Immune System

The immune system, which describes the tissues, cells and molecules involved in the host defenses, plays a vital role in the protection of animals from foreign, non-self invaders. This essential system consists of lymphoid organs, barriers, leukocytes and proteins, such as antibodies and complement components. The blood and lymphatic vessels transport and redistribute the cells and proteins within the body of an animal, allowing for a process of 'patrol' for foreign invaders (1).

The immune system defends the host against infection, using the innate immunity as the primary and first form of defense. Innate immunity is a non-discriminating mechanism present from birth and not altering during its following interactions with antigens. It involves phagocytes, complement proteins, acute inflammatory reactions and the body's physical and chemical barriers, such as the skin. However, it lacks any ability to recognize certain pathogens and to provide specific protective immunity that is capable of preventing re-infection. These deficiencies are provided by the mechanism of adaptive immunity. In the adaptive immune response, antigen-specific lymphocytes proliferate and differentiate into effector cells, and memory cells that eliminate pathogens, when exposed to pathogens and foreign particles. However, all the components of the immune system work together towards preventing disease.

Immunization

Upon immunization of a mouse with chicken erythrocytes (RBCs), which are seen as foreign (non-self), the immune system begins to mount a response to the chicken erythrocytes. By injecting the chicken RBCs into the mouse's peritoneal cavity, rather than applying them onto the mouse's skin, which would prevent their entrance into the body, you can overcome the physical and chemical barriers provided by the skin and peritoneum. Resident tissue macrophages and dendritic cells engulf the chicken RBCs, process these cells intracellularly and present peptide fragments of these molecules on their surfaces through MHC I and MHC II (MHC = major histocompatibility complex). However, if the macrophages had engulfed bacteria, LPS on the bacterial surface would have stimulated the macrophages through toll-like receptors to secrete cytokines and produce inflammation. The macrophages and dendritic cells, leave the interstitial fluid of the peritoneal cavity and migrate into the afferent lymphatics, which flow them to regional lymph nodes. In the lymph nodes, naive/resting lymphocytes interact with the MHC-peptide complexes displayed on the antigen presenting cells surface (APC). Any interaction that results in a productive T cell receptor-MHCII interaction (recognizes and stimulates correct binding, e.g. T-cell receptor and co-stimulatory molecules, CD28 to the MHC II-chicken RBC peptide and costimulatory molecules B7.1-B7.2) will stimulate the cells to become active, enlarge and proliferate and differentiate into memory cells and effector cells, such as helper T cells that can stimulate and activate B cells to secrete antibodies against the specific antigen (an example of the cross-talk between innate and adaptive immunity) (process requires a lag period of 4-5 days, before any clearance of the chicken RBCs can occur - growth, and differentiation). These cells are now effectors and increased in numbers can begin to clear the chicken RBCs. Cytotoxic T cells kill any cells containing the foreign antigens intracellularly, T helper cells 'help' stimulate B cells and antibodies specific to surface antigens found on the chicken RBCs are secrete by the activated B cells, mainly IgG as the chicken RBCs are found in tissues, the peritoneum. IgG is an effective immunoglobulin for clearing the chicken RBCs because of its small size compared to the other Ig isotypes. This allows for its' differentiation and the ability to engage specific transporters to be delivered across various epithelia, in this case, into the peritoneum from the blood. IgG is the principal isotype in the blood and extracellular fluid. IgG efficiently opsoniZes pathogens and foreign invaders for engulfment by phagocytes and also activates the complement system. Therefore, IgG operates favorably in the body tissues where accessory molecules and cells, such as tissue macrophages are. In the immunized mouse, IgG was secreted by the activated B cells (T helper cell stimulate B cell to switch to IgG production), which circulated through the blood and entered into the peritoneum. These IgG's specific for the antigens found on chicken RBCs, bind to the chicken RBCs, agglutinate them into immune complexes in the blood which are cleared by the spleen, but mainly coat their surface for phagocytosis in the tissues (1,2).

References:

1. Janeway, C.A., Travers P., Walport M., and Capra J.D. 1999. Immunobiology: The immune system in health and disease. Garland Publishing, 4th ed., New York, USA, pages 1-40, 2.5-2.22, 3.1-3.12

2. DeFranco, A.I. 1987. Molecular aspects of B-lymphocyte activation. Annu. Rev. Cell Biol. 3:143-178

3. MacLennan, I.C.M. 1994. Germinal centers. Annu. Rev. Immunol. 3:117-139

4. Ravetch, J.V. and Kinet, J. 1993. Fc receptors. Annu. Rev. Immunol. 9:457-492