Human immune system. By as. E.V. Pokryshko Medical biology, microbiology, virology, immunology department.

Human immune Human immune systemsystem..

By as. E.V. Pokryshko

Medical biology, microbiology, virology, immunology

department

Structure of the immune system

Lymphoid organs can be classified into

primary (central) lymphoid organs

secondary (peripheral) lymphoid organs

Structure of the immune system

Primary (central) lymphoid organs:

thymusavian bursa of Fabricius (the

equivalent of it in mammals is bone marrow)

foetal liver (during embrionic development)

Structure of the immune system

Secondary (peripheral) lymphoid organs:

lymph nodesspleenmucosa-associated lymphoid tissues

ORIGIN OF IMMUNE CELLS

The capability of responding to immunologic stimuli rests mainly with lymphoid cells. During embryonic development, blood cell precursors originate mainly in the fetal liver and yolk sac; in post natal life, the stem cells reside in the bone marrow. Stem cells differentiate into cells of the erythroid, myeloid, or lymphoid series. The latter evolve into two main lymphocyte populations: T cells and B cells. The ratio of T cells to B cells is approximately 3:1.

Differentiation of stem cells into B cells and T cells. This occurs in the bone marrow and thymus.

T cells T cell precursors differentiate into immunocompetent T cells within the thymus. Stem cells lack antigen receptors and CD3, CD4, and CD8 molecules on their surface, but during passage through the thymus they differentiate into T cells that can express these glycoproteins. The stem cells, which initially express neither CD4 nor CD8 (double-negatives), first differentiate to express both CD4 and CD8 (double-positives) and then proceed to express either CD4 or CD8. A double-positive cell will differentiate into a CD4-positive cell if it contacts a cell bearing class II MHC proteins but will differentiate into a CD8-positive cell if it contacts a cell bearing class I MHC proteins.

Lymphoid progenitors migrate from the bone marrow to the thymus where they develop into mature T

cells

Thymocytes are intimately associated with epithelial cells as they develop in the thymus

B cellsB cells perform two important functions: (1) They differentiate into plasma cells and produce antibodies, and (2) they are antigen-presenting cells (APCs).

Origin. During embryogenesis, B cell precursors are recognized first in the fetal liver. From there they migrate to the bone marrow, which is their main location during adult life. Unlike T cells, they do not require the thymus for maturation. Pre-B cells lack surface immunoglobulins and light chains but do have μ heavy chains in the cytoplasm. The maturation of B cells has two phases: the antigen-independent phase consists of stem cells, pre-B cells, and B.cells, whereas the antigen-dependent phase consists of the cells that arise subsequent to the interaction of antigen with the B cells, eg, activated B cells and plasma cells. B cells display surface IgM, which serves as a receptor for antigens.

Pre-B cells are found in the bone marrow, whereas B cells circulate in the blood stream. B cells constitute about 30% of the recirculating pool of small lymphocytes, and their life span is short, ie. days or weeks. Within lymph nodes, they are located in germinal centers; within the spleen, they are found in the white pulp. They are also found in the gut-associated lymphoid tissue, eg, Peyer's patches.

T Cells perform several important functions, which can be divided into two main categories, namely, regulatory and effector. The regulatory functions are mediated primarily by helper (CD4-positive) T cells, which produce interleukins. For example, helper T cells make (1) interleukin-4 (IL-4) and IL-5, which help B cells produce antibodies; (2) IL-2, which activates CD4 and CD8 cells; and (3) gamma interferon, which activates macrophages, CD4 and CD8 Types of T Cells. Within the thymus, perhaps within the outer cortical epithelial cells (nurse cells), T cell progenitors differentiate under the influence of thymic hormones (thymosins and thymopoietins) into T cell subpopulations. These cells are characterized by certain sur face glycoproteins, eg, CD3, CD4, and CD8. All T cells have CD3 proteins on their surface in asso ciation with antigen receptors (T cell receptor [see below]). The CD3 complex of five transmembrane proteins is involved with transmitting, from the outside of the cell to the inside, the information that the antigen receptor is occupied. CD4 is a single transmembrane polypeptide whereas CD8 consists of two transmembrane polypeptides.

T Cells perform several important functions, which can be divided into two main categories, namely, regulatory and effector.

The regulatory functions are mediated primarily by helper (CD4-positive) T cells, which produce interleukins. For example, helper T cells make

(1) interleukin-4 (IL-4) and IL-5, which help B cells produce antibodies;

(2) IL-2, which activates CD4 and CD8 cells; and

(3) Gamma-interferon, which activates macrophages, effect delayed hypersensitivity (eg, limit infection by M tuberculosis).

These functions are performed by 2 subpopulations of CD4 cells: Th-1 cells help activate cytotoxic T cells by producing IL-2 and help initiate the delayed hypersensitivity response by producing primarily IL-2 and gamma interferon, whereas Th-2 cells perform the B cell helper function by producing primarily IL-4 and IL-5. One important regulator of the balance between Th-l cells and Th-2 cells is interleukin-12 (IL-12), which is produced by macrophages. IL-12 increases the number of Th-1 cells, thereby enhancing host defenses against organisms that are controlled by a delayed hypersensitivity response. Another important regulator is gamma interferon which inhibits the production of Th-2 cells. CD4 cells make up about 65% of peripheral T cells and predominate in the thymic medulla, tonsils, and blood.

CD 8 lymphocytes perform cytotoxic functions; that is, they kill virus infected, tumor, and allograft cells. They kill by either of two mechanisms, namely, the release of performs, which destroy cell membranes, or the induction of programmed cell death (apoptosis). CD 8 cells predominate in human bone marrow and gut lymphoid tissue and constitute about 35% of peripheral T cells.

Types of T cells: After T cells are challenged by antigens, the cells differentiate into one of several types of functioning T cells

T Cell Receptor (TCR) for antigen consists of two polypeptides, alpha and beta ,which are associated with CD3 proteins. TCR proteins are similar to immunoglobulin heavy chains. Note that each T cell has a unique T cell receptor on its surface, which means that hundreds of millions of different T cells exist in each person. Activated T cells, like activated B cells, clonally expand to yield large numbers of cells specific for that antigen. Although TCRs and immunoglobulins are analogous in that they both interact with antigen in a highly specific manner, the T cell receptor is different in two important ways: (1) it has two chains rather than four, and (2) it recognizes antigen only, in conjunction with MHC proteins, whereas immunoglobulins recognize free antigen.

Colorized SEM of a small T lymphocyte attacking two large tumor cells