Essential Microbiology for Dentistry. 5th ed.

Chapter 9. The immune response

Chapter 8 described the development of B and T cell repertoires. At birth, the immature immune system consists of B cells selected for low-affinity antibody production, while the T cell repertoire consists of T cell antigen receptors (TCRs) potentially able to recognize foreign but usually not self peptides presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). The latter must also provide co-stimulatory signals for full T cell activation.

During the vulnerable few months following birth, while immune system maturation is continuing, the infant receives protection against pathogens from the mother's 'experienced' immune system. Maternal immunoglobulin G (IgG) antibodies cross the placenta and provide passive immunity. The IgA antibodies in mother's milk protect the infant's digestive system. By the age of 9 months, all maternal IgG antibodies will have been catabolized and suckling may have been terminated. The infant must now be able to mobilize its own adaptive immune response mechanisms to fight off potential pathogens.


Antibodies, or immunoglobulins (Igs), are the secreted products of B lymphocytes, which have become activated following binding of antigen to their B cell receptors (BCRs). The specificity for antigen of the secreted antibody is the same as that of the BCR, so they will bind to the same antigen that induced their production. The formation of the antigen-antibody complex may result in:

 neutralization of the antigen (e.g., soluble toxins, viruses)

 removal of the complex by phagocytic cells, which bind via Fc receptors (FcRs) to the Ig constant region

 killing of antigen-bearing cells by the membrane attack complex of complement or by natural killer (NK) cells, monocyte/macrophages or granulocytes, which bind antibody-coated cells via FcRs.

The basic Y-shaped, four-chain structure of the antibody molecule is shown in Fig. 9.1. Antigen-binding specificity is provided by the combined variable (V) regions of heavy (H) and light (L) chains. Since the basic Ig unit has two such pairings, the molecule can bind two identical epitopes; i.e., it is bivalent. The Ig heavy-chain constant region, particularly domains 2 and 3, which make up the Fc region, largely determines the biological activity of the molecule.

There are five distinct classes of Ig (IgG, IgA, IgM, IgD, IgE), four subclasses of IgG (IgG1, IgG2, IgG3, IgG4) and two subclasses of IgA (IgA1, IgA2). These are derived from usage of different heavy-chain genes, as described in Chapter 8. The different structures and properties of Ig molecules are summarized in Fig. 9.2.


Cytokines are low-molecular-weight hormone-like glycoproteins secreted by leukocytes and various other cells in response to a number of stimuli, which are involved in communication between cells, particularly those of the immune system. Lymphocyte-derived cytokines are known as lymphokines, those produced by monocyte/macrophages as monokines. Many of the cytokines are referred to as interleukins (ILs), a name indicating that they are secreted by some leukocytes and act upon other leukocytes. They are required for the initiation and regulation of all stages of the immune response, from stem cell differentiation to effector cell activation. Their action is mediated by binding to specific receptors on target cells; often the receptor may be released from the target cell in soluble form so that it may intercept the cytokine and act as an inhibitor. There are also other forms of cytokine inhibitors responsible for keeping these molecules under tight regulation. Each cytokine has several different activities (pleiotropy), and the same activity may be produced by several different cytokines (redundancy). The response of a cell to an individual cytokine depends on the context in which it receives the signal, e.g., its state of differentiation and activation and the presence of other cytokines in the microenvironment.

Chemokines are a family of low-molecular-weight, structurally related cytokines that promote adhesion of cells to endothelium, chemotaxis and activation of leukocytes. They are involved in leukocyte trafficking, providing specific signals for lymphocyte entry into lymphoid and other tissue.

Fig. 9.1 Structure of the immunoglobulin molecule. C, Constant region; H, heavy chain; L, light chain; CH1, CH2, CH3 are globular domains with different biological properties; V, variable region.

Table 9.1 outlines the main sources and activities of cytokines. It is not exhaustive, and new cytokines and activities are undoubtedly awaiting discovery. The exciting field of cytokine research has led to the isolation of genes for cytokines and their receptors and inhibitors and the ability to manufacture these molecules by recombinant DNA technology. There is optimism that therapeutic use of these reagents will, in the near future, benefit patients with infections, autoimmunity, allergy and other immunologically mediated diseases.

B cell activation

B cells are highly efficient APCs. They receive signal 1 for activation by binding antigen, often concentrated on the surface of follicular dendritic cells within lymph node germinal centres, to the BCR, and then proceed to internalize antigen and process peptides on to MHC II molecules for presentation to T-helper cells (Fig. 9.3). They are then induced to express co-stimulatory B7 and can therefore provide signal 2 for T-helper cell activation through CD28. Activated T-helper cells are induced to express CD40L for binding to B cell CD40. Interaction between these two molecules induces B cell activation, Ig production and isotype switching.

Fig. 9.2 Structure, properties and functions of different classes of immunoglobulins (Igs). BCR, B cell receptor; J, joining chain; SC, secretory component.

IL-12 is not usually the dominant cytokine at the site of B-TH interaction, so T-helper cells induced by B-APC will generally be of the TH2 type, secreting IL-4, IL-5 and IL-10. These lymphokines further promote B cell proliferation, activation and isotype switching.

Antigen processing and presentation

The T lymphocytes use their TCRs to recognize short antigenic peptides bound to MHC class I or class II molecules. This requires that protein antigens be processed and directed to the site of MHC assembly within an MHC-expressing cell. While virtually any cell type can process peptides on to MHC I molecules, 'professional' APCs (monocyte/macrophages, dendritic cells, B lymphocytes) are usually the only cell types to present MHC II + peptide (Fig. 9.4).

APCs express a variety of adhesion molecules that bind to counterstructures on T cells during engagement of the TCR.

Fig. 9.3 Activation of B cells. BCR, B cell receptor; FDC, follicular dendritic cell; L, ligand; sIg, surface immunoglobulin.

This maintains the necessary intercellular contact for transfer of activation signal 1. Adhesion molecules include intercellular adhesion molecules ICAM-1 (CD54) and ICAM-2 (CD102) and leukocyte function-associated antigen LFA-3 (CD58) on APCs and LFA-1 (CD11a/CD18), which binds ICAM-1 or -2, and LFA-2 (CD2), which binds LFA-3, on T cells.

Table 9.1 Main producers and major actions of cytokines


Main producers

Major actions



Mediator of inflammation; augments immune response


T cells

T cell activation and proliferation


T cells

Haematopoiesis (early progenitors)


T cells

T cell, B cell, mast cell proliferation; IgE production


T cells

B cell proliferation; IgA production; eosinophil, basophil differentiation


Macrophages, T cells

Mediator of inflammation; B cell differentiation


Bone marrow cells, thymic stroma

Haematopoiesis (lymphocytes)



Neutrophil chemotaxis


T cells

T cell proliferation


Macrophages, T cells

Inhibitor of cytokine production


Bone marrow stromal cells

Haematopoiesis (early progenitors)



T cell differentiation


T cells

Similar to IL-4


T cells

Proliferation of activated B cells


Stromal cells

Similar to IL-2


T cells

T cell chemotaxis


T cells

Mediator of inflammation and haematopoiesis



Similar to IL-12




Leukocytes Fibroblasts T cells, NK cells

Activation of macrophages, NK cells; upregulation of MHC expression; protection of cells against virus infection



T cells

Macrophages, T cells

Mediator of inflammation; killing of tumour cells; inhibition of tumour growth


Macrophages, lymphocytes, endothelial cells, platelets

Wound healing; IgA production; suppression of cytokine production


Macrophages, T cells

Mediator of inflammation; killing of tumour cells



Haematopoiesis (granulocytes)



Haematopoiesis (monocyte/macrophages)


T cells

Haematopoiesis (granulocytes, monocyte/macrophages)

CSF, Colony-stimulating factor; g, granulocyte; Ig, immunoglobulin; IFN, interferon; IL, interleukin; LT, lymphotoxin; m, monocyte/macrophage; MHC, major histocompatibility complex; NK, natural killer; OSM, oncostatin M; TGF, transforming growth factor; TNF, tumour necrosis factor.

Professional APCs also express the B7.1 (CD80) and B7.2 (CD86) co-stimulator molecules, which both interact with CD28 and cytotoxic T-lymphocyte-associated antigen (CTLA-4) on T cells. While CD28 transmits activation signal 2 to the responding T cell, CTLA-4 appears to be involved in termination of activation. Interaction between CD40 on APC and CD40 ligand (CD40L, CD154) on responding T cells is another important signal 2 for activation. Cells other than professional APCs, despite expression of MHC I + peptide, cannot usually stimulate T cells because they lack B7 and CD40.

The MHC + peptide, adhesion molecules and co-stimulator molecules on APCs interact with clusters of TCRs and ligands on T cells, forming an organized interface termed the immunological synapse. It is the overall strength of this multipoint interaction that determines the strength of the activation signal received by the T cell. Strong signals lead to full activation, while weak signals may induce partial or no activation.

There are two separate pathways of antigen processing for endogenous and exogenous antigens. Endogenous antigens are usually processed on to MHC I and presented to CD8+ cytotoxic T cells; exogenous antigens are processed on to MHC II and presented to CD4+ T-helper cells.

Processing of endogenous antigens

Cellular cytoplasmic proteins, including cell surface molecules, which are recycled to the cytoplasm, undergo proteolysis to small peptides in the proteosome, and the peptides are then taken to the endoplasmic reticulum, which is the site of production of MHC I molecules, by the transporter associated with antigen processing (TAP). The assembly of the complete class I molecule, a-chain + β2-microslobulin, requires the introduction of an 8- to 11-amino acid peptide into the peptide-binding groove. 'Empty' MHC molecules are highly unstable. Once assembled, MHC I + peptide is transported to the cell surface.

Fig. 9.4 Antigen processing and presentation to cytotoxic T cells (CTC) and T-helper cells (TH). APC, Antigen-presenting cell; ER, endoplasmic reticulum; ICAM, intercellular adhesion molecule; IL, interleukin; LFA, leukocyte function-associated antigen; MHC, major histocompatibility complex; R, receptor; TAP, transporter associated with antigen processing; TCR, T cell receptor.

Endogenous antigen presentation leads to expression of a target structure recognizable only by CD8+ T cells, since recognition of MHC I and CD8 expression are co-selected in the thymus (see Chapter 8). The CD8 molecule binds to MHC

I and helps to generate an intracellular signal of TCR engagement. Endogenous processing of intracellular pathogens thus leads to activation of cytotoxic effector cells able to destroy the infected cell.

Processing of exogenous antigen

Phagocytic or endocytic uptake of exogenous antigens such as extracellular pathogens results in proteolysis within the endosomal compartment. Here, peptides encounter MHC II molecules consisting of a- and β-chains held together by the invariant chain. Peptides of 15-18 amino acids can replace the invariant chain. MHC II + peptide is transported to the cell surface to be 'seen' by the TCR of a CD4+ T-helper cell. Engagement of the TCR induces signal 1 for T cell activation, interaction of adhesion molecules and of CD4 with MHC

II helps to transfer this signal to the nucleus, and B7-CD28 and/or CD40-CD40L interaction generates signal 2. A clone of activated T-helper cells is produced, each member of which can recognize the original MHC II + peptide and is able to secrete various lymphokines for activation of other immune effector mechanisms.

T-helper subsets

The nature of the immune effector response is largely determined by the range of lymphokines secreted by activated T-helper cells. Upon initial stimulation, an activated T-helper cell will secrete a wide range of lymphokines (TH0 phenotype), but, depending on the type of APC and the environment in which T-helper activation is taking place, the lymphokine secretion profile will usually polarize towards production of either IL-2, interferon-y (IFN-y) and lymphotoxin (LT) (TH1) or IL-4, IL-5 and IL-10 (TH2). While TH1 lymphokines stimulate mainly macrophage and dendritic cell activation, TH2 lymphokines stimulate B cell activation and antibody production (Fig. 9.5).

If the APC is a macrophage or dendritic cell, it will normally be stimulated to produce IL-12 during T-helper cell activation. Neighbouring NK cells and possibly other cell types respond to IL-12 by producing IFN-y, which stimulates the TH1 and suppresses the TH2 secretion profile. If the APC is a non-IL-12 producing cell, such as a B cell, or if TH0 activation takes place in an environment containing IL-4-secreting cells (possibly NK-T cells, a poorly understood population of lymphocytes bearing both NK and T cell markers), IL-4 will be the dominant early lymphokine. IL-4 stimulates production of TH2- and suppresses TH1-type lymphokines.

Fig. 9.5 Secretion profiles of TH0, TH1 and TH2 cells. APC, Antigen-presenting cell; DC, dendritic cell; IFN, interferon; IL, interleukin; LT, lymphotoxin; Mф, macrophage; NK, natural killer; NKT, natural killer T cell; TGF, transforming growth factor.

Fig. 9.6 Target cell killing. CTC, Cytotoxic T cell; L, ligand; MHC, major histocompatibility complex.

Recent studies have identified IL-17-producing CD4+ T cells (Th17) as a distinct effector T-helper subpopulation. With their own set of lineage-specific developmental genes, Th17 cells have been recognized as main pro-inflammatory CD4+ effector T cells involved in autoimmune pathogenesis.

Target cell killing

Cytotoxic T cells carrying CD8, activated via the endogenous antigen presentation pathway, are able to recognize and kill target cells, such as virus-infected cells, expressing MHC I + foreign peptide (Fig. 9.6). Both CD8 and various adhesion proteins are important in enhancing and maintaining target cell-effector cell contact.

When a cytotoxic T cell makes contact with its specific target, cytoplasmic granules polarize to the contact point and are released into the narrow gap between the cells. Cytotoxic granules contain perforin and granzymes. Perforin is related to complement C9, with which it shares the ability to polymerize on the target cell surface, forming transmembrane channels. Granzymes are granular proteases, which gain entry into the target cell through perforin pores. Granzymes activate the target cell's suicide programme (apoptosis), which leads to nuclear fragmentation and packaging of products of nuclear disintegration into apoptotic bodies, which are efficiently removed by phagocytosis.

Target cell apoptosis can also be induced by binding of Fas ligand (FasL), induced during activation of cytotoxic effector T cells, with the death receptor Fas (CD95) on target cells.

NK cells and yδ T cells also employ perforin and granzymes to kill target cells. The yδ TCR can apparently receive signal 1 for activation without participation of classical MHC I or II molecules, and yδ T cells are either CD8- or express CD8aa rather than the usual CD8aβ. The yδ T cells are important in defence against infection, and experimental animals depleted of yδ T cells eliminate microbes inefficiently.

NK cells are apparently responsible for killing target cells that express lower than normal levels of MHC I molecules, such as some malignant or virus-infected cells (see Fig. 8.3). Cells deficient in MHC I cannot be attacked by cytotoxic T cells; however, production of IFN-y by activated NK cells will promote the expression of MHC I on target cells and permit the more efficient T cell cytotoxicity to proceed. The recent molecular characterization of the surface receptors mediating NK cell activation or inactivation have shed new light on how NK cells function. MHC class I-specific inhibitory and activating receptors are now recognized to be responsible for innate recognition of foreign, abnormal or virally infected cells by NK cells.

Certain cells that possess cytotoxic potential express membrane receptors for the Fc region of the antibody molecule. When antibody binds specifically to a target cell, these FcR- bearing cells such as NK cells, macrophages and neutrophils can bind to the Fc portion of antibody and thus to the target cells. Subsequently, these cytotoxic cells cause lysis of the target cell via a process called antibody-dependent cell-mediated cytotoxicity (ADCC).

Activation of macrophages

Macrophages receive activation signal 1 when they bind pathogens to threat receptors (Fig. 9.7). When they present MHC II + peptide and provide activation signals 1 and 2 for T-helper cells, they also receive a second signal for their own activation. Macrophage-derived IL-12 induces T-helper cells of the TH1 phenotype. IFN-y released by TH1 induces macrophages to express receptors for tumour necrosis factor-a (TNF-a). These can bind membrane-bound TNF-a expressed by TH1, inducing the activated state. Activated macrophages secrete autocrine TNF-a for maintaining this state, along with the inflammatory cytokines IL-1 and IL-6.

Following activation, macrophages express increased levels of Fc and complement receptors and thereby have higher phagocytic capability. They also increase expression of MHC and adhesion molecules, increasing the efficiency of antigen presentation. Their ability to kill pathogens increases as a result of raised levels of intracellular and secreted enzymes. Most importantly, powerful microbicidal mechanisms involving generation of reactive oxygen intermediaries (OH, O, O2-, H2O2) and nitric oxide (NO) are induced.

Fig. 9.7 Activation of macrophages. CR, Complement receptor; FcR, Fc receptor; IFN, interferon; IL, interleukin; Mф, macrophage; R, receptor; TNF, tumour necrosis factor.

Regulation of the immune response

The specific immune response involving activation and clonal expansion of B cells and T cells brings into play a variety of non-specific effector mechanisms involving complement, cytokines, granulocytes, macrophages and mast cells. These have the potential to damage normal host tissues, so it is crucial that the specific immune response be swiftly curtailed once the initiating foreign invader has been effectively neutralized.

Anti-idiotypic antibody

The variable regions, or idiotypes (ids), of antibodies, BCRs and TCRs represent novel molecules not previously experienced by the immune system. Tolerance will not have been induced against them and, if present in sufficient quantity, as occurs during a clonally expanded immune response, they will be immunogenic and induce anti-idiotypic antibodies (anti-ids).

Secreted antibody may be recognized by B cells bearing BCRs with anti-id reactivity. This usually takes place on the surface of follicular dendritic cells and transmits activation signal 1 to the anti-id B cell. Further activation signals are received following processing of the id and presentation of its peptides to a specific TH2 cell. The fully activated anti-idiotypic B cell undergoes clonal expansion and secretes anti-id. This will form immune complexes with circulating id, which will be removed by phagocytes.

Anti-id will also bind to id (BCR) on the surface of B cells. This will lead to cross-linking of BCRs and FcRs, which generates an inactivation signal.

The TCR on clonally expanded activated T cells can also lead to the generation of anti-id, which could induce tolerogenic signals when it binds to cell-bound TCR, perhaps by inducing activation signal 1 in the absence of signal 2.

Regulatory T cells

Activation of immune effector mechanisms involving B cells, cytotoxic T cells, macrophages or NK cells all require participation of T-helper cells and their secreted lymphokines.

Termination of a successful immune response could therefore be effectively achieved by silencing the driving T-helper cells.

Although the phenomenon of T-helper inactivation by T-suppressor cells has long been observed, its mode of action is still not fully understood. As T-helper cells recycle their TCRs and process TCR id peptides on to MHC I, CD8+ T cells with appropriate anti-id TCRs might bind to and inactivate the T-helper cell by a cytotoxic mechanism or by transmitting 'off signals' through membrane interactions.

An important mechanism of immune suppression is induction of a different cytokine profile from the one driving the ongoing reaction, e.g., suppression of cell-mediated immunity by type 2 cytokines or suppression of humoral immunity by type 1 cytokines (immune deviation). A T-regulatory cell, a population of suppressor T cell, is functionally defined as a T cell that inhibits an immune response by controlling the activity of another cell type. T-regulatory cells are a minor population of thymus-derived CD4+ T cells that coexpress the CD25 antigen (IL-2R a-chain), which constitute 5%-10% of the peripheral naive CD4+ T cell repertoire of normal mice and humans. Unlike conventional T-helper cells, regulatory T cells express Foxp3, a transcription factor essential for the development and function of regulatory T cells. Several types of T-regulatory cell populations including CD8+ regulatory T cells have been identified, each with a specific surface phenotype and cytokine production potential. After activation, T-regulatory cells secrete mainly transforming growth factor-в and/or IL-10 and mediate peripheral tolerance by suppressing cytokine-dependent immune reactions.

Immunological memory

The initial encounter with foreign antigen leads to an immune response that evolves slowly over days or weeks and eventually neutralizes and eliminates the invader. Although effector mechanisms are switched off once they are no longer required, the original antigenic experience is not forgotten. Long-lived T and B memory cells are selected for survival and mount an accelerated and enhanced response on encountering the antigen for a second time (Fig. 9.8).

Fig. 9.8 Induction of memory cells. Ag-Ab, Antigen-antibody; FDC, follicular dendritic cell; L, ligand.

Memory B cells

The primary B cell response leads to the production of mainly low-affinity IgM antibodies, but some responding B cells undergo heavy-chain class-switching and V-region somatic mutation to produce higher-affinity IgG, IgA or IgE antibodies. Memory B cells are selected from this latter population because their BCRs can interact with antigen-antibody complexes formed during the primary response. These remain for long periods on the surface of follicular dendritic cells within germinal centres of secondary lymphoid tissue. High-affinity BCRs compete successfully with the lower-affinity antibody within the complex and bind antigen. Signalling between B cell CD40 and CD40L on activated T cells also appears to be required for memory B cell survival. This interaction induces activation of the bcl-2 oncogene, an inhibitor of programmed cell death.

When memory B cells re-encounter their specific antigen, they rapidly produce high-affinity IgG, IgA or IgE. This requires fewer T-helper cells and lower levels of lymphokines than the primary response. Recent studies have demonstrated that some antibody-secreting plasma cells localized in the bone marrow are long-lived and maintain high antibody titres for years upon repeated immunization with same antigen. Thus, these long-lived plasma cells are responsible for maintaining humoral antibody memory.

Memory T cells

Memory T cells cannot be distinguished from naive T cells on the basis of isotype switch or affinity maturation because TCRs do not undergo these processes. Memory and naive T cells, at least those of the CD4+ T-helper subset, can at present best be distinguished by expression of different isoforms of the common leukocyte antigen CD45, CD45RO on the former and CD45RA on the latter. The two isoforms of CD45 are also segregated on subsets of CD8+ cells.

While CD4+CD45RO+ memory T cells provide help for B cell activation, CD4+CD45RA+ naive cells preferentially induce T-suppressor cells. This may be related to the different lymphokine secretion profiles of the two subsets, with naive T cells producing mainly IL-2 and memory T cells producing multiple lymphokines.

Memory T cells express higher levels of various adhesion and co-stimulatory molecules than naive T cells and are much more efficient at interacting with other cell types.

As with memory B cells, long-term survival of memory T cells is triggered by re-exposure to the same antigen. Antigen is retained in the body for prolonged periods, mainly in the form of immune complexes on the surface of follicular dendritic cells, and is only available to the high-affinity BCRs of memory B cells. Therefore, selection of memory T cells probably requires recognition, processing and presentation of MHC II + peptide by memory B cells.

Key facts

• Antibodies, the secreted products of B lymphocytes, neutralize antigens, induce killing of target cells by complement and natural killer cells and opsonize particles for phagocytosis.

 Cytokines and chemokines mediate intercellular communication within the immune system, being required for initiation and regulation of all stages of the immune response. Type 1 cytokines induce mainly macrophage activation, while type 2 cytokines induce mainly antibody secretion.

 B cells are activated when they present antigen to T-helper cells and receive both a first signal through the B cell receptor

(BCR) and a second signal from CD40L binding to CD40.

Type 2 cytokines, including interleukin-4 (IL-4), stimulate clonal proliferation, antibody secretion, affinity maturation and isotype switching of antibody.

T cells and B cells require two signals for activation, the first through the T cell receptor (TCR)/BCR, the second through B7-CD28 or CD40-CD40L interaction. Receipt of only the first signal usually results in anergy or cell death.

Cytotoxic T cells become activated when they encounter endogenous antigen processed on to major histocompatibility complex I (MHC I) and are stimulated by signal 1, signal 2 and type 1 cytokines. They kill by secreting perforin and granzymes towards the target cell or by inducing apoptosis of Fas-expressing cells.

 Macrophages are activated when they process exogenous antigen on to MHC II and present peptides to T-helper cells. The latter become activated and secrete type 1 cytokines, including interferon-y, a powerful macrophage activator. Activated macrophages secrete inflammatory cytokines and are highly efficient at phagocytosis, antigen presentation and microbial killing.

 Termination of the immune response is essential to prevent widespread damage to healthy tissues. Anti-idiotypic antibodies bind to BCRs and TCRs and switch off activated cells. Regulatory T cells can switch off the responses of activated T-helper cells. Type 1 cytokine production can be suppressed by the induction of type 2 cytokines, and vice versa.

• At the end of an immune response, responding high-affinity B cells and T cells survive in a resting state for long periods and respond rapidly and efficiently on re-encountering the same antigen (immunological memory).

Review questions (answers on p. 364)

Please indicate which answers are true, and which are false.

9.1 Features of immunoglobulin (Ig) structure include:

A. typical Y-shaped antibody consisting of two polypeptide chains, one heavy chain and one light chain

B. Ig heavy chains have both constant region and variable region

C. Ig light chains have no constant region

D. the antigen-binding site is located in the Fc portion of Ig molecule

E. the constant regions form the antigen-binding site

9.2 The functions of antibodies include:

A. neutralization

B. opsonization

C. complement activation

D. recognizing specific antigens only when peptides are bound to major histocompatibility complex (MHC) molecule

E. enhancing phagocytosis

9.3 Which of the following statements on B cell differentiation and maturation are true?

A. the first Ig molecule expressed by a B cell is IgE

B. mature B cells can develop into memory cells after antigenic stimulation

C. plasma cells differentiate into memory B cells

D. B cell receptor is expressed by natural killer cells

E. B cell activation usually does not need a signal from T-helper cells

9.4 Which of the following is/are not involved in cytotoxic T cell killing?

A. granzymes

B. perforin


D. Fas ligand


Further reading

Janeway, C. A., Jr., Travers, P., Walport, M., et al. (2001). Immunobiology (5th ed.). New York: Garland Publishing.

Mims, C., Playfair, J., Roitt, I., et al. (1998). Vaccination. In Medical microbiology (2nd ed.). Ch. 15. St Louis: Mosby Year Book.

Roitt, I. M. (1997). Roitt's essential immunology (9th ed.). Oxford: Blackwell.

Roitt, I., Brostoff, J., & Male, D. (1998). Immunology (5th ed.). London: Mosby.

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