and β chains

C Is an inherent property of CD3

D Is decreased

E Is unrelated to phosphorylation of the CD3-associated ζ chains

The correct answer is A. The tyrosine kinase activates the phospholipase, which
accelerates the hydrolysis of phosphatidylinositol 4,5-diphosphate to diacylglycerol
and inositol 1,4,5-triphosphate. The T-cell receptor heterodimer does not have
kinase activity. The molecules that comprise the cell surface complex with the TCR,
such as CD4 and the CD3-associated ζ chains, interact with the kinases Lck and ZAP-
70, respectively. The CD3 molecules associate with the ζ chains which contain
immunostimulatory tyrosine-based activation motifs (ITAMs). The ZAP-70 protein
tyrosine kinase binds to, and phosphorylates, these motifs. Protein tyrosine kinase
activity is increased following T-cell stimulation. The ζ chains are very rapidly
phosphorylated following T-cell stimulation.

The early increase in phospholipase Cγ1 activity following T-cell

stimulation:

A Represents a sensitive regulatory negative feedback control mechanism

B Dephosphorylates protein tyrosine kinase inhibitors

C Accelerates hydrolysis of diacylglycerol

D Accelerates hydrolysis of phosphatidylinositol diphosphate

E Accelerates hydrolysis of inositol triphosphate

The correct answer is D. The enzyme splits phosphatidylinositol diphosphate to

diacylglycerol and inositol triphosphate. The phospholipase is part of the stimulatory
mechanism. The enzyme splits phospholipids but it is not a phosphatase. The
enzyme catalyzes the production of diacylglycerol. The enzyme catalyzes the
production of inositol triphosphate.

The nuclear AP-1 site responsible for 90% of IL-2 enhancer activity binds:

A The Oct-1 transcriptional factor

B The Fos/Jun transcription factors

C The nuclear factor of activated T-cells (NFAT)

D The NFκB transcriptional factor

E Polyclonal mitogenic agents such as ConA

The correct answer is B. Deletion of the Fos/Jun AP-1 binding sites from the IL-2
promoter abrogates 90% of IL-2 enhancer activity. Oct-1 binds to specific octamer-
binding sequence motifs. Upon activation, the cytoplasmic component of NFAT
translocates to the nucleus where it forms a binary complex with the constitutively
expressed nuclear NFAT subunit. This complex binds to NFAT-binding motifs.
Following release from the inhibitor IκB, this transcription factor enters the nucleus
where it binds to NFκB binding motifs on the DNA. Polyclonal mitogenic agents such
as ConA bind to receptors on the cell surface.

Next question

Lipopolysaccharide (LPS) from Gram-negative bacteria is:

A A thymus-dependent antigen

B A type 2 thymus-independent antigen

C A polyclonal activator of murine B-cells

D Cross-links Ig receptors on B-cells

E Produces high affinity IgG memory responses

The correct answer is C. LPS reacts with a specific receptor on most murine B-cells
and therefore is not selective for B-cells of any particular antigen specificity. LPS
stimulates B-cells without the presence of T-cells. LPS stimulates T-cells without
reacting with the Ig receptors; type 2 thymus-independent antigens are polymeric
and combine with and cross-link Ig receptors. The LPS does not react with Ig
receptors except on the specific B-cells that have surface Ig complementary to LPS
itself. As the response is thymus-independent, high affinity IgG memory responses
cannot be produced.

Next question

The carrier T-cell epitope on a thymus-dependent antigen:

A Behaves like a hapten

B Needs to be polymeric

C Need not be physically connected to the B-cell epitope

D Is a carbohydrate
 E Stimulates help for the B-cell response

The correct answer is E. The presentation of the T-cell epitope by the B-cell recruits
the T-cell help for activating the B-cell causing its proliferation and final maturation.
The antigen possessing the carrier epitope binds to the B-cell but, unlike a hapten, it
will stimulate the T-cell, provided of course T-cells are also present. It can be
univalent. It is necessary for T- and B-cell epitopes to be connected because the B-
cell captures the antigen through the B-cell epitope, processes the antigen and
presents the peptide from the T-cell epitope to the helper T-cell. Carbohydrates are
not processed to form carrier T-cell epitopes for B-cell responses.

T-cell help for antibody production:

A Depends on T-cell recognition of native antigen bound to B-cell surface Ig

B Depends on T-cell recognition of antigen processed by the B-cell

C Involves class I MHC on the B-cell

D Can occur in X-irradiated mice

E Is a feature of the antibody response to pneumococcal polysaccharide SIII

The correct answer is B. The native antigen binds to B-cell surface Ig, is taken inside
the cell, processed and the peptide placed as a complex with class II MHC on the
cell surface where it is recognized by T-helper cells. T-cells do not recognize native
antigen. Cytotoxic cells generally recognize class I MHC plus peptide whereas helper
cells generally see class II. The clonal expansion required for effective antibody
production cannot occur after X-irradiation which inhibits cell division. Pneumococcal
polysaccharide cannot be processed for presentation with class II MHC and is
therefore thymus-independent as an antigen.

Cross-linking of B-cell surface receptors:

A Is a characteristic feature of thymus-dependent antigens

B Lowers the intracellular Ca2+ concentration

C Rapidly phosphorylates the Ig-α and Ig-β chains of the surface Ig receptor

D Requires contiguity of two B-cell epitopes of different specificity on the same

antigen molecule
 E Cannot be achieved by anti-idiotypic antibodies

The correct answer is C. Within 1 minute of surface Ig ligation there is rapid

phosphorylation of the Ig-α and Ig-β chains and a subsequent rise in intracellular
calcium. Thymus-dependent antigens can be univalent and are processed after
binding to the cell surface Ig. The intracellular calcium concentration is increased on
activation. Contiguity of two B-cell epitopes of different specificity on the same
antigen molecule cannot occur because all the surface receptors on a given B-cell
have the same specificity. Because they are divalent, anti-Id can cross-link to surface
receptors bearing idiotype.

Activation of resting B-cells by T-helper cells depends directly upon

costimulatory interaction between:

A CD40 and CD40L

B B7 and CD28

C B7 and CTLA-4

D CD4 and MHC class II

E ICAM-1 and LFA-1

The correct answer is A. Costimulatory signals arising from the interaction of CD40
on the resting B-cell with CD40L (CD40 ligand, CD154) on the activated T-helper cell
ensure effective B-cell activation. The B7 and CD28 interaction activates T-helper
cells. The B7 and CTLA-4 interaction downregulates T-cells. The CD4 and MHC class
II interaction in itself is one part of the recognition of antigen-presenting cells by T-
cells but, without the CD40–CD40L costimulatory interaction, resting cells cannot be
activated. ICAM-1 and LFA-1 help the initial interaction between APC and T-helpers
by increasing adhesiveness. Engagement of ICAM-1 on the B-cell by LFA-1 on the T-
cell is not thought to be substantially involved in direct activation of resting B-cells
by T-helper cells.

B-cells as distinct from T-cells:

A Are polyclonally activated by phytohemagglutinin

B Bear surface Ig receptors for antigen

C Bear surface CD3 molecules

 D Are lymphocytes

E Can be activated by stimulation through the antigen receptor alone

The correct answer is B. The specific receptor for antigen on B-cells is surface
immunoglobulin whereas that on T-cells is the αβ or γδ TCR. Phytohemagglutinin is
a polyclonal activator of T-cells independently of their T-cell receptor specificity. The
T-cell receptor transduces its signal through the chains of the CD3 complex. Both T-
and B-cells are types of lymphocyte. Both T- and B-cells require costimulatory
signals in order to be activated.

The T-cell receptor link to MHC–peptide is enhanced by interaction

between MHC class II on the antigen-presenting cells with the following
molecule on the T-cell:

A LFA-1

B CD2

C CD4

D CD8

E CD28

The correct answer is C. CD4 on helper T-cells binds to the non-polymorphic part of
the MHC class II molecule. LFA-1 binds to ICAM-1. CD2 binds to LFA-3. CD8 on
cytotoxic T-cells binds to the non-polymorphic part of MHC class I on the antigen-
presenting target cell. CD28 is ligated by the B7 molecule on the antigen-presenting
cell.

The main costimulatory signal for activation of resting T-cells is provided

by ligation of:

A CD28

B Surface Ig

C LFA-1

D VLA-4

E IL-2
The correct answer is A. B7 (CD80 and CD86) on the antigen-presenting cell ligating
CD28 on the T-cell provides the main costimulatory signal for the activation of
resting T-cells. Surface Ig on B-cells does not provide a costimulatory signal for T-
cells. However, the surface Ig on the B-cell can pick up antigen which can then be
processed and presented to activated T-helper cells. LFA-1, by binding to ICAM-1,
augments activation signals but does not provide the main costimulatory signal
necessary for activation of resting T-cells. VLA-4, which binds to VCAM-1 on the
antigen-presenting cell, does not provide the main costimulatory signal but does
augment the effect of other signals. The cytokine, IL-2, binding to the IL-2 receptor
will cause proliferation of activated T-cells.

Which of the following events occurs earliest in T-cell signaling?

A Activation of phospholipase C

B Activation of protein kinase C

C Production of inositol triphosphate

D Activation of protein tyrosine kinase

E Mobilization of intracellular calcium

The correct answer is D. Activation of protein tyrosine kinase activity is responsible

for subsequent activation of membrane components by phosphorylation.
Phospholipase C is activated by phosphorylation and then splits phosphatidylinositol
diphosphate. Protein kinase C becomes activated by diacylglycerol produced through
the action of phospholipase C. Inositol triphosphate is produced from
phosphatidylinositol diphosphate by the action of phospholipase C. Intracellular
calcium is mobilized at a later stage through binding of inositol triphosphate to
specific receptors on specialized calcium storage vesicles.

On injection into mice, bovine serum albumin conjugated with

dinitrophenol (DNP) behaves as a:

A Type 1 thymus-independent antigen

B Type 2 thymus-independent antigen

C Thymus-dependent antigen
 D A polyclonal T-cell activator

E Hapten

The correct answer is C. BSA-DNP is thymus-dependent in that the BSA acts as a T-

dependent carrier which is processed by an anti-DNP B-cell which binds the
conjugate and presents the processed peptide with MHC class II to the T-helper cell.
The T-cell helps the B-cell to mature into an anti-DNP clone. Type 1 thymus-
independent antigens are polyclonal activators like LPS which bind to specific
receptors on the lymphocyte, focused there by surface immunoglobulins specific for
the polyclonal activator. Type 2 thymus-independent antigens are polymeric
molecules which cross-link surface Ig. Examples of polyclonal T-cell activators are
phytohemagglutinin and concanavalin A. The DNP is a hapten in that it will bind to
preformed antibody, particularly on the surface of the B-cell, but will not itself
stimulate antibody formation until conjugated to a T-dependent carrier such as the
bovine serum albumin.

Next question