Summary of Immunology Lecture 1 (PDF)

Immunology Lecture 1 Dr. Mouruj Alaubydi and Dr. Jenan Alsaffar Immunology : The science that deal with studying the body's defenses. The immune system is typically associated with defending against foreign...

Immunology Lecture 1 Dr. Mouruj Alaubydi and Dr. Jenan Alsaffar Immunology : The science that deal with studying the body's defenses. The immune system is typically associated with defending against foreign intruders, called pathogens, but it can fight against cancer as well. Basic immunology is a branch of immunology that looks at what generally happens in the immune system. For example, what functions do different types of immune cells and chemicals have? How do they react to different function? Some basic immunologists focus their on the innate immune system, which protects against all possible intruders. Innate immune system cells are neutrophils, Monocytes, Macrophages, Dendritic cells, Natural killer cells, Basophiles, Eosinophil's and others. Another basic immunologists focus is the adaptive immune system, targets specific pathogens. Scientists can study how a type of cell learns to recognize a specific pathogen, and what functions that cell has. Adaptive immune system cells are B lymphocyte which is responsible for antibodies production( humoral immunity), and T lymphocytes which is responsible for cellular immunity. Immunity and its types: Innate and Acquired (adaptive) immunity  Immunity is derived from Latin word “immunis” which means free from burden. In this case burden refers to disease caused by microorganisms or their toxic products.  Therefore Immunity is defined as the state of resistance or in susceptibility to disease caused by particular microorganisms or their toxic products Innate or Natural immunity:  Immunity with which an individual is born is called innate or natural immunity. Innate immunity acts as first line of defense to particular microorganisms. Component of the natural immunity : 1- Cellular / Mast cells, Neutrophils, Macrophages 2- Humoral/ Complement, Lysozyme, Interferon Mechanism of innate immunity: 1- Anatomical barrier: Skin and mucus membrane are the examples of anatomical barriers that provides immunity. *Skin consists of two distinct layer; a thin outer layer called epidermis and thick inner layer called dermis. *Epidermis consists of mostly dead cell filled with keratin. Dermis is composed of connective tissue, hair follicle, sebaceous gland and sweat gland.They have mechanism to kill the pathogen before entry to body. Throughout lysozyme, acidic pH, sebum(oil), high salt concentration in sweat are antimicrobial agents found in skin and mucus membrane. *Skin provides first line of defense by preventing entry of microorganisms. However skin may be penetrated by injury or insects. *Below skin, the mucus membrane prevents the entry of microorganism to the body. And also it is secrets mucus surrounds the body tracts that entrap microorganisms. 2. Physicochemical barrier: includes physiological barrier and chemical barrier.  Physiological conditions of body such as normal body temperature, normal body pH etc provides immunity.  Some species are resistant to certain disease simply because of their higher body temperature. For example, mammals are susceptible to anthrax but birds are resistant to anthrax. It is because Bacillus anthracis are killed by higher body temperature of birds (39°C).  Similarly, body pH also provides immunity. For example acidity of stomach kills most of the ingested bacteria and provides immunity. In infants stomach is less acidic. This is the reason why infants suffer more from gastrointestinal disturbance than adults.   Chemical barriers include various antimicrobial chemicals found in body fluids. For examples, Lysozyme found in tear and mucus kills many Gram +ve bacteria.  Interferon found in blood and lymph kills viruses. Other antimicrobial chemicals found in body fluids include complement proteins, collectins, etc. 3. Phagocytic barrier or Phagocytosis Phagocytosis is an important defense mechanism of host to provide immunity. Most of the bacteria that enter into host are killed by phagocytic cells such as Neutrophils, monocytes and macrophages. 4. Complement: Subset of proteins consider as the main component in natural immunity. 5. Inflammatory barrier or Inflammation  Inflammation is an important defense mechanism of host to prevent infection. It is induced in response to tissue damage caused by microorganism, toxins or by mechanical means.  The inflammation may be acute; for e.g. in response to tissue damage or chromic; for e.g. Arthritis, cancer etc.  Main aim of inflammation is to prevent spread of injected microorganism or toxin from site of injection and kill them on spot by phagocytosis.  Acute phase proteins are sensitive indicators of the presence of the inflammatory disease and are especially useful in monitoring such disease.  The innate immune cells (Mast cells, Neutrophils, Macrophages..etc) in response to inflammation are stimulated to eradicate intruders. Types of innate immunity: 1. Species immunity:  If one species is resistant to certain infection and the other species is susceptible to the same infection then it is called as species immunity.  Physiological and metabolic differences between species determine species immunity. For example, Birds are resistant to anthrax but Human is susceptible. It is simply because higher body temperature of birds kills Bacillus anthracis. 2. Racial immunity:  If one race is susceptible while other race is resistant to same infection, then it is called racial immunity.  For examples; certain African race are more resistant to malaria and yellow fever where are Asian or Americans are susceptible to same infection. Similarly Orientals (East Asia) are relatively resistant to syphilis.   Racial immunity is determined by difference in Socio-economic status, habitat, culture feeding habits, environments, genetic, etc. 3. Individual immunity:  If one individual of certain race or cast is resistant while other individuals of same race or cast are susceptible to certain infection, then it is called as individual immunity  Individual immunity is determined by various factors such as health status, nutritional status, previous illness, personal hygiene, genetic differences etc.  For examples; Individual with genetic deficiency of glucose-6 phosphate dehydrogenase are resistant to Malaria.  Immunology Lecture 2 Dr. Mouruj Alaubydi and Dr. Jenan Alsaffar Cells of the Innate Immune System There are many types of white blood cells or leukocytes that work to defend and protect the human body. In order to patrol the entire body, leukocytes travel by way of the circulatory system. The following cells are leukocytes of the innate immune system:  Phagocytes, or Phagocytic cells: Phagocyte means “eating cell”, which describes what role phagocytes play in the immune response. Phagocytes circulate throughout the body, looking for potential threats, like bacteria and viruses, to engulf and destroy. Phagocytosis diagram Steps in phagocytosis:  1. At first phagocyte approaches to the site of infection 2. Adherance or attachment of antigen on the surface of phagocyte 3. Phagocyte extends pseudopodia around bacterial cell. 4. Pseudopodia gradually increase in size and finally fused so that bacteria is engulfed in the form of phagosome or food vacuole. 5. The phagosome and lysosome come nearer to each other and fuse to form phago- lysosome. 6. Inside phago-lysosome ingested bacteria is killed by hydrolytic and digestive enzyme of lysosome. 7. Required materials released from digested bacteria are absorbed into surrounding cytoplasm and undigested residues are excreted out by exocytosis. Killing Mechanism of phagocytosis: Killing of ingested bacteria during phagocytosis occur by two different mechanism 1. Oxygen dependent mechanism This process is also known as respiratory burst. It is the major mechanism of killing of ingested bacteria during phagocytosis. 2. Oxygen independent mechanism:  In this mechanism, ingested bacteria are killed by hydrolytic and digestive enzymes of lysozyme.  Macrophages: Macrophages, are efficient phagocytic cells that can leave the circulatory system by moving across the walls of capillary vessels. The ability to roam outside of the circulatory system is important, because it allows macrophages to hunt pathogens with less limits. Macrophages can also release cytokines in order to signal and recruit other cells to an area with pathogens.  Mast cells: Mast cells are found in mucous membranes and connective tissues, and are important for wound healing and defense against pathogens via the inflammatory response. When mast cells are activated, they release cytokines and granules that contain chemical molecules to create an inflammatory cascade. Mediators, such as histamine, cause blood vessels to dilate, increasing blood flow and cell trafficking to the area of infection. The cytokines released during this process act as a messenger service, alerting other immune cells, like neutrophils and macrophages, to make their way to the area of infection, or to be on alert for circulating threats.   Neutrophils: Neutrophils are phagocytic cells that are also classified as granulocytes because they contain granules in their cytoplasm. These granules are very toxic to bacteria and fungi, and cause them to stop proliferating or die on contact. The bone marrow of an average healthy adult makes approximately 100 billion new neutrophils per day. Neutrophils are typically the first cells to arrive at the site of an infection because there are so many of them in circulation at any given time.  Eosinophils: Eosinophils are granulocytes target multicellular parasites. Eosinophils secrete a range of highly toxic proteins and free radicals that kill bacteria and parasites. The use of toxic proteins and free radicals also causes tissue damage during allergic reactions, so activation and toxin release by eosinophils is highly regulated to prevent any unnecessary tissue damage. While eosinophils only make up 1-6% of the white blood cells, they are found in many locations, including the thymus, lower gastrointestinal tract, ovaries, uterus, spleen, and lymph nodes.  Basophils: Basophils are also granulocytes that attack multicellular parasites. Basophils release histamine, much like mast cells. The use of histamine makes basophils and mast cells key players in mounting an allergic response.  Natural Killer cells: Natural Killer cells (NK cells), do not attack pathogens directly. Instead, natural killer cells destroy infected host cells in order to stop the spread of an infection. Infected or compromised host cells can signal natural kill cells for destruction through the expression of specific receptors and antigen presentation.  Dendritic cells: Dendritic cells are antigen-presenting cells that are located in tissues, and can contact external environments through the skin, the inner mucosal lining of the nose, lungs, stomach, and intestines. Since dendritic cells are located in tissues that are common points for initial infection, they can identify threats and act as messengers for the rest of the immune system by antigen presentation. Dendritic cells also act as bridge between the innate immune system and the adaptive immune system.  Lecture 5 Dr. Mouruj Alaubydi and Dr. Jenan Al Saffar Third Line of Defense: Acquired or Developed or adaptive immunity:  Immunity which is developed later in life after microbial infection in host is called as Acquired or developed immunity. Acquired immunity is provided by Humoral (Antibodies and cytokines) and certain cellular represented by B , T-lymphocytes and plasma cells.  Components of acquired immunity such as Antibodies and cells are specific to particular microorganism. Therefore, acquired immunity is also known as Specific immunity. Characteristics of Acquired immunity: *Specificity *Self/non-self-recognition *Immunological memory *Diversity Types of acquired immunity: 1. Active immunity 2. Passive immunity 1. Active immunity:  If host itself produces antibodies, it is called active immunity.  It is of two types; artificial active immunity and natural active immunity.  Artificial active immunity: Immunity provided by vaccination.  Natural active immunity: immunity provided by natural infection. 2. Passive immunity:  If host does not produce antibodies itself but antibodies produced in other host provides immunity, then it is known as Passive immunity.  It is of two types; natural passive immunity and Artificial passive immunity  Natural passive immunity: IgG antibody produced in mother cross placenta and protects fetus up to 6-month old age.  Artificial passive immunity: if preformed antibody are injected into host for immunity, e.g. Anti-venom, Rabies vaccine (* it is not a vaccine, it is preformed anti rabies antibody) Diagram illustrate the interaction between innate and adaptive immunity  Table: Illustrate the differences between innate and adaptive immunity S.N. Characteristics Innate Immunity Adaptive immunity Innate immunity is Adaptive immunity is created in response something already to exposure to a foreign substance. Cannot 1. Presence present in the body. be inherited and develops during a Generally inherited person’s lifetime and Present at birth Specific and can distinguish between self 2. Specificity Non-Specific and non-self Fights any foreign Fight only specific infection 3. Response invader and Rapid Slow (1-2 weeks) Limited and Lower 4. Potency High potency potency 5. Memory No memory Long term memory Microbes and non-microbial substances 6. Works Against microbes called antigens 7. Diversity Limited High Complement Alternative and lectin 8. system Classical pathway pathways activation The innate immune system is composed of physical and chemical barriers, Adaptive immune system is composed of B 9. Composition phagocytic cells and T cells. leukocytes, dendritic cells, natural killer cells, and plasma proteins. Adaptive immune cells: Lymphocytes and plasma cells The adaptive immune system is comprised of the humoral and cellular systems. Each of the two arms of the adaptive immune system has fundamental mechanisms allowing the body to attack an invading pathogen. The immunologically specific cellular component of the immune system is organized around two classes of specialized cells, T and B lymphocytes. Lymphocytes recognize foreign antigens, directly destroy some cells, or produce antibodies as plasma cells. Virgin or naïve lymphocytes Virgin or naïve lymphocytes are cells that have not encountered their specific antigen. These cells do express high molecular- weight variants of leukocyte common antigen. Memory cells are populations of long-lived T or B cells that have been stimulated by antigen. They can make a quick response to a previously encountered antigen. Memory B cells carry surface IgG as their antigen receptor; memory T cells express the CD45RO variant of the leukocyte common antigen and increased levels of cell- adhesion molecules , chemical mediators involved in inflammatory processes throughout the body Development of T lymphocytes Most lymphocytes found in the circulating blood are T cells derived from bone marrow progenitor cells that mature in the thymus gland. These cells are responsible for cellular immune responses and are involved in the regulation of antibody reactions in conjunction with B lymphocytes. Approximate Percentage of Lymphocytes in Lymphoid Organs Lymphoid Organ T B Lymphocytes Lymphocytes (%) (%) Thymus 100 0 Blood 80 20 Lymph nodes 60 40 Spleen 45 55 Bone marrow 10 90 Early Cellular Differentiation and Development A.Thymus-derived cells: T cells are the key players in most adaptive immune responses. They participate directly in immune responses as well as orchestrating and regulating the activities of other cells. Lecture 6 Dr. Mouruj Alaubydi and Dr. Jenan Al Saffar * Types of T cells: 1. CD4 + T cells: These cells account for approximately two-thirds of mature CD3+ T cells. CD4 molecules displayed on the surfaces of these T cells recognize a non-peptide- binding portion of MHC class II molecules (Fig. above ). As a result, CD4 + T cells, also known as helper T (Th) cells, are "restricted" to the recognition of pMHC class I I complexes and some act as Regulatory T cells. Regulatory T cells may also maintain tolerance. Characteristically, they inhibit the activity of auto-reactive lymphocytes. Treg cells express both CD4 and CD25 molecules and are thought to be important inhibitors of immune- mediated inflammatory diseases such as inflammatory bowel disease. 2.CD8 +T cells: account for approximately one-third of all mature CD3+ T cells. CD8 molecules displayed on the surfaces of these T cells recognize the non-peptide-binding portion of MHC class I molecules. As a result, CD8 T cells are "restricted" to the recognition of pMHC I complexes. Functionally, CD8+ T cells are also known as cytotoxic T (Tc) and some act as suppressor T (Ts) cells. Tc cells identify body cells that are infected with intracellular organisms, such as viruses and intracellular bacteria, and eliminate the cells harboring these organisms. Ts cells function to down-regulate and thus control adaptive immune responses. B. Bone marrow-derived cells Not all lymphocytes of bone marrow origin are destined for thymus education. Certain cells of lymphoid lineage remain and develop within the bone marrow and are the precursors of immunoglobulin-producing lymphocytes. These bone marrow-derived lymphocytes, also known as B lymphocytes or B cells, synthesize immunoglobulin and display it on their surfaces, where it functions as their BCR. Plasma cells are derived from differentiated , mature B cells and both synthesize and secrete immunoglobulin. 1. B cells arise from pluripotent hematopoietic stem cells in the bone marrow. They do not migrate to the thymus but develop within the bone marrow. B cell is specific, that is, it produces immunoglobulin of only one antibody specificity that recognizes only one epitope. It is the extreme diversity among B cells, each producing a single form of immunoglobulin , that generates the overall diversity of the immunoglobulin (or antibody) response 2. Plasma cells derive from terminally differentiated B cells and are immunoglobulin producing and immunoglobulin-secreting cells. They cease to use immunoglobulin as a membrane receptor and instead secrete it into the fluids around the cells. Plasma cells, with increased size and metabolic activity, are factories that produce large quantities of immunoglobulin during their short life span of less than 30 days. They are characterized by basophilic cytoplasm, a nucleus that has a stellate (star like) pattern with in it, and non-staining Golgi (Fig. down). C. Natural killer cells: Approximately 5% to 10% of peripheral blood lymphocytes lack both T-cell (CD3) and B-cell (surface immunoglobulin) markers. These cells are known as natural killer ( NK) cells to reflect their ability to kill certain virally infected cells and tumor cells without prior sensitization. Their granular appearance is caused by the presence of cytoplasmic granules containing perforin and granzyme that can be released to damage the membranes of the cells they attack. NK cells develop within the bone marrow and lack TCR produced by rearrangement of TCR genes. However, they do bear another set of receptors called killer activation receptors (KARs) and killer inhibition receptors (KIRs) that allow them to recognize host cells that might need to be destroyed. In addition, a unique subset of T cells, designated NKT because they share some functional characteristics with NK cells, develop within the thymus and express a rearranged TCR of extremely limited repertoire (Fig. below). Unlike conventional T cells, NKT cells respond to lipids, glycolipids, or hydrophobic peptides presented by a specialized, non-classical MHC class I molecule, and secrete large amounts of cytokines. Lec-7 Immunology Dr. Jenan Alsaffar and Dr. Muruj Alaubydi IMMUNOGENS AND ANTIGENS Immune responses arise as a result of exposure to foreign stimuli. The compound that evokes the response is referred to either as antigen or as immunogen. An antigen is any agent capable of binding specifically to components of the immune system, such as the B cell receptor (BCR) on B lymphocytes and soluble antibodies. By contrast, an immunogen is any agent capable of inducing an immune response and is therefore immunogenic. The distinction between the terms is necessary because there are many compounds that are incapable of inducing an immune response, yet they are capable of binding with components of the immune system that have been induced specifically against them. Thus all immunogens are antigens, but not all antigens are immunogens. This difference becomes obvious in the case of low molecular weight compounds, a group of substances that includes many antibiotics and drugs. By themselves, these compounds are incapable of inducing an immune response but when they are coupled with much larger entities, such as proteins, the resultant conjugate induces an immune response that is directed against various parts of the conjugate, including the low molecular weight compound. Antigenicity: refers to the ability of a compound to bind with antibodies or with cells of the immune system. This binding is highly specific; the immune components are capable of recognizing various physicochemical aspects of the compound. The binding between antigen and immune components involves several weak forces operating over short distances (van der Waals forces, electrostatic interactions, hydrophobic interactions, and hydrogen bonds); it does not involve covalent bonds. Immunogenicity: is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human and other animal. In other words, immunogenicity is the ability to induce a humoral and/or cell-mediated immune responses. Epitope : is immunologically active regions of an immunogen (or antigen) that binds to antigen-specific membrane receptors on lymphocytes or to secreted antibodies. It is also called antigenic determinants. Hapten: Small foreign molecule that is not antigenic. It's a type of antigen that elicits production of antibodies only when combined with another antigenic molecule, then antibodies are formed when they will recognize hapten. Chemical Nature of Antigens (Immunogens) A. Proteins: The vast majority of immunogens are proteins. These may be pure proteins or they may be glycoproteins or lipoproteins. In general, proteins are usually very good immunogens B. Polysaccharides: Pure polysaccharides and lipopolysaccharides are good immunogens. C. Nucleic Acids: Nucleic acids are usually poorly immunogenic. However, they may become immunogenic when single stranded or when complexed with proteins. D. Lipids: In general lipids are non-immunogenic, although they may be haptens. Types of antigen on the basis of their class (Origin) E. 1. Exogenous antigens *These antigens enter the body or system and start circulating in the body fluids and trapped by the APCs (Antigen presenting cells such as macrophages, dendritic cells, etc.). *The uptakes of these exogenous antigens by APCs are mainly mediated by the phagocytosis. Examples: bacteria, viruses, fungi …etc. *Some antigens start out as exogenous antigens, and later become endogenous (for example, intracellular viruses). 2. Endogenous antigens lecture 8 Dr. Mouruj Alaubydi and Dr. Jenan Alsaffar Antibody An antibody (AB), also known as an immunoglobulin (Ig), is a large Y-shape produced by plasma cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign antigen, called an epitope. Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. The production of antibodies is the main function of the humoral immune system. Antibodies can occur in two physical forms, a soluble form that is secreted from the cell, and a membrane-bound form that is attached to the surface of a B cell and is referred to as the B cell receptor (BCR). The BCR is found only on the surface of B cells and facilitates the activation of these cells and their subsequent differentiation into either antibody factories called plasma cells or memory B cells (that will survive in the body and remember that same antigen).Thus the B cells can respond faster upon future exposure. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, antibody generation following antigen binding. Soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms. Structure Antibodies are heavy (~150 kDa) globular plasma proteins. They have sugar chains added to some of their amino acid residues. In other words, antibodies are glycoproteins. The basic functional unit of each antibody is an immunoglobulin (Ig) monomer (containing only one Ig unit); secreted antibodies can also be dimeric with two Ig units as with IgA, or pentameric with five Ig units, like mammalian IgM. Immunoglobulin domains. The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds. Each chain is composed of structural domains called immunoglobulin domains. These domains contain about 70–110 amino acids and are classified into different categories (for example, variable and constant) according to their size and function. Heavy chain There are five types of mammalian Ig heavy chain denoted by the Greek letters: α, δ, ε, γ, and μ. The type of heavy chain present defines the class of antibody; these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies, respectively. Distinct heavy chains differ in size and composition. Each heavy chain has two regions, the constant region and the variable region. The constant region is identical in all antibodies of the same isotype, but differs in antibodies of different isotypes. The variable region of each heavy chain is approximately 110 amino acids long and is composed of a single Ig domain. Light chain In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). A light chain has two successive domains: one constant domain and one variable domain. CDRs, Fab and Fc Regions Some parts of an antibody have the same functions. The arms of the Y, for example, contain the sites that can bind to antigens (in general, identical) and, therefore, recognize specific foreign objects. This region of the antibody is called the Fab (fragment, antigen-binding) region. It is composed of one constant and one variable domain from each heavy and light chain of the antibody. The paratope is shaped at the amino terminal end of the antibody monomer by the variable domains from the heavy and light chains. the complementarity determining regions (CDRs), are also called idiotypes( The variable part of an antibody including the unique antigen binding site). the adaptive immune system is regulated by interactions between idiotypes. The base of the Y plays a role in modulating immune cell activity. This region is called the Fc (Fragment, crystallizable) region, and is composed of two heavy chains that contribute two or three constant domains depending on the class of the antibody. Thus, the Fc region ensures that each antibody generates an appropriate immune response for a given antigen, by binding to a specific class of Fc receptors, and other immune molecules, such as complement proteins. By doing this, it mediates different physiological effects including recognition of opsonized particles, lysis of cells, and degranulation of mast cells, basophils, and eosinophils. In summary, whilst the Fab region of the antibody determines its antigen specificity, the Fc region of the antibody determines the antibody's class effect. Since possible classes of heavy chains in antibodies include alpha, gamma, delta, epsilon, and mu, and they define the antibody's isotypes IgA, G, D, E, and M, respectively. It also implies that Fab-mediated effects are directed at microbes or toxins, while Fc mediated effects are directed at effector cells or effector molecules (though this class effect may be mediated by the Fab region rather than the Fc region). Function: Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. Possible class effects of antibodies include: Opsonisation, agglutination, hemolysis, complement activation, mast cell degranulation, and neutralization. At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody productions vary for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Though the general structure of all antibodies is very similar, a small region at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures, or antigen-binding sites, to exist. This region is known as the hyper variable region. This enormous diversity of antibodies allows the immune system to recognize an equally wide variety of antigens. The large and diverse population of antibodies is generated by 1- Random combinations of a set of gene segments that encode different antigen-binding sites (or paratopes), followed by 2- Random mutations in this area of the antibody gene, which create further diversity. Antibody genes also re-organize in a process called class switching that changes the base of the heavy chain to another, creating a different isotype of the antibody that retains the antigen-specific variable region. This allows a single antibody to be used by several different parts of the immune system. Name Types Description Antibody Complexes Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization IgA 2 by pathogens. Also found in saliva, tears, and breast milk as dimer, while in blood as monomer. Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It has been shown IgD 1 to activate basophils and mast cells to produce antimicrobial factors. Binds to allergens and triggers histamine release IgE 1 from mast cells and basophils, and is involved in allergy. Also protects against parasitic worms. In its four forms (IgG1, IgG2, IgG3, IgG4), provides the majority of antibody-based immunity against IgG 4 invading pathogens. The only antibody capable of crossing the placenta to give passive immunity to the fetus. Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very high avidity. IgM 1 Eliminates pathogens in the early stages of B cell- mediated (humoral) immunity before there is sufficient IgG. Isotypes Antibodies can come in different varieties known as isotypes or classes. In placental mammals there are five antibody isotypes known as IgA, IgD, IgE, IgG, and IgM. They are each named with an "Ig" prefix that stands for immunoglobulin, another name for antibody, and differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table. The different suffixes of the antibody isotypes denote the different types of heavy chains the antibody contains, with each heavy chain class named alphabetically: α, γ, δ, ε, and μ. This gives rise to IgA, IgG, IgD, IgE, and IgM, respectively. The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM+ isotype in a cell surface bound form. The B lymphocyte, in its mature ready-to-respond form, is known as "naive B lymphocyte." The naive B lymphocyte express both surface IgM+ and IgD+. The co-expression of both these immunoglobulin isotypes renders the B cell 'mature' and ready to respond to antigen. B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Some daughter cells of the activated B cells undergo isotype switching, a mechanism that causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA, or IgG, that have defined roles in the immune system. Antibodies contribute to immunity by : 1-They prevent pathogens or its toxins from entering or damaging cells by binding to them. 2-they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway.