Parts of the immune system
Knowledge of the various parts of the immune system is a key to understanding its function and importance. Knowing the medical terminology also helps. In addition to mechanical barriers there are various components which comprise the innate immune system and the adaptive immune system. Those components are molecules, cells, tissues, organs, and chemical mediators. The chief molecules are surface markers and receptors which recognize antigens and respond to mediators. The main cells of the immune system are various types of white blood cells. They all originate in the bone marrow but develop into more specialized cells in other lymphoid organs and tissues. The chemical mediators are cytokines which transmit signals from one cell to another.
Antibody – It is a protein complex that binds specifically to an antigen. Antibodies have a basic Y structure. The stem of the Y is constant in terms of his chemical composition and is the same for all antibodies of a given class. The arms comprise a unique in variable portion of the molecule which allows for unique and specific antigen recognition and binding. All antibodies are members of a special class of proteins termed immunoglobulins (Ig).
Antibodies are products of B cells’ response to the entry of pathogens into the body. They don’t kill microbes directly but can rid the body of them and prevent them from causing disease in three major ways. The first way is neutralization. It consists of antibodies binding to microbes or their toxins so they cannot enter cells and cause disease. Macrophages then eventually scavenge the bound antibody/antigen complexes. The second way in which antibodies work is through opsonization. It involves coating the foreign antigen and promoting its ingestion and destruction by neutrophils and macrophages. The constant portion of the antibody makes the antigen more recognizable by the phagocytes. The coating also changes the surface of the pathogen or other foreign particle so phagocytes can ingest it. The third function of antibodies is their activation of the complement system. It also involves opsonization with coating of pathogens by complement in much the same way as antibodies. In contrast to antibodies though, complement can kill certain pathogens directly in some instances. But its major function is to promote destruction of microbes by phagocytes.
In light of their three main functions, it is apparent that antibiotics have important roles in both innate immunity and adaptive immunity even though they are products of the adaptive immune response.
It is important not to confuse antibodies with antibiotics. The chemical structure of an antibiotic is totally different from that of an antibody. Humans don’t produce antibiotics. Rather, they are products of microorganisms, mainly some bacteria and molds. Antibiotics kill or slow the growth of bacteria but do not have those effects on other microbes such as viruses, fungi, etc. The general term for a medicine that treats infection caused by various microbes is an antimicrobial.
Antigen – Is any substance that binds to an antibody. Some, but not all trigger an antibody response. The ones that do are termed immunogens. Many antigens are proteins or peptides. Peptides are protein subunits comprised of short strings of amino acids. Amino acids are compounds containing nitrogen, hydrogen, oxygen, and carbon molecules arranged and bonded in a certain way.
Antigen presenting cell (APC) – It is a cell of the immune system which bears both an MHC I and MHC II molecule on its surface and displays a foreign antigen on its surface for recognition via a CD8 or CD4 cell. It first cleaves the foreign substance into pieces of protein via chemical reactions within its cytoplasm, and then transports a piece to the surface portion of its MHC I or MHC II molecule. In order for a CD8 or CD4 T cell to recognize the fragment it must be bound to the MHC I or MHC II surface molecule respectively. Stated differently, in order for CD8 and CD4 T cells to recognize and bind foreign antigen, it must be in the context of self. The main antigen presenting cells of the immune system are dendritic cells, macrophages and B lymphocytes. Microglia are less recognized APCs in the brain.
Basophils – They are blue staining granulocytes. Their release of the contents of those granules causes many of the signs and symptoms of allergic and inflammatory reactions. They have some phagocytic properties, but that is not their main function.
B cell receptor (BCR) – It is the molecule on the surface of a B cell that binds to an antigen. In contrast to a T cell receptor (TCR), a BCR is identical to the specific antibody the B cell produces following its activation. Another distinction compared to a TCR is the BCR is also a portal of entry for pathogens and other foreign particles into the B cell where their processing for antigen display on the MCH2 molecule occurs.
Bone marrow – It is one of the two central lymphoid organs. It is the soft central hollow portion of bones that produces the precursors of all blood cells, including those involved in immunity.
CD8 – It is a protein on the surface of a T lymphocyte which identifies it as a CD8 cell. It must be present for a T cell receptor to recognize an antigen on an MHC I molecule of an antigen presenting cell.
CD4 T cell – It is a T lymphocyte that has a CD4 protein on its surface. With its T cell receptor it recognizes a protein fragment of a pathogen bound to the surface MHC II molecule of an antigen presenting cell. That recognition causes it to differentiate into a more specialized CD4 T cell which assists in various aspects of an immune response. For this reason, other names for CD4 cell are helper T cell and helper CD4 T cell. The help they provide is in the following areas.
- Initiation of cytotoxic lymphocyte activity, especially in the absence of inflammation
- Proliferation of cytotoxic CD8 cells
- Proliferation of antibody producing B cells (plasma cells)
- Activation of macrophages to perform phagocytosis
- Development and maintenance of immunological memory
Before a CD4 T cell is an effector lymphocyte it must undergo additional differentiation and become a specialized T cell. There are many different specialized CD4 T cells, but the two main subtypes are TH1 and TH2 cells. Their special actions depend primarily on the cytokines they produce. Both produce a variety of different cytokines, but each secretes a signature one. The signature cytokine of TH1 cells is gamma interferon (IFN-γ). The signature cytokine of TH2 is interleukin-4 (IL-4). TH1 cells are involved in cell mediated immunity through macrophage activation. TH2 cells mediate humoral immunity or antibody production.
CD8 T cell – it is a T lymphocyte bearing a CD8 protein on its surface. When activated it becomes a cytotoxic lymphocyte. Activation requires interaction with antigen bound to the surface MHC 1 molecule of an antigen presenting cell or any other infected cell. Following a dual signal involving the two cells and assistance from a CD4 T cell, the CD8 T cell undergoes activation. It then becomes an effector cell capable of carrying out its required function. Cytotoxic CD8 cell is another name for cytotoxic lymphocyte.
Cytokine – It is a general term for a non-antibody protein substance that a cell releases upon contact with an antigen which affects the behavior of another cell upon interaction with its special cytokine receptor. The actions of cytokines are the result of chemical reactions within the cells they influence. The communication signals which cytokines send to the cells they influence operate through specific enzymes known as kinases. The main kinases of the immune system are interleukins, interferons, and growth factors.
Complement – It is a set of proteins in blood which act in concert to attack pathogens located outside of cells. By coating the pathogens they can kill directly or promote killing by neutrophils. Complement circulates in the blood stream in an inactive form. The presence of certain pathogens or their binding by antibodies activates it. The name signifies that it complements the actions of antibodies.
Co-receptor – It is a protein on the surface of a T cell or B cell that increases its antigen receptor’s sensitivity to the antigen it recognizes and binds to. It does so by binding to a portion of the MHC molecule of an antigen presenting cell and participating in the signaling required for activation of the T cell or B cell.
Cytotoxic lymphocytes (CTLs) – They are killer T lymphocytes that bear the CD8 marker on their surfaces and that have undergone CD8 T cell activation. They attack and destroy intracellular pathogens – primarily viruses, but only in the context of self. Stated differently, they attack and destroy microbes within cells but only if an antigen of the pathogen is in the grasp of the MHC I molecule of the infected cell. The infected cell can be any cell of the body including an antigen presenting cell, chiefly a macrophage. It kills the pathogen(s) and the infected cell through release of potent chemicals contained in granules. Many times this massacre is beneficial because it rids the body of infection. At other times though, it might be detrimental in that the immune response does more damage than the infection itself. One such example is fulminant hepatitis B.
Dendritic cell – It is an antigen presenting cell that presents antigen to immature T cells in the thymus and to naïve T lymphocytes in lymph nodes. Its actions in the thymus play a role in the establishment of T cell tolerance. In the lymph nodes it causes naïve T cells to become activated and specific for the particular antigen presented.
Eosinophils – They are red staining granulocytes that mount a defense against parasites. They are usually present in low levels in the blood stream. But increase significantly in certain allergic states such as hay fever or allergic asthma. They are also present in increased numbers in a setting of infection by parasites.
Effector lymphocytes – They are fully functional lymphocytes which can participate in the removal of pathogens from the body. In contrast to naïve lymphocytes, they do not need to differentiate before being able to perform their function. When a naïve lymphocyte encounters an antigen with which it interacts a number of events occur that result in activation of the cell. Activation is the process of a foreign antigen turning the cell on to recognize it. In that the turned-on cell also proliferates, the end result is a clone of cells that react to the same specific antigen that induced them. Thus, the activated cell and its daughter cells are termed antigen-specific lymphocytes.
Following clonal expansion the cells fully differentiate into effector lymphocytes capable of performing their required functions. Those functions are the result of genetic events involving rearrangements of the DNA within the nuclei of the cells. Those events result in changes in cell surface receptors and in the secretion of cytokines and antibodies by T cells and B cells respectively.
Granulocytes – They are white blood cells that have granules filled with potent chemicals in their cytoplasm. Those chemicals kill microorganisms and cause inflammation when released. Because they have a multi-lobulated nucleus they also bear the name polymorphonuclear leukocytes. The main ones are neutrophils, eosinophils and basophils. The names are based on the color of their cytoplasm a stain is applied.
Immunoglobulins – They are a family of plasma proteins with the structure and function of an antibody. They are also the specific antigen receptors on the surface of B cells. There are three main classes. They are IgM, IgG, IgE, IgA, and IgD.
- IgA is present on various barriers of the immune system such as the surface lining of the gut and respiratory tract.
- IgD function is not well-defined although it appears early on the surface of naive B cells that have not undergone activation.
- IgE is involved primarily in allergic reactions and defense against parasites. When used as a test its elevation in the blood can help diagnose certain allergic conditions or infection by parasites.
- IgG is the most abundant class of antibodies in plasma. It is the final form of the antigen receptor on B cells and the final class of antibody B cells secrete during an immune response. When used as a diagnostic test its elevation in the blood is indicative of established or chronic infection because of the timing of its appearance. IgG also activates the complement system.
- IgM is the first type of immunoglobulin a B-cell expresses on its surface and secretes during an immune response. Its elevation in blood when measured helps distinguish between recent and chronic infection because of the timing of its appearance.
Interferon – It is a family of cytokines that have a number of effects on cells. The most notable is the hindrance of duplication by viruses.
Lymphocyte – It is a class of white blood cell (WBC) that has a receptor for antigen binding on its surface. The receptor varies based on the specific antigen it is destined to bind with. Sets of genes and rearranging of their combinations during lymphocyte development determine the biochemical structure of a receptor. There are two main classes of lymphocytes – B lymphocytes and T lymphocytes.
The terms B lymphocyte and B cell refer to the same type of immune cell. Thus their use is interchangeable in this and other literature. B is a mnemonic for its site of origin and early development which is the bone marrow. Its finished development though is in lymphoid organs (primarily lymph nodes and the spleen) where B cell activation occurs. B cells are the orchestrators of humoral immunity.
The terms T lymphocyte and T cell are synonymous. T is a mnemonic for its site of development and maturation in the thymus. Its origin is also in the bone marrow though. T cells are the chief regulators of cell-mediated immunity. They are categorized based on their level of development and function. The relevant designations are naïve T cells and effector T lymphocytes.
Lymph node – It is a type of lymphoid organ scattered throughout the body into which lymph vessels drain. Lymph nodes are the main lymphoid organ where the adaptive immune response begins with the interaction between T cells and antigen presenting cells.
Lymphoid organs – They are organized tissues consisting of large numbers of lymphocytes arranged in stroma. They serve as a habitat for the development and differentiation of lymphocytes. The central or primary organs are the bone marrow and thymus. The main peripheral or secondary organs are the lymph nodes, spleen, tonsils and Peyer’s patches.
Macrophages – They are white blood cells which have roles in innate and adaptive immunity. They are newly recruited monocytes which settle in tissues. Histiocytes are macrophages settled in connective tissue. When present in the sinus-like structures of the liver they bear the name Kupffer cells, but mobilize to sites of infection when inflammation is present. Macrophages in various locations perform phagocytosis during both the innate and adaptive immune response. They are usually first responders to local invasion of bacteria. In addition to pathogens they also phagocytize cancer cells. During the adaptive immune response they present antigen to T cells, particularly memory cells. Through the release of cytokines and other chemical substances they also have other roles within and outside of the immune system. One of those other roles is tissue repair.
Major histocompatibility complex (MHC) – Is a set of genes which contain the codes that determine the protein markers on cells. Another name for these markers is histocompatibility antigens. The same markers are on every cell of the body except for red blood cells which have different types of markers. In humans human leukocyte antigen (HLA) is a term which also refers to them. They clearly identify each cell as self as opposed to foreign or non-self. The markers are molecules composed of sets of proteins. The number of functional proteins comprising a marker depends on which of the two classes it belongs to. Class I MCH molecules largely have 6 proteins and class II markers consist of 8. There are more than 200 possible variations in the form of the proteins that form the molecules depending on one’s genetic makeup. Therefore, it is not surprising that it is very unlikely for any two individuals, except for identical twins, to have the same markers on their cell surfaces. This fact explains why an identical twin is the best donor for tissue or organ transplantation from a rejection viewpoint.
MHC class I molecules are on all human cells with nuclei. When foreign antigens occupy them killer T lymphocytes attack and destroy the particles. Even if the molecule is empty of a foreign particle it can still cause T lymphocytes to mount an attack if its structure is different from that which the genes code for. Such is the case with organ and tissue transplantation from a donor with different cell markers. MHC class I molecules also deliver fragments of infectious organisms that have entered the fluid portion of the inside of a cell (cytoplasm) to the surface for recognition and attack by killer T lymphocytes.
MHC class II molecules are on the surfaces of all human cells with nuclei, antigen presenting cells and thymic cells. They transport processed fragments of foreign particles from the inside of a cell to the surface for presentation to helper T lymphocytes that they activate.
Memory cells – They are the B and T cells that serve as mediators of immunological memory. They are more sensitive to antigen than naïve lymphocytes and respond more rapidly upon re-exposure to the antigen that induced them.
Microglia – They are differentiated macrophages in tissues of the brain and spinal cord. They act as scavengers in that they remove waste material, damaged neurons and infectious agents. They are also antigen presenting cells.
Monocytes – They are phagocytic white blood cells that circulate in the blood stream. They differentiate to become macrophages.
Naïve lymphocyte – It is a mature B or T cell which has never encountered an antigen which activates it. Therefore it is not capable of responding to a specific antigen and removing it from the body.
Natural killer cells (NK cells) – They are a third type of lymphocyte distinct from T cells and B cells in that they like specific receptors on their surfaces. They therefore kill nonspecifically and don’t require foreign antigen to be bound to an MHC molecule of a cell in order to attack. They can kill any type of foreign cell. Much like cytotoxic CD8 cells they contain granules with toxic chemicals which they release. They are part of the inmate immune system.
Neutrophil – It is the most abundant leukocyte of the human body. It is the primary cell involved in the inflammatory phase of an immune response. Neutrophils are a product of the bone marrow which releases them in response to bacterial infection. It is a phagocyte in that it destroys bacteria by engulfing and digesting them. The digestion involves the release of chemicals stored in granules. The presence of those granules distinguishes it as a granulocyte.
Phagocytes – Any of the cells of the immune system capable of engulfing and digesting pathogens. The main ones are neutrophils, macrophages and monocytes.
Plasma cells – They are effector B cells capable of producing large amounts of antibodies.
Spleen – It is an organ in the left upper abdominal cavity consisting of red pulp and white pulp. The red pulp primarily filters old and damaged red blood cells, microorganisms and cellular debris from the circulation. The white pulp is where lymphocyte and antigen interactions occur as part of adaptive immunity. It is one of the two primary sites where B cell activation and differentiation into plasma cells occurs.
T-cell receptor (TCR) – It is the molecule on the surface of a T cell that binds to the MHC molecule of an antigen presenting cell during T cell activation. The TCR of a CD8 cell binds to an MHC I molecule. The TCR of a CD4 cell binds to an MHC II molecule.
Thymus – It is the lymphoid organ in the upper chest behind the breast bone where T-cell development occurs. The outer portion of the gland is the cortex. The inner or central portion is the medulla. It is the site of antigen presentation by dendritic cells. – Thymic adj. cortical thymic cells are the epithelial cells in the cortex of the gland. Medullary thymic cells are epithelial cells in the medulla of the gland.
White blood cells (WBCs) – They are a group of several types of cells which originate in the bone marrow and have an active role in the immune system. They can be categorized based on their ancestor cells, their actions, the shape of their nucleus and the presence or absence of granules within them. The two main categories based on their bone marrow predecessors are lymphocytes and granulocytes. Leukocyte is another name for white blood cell.