This lecture is about the principal cell types and tissues of the immune system. The essence of this lecture is to lay a foundation for a proper understanding of immune responses.
In order to make the concept easier to understand, we shall study the principal cells under three functional cell groups:
- Antigen presenting cells
- Effector cells
Antigen presenting cells
Antigen presenting cells are cells of the immune system that capture, internalize pathogens, and display fragments of antigens derived from the pathogen using class-II MHC proteins. Throughout the body, you will most likely find antigen-presenting cells in the peripheral sites where they stay on alert to capture any pathogen that invades the body.
Antigen-presenting cells (APCs) perform two important roles in immune responses
- They present antigens to lymphocytes that can recognize the foreign antigen
- They secrete cytokines that co-activate specific lymphocytes, which is very necessary in immune response.
Antigen presenting cells express receptors that enable them to recognize pathogens broadly. When an APC recognizes a pathogen, it ingests and kills the (ingested) pathogen and displays foreign antigens derived from the pathogen on its surface with the help of class II MHC molecules. After displaying the antigen fragments on its MHC-II proteins, the antigen-presenting cells migrate and travel to nearby lymph vessel, which carries the APC to nearby lymph node; cytokines direct and control this migration to lymph node.
Once in the lymph node, the APC secretes and releases some other cytokines that will co-activate lymphocytes in the lymph node. Well-known antigen presenting cells are
- Dendritic cells,
- Macrophages and
Lymphocytes are at the heart of the acquired immune system; together with antigen-presenting cells, they form the active components of acquired immune system. Lymphocytes, a class of cells that arise from the pleuripotent hematopoietic stem cell in the bone marrow, are relatively small round cells with a centrally placed nucleus that takes up a large portion of the cell leaving a scanty cytoplasm.
Morphologically, all lymphocytes in the body look alike; however, we have three types of lymphocytes with different functional properties and different glycoproteins on their surface membranes.
- Natural killer cells
B and T lymphocytes have surface receptors that can recognize a vast array of foreign antigens and are highly specific for each foreign antigen. B-lymphocytes produce antibodies, which mediate humoral immunity. T-lymphocytes mediate cell-mediated immunity.
When its specific antigen activates a T-lymphocyte, it divides, proliferates and differentiates into two groups of effector cells, Helper T-cells and Cytotoxic T-cells. Helper T-cells activate both humoral and cellular components of acquired immunity. First, they secrete cytokines that activate and help B-lymphocytes to secrete adequate amount of antibodies. Second, they stimulate pre-cytotoxic T-cells to become cytotoxic T-cells and help macrophages in killing engulfed or phagocytosed intracellular pathogens.
Cytotoxic T-cells participate in fighting viral infections mainly. Cytotoxic T-cells kill virus infected host cells directly. Virus-infected host cells call the attention of cytotoxic T-cells by displaying protein fragments (antigens) derived from the infecting virus; Cytotoxic T-cells, which bear receptors that, can recognize the expressed foreign antigen bind and destroy the infected host cell.
Natural killer cells are lymphocytes; like T-lymphocytes, they have surface receptors for antigens but these receptors are not as antigen specific as those of T-lymphocytes. Natural killer cells just like cytotoxic help kill virus-infected host cells. Thus, NK cells participate in innate host defense against viral infections.
Lymphocyte development and maturation
Development: At this point, we expect you to know that all blood cells form in the bone marrow. After birth, T-cells and B-cells mature in thymus and bone marrow respectively. Primary lymphoid organs (bone marrow and thymus) are sites in the body where lymphocytes form and mature; they provide an environment for stem cells to divide, differentiate and mature into B and T-cells.
Maturation: recall that B-lymphocytes mature in bone marrow whereas T-lymphocytes mature in thymus. The most significant event in the maturation of lymphocytes is the acquisition of surface receptors. As lymphocytes mature in bone marrow and thymus gland, random gene recombination occurs in the DNA regions that encode antigen receptors for each maturing B or T-lymphocyte. These random gene recombination and rearrangements are responsible for the vast variations in lymphocyte receptors such that your lymphocyte pool constitutes different lymphocytes with antigen-specific receptors for all possible foreign antigens that can ever infect you. In other words, the net effect of this random gene recombination during lymphocyte maturation is a population of different mature lymphocytes that can recognize and bind all possible foreign antigens.
The receptor a B or T lymphocyte bears determines which foreign antigen it will attack and destroy with high affinity. Nevertheless, a lymphocyte can recognize foreign antigens that are closely related to its own specific antigen, but will be unable to bind the antigen strongly enough.
Negative selection of self-reactive B and T-lymphocytes: Before mature B-lymphocytes leave bone marrow into circulation, the system screens them and kills or inactivates B cells that bear self-reactive immunoglobulin antigen receptors. Thymus also screens all mature T-lymphocytes and kills those that carry T-cell receptors that recognize self-antigens. The negative selection and deletion of self-reactive prevents autoimmunity.
Lymphocyte screening is a very important process because if self-reactive lymphocytes find their way into circulating lymphocyte pool, they produce antibodies against host tissues in the case of B-lymphocytes and self-reactive T-cell receptors in the case of T-lymphocytes; in either case, it results in autoimmunity.
Recirculation of mature lymphocytes: Lymphocyte recirculation is the process of constant migration of lymphocytes from blood to lymph and then back to blood and the cycle continues. The primary lymphoid organs (bone marrow and thymus) release mature B and T lymphocytes, which do not react to self-antigens, into peripheral lymph flow. As lymphocytes recirculate in peripheral lymphatic vessels, they “look out” for their specific foreign antigens. In addition, they pass from one secondary (peripheral) lymphoid tissue to another. If they fail to encounter their specific antigen, they die, by apoptosis, after few days of recirculation. However, if a naïve lymphocyte encounters its specific antigen, the antigen activates the lymphocyte, which begins an acquired immune response.
Effector cells and their effector mechanisms
Finally let us consider the effector cells of the immune system functions; effector cells are cells of the immune system that actually kill pathogenic microbe. However, harmful foreign cells must activate the effector cells to make them potent in killing the microbes. Effector cell include lymphoid and non-lymphoid cells of the immune system and they participate in both innate and acquired immune responses.
Activated B-cells (plasma cells) produce antibodies, which bind foreign antigens for destruction; activated Helper T-cells stimulate macrophages to kill phagocytosed intracellular pathogens; activated cytotoxic T-cells and natural killer (NK) cells directly kill host cell that display fragments of foreign proteins (foreign antigens) on their surface. Neutrophils phagocytose and kill bacterial cells mainly. Eosinophils are most effective in killing parasites.
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