Primary and secondary immune response

Humoral immune responses can be divided into two types primary and secondary responses, which reflect the cellular dynamics of the immune system and the immune state of the host. A primary response is caused by the first exposure to a given immunogen and results in the appearance of predominantly IgM antibodies after a relatively long lag period, followed by a peak and a decline of antibody formation. After a lapse of time, another exposure to the immunogen produces a quite different, secondary response which is characterized by a shorter lag period, a stronger response with predominantly IgG antibodies and, after a peak has been reached, a slower decrease. 

Moreover, antibodies of the secondary response usually have a higher affinity which may increase even more with time (maturation, see Section 8.5). The immune system stores information of the first contact with the immunogen ( priming ) in so-called memory cells. 

The lymphoid tissues include primary (or central) lymphoid organs (bone marrow, thymus and bursa of Fabricius in birds), and secondary (or peripheral) lymphoid organs (lymph nodes, spleen, tonsils, appendix, Peyer s patches). 

Lymphocytes, erythrocytes, macrophages, granulocytes and platelets are all derived from a pluripotent hemopoietic stem cell. This 

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Gottlieb, A. et al., Impact of a 12-week course of alefacept therapy on primary and secondary immune responses in psoriasis patients, J. Eur. Acad. Dermatol. Venereol., 15 (Suppl. 2), 242 (Abst. P24-21), 2001. 

Fig 1. The primary and secondary immune responses to injections of antigen. 

Hoffman et al.52, presented evidence that a single oral dose of tilorone enhanced the primary immune response to sheep red blood cells (SRBC) in mice as measured by the Jerne Plaque technique. They also reported an increase in hemolysin titer after tilorone administration. To further evaluate the action of tilorone on humoral antibody responses, Megel ef a/.3 have studied its effect on 19S and 7S production in the primary and secondary immune responses in mice. It was found that tilorone elevated 19S antibody titer on days 3 and 4 after immunization. After 9 days of continuous drug administration, the 19 S response for both groups was diminished compared to days 3 and 4 however tilorone was found to cause a significant increase in the 7S antibody production compared to controls. Tilorone also stimulated the 19S response to E. coli endotoxin, a thymus-independent antigen, on days 3 and 4 after immunization. 

Figure 6-2. Primary and secondary immune responses. After the first exposure to antigen, antibody production in the animal is stimulated. In the primary response, antibodies of low affinity and specificity are produced in relatively low...

Courtenay-Luck NS, Epenetos AA, Moore R, Larche M, Pectasides D, Dhokia B, Ritter MA. Development of primary and secondary immune responses to mouse monoclonal antibodies used in the diagnosis and therapy of malignant neoplasms. Cancer Res 1986 46(12 Pt l) 6489-93. 

Baczynsky WO, Zimmerman AM (1983a) Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol on the immune system in mice. I. In vivo investigation of the primary and secondary immune response. Pharmacology 26 1-11... 

DC have the unique capacity to initiate primary and secondary immune responses. They take-up antigens in peripheral tissues and migrate to lymphoid organs where they present processed peptides to T-cells. During migration DC undergo maturation from a immature to a mature functional phenotype, characterized by the expression of co-stimulatory molecules, cytokine production and high ability to stimulate T-cell proliferation. 

In a study utilizing over 4000 mice (Spallholz et al., 1974) where the route of administration (ip, sc or intradermal) of Se and Vitamin E (0-100 yg Se and /or 0-5 mg Vitamin E) upon the primary and secondary immune responses to SRBC antigens or tetanus toxoid (TT) were studied, synergism between Se and Vitamin E in increasing antibody titers was observed. No increases in anti-TT titers were observed in the primary immune response, but were increased in the secondary immune response. Anti-SRBC antibodies were enhanced in both primary and secondary immune responses. The primary Immune response to both antigens was measured over a 21-day period while the secondary response was also measured over 21-day period following the second immunization-sensitization. 

J. L. (1974) The effect of selenite, tocopherol acetate and selenite, tocopherol acetate on the primary and secondary immune responses of mice administered tetanus toxoid or sheep red blood cell antigen. Fed. Proc. Abs. 33 694. 

LAMERS, c.H.J. and MUiswiNKEL, W.B. (1984) Primary and secondary immune responses in carp (Cyprinus carpio) after administration of Yersinia ruckeri O-antigen. In Acuigrup (ed.) Fish Diseases, Madrid, Editora ATP, p.119-127. 

Although most drugs are absorbed from the intestine by the blood capillary network in the villi, they can also be taken up by the lymphatic system (an integral and necessary part of the vascular system, the function of which is to collect extra tissue fluid and return it to the vascular compartment), particularly by M cells that reside in the Peyer s patch regions of the intestine. Peyer s patches have also been implicated in the regulation of the secretory immune response. Wachsmann et al. [277] reported that an antigenic material encapsulated within a liposome, when administered perorally, is taken up by these M cells and exhibited better saliva and serum IgA (primary and secondary)... 

Psychological stress may influence the immune system by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary axis (SAM). The well-described innervation of primary and secondary lymphoid tissues by the autonomic nervous system also has been implicated in stress-related modulation of the immune response. These pathways operate by producing biological mediators that interact with and affect cellular components of the immune system.13... 

This primary response takes some 10 days and is accompanied by the generation of memory B- and T-cells for secondary immune responses. It should be noted that immunosuppression is more effective for primary responses than for secondary responses. 

Thus, human exposure to PCBs in Japan (Yusho accident) and China has been associated with increased respiratory infections and decreased levels of immunoglobulins in serum. In animals exposed to these compounds, there is atrophy of both primary and secondary lymphoid organs, lower circulating immunoglobulins, and decreased antibody responses after exposure to antigens. Similarly, the exposure of both humans and farm animals to polybrominated biphenyls, which occurred in Michigan in 1973, resulted in depressed immune responses. 

Another basic characteristic of immune responses is the development of immunologic memory.38-40 This is exemplified by the fact that vaccination can sometimes impart immunity for a person s lifetime. If a foreign protein is injected into an animal, after a lag period of 2-5 days the animal will synthesize antibodies against this foreign antigen. This is called a primary adaptive immune response. If after a few days or weeks a second injection of the same protein is made, a much more rapid synthesis of additional antibodies occurs. This secondary immune response may take place within hours and will last longer than... 

Antibodies are molecules secreted by terminally differentiated B cells (a type of lymphocyte) known as plasma cells. Nearly all rabbit primary antibodies and most mouse monoclonal antibodies are immunoglobulins (Igs). There are five classes of Igs that differ structurally and functionally. Immunoglobulin G (IgG) molecules are the major class of Igs in the blood, which are predominantly produced in the secondary immune response. 

We now turn to an anatomical description of lymph nodes. The lymph node is surrounded by a thick, fibrous capsule and is subdivided into compartments by trabeculae. Inside the capsule is the subcapsular or marginal sinus, which forms the entry point of lymphatic fluid into the node, via the afferent vessel. The lymph node cortex, which lies beneath the subcapsular sinus, is the location of the primary and secondary lymphoid follicles. The primary follicles are comprised of B-lymphocytes. An immune response stimulates B-cells to replicate and differentiate, converting the primary follicle into a secondary follicle or germinal center, surrounded by a zone of small lymphocytes. The paracortex surrounds the germinal centers and primary follicles and contains mostly T-lymphocytes. The medulla is composed of medullary cords, consisting of macrophages and plasma cells, and medullary sinuses. The medullary vessels include the arteries and veins, and the afferent and efferent lymphatic vessels, respectively, deliver the lymphatic fluid into and out of the lymph node. 

Fig. 14.1 Primary and secondary lymphoid organs. The primary lymphoid organs are the tissues where the lymphocytes develop from haematopoietic stem cells. The encounter with antigen, the immune response, occurs in the peripheral, secondary lymphoid organs. T cells are responsible for the cell-mediated immune response and B cells for the antigen-stimulated synthesis and secretion of circulating antibodies.

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