Antibody-mediated immune response (AMI) provides protection to the host by secreting antibodies; that prevent invasion of microbes present on the surface of the host cells and in the extracellular environment, but has no role against intracellular microbes. AMI occurs through the following three sequential steps:

 1. Activation of B cells following contact with the microbial antigen (B cells act as APCs)

2. Proliferation and differentiation of B cells into effector cells (antibody producing plasma cells) and memory cells

 3. Effector function: Production of antibodies by plasma cells which in turn counter act with the microbes in many ways, such as neutralization, opsonization, complement activation, etc.

Activation of B Cells

Antigens that activate B cells fall into two categories.

 1. Most antigens are thymus-dependent (TD); they activate B cells indirectly via activation of T cells. TD antigens are processed by APCs, presented to TH cells following which the activated TH cells secrete cytokines that in turn activate the B cells

2. The thymus independent (TI) antigens (e.g. bacterial capsule) are not processed by APC. They can directly activate B cells without the help of T cell induced cytokines.

TD antigens induced activation of B cell is described below.

Antigen Presentation of B Cells to Activated T_H Cells

The first and foremost step that occurs is recognition of microbial antigen (TD antigen) by B cell membrane immunoglobulin receptors (mIg) followed by receptor mediated endocytosis of antigen. Then the antigen is processed into smaller antigenic peptides that are presented in complex with MHC-II to activated TH cells (by endocytic pathway). This leads to induction of three signals.

 Signal Induction

 The naive B cells are in the resting stage. Activation requires induction of three signals (Fig. 1).

1. Signal 1: It is induced by the cross linking of IgM on B cell membrane with the microbial antigen

2. Signal 2: It is an additional signal provided by binding of CD40 on B cell with CD40L (ligand) on activated TH cells

3. Signal 3: It is usually a cytokine stimulus. Cytokines produced by the activated TH cells bind to specific cytokine receptor on B cells.

Fig1. Antigen presentation of B cells to activated TH cells and signal induction

 Signal Transduction

 Following induction of signal, its transmission is essential for B cell activation.

* Signal transduction is initiated by the B cell receptor (BCR). The BCR comprises of two parts (Fig. 2)

1. Antigen-binding membrane Ig

2. Ig-α/Ig-β heterodimer.

* Following antigen cross linkage to membrane Ig, the Ig-α/Ig-β heterodimer is activated and in turn transmits the signal, ultimately leading to activation of B cells.

Fig2. B cell signal transduction.  

proliferation and Differentiation of B Cells

 As described in Chapter 14, the naive B cells, released from bone marrow go and house in the B cell areas of peripheral lymphoid organs (e.g. cortex of lymph node and marginal zone of spleen). There, the naive B cells are organized to form primary lymphoid follicles.

* Following the antigenic exposure, the naive B cells are activated and then they proliferate

* Eventually, the primary lymphoid follicles transform into secondary lymphoid follicles

* Secondary lymphoid follicles bear a germinal center which in turn has two areas; dark zone and light zone. Events occurring in the secondary lymphoid follicles are as follows.

 Events in the Dark Zone of Germinal Center (Fig. 3)

The activated B cells differentiate into larger dividing cells called centroblasts, which further transform into smaller non dividing cells called centrocytes by expressing membrane Ig.

* Centroblasts express the membrane Ig by undergoing a type of mutation called somatic hypermutations. These are point mutations arising due to insertion or deletion in the variable region of Ig gene

* This results in alteration of the membrane Ig affinity by which it binds with the corresponding antigen. Thus, the resultant centrocytes would bear membrane Ig with altered affinity

* Because somatic hypermutations occur randomly; they generate membrane Ig with both high and low affinity

- The centrocytes with low affinity membrane Ig undergo apoptosis and then are phagocytosed by special type of macrophages found in lymphoid follicles called tingible body macrophages

 - The centrocytes with high affinity membrane Ig are allowed to survive, following which they migrate to the light zone. The process of enhancement of affinity of membrane Ig for antigen binding is called affinity maturation.

 Events in the Light Zone of Germinal Center (Fig. 3)

* Binding of centrocytes to follicular dendritic cells: The centrocytes with high affinity membrane Ig undergo maturation by binding to a special type of dendritic cell called follicular dendritic cell (see box below). Then the mature centrocytes undergo class switch over

* Class switch over: Early in the immune response, IgM is the predominant immunoglobulin secreted by the B cells. But as the maturation progresses, the same B cells undergo a phenomenon called class switch over to produce Ig of other classes (Fig. 3)

- Class switch over occus in the light zone of lymphoid follicles, where the positively selected centrocytes interact with activated TH cells and receive a cytokine signal for class switching

- Binding of cytokines produced by T_H cells to cytokine receptors present on centrocytes surface induces class switch over

 - Different cytokines induce production of different classes of Ig by switching mechanism (Table 1).

* Differentiation of centrocytes into plasma cells and memory cells:

- After undergoing class switch over, the selected centrocytes further undergo differentiation into effector cells (plasma cells) and memory cells in the light zone of germinal center

- Plasma cells are large antibody-secreting cells; produce secretory Ig enormously, but do not synthesize membrane Ig. They do not have MHC-II molecules and do not undergo further class switch over

- Memory cells bear high affinity membrane Ig molecules of all classes as compared to naive B cell that bear only low affinity IgM or IgD membrane Ig. They are long lived cells which respond to the secondary antigenic stimulus.

Fig3. Differentiation of B cells in secondary lymphoid follicles.

Table1. Cytokines secreted by T_H cells and the respective Ig class/subclass they induce.

Effector Functions of AMI

 Antibodies secreted from plasma cells mediate a number of biological functions through their Fc portions that bind to Fc receptors (FcRs) expressed by many cell types.

* Promotes opsonization: FcRs present on phagocyte surface recognize antibody coated microbes, bind to them and that leads to enhanced phagocytosis (Fig. 4)

* Transcytosis: Poly-Ig receptors are expressed on the inner (basolateral) surface of epithelial cells (facing the blood). They bind to dimers of IgA and multimers of IgM antibodies and transfer them through the cell to their apical (outer) surface and into the lumen of an organ (e.g. the intestine). This is a process referred to as transcytosis and is responsible for the accumulation of antibodies in the lumen of the organ (Fig.5)

* Mediates mucosal immunity: Transcytosis of IgA to gut lumen provides mucosal immunity by neutralizing the microbes at local mucosal sites

* Activates complement-mediated inflammation and cytolysis: Antigen antibody complex activates the classical complement pathway (Fig. 6). The final complement factors (C5-C9), also called membrane attack complex which has lethal activity by forming pores on the target cells

* Promotes ADCC: Though ADCC is principally cell mediated (described under CMI section); antibodies direct the cells to reach to the target cells. ADCC is important to provide immunity against:

- Helminths (eosinophil-IgE mediated)

- Tumor cells and virus infected cells (NK cell-IgG mediated).

Fig4. Opsonization of bacteria and phagocytosis.

Fig5. Transcytosis of dimeric IgA.

Fig6. Complement-mediated cytolysis.

اخر الاخبار

اخبار العتبة العباسية المقدسة

وفد العتبة العباسية المقدسة يجري جولة في أروقة معرض بغداد الدولي للكتاب

شعبة التوجيه الديني النسوي تطلق برنامجًا قرآنيًّا لزائرات مرقد أبي الفضل العباس (عليه السلام)

جامعة الكفيل تطلق دورة تدريبية عن تقييم الأداء الجامعي لعدد من ملاكاتها

المجمع العلمي يقيم محفلًا قرآنيًا بذكرى ولادة الصادقين (صلوات الله عليهما)

المزيد

الآخبار الصحية

هل يتنبأ الذكاء الاصطناعي بأمراضنا قبل حدوثها؟

وداعا للنظارات.. قطرة عين واحدة قد تغير كل شيء ؟

دراسة تكشف تأثير "تيك توك" وتطبيقات الفيديو على سلوك الأطفال

"أسرار خفية" في الشاي الأخضر.. تغير قواعد الصحة والوزن

المزيد

الآخبار التكنلوجية

أول قطار يعمل بالهيدروجين في أميركا يدخل الخدمة رسميًا

أجهزة أبل القادمة.. "حصن منيع" في عصر الهجمات الرقمية !

روسيا: تطلق قمرين اصطناعيين بواسطة الصاروخ سويوز 2.1

ميزة ثورية.. أبل تدخل عالم قياس ضغط الدم

المزيد

مواضيع ذات صلة

Hypersensitivity Reactions

Cell-Mediated Immune Response

Helper T Cells (Activation AND Differentiation)

Type III (Immune Complex) Reactions

Influenza virus immunology

Type II Antibody-Dependent, Complement-Mediated Cytotoxic Reactions

Immunologic Manifestations of Rubella infection

Antigen presentation

Cytokines

Structure of MHC Molecule

MHC Genes and Their Products

Macrophage