The structure and functions of BCR Complex

It’s a membrane Ig (IgM), associated glycoporotein, Ig α and Igβ , which has a moderately large cytoplasmic domain. These domains each include a short region important for transmitting a signal indicating antigen has bound. This region is called immune tyrosin based activation motif ( ITAM ).

Functions of BCR complex

On activation by antigen, B cells differentiate into plasma cells producing antibody molecules of the same antigen specificity as the receptors.

Organization of Immunoglobulins

Molecular Structure of Immunoglobulins

Immunoglobulins are enormous families of related but non-identical glycoproteins. It has been estimated that every human being is capable of producing at least 10⁸ different antibody molecules.

The Four-Chain Basic Unit

Immunoglubulin molecule is made up of two different types of polypeptides. The larger, heavy (H) chains are roughly twice as large as smaller, light (L) chain. Every immunoglobulin contains equal number of heavy and light chain poly peptides. The heavy and light polypeptide chains are both composed of folded globular domains, each of which is 100-110 amino acids long ad contains a single intra chain disulfide bond.

Immunoglobulin Variable Regions and Constant Regions

All the light chains and all the heavy chains in any single immunoglobulin protein are identical. However when compared with different immunoglobulins, there is a wide variation in sequences of the chain. This variation is mostly occurred in N-terminal domain, where as the sequences of other domain remain constant. Therefore N-terminal domain in heavy or light chain poly peptide is referred as variable region.

Hinge Region  

A short additional segment of amino acid located between the C_H1 and C_H2 domains of H chain is called hinge region. It is made up of predominant of cysteine and proline residues. The hinge region permits flexibility between the two Fab arms of the Y-shaped antibody molecule.

Hypervariable Region

Consists of relatively invariant stenches of 15-30 amino acids, separated by shorter region of extreme variability called hypervariable region that are each 9-12 amino acids long. Hypervariable regions are also called complementarity-determining regions.

J Chain and Secretary Components

J Chain

The secreted form of IgM and IgA generally exist as polymers of the basic four-chain unit that include a single additional polypeptide called the J chain.

The Secretary Components

Secretary component is a single glycopeptide with a peptide molecular weight of approximately 70,000 and a high carbohydrate content. The function of secretary component is to facilitate the trasepithelial passage of IgA.

Classification of Antigen, T- dependent antigen and T- Independent antigen

T- Dependent antigen

The consequences of antigen contact with RBC depend on the types of antigen or nature of antigen and signals received by the B cells. Contacting antigen alone is not enough to activate B cells because nearly all protein antigen need antigen specific T cell help to generate an antibody response. Basically immune response to all most all the antigens depend on both T cells and B cells understanding the antigen in a related fashion. This type of antigen is called T-dependent antigen (TD-Ag).

T- Independent antigen  

Several  antigens do not require the presence of helper T cells, they are called T- independent antigen or TI-Ag. They can be classified into two categories.

1  TI-1 group, at high concentration induce activation of many B cells both specific and non specific.

2  TI-2 do not have polyclonal cell activator properties, nor do they activate macrophages. These antigens are highly repetitive polymetric antigens such as polysaccharides from bacterial cell wall. 

Classification based on Relationship with Host

Heterophilic Antigen

It is a type of common antigen present in human, animals and microorganisms.

Xenogenic Antigen

This antigen comes from different genus and generic. The important xenogenic antigen are pathogenic microorganisms, plant proteins, animal serum.

Allogenic Antigen

A specific antigen that exists in different individual of same genus. The important human allogenic antigen include

• Red cell blood type antigen
• Rh antigen system  et al
• Human leukocyte antigen

Auto Antigen

A tissue constituent that usually induce an immune response to the host's tissues

Secondary lymphoid tissues and organs

Lymph Nodes

During its passage along the lymphatic vessels, lymph flows through a series of bean – shaped or a gans called lymph nodes. The node functions as a physical and biological filter, as lymph fluids percolates through its internal lattice of the cells, the macrophages and lymphocytes survey the fluids for any bacteria, viruses or foreign macromolecules.

The lymph node cortex usually contains several discrete spherical or void cellular aggregates called lymphoid follicles. These follicles are mainly composed of memory B lymphocytes, few T cells and a specialized type of supporting cell called the follicular dendritic cell. Lymphoid follicles are labile structures that can disappear and reform at different sites overtime and can enlarge in response to infections or other immune challenges.

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Primary follicles

Contains predominantly mature, resting B cells, since they have dense nuclei and little cytoplasm, a primary follicle appears as a relatively dark staining mass on conventional histological preparation

Secondary follicle

Secondary follicles are not present at birth and they form only after repeated exposure to substances that provoke an immune response. The presence of secondary follicles clearly denotes an ongoing B cell immuneresponse.

Spleen 

The spleen filers blood as much as lymph nodes filter lymph. Approximately half of the total blood volume passes through the spleen, where lymphocytes, dendritic cells and macrophages survey it continuously it for presence of infectious agent or other contaminant. Spleen also recognizes and eliminates any abnormal or damaged white cells in the blood.

Mucosal Associated Lymphoid tissue (MALT)

Large number of individual T and B lymphocytes, macrophages, ad plasma cells lies just below the mucosal epithelium in many regions of the alimentary, genitourinary and respiratory tract. MALT is the largest lymphoid organ containing roughly half of the lymphoid cells in the body. The important function of these tissues is to secrete antibodies across the mucosal surface as a defense against external pathogens 

Lymphoid tissues and organs- The role of Thymus and Bone Marrow

Immune system is made up of lymphoid tissues and organs, the immune cells cooperate with each other to carry out their functions. Lymphoid organs are divided into primary lymphoid organ and secondary lymphoid organs. The thymus and bone marrow are referred as primary lymphoid tissues.

The primary lymphoid Organs

Bone Marrow

T and B lineage cells both arise from a subset of hematopoietic stem cells (HSC) in the bone marrow or fetal live that become committed to the lymphoid pathway of development. Human B lymphocyte development take place entirely within the bone marrow. T cells on other hand develop from immature precursor that leave the bone marrow and travel through the blood stream to the thymus, where they proliferate and differentiate into mature T – lymphocytes.

Thymus

The thymus is consists of thymic stromal cells and thymocytes. The fully developed thymus consists of two lobes, each comprising multiple lobes. Thymus is the primary site at which T lymphocytes develop and become functionally competent. 

Fundamentals of Immunology

Immunology

Human body has several mechanisms that defend against invasion and colonization of foreign organism. This defensive ability is called immunity. Immunology is the study of the ways in which the body defends itself from infectious agents and other foreign substances in its surrounding environment.

Immune Cells

Immune cells arise from hematopoietic stem cells (HSC), which resides in the bone marrow and have unique ability to give rise to all of the different mature blood cell types under favorable conditions.

The progeny of HSCs initially commit to one of three main alternatives differentiation pathways (lineage) that yield erythrocytes, lymphocytes or myeloid cells, respectively. The mature cells of myeloid lieage includes neutrophils, monocytes, mast cells, eosinophils, basophils, and megakaryocytes.

Mature cells of the lymphatic lineage include B-lymphocytes, T-lymphocytes, and also Natueal killer cells (NK).

Phagocytes

All types of leukocytes contribute to host defense, three types play a special prominent roles, two of these (the neutrophils and the monocyte-macrophage series) are phagocyte cells, which act primary by engulfing and digesting bacteria, cellular debris etc. The third groups, made up of lymphocytes and their relative, have a little phagocytic capacity but carry out a host of other protective reactions, known as immune responses. Phagocytes are able to recognize and kill pathogen directly and are therefore considered as the most important cellular effectors of the inmate immune system.

Neutrophils

Neutrophils grow and mature in bone marrow, they are then released into blood stream. An adult has approximately 50 billion neutrophils and each cell dies by approximately 12 hours after entering into the blood stream. However bone marrow continues to produce neutrophils to maintain the stable circulation of neutrophils in the blood.

If the neutophile finds an inflamed tissue while circulating in the blood, the cells rapidly adhere to the activated endothelium of the local post capillary venules, migrate through the wall of the vessels and invade the affected tissues and neutrophil immediately begin the process of engulfing any bacteria, cellular debris or foreign bodies in the area.

Mononuclear Phagocytes: The Monocyte-Macrophage System

Monocytes are produced in the bone marrow and released into the blood circulation. Monocytes are not abundant in peripherical circulation, accounting 1% - 6% of nucleated blood cells. Once they are released into blood stream, they circulate for only about a day before settling into a permanent site of the tissue. Once they are settled, the cells are called tissue macrophages or histiocytes.

A tissue macrophage lives approximately 2-4 months. During this time, some macrophages remain immobile and others wander incessantly by ameboid motion. In either case the cells continuously monitor the surrounding by pinocytosis through an extensive array of receptors on its surface. Whenever it encounters certain inflammatory mediators or other signals of tissue distress, the cells undergo a process known as macrophage activation, in which bacteria and other pathogens are killed more efficiently.

Lymphocytes

The typical lymphocyte is a small, round or cuboidal in shape, spherical nucleus,. The most fundamental distinction is the division of these cells into two major lineages known as T-cells and B-cells.

B- Lymphocytes

The definitive feature of the cells in the B-cell lineage is their ability to synthesize protein called immunoglobulin. No other cells express these proteins.

Mature B cells can express immunoglobulin in two different forms that each serve as unique function. In resting (naïve or memory) B lymphocytes, immunoglobulins are expressed only on the cell surface, where they serve as membrane-bound receptors for specific antigens. In contrast, the effector cells of the B lineage (plasma cells) are uniquely specialized to secrete large amount of immunoglobulin protein into their surrounding milieu. The secreted immunoglobulins retain the ability to recognize and bind their specific ligands and are often referred as antibodies.

T – Lymphocytes

T-lymphocytes do not express immunoglobulins, instead, detect the presence of foreign substances with the help of surface protein called T cell receptors. T-cells lack the ability to strike their target at long distance, instead they exert their protective effects either through direct contact with a target or by influencing the activity of their immune cells.