Immunology

Abstract

Immunology is the study of how the body defends itself against infection and disease. It is important that the body is able to recognize ‘self’ as not harmful, and target for destruction anything foreign as ‘non-self’ because it may be harmful. Differentiation between self and non-self, and the body's reaction to non-self, forms the basis of the immune response. Immunology as it relates to blood transfusion technology is focused mainly on the way in which red cell antigens and serum/plasma antibodies react with each other. Without a clear understanding of immunology, blood transfusion technologists may have difficulty interpreting antigen–antibody reactions correctly in the laboratory. The human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC) in humans. Although this system relates to immunology, in this publication the HLA system and white cell groups are described in Section 6: Blood group systems. By the end of this section, the student should be able to define and describe the following: Immune system Role of the immune system Protection strategies of the immune system natural inflammation phagocytosis and humoral agents complement acquired T-lymphocytes: cell-mediated immunity B-lymphocytes: antibody response Antigens and antibodies (immunoglobulins) Nature of immunogenicity Factors influencing the immune response Primary and secondary response Active and passive immunity Characteristics of immunoglobulins Immune paralysis and immune tolerance Autoimmunity Immunodeficiency. The major components of the immune system are located as follows: Bone marrow Liver Thymus Lymph nodes Spleen Lymphoid tissue (gastrointestinal tract and lungs). The liver, spleen and lymph nodes together constitute what is known as the reticulo-endothelial system. Leucocytes also have very important functions within the immune defence system. Figure 2·1 shows a simplified version of the location of the components of the immune system. Sketch of immune system components. The role of the immune system is to defend the body against foreign substances that may be harmful, and to identify and destroy abnormal cells within the body. The first line of defence is the natural barriers of the body: the skin and mucous membranes. Microbes and other foreign substances are not able to pass through intact skin to gain access to the body. Mucous membranes are found in various parts of the body, usually where there is exposure to the environment. Examples are the nostrils and eyes, and internally, the lungs. The mucous secreted by these membranes acts as a barrier, slowing down and hindering the entry of microbes and other foreign matter. The skin and mucous membranes are part of the defence against invasion by foreign matter, but micro-organisms are able to gain entry through broken skin or by penetrating mucous membranes. The body is constantly exposed to the environment, and the immune system is therefore constantly on the defensive in order to maintain health. If the immune response is not able to successfully defend the body, harmful agents that gain access are able to multiply unchecked and cause disease. So, a strong immune system is essential to a healthy life. There are two main types of immunity; the first one in which the body reacts in the same way each time it is challenged by a foreign substance, and the second one, in which the body reacts in a more specific and more effective way each time the same challenge is presented. The first strategy is natural or inborn (innate), whereas the second strategy is learned or acquired. Only vertebrates (animals with a backbone) are able to adapt their immune response as seen in acquired immunity. This means that they are able to recognize and respond to foreign matter and adapt in some way to more effectively eliminate it. Foreign matter that elicits an immune response in the form of antibody production is usually referred to as an immunogen. Natural immunity: Provides a protective barrier from the environment by intact skin, mucous membranes, and body secretions Provides protection from invading substances by the following means inflammation cellular defence by phagocytosis humoral defence by soluble agents including complement Acquired immunity: Cellular defence by T-lymphocyte adaptation Humoral defence by B-lymphocyte adaptation and production of antibodies. Table 2·1 provides a summary to compare natural and acquired immunity. External defence is maintained by means of intact skin, by mucous, which traps and eliminates micro-organisms, and by body secretions such as saliva and perspiration, which have disinfectant properties. Inflammation plays a major role in the innate immune defence of the body by the promotion of healing. It is stimulated by tissue damage, such as when the skin is breached or bones are broken. Inflammation is also initiated as a result of infection. Using the example of a skin wound, the major signs of inflammation are: Increased blood flow (feeling of heat) Increased blood supply to the closest capillaries (redness) Attraction of phagocytic cells (evidence of pus as a result of phagocytic activity). The aim of inflammation is to bring more blood to the affected area and in so doing, contain the invasion, eliminate micro-organisms that may have gained entry, and limit the dangers of infection. Internal defence is carried out by phagocytes (engulfing white cells) that are either sessile (fixed to body tissue) or wandering (move about within the circulation). The white cells that participate in the engulfing, ingesting and denaturing of micro-organisms include the following: Macrophages Monocytes Polymorphonuclear cells (neutrophils, eosinophils and basophils) Natural killer cells. Humoral agents include opsonins, which are chemicals produced by the body and that promote phagocytosis. Once phagocytes are activated, they release soluble substances called cytokines that regulate the strength of the immune response. Natural killer cells are able to recognize, and then attack and destroy tumour cells or body cells infected with viruses, which killer cells recognize because of the abnormal molecular structures on their surfaces. The elimination of these altered cells is achieved by the release of many types of cytokines, which are also humoral agents, and include interferon and interleukin-2. Interferon is an antiviral agent. Interleukins send messages to other immune response cells. Interleukin-2 is a growth factor or colony-stimulating factor (CSF) and activator for cells that produce cytotoxic anti-cancer substances to destroy abnormal cells like tumour cells. Complement (C′) consists of a group of soluble proteins that play a pivotal role in humoral immune response. These proteins are present in the plasma in an inactive form until stimulated. It usually takes one immunoglobulin M (IgM) antibody molecule or two immunoglobulin G (IgG) antibody molecules in juxtaposition (close together) on a target cell, to initiate the complement response. Each complement protein then acts in sequential fashion, one activating the next like a cascade. The result is that complement either becomes attached to the target cell membrane, making it more susceptible to phagocytosis, or continues in a chain reaction to its end, which results in the breakage or lysis of the cell membrane. The consequence of cell lysis is loss of cell contents, and cell death. Complement activity is therefore an important immunological process to address threats to the host. The complement cascade is a complicated sequence that in simple terms consists of nine major protein components, C1 to C9. When a component is activated, it is written with a line on top. The sequence of activation is C1, C4, C2, C3, C5, C6, C7, C8, C9. The activation stage involves C1, C4 and C2. The activation is amplified when hundreds of molecules of C3 are then activated and become target cell bound, first as C3b and later as C3d. The cascade sometimes stops at this point. If it continues to the point of cell lysis, then the remaining components from C5 onwards play a role, with the membrane attack unit consisting of C7, C8 and C9. The complement cascade is discussed in more detail in Section 3: Antigen-antibody reactions, from the perspective of its involvement in antigen–antibody reactions in the laboratory. The major actions of complement are: Participation in acute inflammatory processes Assisting in opsonization that helps the process of phagocytosis Modification of cell membranes that results in lysis (breakage of cell envelope). Complement becomes activated in one of two ways: Classical pathway: initiated as a result of some antigen-antibody reactions Alternative pathway: triggered by the presence of polysaccharides and lipopolysaccharides, found on the surfaces of micro-organisms and tumour cells. Figure 2·2 shows the sequential activation of complement via the classical pathway. Sequential activation of complement – classical pathway. Acquired immunity is the result of a process of improved defence by means of: Cellular defence by lymphocyte adaptation Antigen-presenting cells (macrophages and other cells that are able to display the actual antigenic determinants, called epitopes, on their surface) Antibody formation. Should immunogenic substances be produced as a result of phagocytic activity, the lymphocytic response may be initiated. This leads to the activation of the cellular and/or humoral immune mechanisms, involving T cells and B cells, respectively. These two forms of lymphocytic response cells assist each other and together result in the effective maintenance of health. Thymus (T)-dependent lymphocytes are responsible for cellular defence. These T-lymphocytes circulate throughout the body as small lymphocytes. Peripheral (surface) antigens on micro-organisms or on other foreign cells, which are identified as non-self by macrophages, are presented to T-lymphocytes by the macrophages. The results of this contact are: T-lymphocytes with a specific reactivity site are produced, which can then react directly with the particular foreign immunogen that was presented to them by the macrophage. These activated T cells also release soluble substances called lymphokines, which instruct uncommitted lymphocytes on the nature of these immunogens, so that they too can react with the immunogens and destroy the cells on which they are situated. This greatly amplifies or multiplies the intensity of the immune response. Circulating memory cells are produced. These are responsible for the anamnestic or ‘memory’ response, which occurs on subsequent contact with the same immunogen. This facility allows for the recognition and rapid elimination of micro-organisms containing immunogens that were encountered before. It is cell-mediated immunity that causes delayed hypersensitivity. This is an inflammatory reaction that occurs a few days after exposure to immunogen. Such a response is caused by T cells and macrophages and not by antibodies. One of the unfortunate consequences of delayed-type hypersensitivity is the rejection of a graft such as a transplanted organ. The humoral immune response is initiated when soluble immunogens entering the lymphatic system (usually via lymph nodes), encounter macrophages, which trap these immunogens and ‘show’ or present them to CD4+ (helper) T-lymphocytes. The activated helper cells then stimulate B-lymphocytes to become plasma cells and excrete antibody. The B cells become differentiated into plasmacytes (plasma cells), which initially produce type IgM antibodies. Sufficient contact with the same immunogen results in a memory response and ongoing contact causes a more intensive production of antibodies, usually of the type IgG. The strength of the response is regulated by CD4+ (T helper) and CD8+ (T suppressor) lymphocytes. Helper cells boost the immune response; suppressor cells stop or regulate the production of antibody. ‘Naturally occurring’ antibodies found in the ABO blood group system are formed as a result of humoral immune response to environmental A and B antigens, that are antigenically similar to human red cell antigens. For example, A and B substances may be present on ingested particles, or in medical vaccinations or on bacteria. Newborns do not have their own ABO antibodies; it takes time and exposure to the environment, before they develop. Blood bankers are concerned mainly with reactions between serum/plasma and red cells. Antibodies in the serum/plasma react with red cells carrying the corresponding antigens. Although the use of the term antigen is always correct when discussing laboratory testing, when an antibody is first stimulated to be produced, the foreign substance that elicits the immune response is correctly called an immunogen. Because of the common usage of the terms ‘antigen’ and ‘immunogen’, they are viewed as synonyms. Although antigens can stimulate the production of antibodies, they must be immunogenic to do so. Most antigens are of biologic origin. These are usually proteins, but they may also be polysaccharides, lipids or nucleic acids. The actual antigenic determinant (or epitope) is usually small, with a molecular mass of at least 10 000 Da. This determinant is often coupled to a carrier such as a red blood cell (which has on its surface many different antigenic determinants or epitopes). Haptens are substances with a molecular mass of less than 10 000 Da, which when coupled with larger carrier proteins become immunogenic (capable of provoking antibody response) but are not immunogenic on their own. Despite their small size, haptens are, however, capable of reacting with antibodies. An immunogen is a foreign substance, that when it gains entry into the body of an immunocompetent vertebrate animal that lacks that substance, is capable of provoking the formation of antibodies that will react specifically with it. The term antigen is sometimes used as a synonym for immunogen and although antigens are capable of reacting with specific antibodies, they may not necessarily be able to provoke an antibody response. Immunogens and antigens are widespread; such as in the surrounding air, in foods and in vaccinations. They are also found on micro-organisms and on blood and other cells. An antigen (Ag) is a substance that when introduced into the circulation of a subject lacking that antigen, can stimulate the production of a specific antibody. In blood banking, the term antigen is used as the point of reference because the blood group systems are defined by antigens on red blood cells. When an immunogen enters the body, an immune response may occur. This means that the immunogen is recognized as foreign by the lymphocytes, which then proceed to manufacture specific antibodies. This occurs in the lymph nodes, together with the liver and spleen, which form the reticulo-endothelial system. Antibodies are usually released into the plasma, although certain antibodies do not appear to circulate but are fixed to body tissues or cells. An antibody (Ab) is a specifically reactive immunoglobulin produced in response to immunogenic stimulus, the object of the antibody being to react with and destroy the immunogen that stimulated its production. The antigen–antibody recognition may be compared with a lock and key, the concept of which is depicted in Figure 2·3. Antigen and antibody must match each other for a reaction to take place. Figuratively speaking, the key needs to fit the lock (for the recognition to occur). The ‘match’ may also be likened to the way in which one jigsaw puzzle piece fits the next. Lock and key principle of antigen-antibody reaction. For a substance to be immunogenic, and stimulate a response, it is usually: Foreign to the host Of a molecular mass of at least 10 000 Da A protein (such as the Rh blood group antigens) or A carbohydrate or sugar (such as the ABO blood group antigens) or A lipid Present in sufficient quantity. An immunogen consists of two parts – the antigenic determinant or epitope and the carrier macromolecule. The antigenic determinant gives specificity and reacts with antibody. The much larger carrier molecule may be inactive itself but because of its size, is able to trigger immune recognition and response and stimulate the production of antibodies against the specificity of the epitope. The strength and quality of the immune response depends on many variables. When deliberately initiating an immune response, such as in a medical immunization programme, many factors play a role such as: Age and physiological state of the individual (host) being immunized Capacity of the individual to respond (individuals vary greatly) Chemical nature and molecular size of the immunogen (degree of immunogenicity) Volume and frequency of each inoculum (dose of immunogen administered, and timing) Route of administration (e.g. subcutaneous, intravascular) Presence or absence of adjuvants (see meaning below). Adjuvants are inert substances injected together with immunogen when deliberately provoking an antibody response, as in medical immunization programmes. They amplify antibody response and their action is largely threefold: There is a better response to a smaller dose of immunogen. There is a more sustained or longer lasting response. There is greater production of antibody. If the immunogen has not been encountered by the host before, antibody may become detectable in the plasma between 5 and 180 days afterwards. The antibody level rises gradually, remains fairly stable for a while and then gradually declines. The class of antibody produced is usually IgM. If during the first encounter with an immunogen, the immune system is stimulated sufficiently to produce cloning (replication of chosen lymphocytes) but not to produce detectable circulating antibody, a subsequent exposure to that immunogen will probably result in rapid production of antibody. Cells that have cloned but not differentiated are called primed cells. When a second or subsequent exposure to the same immunogen occurs, antibody response is usually much more rapid. Higher levels of antibody are produced, and the response is much more sustained. This is because the body is able to recognize immunogens encountered in primary response and react more efficiently and effectively. Secondary response is therefore also referred to as recall or anamnestic response. The antibodies produced in the secondary response are usually IgG. Figure 2·4 is a graph showing the lag, log (increase in strength), plateau and decline phases of primary (IgM) and secondary (IgG) immunoglobulin response to immunogenic stimulation. Graph showing immunoglobulin response. In general terms, antibodies produced as a result of primary response appear 5–180 days after initial exposure to immunogen, and are IgM. However, some antibodies do not always behave in this way and may take much longer to become detectable. It is also not always evident that the first antibodies to appear are IgM. For example, some blood group antibodies are mixtures of IgG and IgM early in the primary response (such as Rh blood group system antibodies) whereas others (anti-P1 of the P blood group system) remain largely as IgM antibodies even after secondary response. Active immunity is known as such because the host is actively involved in antibody production as a result of the introduction of an immunogen. Because the immune response was initiated in the host, the immunity that results is long lasting. The immunity may be natural or artificial. When an individual contracts measles or mumps or some other infectious disease, the body responds by producing antibodies against the infectious agent and overcoming it. The individual usually recovers and does not suffer the same infection again. This is because if the same infectious agent enters the body in the future, it is recognized and eliminated. Lifelong immunity as described previously may be provoked artificially by medical immunization programmes, such as hepatitis B vaccination. In this case, controlled doses of attenuated organisms (organisms that have been rendered harmless) are administered, so that the individual does not become ill yet mounts an antibody response and becomes immune and protected against the infection in the future. Some viruses persist because they cannot totally be cleared by the host. Such viruses, an example of which is the human immunodeficiency virus (HIV), may eventually destroy the host. Other viral diseases recur, such as influenza, which may infect the same individual many times. This is because there are many different forms of viruses that cause influenza. Each time a new influenza virus invades the host, it is seen as being encountered for the first time and therefore a primary immune response is initiated. Passive immunity does not involve the immune system of the individual. Immunity is conferred by introduction of antibodies (immunoglobulins) from some other source. Because the immune response of the host is not involved, there will be no memory or recall regarding the infectious agent and therefore no immunity beyond the lifespan of the introduced immunoglobulin. Passive immunity may be natural or artificial. Placental transfer of maternal antibodies to the fetus, or transfer of maternal antibodies to the newborn during breastfeeding, ensures that the infant will have protection against those infections to which its mother is immune. The protection afforded by the mother is limited to the lifespan of the transferred immunoglobulins, and the infant is just as susceptible as any other non-immune individual when the maternal antibodies reach the end of their lifespan. Administration of specific immunoglobulins to non-immune individuals at the time of exposure to infectious agents may prevent illness in the short term. Concentrated immunoglobulins are obtained by fractionation of specially selected donations of plasma. For example, plasma from blood donations with a high level of anti-hepatitis B antibodies may be fractionated to extract the hepatitis B immunoglobulin. This concentrate, if given to a susceptible, non-immune host, would help prevent infection with hepatitis B on that occasion. The state of immunity is only effective for as long as the immunoglobulin from the donated plasma remains in the circulation of the host. In humans, five distinct classes of immunoglobulins or antibodies are found. These are IgM, IgG, IgA, IgD and IgE. Immunoglobulin M is usually the first immunoglobulin produced as a result of primary response. IgM constitutes 5–10% of circulating antibodies. As a large molecule (900 000 Da in mass), it is mainly confined to the bloodstream. The molecule consists of five monomers joined in a cyclic manner, and although there are theoretically 10 antigen-combining sites, only five sites are readily available to combine with antigen. IgM is therefore referred to as a pentavalent antibody or a cyclic pentamer. When IgM red cell antibodies are mixed with a suspension of red cells with the corresponding antigens, each IgM molecule is large enough to simultaneously bind to red cell antigen sites on adjacent red cells. This activity results in a latticework of haemagglutination and is readily visible as a clumping reaction in the laboratory. An important result of some IgM activity is the activation of complement. However, IgM antibodies cannot cross the placenta from mother to fetus, so they play no role in causing haemolytic disease of the fetus and newborn. Figure 2·5 is a diagrammatic representation of IgM. Immunoglobulin M. Figure 2·6 is a diagrammatic representation of haemagglutination, depicting the antigenic determinants on the red cells, as ‘dots’. Diagrammatic representation of haemagglutination. About 80% of circulating antibodies are of type IgG, and this immunoglobulin is small enough (160 000 Da) to infiltrate the tissues of the body. IgG molecules are equally distributed in both intra- and extracellular space. Although each IgG molecule has two antigen-combining sites, it acts as a monomer or monovalent antibody that coats or sensitizes a single antigen on a single cell. Sensitization is not a visible reaction, even with the use of a microscope, and requires the addition of other agents in order to be detected in the laboratory. The in vivo coating of cells by IgG antibodies is a catalyst or trigger for the activation of neutrophils and macrophages. IgG is found in various subtypes: IgG1, IgG2, IgG3 and IgG4. All IgG subtypes, with the exception of IgG2, cross the placenta and may therefore be implicated in haemolytic disease of the fetus and newborn, and all, with the exception of IgG4, can activate complement. Each subtype has a highly specific role to play in the immune response. Figure 2·7 is a diagrammatic representation of IgG. It illustrates the two fragment antigen binding (Fab) portions, which are responsible for the attachment to antigen at the time of reaction, and the fragment crystallizable portion that initiates the involvement of complement and to which antihuman globulin is specifically directed. The role of complement and of antihuman globulin in antigen-antibody reactions in vitro is described in detail in Section 3: Antigen-antibody reactions. Immunoglobulin G. Figure 2·8 is a diagrammatic representation of red cell sensitization by IgG antibodies. Diagrammatic representation of sensitization. IgA is found mainly in mucosal secretions, although it is also present in the bloodstream, particularly after immunization. IgD is only present in minute amounts in the bloodstream and its function and role are not clearly understood. IgE plays a major role in allergy, allergic reactions and conditions such as asthma and anaphylaxis. It is present in trace amounts, even in severely allergic individuals. Immunoglobulins are commonly referred to as antibodies or agglutinins. Alloantibodies or alloagglutinins are terms used to describe antibodies against antigens found in members of the same species (e.g. antibodies against the red cells of individuals who are group A are found in the plasma of individuals who are group B). Heteroagglutinins or heterophile antibodies are those directed against different interspecies-specific antigens (e.g. Forssman antigen). Autoantibodies or autoagglutinins describe those that are directed towards antigens within the same individual (e.g. antibodies found in the plasma of an individual and that react specifically with that individual's own cells). Table 2·2 gives the general properties of IgM and IgG antibodies. The immune system of the host may fail to respond when large amounts of foreign immunogens are presented to it. This may be caused by the immune system being overwhelmed with immunogens, and therefore failing to act (becoming transiently or temporarily paralysed), or by the immune system becoming ‘confused’ by the presence of several different immunogens present at the same time. The result is immune paralysis; there is no response, and antibodies are not developed. On the other hand, immune tolerance can occur when the host ‘tolerates’ a foreign immunogen such as a group O chimera with tolerance for A antigen, lacking the expected anti-A antibody in the serum/plasma. A chimera is an individual whose cells originate from more than one zygote. The one zygote develops into the individual, whereas the other implants in the host. Although the implant contains different antigens, they are tolerated by the host as ‘self’. This is a rare occurrence but aptly describes immune tolerance. Immune tolerance is also used to describe the fact that an individual does not usually produce antibodies against his/her own antigens. A breakdown in this immune tolerance or recognition of self results in the production of autoantibodies. Expected antibodies may also be absent in hypogammaglobinaemia (lack of immunoglobulin), after transplantation, and in old age. An autoantibody is an antibody that the body directs against itself. When this situation results in illness, the individual is said to have an autoimmune disease. Examples of such diseases are: Systemic lupus erythematosus (SLE) results in inflammation and tissue damage and can affect many parts of the body. The signs and symptoms of SLE occur intermittently as episodes or ‘flares’ of illness alternating with periods of absence of disease. SLE does not target specific parts of the body, but is widespread. Immune thrombocytopaenic purpura targets only platelets, causing thrombocytopaenia. Autoimmune haemolytic anaemia is the result of the body producing antibodies against its own red cells. The reason why the body starts producing autoantibodies is not clearly understood. It may be that some individuals are genetically prone to do so, or it may be that the condition is triggered by the presence of harmful substances such as viruses, or toxic contaminants in the environment. Immunodeficiency describes a condition in which the host is unable to react effectively with and overcome harmful agents, such as viruses, bacteria or abnormal (tumour) cells. The immune system malfunctions and the individual is said to be immunocompromised. This state is either inherited, in which case the individual is born with the problem, or it is acquired as the result of some trigger. Stimuli are known to include viruses, immunosuppressant drugs, malnutrition and stress. Immunodeficiency leads to the individual becoming vulnerable to opportunistic infections; those that do not normally cause disease in healthy individuals. Examples of why an individual would be immunocompromised include the following: Inherited primary immunodeficiency is a rare state in which the individual is unable to produce antibodies. Acquired secondary immunodeficiency e.g. infection with HIV means that the individual's immune response becomes impaired by the virus and cannot respond adequately to infection by micro-organisms. Immunodeficiency may also be acquired by other factors including poor diet, stress or during drug treatment such as chemotherapy, as the drugs administered (in this case to control cancer) adversely affect the cells of the immune system. The major components of the immune system are the bone marrow, liver and thymus. The lymph nodes, spleen and lymphoid tissue also form part of immunological defence. The liver, spleen and lymph nodes are collectively known as the reticulo-endothelial system. White cells are an integral part of immune function, with phagocytosis and antibody production being their key contributions. There are two strategies for body defence; inborn or innate, and learned or acquired. Innate or natural defence does not vary following multiple exposures to foreign substances, whereas acquired defence becomes stronger every time it is stimulated to respond. Acquired immunity is seen only in vertebrates (animals with a backbone). Immune defence is multifaceted – it has many options including phagocytosis, chemical agents, complement and the production of antibodies for removing harmful agents. Opsonins are chemicals produced by the body that promote phagocytosis. Once phagocytes are activated, they release soluble substances called cytokines, which regulate the strength of the immune response. The elimination of abnormal cells is achieved by the release of many types of cytokines, which are also humoral agents, and include interferon and interleukin-2. Complement consists of a group of soluble proteins that are present in the plasma in an inactive form until stimulated by an antigen-antibody reaction. They then act in a sequential fashion, each activating the next. Complement either becomes fixed to target cells that are then more easily subjected to phagocytosis, or continues its chain reaction to its end, which results in cell lysis. Lymphocytes are the white cells critical to learned immunity. T-lymphocytes are responsible for cellular defence (delayed hypersensitivity) and the production of lymphokines, whereas B-lymphocytes are responsible for the development of antibodies. An antigen is material capable of specific combination with antibody. It is frequently used as a synonym for immunogen, although some antigens that react with antibodies are not capable of eliciting an immune response. An immunogen is capable of provoking an immune response when introduced into an immunocompetent vertebrate in which it is foreign. To be immunogenic, the substance must appear foreign to the host. A good immunogen has a molecular mass of more than 10 000 Da and is usually a protein or polysaccharide. A hapten is a substance with a molecular mass of less than 10 000 Da, which when coupled with a larger carrier protein can become immunogenic. During primary response, when the host encounters an immunogen for the first time, IgM antibodies are formed. After secondary response, most circulating antibodies are IgG. An adjuvant is a substance combined with an immunogen to make it more immunogenic to the host. This tactic is sometimes used to increase the effectiveness of vaccination. Active immunity signifies that the immune system of the host is activated, so the response will be long lasting; passive immunity is the term used when the immune system in not activated, and defence is carried out by the antibodies of another – such as maternal antibodies crossing the placenta and protecting the newborn – for only a limited period of time. In certain circumstances the body does not respond to the presence of foreign immunogens. This results either in immune paralysis or in immune tolerance. An alternative name for an antibody is an immunoglobulin. They fall into five major classes: the two of most practical importance in blood transfusion practice are IgM and IgG; the others are IgA, IgD and IgE. There are many characteristics that differentiate IgM and IgG antibodies, such as the ability to cross the placenta and activate complement. (1) It is suggested that students use a medical dictionary and/or the Internet to clarify the meaning of words and phrases and to add to the information provided in this section. A list of key words that may be useful in this regard is provided below. Thymus Lymphoid tissue Phagocytosis Complement in plasma Inflammation Antigen Immunogen Antibody Antigen-presenting cells Humoral response Major histocompatibility complex Human leucocyte antigen. (2) It is also suggested to locate a publication devoted to the science of immunology, such as at the local library. Borrow the book and browse through it to get an idea of the complexity of this subject. Study those pages that relate particularly to ‘antigen’ and ‘immunogen’, and read about the production of antibodies, as well as any other sections that are particularly interesting. The contributing author of this section on Immunology (BA) has not received grants, speakers fees etc., from any commercial body within the past 2 years. This author has no potential conflicts.