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12.4: B Lymphocytes and Antibodies - Biology

12.4: B Lymphocytes and Antibodies - Biology


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Skills to Develop

  • Describe the production and maturation of B cells
  • Compare the structure of B-cell receptors and T-cell receptors
  • Compare T-dependent and T-independent activation of B cells
  • Compare the primary and secondary antibody responses

Humoral immunity refers to mechanisms of the adaptive immune defenses that are mediated by antibodies secreted by B lymphocytes, or B cells. This section will focus on B cells and discuss their production and maturation, receptors, and mechanisms of activation.

B Cell Production and Maturation

Like T cells, B cells are formed from multipotent hematopoietic stem cells (HSCs) in the bone marrow and follow a pathway through lymphoid stem cell and lymphoblast (see [link]). Unlike T cells, however, lymphoblasts destined to become B cells do not leave the bone marrow and travel to the thymus for maturation. Rather, eventual B cells continue to mature in the bone marrow.

The first step of B cell maturation is an assessment of the functionality of their antigen-binding receptors. This occurs through positive selection for B cells with normal functional receptors. A mechanism of negative selection is then used to eliminate self-reacting B cells and minimize the risk of autoimmunity. Negative selection of self-reacting B cells can involve elimination by apoptosis, editing or modification of the receptors so they are no longer self-reactive, or induction of anergy in the B cell. Immature B cells that pass the selection in the bone marrow then travel to the spleenfor their final stages of maturation. There they become naïve mature B cells, i.e., mature B cells that have not yet been activated.

Exercise (PageIndex{1})

Compare the maturation of B cells with the maturation of T cells.

Like T cells, B cells possess antigen-specific receptors with diverse specificities. Although they rely on T cells for optimum function, B cells can be activated without help from T cells. B-cell receptors (BCRs) for naïve mature B cells are membrane-bound monomeric forms of IgD and IgM. They have two identical heavy chains and two identical light chains connected by disulfide bonds into a basic “Y” shape (Figure (PageIndex{1})). The trunk of the Y-shaped molecule, the constant region of the two heavy chains, spans the B cell membrane. The two antigen-binding sites exposed to the exterior of the B cell are involved in the binding of specific pathogen epitopes to initiate the activation process. It is estimated that each naïve mature B cell has upwards of 100,000 BCRs on its membrane, and each of these BCRs has an identical epitope-binding specificity.

In order to be prepared to react to a wide range of microbial epitopes, B cells, like T cells, use genetic rearrangementof hundreds of gene segments to provide the necessary diversity of receptor specificities. The variable region of the BCR heavy chain is made up of V, D, and J segments, similar to the β chain of the TCR. The variable region of the BCR light chain is made up of V and J segments, similar to the α chain of the TCR. Genetic rearrangement of all possible combinations of V-J-D (heavy chain) and V-J (light chain) provides for millions of unique antigen-binding sites for the BCR and for the antibodies secreted after activation.

One important difference between BCRs and TCRs is the way they can interact with antigenic epitopes. Whereas TCRs can only interact with antigenic epitopes that are presented within the antigen-binding cleft of MHC I or MHC II, BCRs do not require antigen presentation with MHC; they can interact with epitopes on free antigens or with epitopesdisplayed on the surface of intact pathogens. Another important difference is that TCRs only recognize protein epitopes, whereas BCRs can recognize epitopes associated with different molecular classes (e.g., proteins, polysaccharides, lipopolysaccharides).

Activation of B cells occurs through different mechanisms depending on the molecular class of the antigen. Activation of a B cell by a protein antigen requires the B cell to function as an APC, presenting the protein epitopes with MHC II to helper T cells. Because of their dependence on T cells for activation of B cells, protein antigens are classified as T-dependent antigens. In contrast, polysaccharides, lipopolysaccharides, and other nonprotein antigens are considered T-independent antigens because they can activate B cells without antigen processing and presentation to T cells.

Figure (PageIndex{1}): B-cell receptors are embedded in the membranes of B cells. The variable regions of all of the receptors on a single cell bind the same specific antigen.

Exercise (PageIndex{2})

  1. What types of molecules serve as the BCR?
  2. What are the differences between TCRs and BCRs with respect to antigen recognition?
  3. Which molecule classes are T-dependent antigens and which are T-independent antigens?

T Cell-Independent Activation of B cells

Activation of B cells without the cooperation of helper T cells is referred to as T cell-independent activation and occurs when BCRs interact with T-independent antigens. T-independent antigens (e.g., polysaccharide capsules, lipopolysaccharide) have repetitive epitope units within their structure, and this repetition allows for the cross-linkageof multiple BCRs, providing the first signal for activation (Figure (PageIndex{2})). Because T cells are not involved, the second signal has to come from other sources, such as interactions of toll-like receptors with PAMPs or interactions with factors from the complement system.

Once a B cell is activated, it undergoes clonal proliferation and daughter cells differentiate into plasma cells. Plasma cells are antibody factories that secrete large quantities of antibodies. After differentiation, the surface BCRs disappear and the plasma cell secretes pentameric IgM molecules that have the same antigen specificity as the BCRs (Figure (PageIndex{2})).

The T cell-independent response is short-lived and does not result in the production of memory B cells. Thus it will not result in a secondary response to subsequent exposures to T-independent antigens.

Figure (PageIndex{2}): T-independent antigens have repeating epitopes that can induce B cell recognition and activation without involvement from T cells. A second signal, such as interaction of TLRs with PAMPs (not shown), is also required for activation of the B cell. Once activated, the B cell proliferates and differentiates into antibody-secreting plasma cells.

Exercise (PageIndex{3})

  1. What are the two signals required for T cell-independent activation of B cells?
  2. What is the function of a plasma cell?

T Cell-Dependent Activation of B cells

T cell-dependent activation of B cells is more complex than T cell-independent activation, but the resulting immune response is stronger and develops memory. T cell-dependent activation can occur either in response to free protein antigens or to protein antigens associated with an intact pathogen. Interaction between the BCRs on a naïve mature B cell and a free protein antigen stimulate internalization of the antigen, whereas interaction with antigens associated with an intact pathogen initiates the extraction of the antigen from the pathogen before internalization. Once internalized inside the B cell, the protein antigen is processed and presented with MHC II. The presented antigen is then recognized by helper T cells specific to the same antigen. The TCR of the helper T cell recognizes the foreign antigen, and the T cell’s CD4 molecule interacts with MHC II on the B cell. The coordination between B cells and helper T cells that are specific to the same antigen is referred to as linked recognition.

Once activated by linked recognition, TH2 cells produce and secrete cytokines that activate the B cell and cause proliferation into clonal daughter cells. After several rounds of proliferation, additional cytokines provided by the TH2 cells stimulate the differentiation of activated B cell clones into memory B cells, which will quickly respond to subsequent exposures to the same protein epitope, and plasma cells that lose their membrane BCRs and initially secrete pentameric IgM (Figure (PageIndex{3})).

After initial secretion of IgM, cytokines secreted by TH2 cells stimulate the plasma cells to switch from IgM production to production of IgG, IgA, or IgE. This process, called class switching or isotype switching, allows plasma cellscloned from the same activated B cell to produce a variety of antibody classes with the same epitope specificity. Class switching is accomplished by genetic rearrangement of gene segments encoding the constant region, which determines an antibody’s class. The variable region is not changed, so the new class of antibody retains the original epitope specificity.

Figure (PageIndex{3}): In T cell-dependent activation of B cells, the B cell recognizes and internalizes an antigen and presents it to a helper T cell that is specific to the same antigen. The helper T cell interacts with the antigen presented by the B cell, which activates the T cell and stimulates the release of cytokines that then activate the B cell. Activation of the B cell triggers proliferation and differentiation into B cells and plasma cells.

Exercise (PageIndex{4})

  1. What steps are required for T cell-dependent activation of B cells?
  2. What is antibody class switching and why is it important?

Primary and Secondary Responses

T cell-dependent activation of B cells plays an important role in both the primary and secondary responses associated with adaptive immunity. With the first exposure to a protein antigen, a T cell-dependent primary antibody responseoccurs. The initial stage of the primary response is a lag period, or latent period, of approximately 10 days, during which no antibody can be detected in serum. This lag period is the time required for all of the steps of the primary response, including naïve mature B cell binding of antigen with BCRs, antigen processing and presentation, helper T cell activation, B cell activation, and clonal proliferation. The end of the lag period is characterized by a rise in IgM levels in the serum, as TH2 cells stimulate B cell differentiation into plasma cells. IgM levels reach their peak around 14 days after primary antigen exposure; at about this same time, TH2 stimulates antibody class switching, and IgM levels in serum begin to decline. Meanwhile, levels of IgG increase until they reach a peak about three weeks into the primary response (Figure (PageIndex{4})).

During the primary response, some of the cloned B cells are differentiated into memory B cells programmed to respond to subsequent exposures. This secondary response occurs more quickly and forcefully than the primary response. The lag period is decreased to only a few days and the production of IgG is significantly higher than observed for the primary response (Figure (PageIndex{4})). In addition, the antibodies produced during the secondary response are more effective and bind with higher affinity to the targeted epitopes. Plasma cells produced during secondary responses live longer than those produced during the primary response, so levels of specific antibody remain elevated for a longer period of time.

Figure (PageIndex{4}): Compared to the primary response, the secondary antibody response occurs more quickly and produces antibody levels that are higher and more sustained. The secondary response mostly involves IgG.

Exercise (PageIndex{5})

  1. What events occur during the lag period of the primary antibody response?
  2. Why do antibody levels remain elevated longer during the secondary antibody response?
  • B lymphocytes or B cells produce antibodies involved in humoral immunity. B cells are produced in the bone marrow, where the initial stages of maturation occur, and travel to the spleen for final steps of maturation into naïve mature B cells.
  • B-cell receptors (BCRs) are membrane-bound monomeric forms of IgD and IgM that bind specific antigen epitopes with their Fab antigen-binding regions. Diversity of antigen binding specificity is created by genetic rearrangement of V, D, and J segments similar to the mechanism used for TCR diversity.
  • Protein antigens are called T-dependent antigens because they can only activate B cells with the cooperation of helper T cells. Other molecule classes do not require T cell cooperation and are called T-independent antigens.
  • T cell-independent activation of B cells involves cross-linkage of BCRs by repetitive nonprotein antigen epitopes. It is characterized by the production of IgM by plasma cells and does not produce memory B cells.
  • T cell-dependent activation of B cells involves processing and presentation of protein antigens to helper T cells, activation of the B cells by cytokines secreted from activated TH2 cells, and plasma cells that produce different classes of antibodies as a result of class switching. Memory B cells are also produced.
  • Secondary exposures to T-dependent antigens result in a secondary antibody response initiated by memory B cells. The secondary response develops more quickly and produces higher and more sustained levels of antibody with higher affinity for the specific antigen.

Multiple Choice

Which of the following would be a T-dependent antigen?

A. lipopolysaccharide
B. glycolipid
C. protein
D. carbohydrate

C

Which of the following would be a BCR?

A. CD4
B. MHC II
C. MHC I
D. IgD

D

Which of the following does not occur during the lag period of the primary antibody response?

A. activation of helper T cells
B. class switching to IgG
C. presentation of antigen with MHC II
D. binding of antigen to BCRs

B

Fill in the Blank

________ antigens can stimulate B cells to become activated but require cytokine assistance delivered by helper T cells.

T-dependent

T-independent antigens can stimulate B cells to become activated and secrete antibodies without assistance from helper T cells. These antigens possess ________ antigenic epitopes that cross-link BCRs.

repetitive

Critical Thinking

A patient lacks the ability to make functioning T cells because of a genetic disorder. Would this patient’s B cells be able to produce antibodies in response to an infection? Explain your answer.

Contributor

  • Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at https://openstax.org/books/microbiology/pages/1-introduction)


B Lymphocytes and the Immune Response (With Diagram)

Read this article to learn about B Lymphocytes and the Immune Response !

To understand how B lymphocytes are caused to se­crete antibodies during an immune response, let’s consider a case in which a person acquires either a bacterial or viral infection.

Two events must generally occur if B lymphocytes are to be activated (Fig. 25- 12).

First, antigens present on the surface of (or re­leased by) the pathogen become bound to antibodies in the plasma membranes of one or more of the millions of clones of B lymphocytes. Binding of the antigen to the surface of the B lymphocytes does not by itself cause activation of the clone. Instead, antigens must also be taken up during nonspecific phagocytosis of antigen-bearing particles by macrophages (i.e., phagocytic cells that act as scavengers in the body’s tissues). The antigens taken up by the macrophages are degraded or “processed” and fragments contain­ing antigenic determinants are then displayed at the cell surface.

Macrophages that carry out this process are referred to as antigen-presenting cells. The anti­genic determinant is then recognized by one or more clones of T cells possessing T-cell receptors for the an­tigen. T cells that recognize and are activated by antigen-presenting cells are called T helper cells.

Ac­tivated T helper cells then interact with the B lympho­cytes to which antigen had already been bound. The interaction between T helper cells and B lymphocytes serves to activate the B lymphocytes causing the rapid proliferation of the clone, thereby yielding plasma cells and memory cells (Fig. 25-12). Only the plasma cells produce and secrete antibodies. The memory cells are kept in reserve and will be called on to re­spond during a second (or subsequent) infection by the same antigen-bearing pathogen.

Antibodies secreted by plasma cells may have sev­eral different effects:

(1) They may interact with free (i.e., soluble) antigens causing precipitation

(2) They may interact with surface antigens of the pathogen (i.e., particulate antigens) causing agglutination or

(3) They may promote complement fixation.

Precipitation of Soluble Antigens:

Antigens may have one or more antigenic determi­nants (Fig. 25-13). If one antigenic determinant is present, the antigen is said to be mono-determinant if two are present, the antigen is bi-determinant, and so on. Most antibodies are bivalent, meaning that they can simultaneously combine with up to two antigenic determinants.

As Figure 25-13 illustrates the prod­ucts formed by interaction of immunoglobulin and antigen depend on the number of antigenic determi­nants that are present. Two mono-determinant anti­gens can be cross-linked by a single antibody (Fig. 25- 13a), but the product is not usually insoluble unless the antigen itself is very large. However, if two anti­genic determinants are present, cross-linking by the antibody can produce chains of antigens that are in­soluble and form precipitates (Fig. 25-13b). Multi- determinant antigens react with antibody to produce cross-linked networks or lattices that are insoluble (Fig. 25-13c).

Interactions between antibodies and free antigens can be considerably more complex than those illus­trated in Figure 25-13. For example, some antibodies may exist as dimers (e.g., IgA) or pentamers (e.g., IgM) (see Fig. 25-3) these antibodies can simulta­neously bind four or more antigenic determinants. Moreover, antigens may possess more than one kind of antigenic determinant, each determinant capable of reacting with a different antibody.

Finally, the pre­dominant form of interaction that takes place between antibodies and antigens is influenced by the respec­tive concentrations of the interacting species. Small soluble complexes are favored when there is an excess of antibody chains of cross-linked antigens are fa­vored when there is an antigen excess and cross- linked lattices are favored by nearly equal amounts of antibody and antigen. Regardless of the nature of the products formed, antigen-antibody complexes are eventually eliminated by the phagocytic action of mac­rophages.

Antibodies that interact with antigens present in the surfaces of invading microorganisms or other foreign particles cause agglutination (Fig. 25-14). During ag­glutination the particles become cross-linked to form small masses, and the masses are eliminated by the phagocytic action of macrophages.

As illustrated in Figure 25-14, the plasma mem­branes of macrophages possess receptors that recog­nize and bind the C-terminal or Fc regions of immunoglobulin heavy chains (see Fig. 4-35). Conse­quently, the macrophage receptors are called Fc re­ceptors. Because the Fc regions of the immunoglobulin’s include constant domains, macrophage Fc receptors can bind a variety of different antibodies. Interaction between a macrophage and a mass of ag­glutinated cells is followed by phagocytosis.

Although the mechanism is not fully understood, foreign cells that have attached antibodies can also be destroyed by K (or killer) cells. Killer cells bind the agglutinated mass by interacting with the Fc regions of antibodies but do not internalize it. Instead, it is thought that there is the transfer of toxic substances from the K cell to the pathogen.

Complement Fixation:

The complement system is part of still another mecha­nism by which antibodies defend the body against in­vasion by pathogens. Complement consists of more than a dozen proteins that circulate in the blood. The binding of antibodies to a cluster of antigenic determi­nants in the surfaces of bacteria triggers a cascade of reactions in which the complement proteins (many of which are proenzymes) are sequentially activated.

The cascade is initiated by the binding of a small com­plex of the complement proteins to the constant re­gions of antibodies that are bound to the bacterial an­tigens. In the ensuing reactions, additional complement proteins are bound and activated, eventu­ally forming a lytic complex that creates an open chan­nel through the bacterial surface.

By disorganizing the bacterium’s plasma membrane and allowing water to enter the cell by osmosis, the bacterium is killed. Complement fixation by antibody-coated bacteria and the lysis of the invading cells that follows is the most common defense mechanism attributable to B-cell- secreted antibodies.

Immunologic Memory:

Figure 25-15 shows the relationship between time and the appearance of antibodies in response to a first exposure to a given antigen. Following a short lag pe­riod, antibodies begin to appear in the blood, rising to and maintaining a plateau level for some time before falling again. This characteristic response curve is called a primary immune response.

As long as the an­tibody content of the blood remains at its plateau level, a condition of active immunity exists. The re­sponse to a second exposure to the same antigen—the secondary immune response—is much more dra­matic.

The lag period is shorter, the response is more intense (i.e., greater quantities of antibody are pro­duced) and the elevated antibody level is maintained for a longer period of time. The difference between the two responses indicates that the body has “re­membered” its earlier exposure to the antigen.

Immunologic memory may be explained in the fol­lowing way. The initial exposure to antigen causes dif­ferentiation of B lymphocytes into memory cells as well as plasma cells. Whereas the plasma cells have a relatively short life span in which they are actively en­gaged in antibody secretion, memory cells do not se­crete antibody and continue to circulate in the blood and lymph for months or years. These memory cells are able to respond more quickly to the reappearance of the same antigen than undifferentiated B lympho­cytes. Memory cells are also produced by the multi­plication and differentiation of T lymphocytes.

Autoimmune Diseases:

The immune system normally produces antibodies against foreign proteins but not against the native proteins of the body, that is, the immune system can distinguish between “self” and “non-self.” Yet one’s own proteins will readily be regarded as antigens by the immune system of another organism. Thus, each individual’s tissues possess a myriad of proteins (and other chemical substances) that are potential anti­gens.

The capability to distinguish self from non-self de­velops very early in life. In the 1950s, P. B. Medawar carried out a series of elegant experiments that bear on this concept. Adult mice from one strain reject skin grafts from another strain that is, the recipient’s im­mune system produces antibodies against antigens in the donor’s tissue and this leads to the destruction of the donor’s cells.

However, when living spleen cells (which carry the same antigens as skin cells) from one strain of mice were injected into newborn mice of a different strain and the skin graft experiments re­peated when the newborn mice reached adulthood, the results were entirely different.

Newborn mice that had been exposed to the spleen cells of another strain accepted skin grafts from that strain later in life. This is interpreted to mean that the spleen cells had been transferred to the new born mice while the mice were at an early enough stage of development to accept the spleen cells as “self’ by the maturing mouse immune system.

In rare cases, individuals begin to produce antibod­ies against their own antigens. These antibodies are called autoantibodies and the diseases resulting from their presence are the autoimmune diseases. Among these diseases are paroxysmal cold hemoglobinuria (antibodies against one’s own red blood cells), myas­thenia gravis (antibodies against one’s own muscle cell acetylcholine receptors), and systemic lupus erythe­matosus (antibodies against one’s own nuclear DNA).

The causes of autoimmune diseases are not entirely clear and several different mechanisms seem to be in­volved. Clones of lymphocytes prepared to respond to a non-self (i.e., foreign) antigen that is structurally similar to self may undergo mutation during clonal ex­pansion, thereby producing cells that now respond to self.

It has recently become clear that T and B cells re­ active to self antigens are present even in normal indi­viduals. However, in normal individuals T suppressor cells serve to suppress the activity of these cells and thereby prevent autoimmune diseases.


B-lymphocytes

B lymphocytes are the effectors of humoral immunity, providing defense from pathogens through different functions including antibody production. B lymphocytes (B cells) constitute approximately 15% of peripheral blood leukocytes and arise from hemopoietic stem cells in the bone marrow 8) . It is here that their antigen receptors (surface immunoglobulin) are assembled. In the context of autoimmune diseases defined by B and/or T lymphocyte auto-reactive that upon activation lead to chronic tissue inflammation and often irreversible structural and functional damage B lymphocytes play an essential role by not only producing auto-antibodies but also functioning as Antigen-Presenting Cells (APC) and as a source of cytokines.


Diseases of Immunity1

B Lymphocytes

B lymphocytes constitute 5% to 20% of the peripheral blood mononuclear cells. B lymphocyte development occurs in two phases, an antigen-independent phase in the primary lymphoid tissues, followed by an antigen-dependent phase in secondary lymphoid tissues. B lymphocytes can be found in primary lymphoid tissues, such as the bone marrow and ileal Peyer's patches (a primary lymphoid tissue in some species because it is the site of B lymphocyte development, rather than the bone marrow), and in secondary lymphoid tissues, such as the spleen, lymph nodes, tonsils, and Peyer's patches. Within secondary lymphoid tissues, B lymphocytes are aggregated in the form of distinct lymphoid follicles, which on activation expand to form prominent pale regions called germinal centers ( Fig. 5-9 ). This anatomic localization, similar to T lymphocytes in the PALS and paracortex, is the result of elaboration of chemokines for which the B lymphocyte has receptors. The antigen receptor of the B lymphocyte is the membrane-bound immunoglobulin. After the antigen-independent phase of development, B lymphocytes express IgM and IgD on their surface, which signifies a mature B lymphocyte. In the antigen-dependent phase, antigen-activated mature B lymphocytes differentiate into IgM-secreting plasma cells or switch to another antibody isotype. Immunoglobulins can be generated against an almost unlimited number of antigenic determinants through the rearrangement of genes encoding the light chain and heavy chain components. As in the case of the TCR, an evaluation of the rearranged genes of a B lymphocyte can be used to molecularly phenotype B lymphocyte neoplasms (see Chapter 6 ).

Like the T lymphocyte, the B lymphocyte also has accessory molecules that function to form the antigen receptor complex ( Fig. 5-10 ). These nonpolymorphic molecules are nonpolymorphic heterodimers composed of Ig-α (CD79a) and Ig-β (CD79b) that do not bind antigen but do interact with the transmembrane portion of surface immunoglobulin involved in cell activation. B lymphocytes, unlike T lymphocytes, can recognize soluble antigens. Additional nonpolymorphic molecules that are important to B lymphocyte functions are CD21 and CD40. The CD21 molecule is the complement receptor 2 molecule whose ligands are C3b and C3d. B lymphocyte responses to protein antigens are dependent on cytokines produced by activated T lymphocytes (CD4 + ). The CD40 molecule interacts with CD40 ligand on the surface of TH lymphocytes and functions to allow B lymphocyte development into antibody-secreting plasma cells. A failure to express CD40 ligand has been associated with an inability to isotype switch, resulting in a hyper-IgM syndrome. B lymphocytes activated by antigen develop into antibody-secreting plasma cells and memory lymphocytes of the same antigenic specificity.


AS Biology Chapter 11 - Immunity

mature in bone marrow
Involved in humoral immunity
B-cells are activated by t-cells.
B-cells divide by mitosis to give a clone of plasma and memory cells.

a type of lymphocyte that gives rise to plasma cells and secretes antibodies

2)Antibodies are made of four polypeptide chains. One pair of chains are long - heavy chains. The other are short - light chains. Antibodies can change shape (induced fit) to fit around antigens. The binding site is different and is known as the variable region, consisting of a sequence of amino acids forming a specific 3D shape. The rest of the antibody is the same and is known as the constant region, which binds to receptors on cells such as B-cells.

Antibodies have antigen-bonding sites called variable regions. The variable regions are attached to light polypeptide chains. In the center of the antibody is a hinge region which gives flexibility in binding to antigen. The polypeptide chains are held together by disulfide bonds. Attached to the heavy polypeptide chains are chains of sugar molecules.

Produce antibodies which bind to antigens to form an antigen-antibody complex which destroys the phagocyte.

Where are T- and B-lymphocytes formed? Stem cells in the bone marrow.

Where to T-lymphocytes mature? In the thymus gland.

What do T-lymphocytes respond to? - Foreign material inside body cells. And Own cells altered by viruses or cancer or transplants.

How do T-lymphocytes distinguish invader cells from normal cells?
- Phagocytes that have engulfed and broken down a pathogen present some of its antigens on its own cell-surface membrane. And Body cells and cancer cells likewise present antigens on their cell-surface membrane.

Describe the T-lymphocyte response to invading pathogens.
- Pathogen engulfed by phagocyte, which presents antigens on its cell surface membrane. And Receptors on certain specific T-helper cells are complementary to these antigens. This activates other T-cells to divide rapidly by mitosis and form clones.

What do the clones made in the T-lymphocyte response do? (4 points)

a) Develop into memory cells, enabling rapid future responses to the same pathogen. They circulate in the blood and tissue fluid.


Role of B lymphocytes in cell-mediated immunity. I. Requirement for T cells or T-cell products for antigen-induced B-cell activation

Although B lymphocytes can be triggered by B-cell mitogens and by certain other molecules to produce lymphokines, they do not produce lymphokines when stimulated with specific soluble protein antigens. We have investigated whether T-cell help would enable B cells to produce lymphokines when activated by antigens. Addition of small numbers of T cells to B-cell cultures resulted in significant production of a monocyte chemotactic factor. T cells could be replaced by supernates of antigen-stimulated T cells, demonstrating both that the chemotactic factor was B-cell-dervied and that T-cell help was mediated by a soluble factor. Although the T-cell factor was nonantigen specific, B-cell activation required the presence of both antigen and T-cell factor. Thus, it appears that although dependent upon T cells, B lymphocytes may play an important role in amplification of cell-mediated immune responses.


Duality of the Immune System: T Lymphocyte and B Lymphocyte (With Diagram)

There are two ways in which the immune system re­sponds to infection. In the cellular immune response, there is a direct interaction between lymphocytes and invading fungi, bacteria, or virus-infected cells.

In contrast, the humoral immune response acts princi­pally against extracellular phases of infection, that is, through the secretion of proteins called antibodies or immunoglobulin’s into the blood plasma, lymph, and tissue fluid.

These antibodies combine with foreign substances called antigens that are car­ried in the surface of or are released by the pathogen. The combination of antibody with antigen then initi­ates a response leading to the elimination of the anti­gen and, more importantly, its source.

T Lymphocytes and B Lymphocytes:

Cellular immunity is mediated by a class of lympho­cytes called T lymphocytes or T cells. These cells are derived from pluripotent stem cells in the hemopoi­etic tissues of the embryo (i.e., the liver and bone mar­row). From there they migrate to and colonize the thy­mus gland (hence, “T” implies “thymus-derived”).

Many T lymphocytes migrate from the thymus to other lymphoid tissues such as the spleen and lymph nodes and colonize these tissues. Humoral immunity is mediated by B lymphocytes or B cells. In birds, B lymphocytes are derived from the bursa of Fabricius, an out pocketing of the hindgut that is colonized by he­mopoietic stem cells early in embryonic development (thus, “B” implies “bursa-derived”). In mammals, which have no bursa, the origin of B lymphocytes re­mains uncertain, although many are derived from the bone marrow itself.

The activation of T and B lymphocytes by the pres­ence of a foreign agent leads to the production of the effector cells that combat the infection. The T lympho­cytes give rise to cytotoxic, helper and suppressor cells, whereas the B lymphocytes give rise to the plasma cells that secrete antibodies (Fig. 25-1). Both T and B lymphocytes also give rise to memory cells- cells responsible for immunologic memory.

Antigens of the foreign agent are recognized by two families of proteins peculiar to the immune system. The best understood of these proteins are the antibod­ies. Antibodies are found in the plasma membranes of B cells, where they act as antigen receptors, and are also secreted by the plasma cells produced by proliferation of B lymphocytes during an immune response.

Because they are produced in large quantities during infection, antibodies are readily isolated for study and much is known about their structure and action. Less well understood are the T lymphocyte receptor proteins—proteins associated with the plasma mem­branes of these cells. These proteins are not secreted by T cells and are isolated with much greater diffi­culty.

T-cell receptors provide T lymphocytes with the capability to attach directly to foreign cells and to host cells that have been infected by viruses. Despite the disproportion in our knowledge of these two classes of proteins, it is clear that antibodies and T- cell receptors are structurally similar and have a com­mon evolutionary origin.


How Lymphocytes Produce Antibody

The scanning electron micrograph (right) shows a human macrophage (gray) approaching a chain of Streptococcus pyogenes (yellow). Riding atop the macrophage is a spherical lymphocyte. Both macrophages and lymphocytes can be found near an infection, and the interaction between these cells is important in eliminating infection. Below is an animation that illustrates the basic cell-cell interactions that lead to antibody production can be seen in the accompanying animation.

Antigen Processing

When the macrophage eats bacteria, proteins (antigens) from the bacteria are broken down into short peptide chains and those peptides are then "displayed" on the macrophage surface attached to special molecules called MHC II (for Major Histocompatibility Complex Class II). Bacterial peptides are similarly processed and displayed on MHC II molecules on the surface of B lymphocytes.

Helper T Cell Stimulating B Cell

When a T lymphocyte "sees" the same peptide on the macrophage and on the B cell, the T cell stimulates the B cell to turn on antibody production. The helper t cell stimulates b cells through the release of cytokines.

Antibody Production

The stimulated B cell undergoes repeated cell divisions, enlargement and differentiation to form a clone of antibody secreting plasma cells. Hence. through specific antigen recognition of the invader, clonal expansion and B cell differentiation you acquire an effective number of plasma cells all secreting the same needed antibody. That antibody then binds to the bacteria making them easier to ingest by white cells. Antibody combined with a plasma component called "complement" may also kill the bacteria directly.

Monoclonal Antibodies

Using this knowledge scientists can now make large amounts of specific monoclonal antibodies for both antigen detection and treatment of diseases.


B Lymphocyte Biology Studied with Anti-Ig Antibodies

Department of Pathology, Harvard Medical School. Boston, Massachusetts, 02115, U.S.A.

Department of Pathology, Harvard Medical School. Boston, Massachusetts, 02115, U.S.A.

Department of Pathology, Harvard Medical School. Boston, Massachusetts, 02115, U.S.A.

Department of Pathology, Harvard Medical School. Boston, Massachusetts, 02115, U.S.A.


RESTRICTION OF GENE EXPRESSION IN B LYMPHOCYTES AND THEIR PROGENY

To determine whether or not B lymphocytes are committed to the synthesis of a single immunoglobulin heavy chain isotype during their differentiation into plasma cells, rabbit lymph node and Peyer's patch cells were separated into populations with and without membrane IgM, using a fluorescence-activated cell sorter (FACS). The potential of the µ-bearing (µ+) and non-µ-bearing (µ-) cells to give rise to plasma cells both in vivo after transfer into irradiated recipients and in vitro in the presence of pokeweed mitogen was assessed by immunofluorescence techniques, and the relative proportions of the cytoplasmic Ig-stained cells (CSC) synthesizing each class of heavy chains were determined. Most of the CSC arising in vitro from µ-bearing lymph node and Peyer's patch cells contained IgM all IgM CSC appeared to be derived from µ+ cells. Peyer's patch lymphocytes, however, did not generate IgM CSC after cell transfer and thus may be functionally different from lymph node µ+ cells. It was found also that nearly all of the many IgA CSC generated by Peyer's patch lymphocytes either in culture or after transfer were derived from µ- cells. Further fractionation of these µ- cells with the FACS after they had been membrane stained with anti-b locus allotype reagents revealed that the precursors of IgA CSC belong to a minor population of cells which do have b locus light chain determinants on their membranes, although they do not have detectable µ-chains. These cells are not found in lymph nodes. Although the majority of Peyer's patch and lymph node cells were found to be precommitted to the synthesis of a single heavy chain isotype, a small proportion of cells may not be similarly restricted. Some of the CSC with membrane IgM were found to contain cytoplasmic IgA or IgG. In addition, µ+ populations did give rise to low numbers of IgA and IgG CSC. The implications of these results, obtained under experimental conditions, on the normal differentiation of B lymphocytes in situ are discussed.