Activated components can also induce the release of inflammatory mediators from mast cells. Cytokines signal between lymphocytes, phagocytes and other cells of the body Cytokine is the general term for a large group of secreted molecules involved in signaling between cells during immune responses.
All cytokines are proteins or glycoproteins. The different cytokines fall into a number of categories, and the principal subgroups of cytokines are outlined below. IFNs induce a state of antiviral resistance in uninfected cells Fig.
They are produced very early in infection and are important in delaying the spread of a virus until the adaptive immune response has developed. The interleukins ILs are a large group of cytokines produced mainly by T cells, though some are also produced by mononuclear phagocytes or by tissue cells.
They have a variety of functions. Many interleukins cause other cells to divide and differentiate. Colony stimulating factors CSFs are cytokines primarily involved in directing the division and differentiation of bone marrow stem cells, and the precursors of blood leukocytes.
The CSFs partially control how many leukocytes of each type are released from the bone marrow. Some CSFs also promote subsequent differentiation of cells. Chemokines are a large group of chemotactic cytokines that direct the movement of leukocytes around the body, from the blood stream into the tissues and to the appropriate location within each tissue.
Some chemokines also activate cells to carry out particular functions. Tumor necrosis factors, TNFa and TNFb, have a variety of functions, but are particularly important in mediating inflammation and cytotoxic reactions. Transforming growth factors e. TGFb are important in controlling cell division and tissue repair. Each set of cells releases a particular blend of cytokines, depending on the type of cell and whether, and how, it has been activated.
Equally important is the expression of cytokine receptors. Only a cell that has the appropriate receptors can respond to a particular cytokine. For example the receptors for interferons are present on all nucleated cells in the body whereas other receptors are much more restricted in their distribution. In general, cytokine receptors are specific for their own individual cytokine, but this is not always so.
In particular, many chemokine receptors respond to several different chemokines. Pathogens, however come in many different forms, with various modes of transmission and reproductive cycles, so the immune system has evolved different ways of responding to each of them.
The exterior defenses of the body Fig. Very few infectious agents can penetrate intact skin. In contrast, many infectious agents gain access to the body across the epithelia of the gastrointestinal or urogenital tracts; others, such as the virus responsible for the common cold, infect the respiratory epithelium of nasopharynx and lung; a small number of infectious agents infect the body only if they enter the blood directly e.
Once inside the body, the site of the infection and the nature of the pathogen largely determine which type of immune response will be induced — most importantly Fig.
Exterior defenses lysozyme in tears and other secretions commensals skin physical barrier fatty acids commensals removal of particles by rapid passage of air over turbinate bones bronchi mucus, cilia gut acid rapid pH change commensals low pH and commensals of vagina flushing of urinary tract Fig.
The body tolerates a number of commensal organisms, which compete effectively with many potential pathogens. Many are intracellular pathogens and must infect cells of the body to divide and reproduce e. The mycobacteria that cause tuberculosis can divide outside cells or within macrophages.
Some bacteria e. Many bacteria and larger parasites live in tissues, body fluids, or other extracellular spaces, and are susceptible to the multitude of immune defenses, such as antibodies see Chapter 3 and complement see Chapter 4 , that are present in these areas.
Many organisms e. To clear these infections, the immune system has developed ways to specifically recognize and destroy infected cells. This is largely the job of cell-mediated immunity. Intracellular pathogens cannot, however, wholly evade the extracellular defenses see Fig. As a result they are susceptible to humoral immunity during this portion of their life cycle. Innate immune responses are the same on each encounter with antigen Broadly speaking, immune responses fall into two categories — those that become more powerful following repeated encounters with the same antigen adaptive immune responses and those that do not become more powerful following repeated encounters with the same antigen innate immune responses.
Innate immune responses see Chapters 6 and 7 can be thought of as simple though remarkably sophisticated systems present in all animals that are the first line of defense against pathogens and allow a rapid response to invasion. Innate immune response systems range from external barriers skin, mucous membranes, cilia, secretions, and tissue fluids containing antimicrobial agents; see Fig. The innate defenses are closely interlinked with adaptive responses.
Adaptive immune responses display specificity and memory In contrast to the innate immune response, which recognizes common molecular patterns PAMPs , the adaptive immune system takes a highly discriminatory approach, with a very large repertoire of specific antigen receptors that can recognize virtually any component of a foreign invader see Chapters 3 and 5.
These features underlie the phenomenon of specific immunity e. Specific immunity can, very often, be induced by artificial means, allowing the development of vaccines see Chapter These two types of receptor molecules have striking structural relationships and are closely related evolutionarily, but bind to very different types of antigens and carry out quite different biological functions.
Antibody specifically binds to antigen Soluble antibodies are a group of serum molecules closely related to and derived from the antigen receptors on B cells. All antibodies have the same basic Y-shaped structure, with two regions variable regions at the tips of the Y that bind to antigen.
The stem of the Y is referred to as the constant region and is not involved in antigen binding see Chapter 3. The two variable regions contain identical antigen-binding sites that, in general, are specific for only one type of antigen. The amino acid sequences of the variable regions of different antibodies, however, vary greatly between different antibodies. The antibody molecules in the body therefore provide an extremely large repertoire of antigen-binding sites.
The way in which this great diversity of antibody variable regions is generated is explained in Chapter 3. Each antibody binds to a restricted part of the antigen called an epitope Pathogens typically have many different antigens on their surface.
Each antibody binds to an epitope, which is a restricted part of the antigen. A particular antigen can have several different epitopes or repeated epitopes Fig. Antibodies are specific for the epitopes rather than the whole antigen molecule. Many evolutionarily related proteins have conserved amino acid sequences. What consequences might this have in terms of the antigenicity of these proteins?
Related proteins with a high degree of sequence similarity may contain the same epitopes and therefore be recognized by the same antibodies.
Antigen recognition Originally the term antigen was used for any molecule that induced B cells to produce a specific antibody antibody generator. This term is now more widely used to indicate molecules that are specifically recognized by antigen receptors of either B cells or T cells. Antigens, defined broadly, are molecules that initiate adaptive immune responses e.
Antigens are not just components of foreign substances, such as pathogens. Antigens initiate and direct adaptive immune responses The immune system has evolved to recognize antigens, destroy them, and eliminate the source of their production — when antigen is eliminated, immune responses switch off. Antigens and epitopes antigen antibody Ag1 recognition Ag2 recognition Ag3 recognition Fig.
Each antigen Ag1, Ag2, Ag3 may have several epitopes recognized by different antibodies. Some antigens have repeated epitopes Ag3. Consequently, if antibody binds to a pathogen, it can link to a phagocyte and promote phagocytosis. The process in which specific binding of an antibody activates an innate immune defense phagocytosis is an important example of collaboration between the innate and adaptive immune responses.
Other molecules such as activated complement proteins can also enhance phagocytosis when bound to microbial surfaces. Binding and phagocytosis are most effective when more than one type of adapter molecule opsonin is present Fig. Note that antibody can act as an adapter in many other circumstances, not just phagocytosis. Opsonization phagocyte opsonin 1 2 complement C3b 3 antibody 4 antibody and complement C3b Peptides from intracellular pathogens are displayed on the surface of infected cells Antibodies patrol only extracellular spaces and so only recognize and target extracellular pathogens.
Intracellular pathogens such as viruses can escape antibody-mediated responses once they are safely ensconced within a host cell. The adaptive immune system has therefore evolved a specific method of displaying portions of virtually all cell proteins on the surface of each nucleated cell in the body so they can be recognized by T cells. For example, a cell infected with a virus will present fragments of viral proteins peptides on its surface that are recognizable by T cells.
The antigenic peptides are transported to the cell surface and presented to the T cells by MHC molecules a group of molecules encoded with the Major Histocompatibility Complex, see Chapter 5. This is much enhanced if the bacteria have been opsonized by complement C3b 2 or antibody 3 , each of which cross-link the bacteria to receptors on the phagocyte.
Antibody can also activate complement, and if antibody and C3b both opsonize the bacteria, binding is greatly enhanced 4. T cell recognition of antigen Antibody acts as an adapter that links a microbe to a phagocyte infected cell microbe MHC molecule presents peptide antigen antigen peptide bound to MHC molecule antigen-binding site epitope Fab region T cell receptor recognizes MHC and peptide antibody Fc region Fc receptor T phagocyte Fig.
These sites are in the Fab regions of the antibody. The stem of the antibody, the Fc region, can attach to receptors on the surface of the phagocytes. Why is it necessary to have a mechanism that transports antigen fragments to the host cell surface for cytotoxic T cells to recognize infected cells? Its antigen receptor can only interact with and recognize what is present on the surface of cells.
Therefore antigen fragments need to be transported to the cell surface for recognition, and this is the key function of MHC molecules. T cell responses require proper presentation of antigen by MHC molecules antigen presentation. To activate T cell responses this must occur on the surface of specialized antigen-presenting cells APCs , which internalize antigens by phagocytosis or endocytosis.
Several different types of leukocyte can act as APCs, including dendritic cells, macrophages, and B cells. APCs not only display antigenic peptide—MHC complexes on their surface, but also express co-stimulatory molecules that are essential for initiating immune responses see Chapter 8. Co-stimulatory signals are upregulated by the presence of pathogens, which can be detected by the engagement of innate immune receptors that recognize PAMPs. The two major phases of any immune response are antigen recognition and a reaction to eradicate the antigen.
Antigen activates specific clones of lymphocytes In adaptive immune responses, lymphocytes are responsible for immune recognition, and this is achieved by clonal selection. Each lymphocyte is genetically programmed to be capable of recognizing just one particular antigen. However, the immune system as a whole can specifically recognize many thousands of antigens, so the lymphocytes that recognize any particular antigen are only a tiny proportion of the total.
How then is an adequate immune response to an infectious agent generated? The answer is that, when an antigen binds to the few lymphocytes that can recognize it, they are induced to proliferate rapidly. Within a few days there is a sufficient number to mount an adequate immune response.
In other words, the antigen selects and activates the specific clones to which it binds Fig. This operates for both B cells and T cells. It does not know. The immune system generates antibodies and T cell receptors that can recognize an enormous range of antigens even before it encounters them. Many of these specificities, which are generated more or less at random see Chapters 3 and 5 , will never be called upon to protect the individual against infection.
Antigen binds only to those B cells with the specific antibody number 2 in this example , driving these cells to divide and differentiate into plasma cells and memory cells, all having the same specificity as the original B cell. Thus an antigen selects just the clones of B cells that can react against it. What advantage could there be in having an immune system that generates billions of lymphocytes that do not recognize any known infectious agent?
Many pathogens mutate their surface antigens. If the immune system could not recognize new variants of pathogens, it would not be able to make an effective response.
By having a wide range of antigen receptors, at least some of the lymphocytes will be able to recognize any pathogen that enters the body. Lymphocytes that have been stimulated, by binding to their specific antigen, take the first steps towards cell division. Even when the infection has been overcome, some of the newly produced lymphocytes remain, available for restimulation if the antigen is ever encountered again. These cells are called memory cells, because they are generated by past encounters with particular antigens.
Memory cells confer lasting immunity to a particular pathogen. These defense mechanisms are often referred to as effector systems. Antibodies can directly neutralise some pathogens In one of the simplest effector systems, antibodies can combat certain pathogens just by binding to them.
For example, antibody to the outer coat proteins of some rhinoviruses which cause colds can prevent the viral particles from binding to and infecting host cells. Phagocytosis is promoted by opsonins More often antibody activates complement or acts as an opsonin to promote ingestion by phagocytes. Phagocytes that have bound to an opsonized microbe, engulf it by extending pseudopodia around it.
These fuse and the microorganism is internalized endocytosed in a phagosome. Granules and lysosomes fuse with the phagosome, pouring enzymes into the resulting phagolysosome, to digest the contents Fig. Phagocytes have several ways of dealing with internalized opsonized microbes in phagosomes.
Cytotoxic cells kill infected target cells Cytotoxic reactions are effector systems directed against whole cells that are in general too large for phagocytosis. Phagocytosis phagosome forming phagocytosis lysosome damage and digestion lysosome fusion release of microbial products Fig.
Pseudopods extend around the microorganism and fuse to form a phagosome. Killing mechanisms are activated and lysosomes fuse with the phagosomes, releasing digestive enzymes that break down the microbe. Undigested microbial products may be released to the outside.
As a result granules are discharged into the extracellular space close to the target cell. The granules of CTLs and NK cells contain molecules called perforins, which can punch holes in the outer membrane of the target. Some cytotoxic cells can signal to the target cell to initiate programmed cell death — a process called apoptosis.
What risks are associated with discharging granule contents into the extracellular space? Cells other than the target cell may be damaged. This is minimized by close intercellular contact between the CTL and the target cell. Termination of immune responses limits damage to host tissues Although it is important to initiate immune responses quickly, it is also critical to terminate them appropriately once the threat has ended.
These responses, if left unchecked, can also damage host tissues. A number of mechanisms are employed to dampen or terminate immune responses. One is a passive process — that is, simple clearance of antigen should lead to a diminution of immune responses. Why would removal of antigen lead to the decline in an immune response? Antigen is required to stimulate B cell proliferation and differentiation, with the consequent production of antibody. Antigen combined with antibody activates several effector systems e.
Antigen is also required to stimulate T cells with consequent production of cytokines. Therefore removal of antigen takes away the primary stimulus for lymphocyte activation. Antigen elimination can be a slow process, however, so the immune system also employs a variety of active mechanisms to downregulate responses, as discussed in Chapter Immune responses to extracellular and intracellular pathogens differ In dealing with extracellular pathogens, the immune system aims to destroy the pathogen itself and neutralize its products.
Reaction to extracellular and intracellular pathogens complement Principle of vaccination antibody primary vaccination antibody response CTL toxoid virus infection viral replication killing infected cell antiviral 1 CHAPTER Inflammation natural infection toxin secondary antibody response acquired immunity antibody response resistance interferons memory cells formed Fig. Antibodies and complement can block the extracellular phase of the life cycle and promote phagocytosis of the virus.
Interferons produced by infected cells signal to uninfected cells to induce a state of antiviral resistance. Viruses can multiply only within living cells; cytotoxic T lymphocytes CTLs recognize and destroy the infected cells. Because many pathogens have both intracellular and extracellular phases of infection, different mechanisms are usually effective at different times. For example, the polio virus travels from the gut, through the blood stream to infect nerve cells in the spinal cord.
Antibody is particularly effective at blocking the early phase of infection while the virus is in the blood stream, but to clear an established infection CTLs must kill any cell that has become infected. Consequently, antibody is important in limiting the spread of infection and preventing reinfection with the same virus, while CTLs are essential to deal with infected cells Fig. These factors play an important part in the development of effective vaccines.
Vaccination The study of immunology has had its most successful application in vaccination see Chapter 18 , which is based on the key elements of adaptive immunity, namely specificity and memory.
Memory cells allow the immune system to mount a much stronger response on a second encounter with antigen. The aim in vaccine development is to alter a pathogen or its toxins in such a way that they become innocuous without losing antigenicity.
This is possible because antibodies and T cells recognize particular parts of antigens the epitopes , and not the whole organism or toxin.
A primary antibody response to these epitopes is produced following vaccination with the toxoid. If a natural infection occurs, the toxin restimulates memory B cells, which produce a faster and more intense secondary response against that epitope, so neutralizing the toxin. Take, for example, vaccination against tetanus. The tetanus bacterium produces a toxin that acts on receptors to cause tetanic contractions of muscle. The toxin can be modified by formalin treatment so that it retains its epitopes, but loses its toxicity.
The resulting molecule known as a toxoid is used as a vaccine Fig. Whole infectious agents, such as the poliovirus, can be attenuated so they retain their antigenicity, but lose their pathogenicity.
Inflammation Tissue damage caused by physical agents e. What advantage could the inflammatory responses have in the defense against infection?
The inflammatory responses allow leukocytes, antibodies, and complement system molecules all of which are required for the phagocytosis and destruction of pathogens to enter the tissues at the site of infection. Lymphocytes are also required for the recognition and destruction of infected cells in the tissues. It extends its pseudopodium between the endothelial cells and migrates towards the basement membrane 2. After the neutrophil has crossed into the tissue, the endothelium reseals behind 3.
The entire process is referred to as diapedesis. Courtesy of Dr I Jovis. Leukocytes enter inflamed tissue by crossing venular endothelium The process of leukocyte migration is controlled by chemokines a particular class of cytokines on the surface of venular endothelium in inflamed tissues. Chemokines activate the circulating leukocytes causing them to bind to the endothelium and initiate migration across the endothelium Fig.
Once in the tissues, the leukocytes migrate towards the site of infection by a process of chemical attraction known as chemotaxis. For example, phagocytes will actively migrate up concentration gradients of certain chemotactic molecules. A particularly active chemotactic molecule is C5a, which is a fragment of one of the complement components Fig. When purified C5a is applied to the base of a blister in vivo, neutrophils can be seen sticking to the endothelium of nearby venules shortly afterwards.
The cells then squeeze between the endothelial cells and move through the basement membrane of the microvessels to reach the tissues.
This process is described more fully in Chapter 6. Chemotaxis venule endothelium phagocyte site of inflammation basement membrane endothelial activation mediators of inflammation chemotactic mediators chemotaxis Immunopathology Strong evolutionary pressure from infectious microbes has led to the development of the immune system in its present form. Deficiencies in any part of the system leave the individual exposed to a greater risk of infection, but other parts of the system may partly compensate for such deficiencies.
However, there are occasions when the immune system is itself a cause of disease or other undesirable consequences. In essence the immune system can fail in one of three ways Fig.
Activated cells migrate across the vessel wall and move up a concentration gradient of chemotactic molecules towards the site of inflammation. Ineffective immune response — immunodeficiency If any elements of the immune system are defective, the individual may not be able to fight infections adequately, resulting in immunodeficiency.
Some immunodeficiency conditions: Sometimes immune reactions are out of all proportion to the damage that may be caused by a pathogen. The immune system may also mount a reaction to a harmless antigen, such as a food molecule. Such immune reactions hypersensitivity may cause more damage than the pathogen or antigen see Chapters 23— For example, molecules on the surface of pollen grains are recognized as antigens by particular individuals, leading to the symptoms of hay fever or asthma.
Normal but inconvenient immune reactions Q. Can you think of an instance where an individual is treated to suppress an immune reaction that does not fall into one of the three categories of immunopathology described above? Immunosuppression to prevent graft rejection. In these cases it is necessary to carefully match the donor and recipient tissues so that the immune system of the recipient does not attack the donated blood or graft tissue.
Two examples are given in the table. For tetanus, the vaccine is a modified form of the toxin released by the tetanus bacterium. The vaccine for influenza is either an attenuated non-pathogenic variant of the virus, given intranasally, or a killed preparation of virus, given intradermally.
Both vaccines induce antibodies that are specific for the inducing antigen. The primary lymphoid organs in mammals are the thymus and bone marrow, where lymphocyte differentiation occurs. Monocytes differentiate into macrophages that reside in tissues e. Kupffer cells in the liver.
Neutrophils are shortlived phagocytes present in high numbers in the blood and at sites of acute inflammation. Cells of the immune system There is great heterogeneity in the cells of the immune system, most of which originate from hematopoietic stem cells in the fetal liver and in the postnatal bone marrow — mainly in the vertebrae, sternum, ribs, femur and tibia Fig. In general, cells of the immune system can be divided into two broad functional categories, which work together to provide innate immunity and the adaptive immune response.
This process continues throughout life. B cells also undergo a negative selection process at the site of B cell generation. Adaptive immunity, a more recent evolutionary innovation, recognizes novel molecules produced by pathogens by virtue of a large repertoire of specific antigen receptors.
Platelets — cellular fragments produced by megakaryocytes — are released into the circulation. Polymorphonuclear granulocytes and monocytes pass from the circulation into the tissues.
Mast cells are identifiable in all tissues. B cells mature in the fetal liver and bone marrow in mammals, whereas T cells mature in the thymus. The origin of the large granular lymphocytes with natural killer NK activity is probably the bone marrow.
Lymphocytes recirculate through secondary lymphoid tissues. Interdigitating cells and dendritic cells act as antigen-presenting cells APCs in secondary lymphoid tissues. All phagocytic cells are mainly involved in defense from extracellular microbes. Natural killer NK cells are mainly involved in the defense against intracellular microbes and are responsible for killing virus-infected cells. Mast cells and platelets are pivotal in inducing and maintaining inflammation.
Microbes express various cell surface and intracellular molecules called pathogen-associated molecular patterns PAMPs. PRR have broad specificity and a non-clonal distribution, features which distinguish them from the specific antigen receptors of the adaptive immune system see Chapter 6.
Antigen-presenting cells APCs link the innate and adaptive immune systems A specialized group of cells termed antigen-presenting cells APCs link the innate and adaptive immune systems by taking up and processing antigens so they can be recognized 18 by T cells, and by producing cytokines.
APCs enhance innate immune cell function and they are essential for activation of T cells Fig. Adaptive immune system cells are lymphocytes Lymphocytes T and B cells recognize antigens through clonally expressed, highly specific antigen receptors see Chapters 3 and Chapter 5. T cells are produced in the thymus see Fig. Whereas the cells of the innate immune system are found in the blood stream and in most organs of the body, lymphocytes are localized to specialized organs and tissues.
It is in the primary lymphoid organs that the lymphocytes undergo the antigen independent portion of their differentiation program. In the secondary lymphoid organs and tissues, lymphocytes undergo their final differentiation steps, which occur in the presence of antigen. Effector B and T cells generated in the secondary lymphoid tissues account for the two major cell types participating in adaptive immune responses of humoral and cellular immunity, respectively.
As the cells of the immune system develop, they acquire molecules that are important for their function. Other marker molecules include those involved in regulating cell differentiation maturation, development , proliferation and function and those involved in regulating the number of cells participating in the immune response. Myeloid cells Mononuclear phagocytes and polymorphonuclear granulocytes are the two major phagocyte lineages Phagocytic cells are found both in the circulation and in tissues.
The mononuclear phagocytes consist of circulating cells the monocytes and macrophages, that differentiate from monocytes and reside in a variety of organs e.
The other family of phagocytes, polymorphonuclear granulocytes, have a lobed, irregularly shaped polymorphic nucleus. The mononuclear phagocytes and polymorphonuclear granulocytes develop from a common precursor. Mononuclear phagocytes are widely distributed throughout the body Cells of the mononuclear phagocytic system are found in virtually all organs of the body where the local microenvironment determines their morphology and functional characteristics, e.
Myeloid progenitors in the bone marrow differentiate into pro-monocytes and then into circulating monocytes, which migrate through the blood vessel walls into organs to become macrophages. Kupffer cells Q. How do macrophages recognize microbes that have been coated with antibody? Macrophages have Fc receptors that recognize the constant domains of the heavy chains of an antibody molecule see Figs 1.
There are three different types of polymorphonuclear granulocyte Fig. Inset: Light microscope image of a monocyte from the blood. Courtesy of Dr B Nichols. The lysosomes contain peroxidase and several acid hydrolases, which are important for killing phagocytosed microorganisms. Microbial adherence occurs through pattern recognition receptors see Chapters 6 and 7 , followed by phagocytosis.
Like monocytes, PMNs marginate adhere to endothelial cells lining the blood vessels and extravasate by squeezing between the endothelial cells to leave the circulation see Fig.
This process is known as diapedesis. Adhesion is mediated by receptors on the granulocytes and ligands on the endothelial cells, and is promoted by chemo-attractants chemokines such as interleukin-8 IL-8 see Chapter 6. Their predominant role is phagocytosis and destruction of pathogens. The importance of granulocytes is evident from the observation of individuals who have a reduced number of white cells or who have rare genetic defects that prevent polymorph extravasation in response to chemotactic stimuli see Chapter These individuals have a markedly increased susceptibility to bacterial and fungal infection.
At the ultrastructural level, the azurophilic primary granules are larger than the secondary specific granules with a strongly electron-dense matrix; the majority of granules are specific granules and contain a variety of toxic materials to kill microbes.
A pseudopod to the right is devoid of granules. Arrows indicate nuclear pores. Go: Golgi region. Inset: A mature neutrophil in a blood smear showing a multilobed nucleus. Atlas of blood cells: function and pathology, 3rd edn. Milan: Edi Ermes; During phagocytosis the lysosomes containing the antimicrobial proteins fuse with vacuoles containing ingested microbes termed phagosomes to become phagolysosomes where the killing takes place.
Neutrophils can also release granules and cytotoxic substances extracellularly when they are activated by immune complexes antibodies bound to their specific antigen molecules through their Fc receptors.
This is an important example of collaboration between the innate and adaptive immune systems, and may be an important pathogenetic mechanism in immune complex diseases type III hypersensitivity, see Chapter Granulocytes and mononuclear phagocytes develop from a common precursor Studies in which colonies have been grown in vitro from individual stems cells have shown that the progenitor of the myeloid lineage CFU-GEMM can give rise to granulocytes, monocytes and megakaryocytes Fig.
Myelopoiesis the development of myeloid cells commences in the liver of the human fetus at about 6 weeks of gestation.
Thrombopoietin TP promotes the growth of megakaryocytes. Bone marrow stromal cells, stromal cell matrix, and cytokines form the microenvironment to support stem cell differentiation into individual cell lineages.
Stromal cells produce an extracellular matrix which is very important in establishing cell—cell interactions and enhancing stem cell differentiation. Other cytokines, such as transforming growth factor-b TGFb may downregulate hemopoiesis. CFU-GMs taking the monocyte pathway give rise initially to proliferating monoblasts. Proliferating monoblasts differentiate into pro-monocytes and finally into mature circulating monocytes which serve as a replacement pool for the tissueresident macrophages e.
Monocytes express CD14 and significant levels of MHC class II molecules The non-differentiated hemopoietic stem cell marker CD34, like other early markers in this lineage, is lost in mature neutrophils and mononuclear phagocytes. Other markers may be lost as differentiation occurs along one pathway, but retained in the other. For example, the common precursor of monocytes and neutrophils, the CFU-GM cell, expresses major histocompatibility complex MHC class II molecules, but only monocytes continue to express significant levels of this marker.
What is the functional significance of the expression of MHC molecules on monocytes? Monocytes can present antigens to helper T cells, but neutrophils generally cannot. If You feel that this book is belong to you and you want to unpublish it, Please Contact us. Immunology 8th Edition. Download e-Book. Posted on. Page Count. Understand the building blocks of the immune system - cells, organs and major receptor molecules - as well as initiation and actions of the immune response, especially in a clinical context.
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