Basic Immunology
and Disorders of The Immune System
Francisco G. La Rosa, MD

I. Organization of the Immune System

A. Introduction
B. Ontogeny of the Immune system
C. Cells of the Immune System:

1. Polymorphonuclear cells:
    -Neutrophils
    -Eosinophils
    -Basophils
2. Macrophages
3. Dendritic and Langerhans’ cells
4. T-lymphocytes
5. B-lymphocytes
6. Natural killer (NK) cells

 
A. INTRODUCTION

When an individual is exposed to antigenic materials, either by injection or infection, a complex series of events ensue, the end result of which will be the production of specific antibodies and antigen-reactive cells. These cells are called lymphocytes and are found in the blood and in the lymphoid system.

Common characteristics of the lymphoid system. The lymphoid system involves organs and tissues where lymphocytic cells originate as lymphocyte precursors, then mature and differentiate, and finally lodge in the lymphoid organs or move throughout the body.

Precursor cells originate in the yolk sac, liver, spleen, or bursa of Fabricius (or its mammalian equivalent, the bone marrow) in an embryo or fetus.

Stem cells from bone marrow or embryonic tissues are deposited and mature into lymphocytes in the central or primary lymphoid organs, which include the thymus and the bursa or bone marrow. Upon maturation, the lymphocytes then seed peripheral or secondary lymphoid tissue (i.e., the lymph nodes, spleen, diffuse lymphoid tissues, and lymphoid follicles) where they undergo further maturation toward immunocompetence and production of immunoglobulins or sensitized lymphocytes.

Thymus-dependent system. If the thymus of experimental animals (particularly if they are young) is removed, the immune response (primarily cell-mediated immunity) is depressed. The cells produced by the thymus-dependent system are called T lymphocytes (T cells).

Thymus-independent system. Discovery of the humoral branch of the immune system came about by an accidental observation in chickens. A lymphoid organ in chickens known as the bursa of Fabricius has a role in immunity involving humoral immunity or circulating antibodies (e.g., IgG, IgA). Removal of the bursa depresses humoral immunity, but not cellular immunity. This system then is referred to as the thymus-independent system or B-cell system, and the cells that arise through this pathway are called B lymphocytes (B cells). Humans have a bursa equivalent that is involved with humoral immunity, but there is argument about its location. There is evidence to indicate it is gut-associated lymphoid tissue (GALT)-perhaps Peyer's patches of the intestine, tonsils, and appendix. The fetal liver or bone marrow may also be involved.

Compartmentalization. An examination of lymph nodes reveals an anatomic division between the two types of lymphocytes.

1. The B-cell-dependent regions of the lymph nodes are called germinal centers and are the sites of antibody production. They undergo change and enlarge when antigens are introduced. If the bursa is removed, a degradation of this area occurs.

2. Removal of the thymus causes a degeneration of the thymus-dependent, or paracortical zone of the lymph nodes and the periarterial zone of the white pulp of the spleen.

3. In the spleen, the B cells are located in the white pulp, whereas the T cells ensheathe the trabecular arteries prior to these vessels entering the white pulp.

B. ONTOGENY OF THE IMMUNE SYSTEM

IgG is the major fetal antibody, and it is acquired from the mother through the placenta. IgM synthesis begins prior to birth and is the major antibody produced by a fetus. If IgM levels are elevated at birth, the infant may be infected. The secretory IgA in colostrum provides local immunity for the infant in the intestinal tract, as well as providing protection for the mammary glands. Several months after birth, the maternal IgG is being rapidly degraded and the infant has not yet begun to synthesize large quantities of IgG. This is the most dangerous time for an infant. The development of full immunocompetence takes several years in humans and occurs in an ordered sequence that, in many ways, parallels the phylogenetic development of immune responses.

C. CELLS OF THE IMMUNE SYSTEM

Macrophages are involved in both in vivo and in vitro immune responses, and have certain functional properties. In the process of Phagocytosis, macrophages function as effector cells as they recognize engulf, and destroy foreign (antigenic) substances. Macrophages are accessory cells in the immune response. They are the major antigen-presenting cells of the body that interact with antigen as a primary step in the induction of an immune response. B cells can also present antigen. Antigen presentation involved:

1. Binding and uptake of antigen by the macrophage surface membrane, which creates a tightly bound antigen that is more immunogenic than free antigen.

2. Processing and later re-expression of antigen on the antigen-presenting cell surface in association with MHC (class II)-encoded glycoproteins.

3. Release of soluble mediators, such as the monokine (macrophage-derived hormone) which stimulate the maturation and proliferation of T cells (the result of this sequence of events is the activation of antigen-specific B cells and T cells).

Lymphocytes are both precursor cells of immunologic function as well as regulators and effectors of immunity. Smaller lymphocytes (T cells) have a long life span of months or years, whereas larger lymphocytes (B cells) have a shorter life span of 5 to 7 days. A general method for detection and quantitation of T cells and B cells depends on the differential reactivity of the two cell types with appropriately prepared red blood cells.

1. T cells accumulate sheep red blood cells (SRBCs) around their surfaces and form clusters referred to as erythrocyte (E) rosettes.

2. There is no such reaction between B cells and SRBCs, unless the red blood cells (indicated as E for erythrocytes) are coated with hemolysin-antibody (A) and special nonhemolytic preparations of guinea pig complement (C), thus called EAC rosettes.

T-Lymphocytes

Surface markers: CD1, CD3, and CD11 are found on most peripheral blood T cells. CD3 is associated with, but distinct from, the T-cell receptor for antigen; CD11, with the SRBC rosette receptor. CD4 is present on T helper cells, effector cells for delayed hypersensitivity, and CD2 cell inducers. CD8 is present on cytotoxic and T suppressor cells. CD10 is present on stem cells, some B cells, and activated peripheral blood T cells.

Subpopulations:

1. Effector T (Te) cells, also called TDTH cells, are the peripheral lymphocytic cells responsible for delayed type hypersensitivity (DTH) reactions.

2. Cytotoxic T (Tc or CTL) cells are induced artificially by immunization with allogeneic tissue and naturally by tumors and virus. To be induced to the killer function, the precursor cells must be stimulated by antigen in association with class II MHC molecules.

3. Memory T (Tm) cells are induced during primary immunization; they recognize the specific antigen and participate in the anamnestic response.

4. Helper T (Th) cells are lymphocytes that recognize a specific antigen in association with a homologous class II MHC molecule and collaborate with B cells and macrophages in the induction of the humoral immune response. Similar cells collaborate with other T cells to facilitate the production of Te cells.

5. Suppressor T (Ts) cells are lymphocytes that recognize a specific antigen and interfere with the development of an immune response either directly or via suppressor factors. These cells may be involved in the prevention of Autoimmunity. Ts cell precursors are activated by antigens in association with a particular type of class II MHC molecule.

B-Lymphocytes

Surface markers:

Surface immunoglobulin binds specific antigens and functions as an antigen recognition site that initiates the differentiation of the B cell, resulting in antibody synthesis. Contact between the antigen epitope and the immunoglobulin in the B-cell membrane triggers cell division. As this process continues, the B cell matures into a plasma cell with abundant rough endoplasmic reticulum, actively secreting large amounts of the antibody specifically reactive with its homologous epitope.

Subpopulations: B cells are divided into subpopulations according to the immunoglobulin class they synthesize: D, M, G, A, and E B-cells respectively.

 
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