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. 

Antigen Presenting Cells - Dendritic Cells, Macrophages, B –Lymphocytes and Natural Killer Cell

The term antigen presenting cell refers to the cells that constitutively express class II MHC molecules and so can present antigen to help T-cells.

Dendritic Cells

Dendritic cells are responsible for launching most adaptive immune response and particularly for primary responses. Dendritic cells arise from either the myeloid or lymphoid lineage of the bone marrow. They are found as diffuse, minor resident population in all surface epithelia and most other solid tissues.

Their unique efficiency at capturing, transporting and presenting antigen and attracting and activating specific T-cells, make mature dendritic cells the most potent  APCs known. Under certain conditions a single dendritic cell can activate up to 3000 T-cells

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Macrophages

Macrophages are widely distributed in lymphoid and non lymphoid tissues and because of their prodigious phagocytic capacity are specially important for presenting antigen from particulate immonogens such bacteria. Their many broad specificity receptors enable macrophages to capture a wide range of pathogens. Macrophages are highly efficient at capturing antibody coated antigens using their surface Fc receptors.

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B –Lymphocytes

Although B cells lack significant phagocytic activity, they are able to capture, process, and represent some antigen to help T cells. They are specially effective in presenting the antigens that bind specifically to surface immunoglobulins.

Natural Killer Cells

Natural killer cells are large granular lymphocytes that use cytoplasmic granules containing perforins to kill the target cells. Unlike T cells, NK cells do not express a cell surface TCR/CD3 complex. They also lack CD4, the maker for T helper cells, about half of human NK cells express CD8, the maker for cytolytic T cells, but only one form of CD8 is expressed.

The most important role of NK cells appear to be in host defense against infection by intracellular agents, including certain viruses, bacteria, and parasites.