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Immunoglobulins: Types and Functions

Immunoglobulins: Types and Functions

Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells Plasma cells Specialized forms of antibody-producing B-lymphocytes. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. Humoral Adaptive Immunity that act in immune responses by recognizing and binding specific antigens. Antibodies undergo processes that improve antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination affinity and provide appropriate defense by class switching. The various Ig Ig X-linked Agammaglobulinemia classes are IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays, and distribution. General functions include opsonization, neutralization of infectivity of the pathogens, cytotoxicity, and complement activation Complement Activation The sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides. Systemic Lupus Erythematosus. Specific classes have unique defensive mechanisms.

Last updated: 29 Apr, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Immunoglobulins (Igs)

  • Glycoprotein molecules produced by plasma cells Plasma cells Specialized forms of antibody-producing B-lymphocytes. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. Humoral Adaptive Immunity that act in immune responses by recognizing and binding particular antigens
  • Structural components: 
    • 2 identical heavy (H) and 2 identical light (L) chains (referring to their molecular weight):
      • Light chains: approximately 25 kDa each
      • Heavy chains: approximately 50 kDa each
    • Disulfide bonds link the heavy chains to the light chains (forming a Y-shaped molecule).
    • Hinge region (confers flexibility)
    • Carbohydrate moieties (associated with the constant region)
  • Different chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure encode the chains:
    • Heavy chains (ÎĽ, δ, Îł, α, or ε): encoded by chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 14
    • Light chains  (Îş or λ):
      • Îş light chain: chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 2
      • λ light chain: chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 22

Ig Ig X-linked Agammaglobulinemia regions and fragments

  • Both heavy and light chains in the Igs have variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables and constant regions.
  • Regions:
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region ( antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding):
      • The amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids sequence at the tips TIPS A type of surgical portasystemic shunt to reduce portal hypertension with associated complications of esophageal varices and ascites. It is performed percutaneously through the jugular vein and involves the creation of an intrahepatic shunt between the hepatic vein and portal vein. The channel is maintained by a metallic stent. The procedure can be performed in patients who have failed sclerotherapy and is an additional option to the surgical techniques of portocaval, mesocaval, and splenorenal shunts. It takes one to three hours to perform. Cirrhosis of the “Y,” which includes ends of both light and heavy chains
      • Has hypervariable region or complementarity-determining region (CDR) at each amino-terminal
      • The CDR provides antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays, as it is complementary in structure to the antigenic determinant (epitope).
    • Constant region (effector functions):
      • Constitutes the remaining polypeptide
      • Binds Fc receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and complement
  • The heavy chain and light chain regions are folded up into 3-dimensional segments called domains. 
    • The light chain has 1 variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables domain and 1 constant domain.
    • The heavy chain has 1 variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables domain but has different numbers of constant domains:
      • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA, IgD: 3 constant domains
      • IgM and IgE: 4 constant domains
  • Fragments (determined by the location where the enzyme papain splits the Ig Ig X-linked Agammaglobulinemia):
    • Fab  (fragment antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding):
      • Contains the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables regions and parts of the constant region of both heavy and light chains
      • Interacts with the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
    • Fc (fragment crystallizable):
      • The remaining part (tail) of the antibody (heavy chain only)
      • Constant region, carbohydrate moieties
      • Complement binding
      • Confers Ig Ig X-linked Agammaglobulinemia isotype (e.g., IgM, IgA)
  • The heavy-chain makeup (constant region and Fc) determines the Ig Ig X-linked Agammaglobulinemia class/isotype: 
    • ÎĽ: IgM
    • δ: IgD
    • Îł: IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis
    • α: IgA
    • ε: IgE
Immunoglobulin domains

Immunoglobulin domains:
The heavy chains and light chains are folded up into domain type structures. The light chain has 1 variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables domain and 1 constant domain. The heavy chain has 1 variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables domain but has different constant domains depending on the Ig molecule Ig molecule Humoral Adaptive Immunity ( IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA, and IgD have 3 constant domains, whereas IgM and IgE have 4 constant domains).

Image by Lecturio.
Structure of the antibody

Structure of the antibody (regions):
Antibody has a unique variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (formed by heavy and light chains) capable of binding a different antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination and a constant region (formed by heavy chains).

Image: “Figure 42.22” by OpenStax College. License: CC BY 4.0
Fragments of the immunoglobulin

Fragments of the Ig Ig X-linked Agammaglobulinemia (determined by location where the enzyme papain splits the Ig Ig X-linked Agammaglobulinemia):
Fab (fragment antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding) contains the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables regions (red) and parts of the constant region (blue) of both heavy and light chains. Fc (fragment crystallizable) contains the remaining part (tail) of the antibody (constant region of the heavy chain only).

Image by Lecturio.

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Immunoglobulin Genes

Ig Ig X-linked Agammaglobulinemia gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments

  • Heavy-chain genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (found within a single gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics, IgH), are assembled from 4 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments:
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (V)
    • Diversity region (D)
    • Joining region (J)
    • Constant region (C)
  • The light chain genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (found as 2 separate gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics loci—the Îş locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics (IgK) and the λ locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics (IgL)) come from 3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments:
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (V)
    • Joining region (J) 
    • Constant region (C)

Gene rearrangements Gene rearrangements The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. Humoral Adaptive Immunity

  • In the B-cell stages of development, gene rearrangements Gene rearrangements The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. Humoral Adaptive Immunity proceed to assemble the Ig molecule Ig molecule Humoral Adaptive Immunity. 
    • In the IgH chains, rearrangement starts with the D and J segments. 
    • IgH gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics VDJ ( variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables-diversity-joining) recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology then occurs, forming a pre-B cell.
    • Light-chain VJ rearrangements follow.
  • From this process, a complete IgM antibody molecule is expressed and the mature B cell Mature B cell Lymphocytes: Histology is formed. 
  • Gene rearrangements Gene rearrangements The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. Humoral Adaptive Immunity contribute to antibody diversity Antibody Diversity The phenomenon of immense variability characteristic of antibodies. It enables the immune system to react specifically against the essentially unlimited kinds of antigens it encounters. Antibody diversity is accounted for by three main theories: (1) the germ line theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the somatic mutation theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the gene rearrangement theory, which holds that antibody diversity is generated by the rearrangement of immunoglobulin variable region gene segments during the differentiation of the antibody-producing cells. B cells: Types and Functions.

Class-switch recombination Class-switch recombination Gene rearrangement of the b-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing. B cells: Types and Functions (CSR)

  • Also called class switching
  • Biologic mechanism by which B-cell production of Igs changes from one class to another.
    • IgM to other Igs → the constant region of the heavy chain (C) changes the ÎĽ (IgM) segment to Îł ( IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis), ε (IgE), or α (IgA). 
    • Switching is influenced by cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.
      • Transforming growth factor β (TGF-β): preferentially switches to IgA
      • IL-4: IgE
      • Interferon IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-É‘ and IFN-β), type II IFN (IFN-ÉŁ), and type III IFN (IFN-Ć›). Interferons-Îł, IL-4: IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis
  • The constant region of the Ig Ig X-linked Agammaglobulinemia heavy chain is changed, but the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region remains unchanged.
  • Because the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region is intact, specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays of the antibody does not change.

Processes of class-switch recombination Class-switch recombination Gene rearrangement of the b-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing. B cells: Types and Functions

  • Excision of exons Exons The parts of a transcript of a split gene remaining after the introns are removed. They are spliced together to become a messenger RNA or other functional RNA. Post-transcriptional Modifications (RNA Processing):
    • When antigens are encountered, mature IgM-positive B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions undergo CSR. 
    • Exons Exons The parts of a transcript of a split gene remaining after the introns are removed. They are spliced together to become a messenger RNA or other functional RNA. Post-transcriptional Modifications (RNA Processing) encoding the constant coding gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment (CÎĽ) of the IgH are excised.
    • These exons Exons The parts of a transcript of a split gene remaining after the introns are removed. They are spliced together to become a messenger RNA or other functional RNA. Post-transcriptional Modifications (RNA Processing) are replaced with a new constant gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment (e.g., CÎł, Cε, or Cα). 
    • Results in the B cell (originally expressing IgM) producing IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgE, or IgA
  • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure deletional- recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology reaction:
    •  Repetitive areas of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure called switch regions are present:
      • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure-modifying enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes ( activation-induced cytidine deaminase Activation-induced cytidine deaminase B cells: Types and Functions (AICDA) and uracil Uracil One of four nucleotide bases in the nucleic acid RNA. Nucleic Acids nucleoside glycosylase ( UNG UNG B cells: Types and Functions)) create DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure double-stranded breaks (DSBs)
      • Determining where the VDJ segment and the new constant region is joined by a repair enzyme
    • New Ig Ig X-linked Agammaglobulinemia molecules are generated with a different constant region (but with the same affinity/ specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays for the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination given that the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region is intact).
Class-switch recombination

Class-switch recombination Class-switch recombination Gene rearrangement of the b-lymphocyte which results in a substitution in the type of heavy-chain constant region that is expressed. This allows the effector response to change while the antigen binding specificity (variable region) remains the same. The majority of class switching occurs by a DNA recombination event but it also can take place at the level of RNA processing. B cells: Types and Functions (CSR):
The heavy chain has different gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments: variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (V), diversity region (D), joining region (J), and constant (C) region.
The heavy-chain C region determines the Ig Ig X-linked Agammaglobulinemia class/isotype. When antigens are encountered, mature IgM-positive B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions undergo CSR. Exons Exons The parts of a transcript of a split gene remaining after the introns are removed. They are spliced together to become a messenger RNA or other functional RNA. Post-transcriptional Modifications (RNA Processing) encoding the constant coding gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment (CÎĽ) of IgH are excised. Repetitive areas of DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, switch regions (the black diamonds), are present.
Switch regions guide enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes (e.g., activation-induced cytidine deaminase Activation-induced cytidine deaminase B cells: Types and Functions (AICDA)) to where to create DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure double-stranded breaks (DSBs) and where the VDJ segment and the new constant region are joined by a repair enzyme. The CÎĽ is replaced with a new constant gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment (e.g., CÎł, Cε, or Cα). In the image, CÎł1 attaches to the VDJ segment and creates IgG1.

Image by Lecturio.

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Antibody Diversity and Specificity

Antibodies that are created have important properties (diversity and specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays) that are essential in the immune response.

Antibody diversity Antibody Diversity The phenomenon of immense variability characteristic of antibodies. It enables the immune system to react specifically against the essentially unlimited kinds of antigens it encounters. Antibody diversity is accounted for by three main theories: (1) the germ line theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the somatic mutation theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the gene rearrangement theory, which holds that antibody diversity is generated by the rearrangement of immunoglobulin variable region gene segments during the differentiation of the antibody-producing cells. B cells: Types and Functions

Unique mechanisms creating antibody diversity Antibody Diversity The phenomenon of immense variability characteristic of antibodies. It enables the immune system to react specifically against the essentially unlimited kinds of antigens it encounters. Antibody diversity is accounted for by three main theories: (1) the germ line theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the somatic mutation theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the gene rearrangement theory, which holds that antibody diversity is generated by the rearrangement of immunoglobulin variable region gene segments during the differentiation of the antibody-producing cells. B cells: Types and Functions include:

  • Having multiple V, D, and J segments: 
    • As already mentioned, in early B-cell development, the heavy chains and light chains have multiple segments:
      • V, D, J, and C for heavy chain
      • V, J, and C for light chain
  • Rearrangements of the V, D, and J segments:
    • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure sequences (called recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology signal sequence (RSS)) flank each gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment.
    • These sequences are recognition sites for the joining process.
    • Recombinase enzyme complexes RAG1 and RAG2 ( recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology activating genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure 1 and 2) recognize the RSS and catalyzes the joining process.
    • Deficiency in RAG1 or RAG2 can produce nonfunctional B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions. 
    • After the heavy-chain segments, the light-chain segments are also recombined.
  • Junctional diversity:
    • Joining of antibody gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments can be imprecise.
    • A number of nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids can be removed and/or can be inserted from the ends of the recombining gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments.
  • Combinatorial diversity:
    • Diversity is created by the random pairing of the heavy and light chains.
  • Somatic hypermutation Somatic hypermutation A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development. B cells: Types and Functions: 
    • Point mutations occur with repeated antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination stimulation (from primary to secondary responses).
    • Increases affinity to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
    • Creates additional diversity to the antibody

Specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays

  • Somatic hypermutation Somatic hypermutation A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development. B cells: Types and Functions leads to affinity maturation Affinity maturation Humoral Adaptive Immunity (in the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region), creating an enhanced ability to recognize and bind BIND Hyperbilirubinemia of the Newborn antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination.
  • Class switching (which affects the constant region) also contributes to antibody specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays.
B-cell activation and maturation processes in the germinal center

B-cell activation and maturation processes taking place in the germinal center:
On activation, the B cell moves from the mantle zone and enters the germinal center. B-cell proliferation ( clonal expansion Clonal Expansion Seborrheic Keratosis) takes place, and antibody affinity to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination is enhanced through the process of somatic hypermutation Somatic hypermutation A programmed mutation process whereby changes are introduced to the nucleotide sequence of immunoglobulin gene DNA during development. B cells: Types and Functions. Repeated cycles of proliferation and hypermutation fine-tune the B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. However, not all B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions continue to differentiate, especially if affinity is weak. Apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage follows if the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–antibody binding is not optimized. B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions with strong affinity survive ( selection Selection Lymphocyte activation by a specific antigen thus triggering clonal expansion of lymphocytes already capable of mounting an immune response to the antigen. B cells: Types and Functions), with the help of survival signals from follicular dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions and T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions. These selected B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions move on to class switching and differentiation into plasma cells Plasma cells Specialized forms of antibody-producing B-lymphocytes. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. Humoral Adaptive Immunity or memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment cells.

Image by Lecturio. License: CC BY-NC-SA 4.0

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Classes and Characteristics

Classes

  • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis:
    • Major class of Ig Ig X-linked Agammaglobulinemia in the serum and extravascular spaces
    • Subclasses: IgG1 (65% of IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis), IgG2, IgG3, IgG4
    • Crosses the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity, thus, the most abundant Ig Ig X-linked Agammaglobulinemia in newborns
  • IgM:
    • 1st antibody produced in response to an antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
    • The pentameric structure of IgM has 10 binding sites, making it the Ig Ig X-linked Agammaglobulinemia with the highest binding capacity.
    • Does not cross the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity
  • IgA:
    • Major Ig Ig X-linked Agammaglobulinemia for mucosal immunity (found in secretions of the respiratory, GI, and genitourinary tracts)
    • About 10%–15% of total Igs in the serum
    • Subclasses: IgA1, IgA2
  • IgE:
    • Lowest quantity in the serum
    • Fc region binds to its receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation, eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation, and mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation.
  • IgD:
    • Low amounts in the serum
    • Major surface Ig Ig X-linked Agammaglobulinemia in mature naive B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions

Monomers and polymers

  • The antibody unit is a small molecule (a monomer).
  • IgA and IgM form antibody polymers (formed from chemically bonded monomers).
    • IgA:
      • A monomer resembling IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis in the serum
      • In mucus, secreted IgA forms dimers, 2 monomers with the J chain (stabilizing molecule), and a secretory component.
    • IgM:
      • Secreted polymers of 5 antibodies (pentamer) bound together by J chain
      • Has 10 identical antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding sites
      • Structure contributes to antibody efficiency, complement fixation, and other antibody– antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination interactions
Monomers and polymers

Monomers and polymers:


IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgD, and IgE are monomers (structure illustrated on the leftmost image). IgA becomes a dimer in mucous secretions. IgM forms a pentamer.

Image by Lecturio.
Five immunoglobulin classes

The 5 Ig Ig X-linked Agammaglobulinemia classes, their structures, and their characteristics

Image: “Five immunoglobulin classes” by OpenStax College. License: CC BY 3.0

Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–antibody interaction

  • The area of the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination recognized by the antibody is called the epitope.
    • A single antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination may have several epitopes Epitopes Sites on an antigen that interact with specific antibodies. Vaccination. 
    • Each epitope can be bound by a different antibody.
  • Antibody binds to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination noncovalently (reversible):
  • Affinity is the strength of the bond formed between the antibody’s antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding site and the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination epitope (between 2 molecules).
  • Avidity is the overall or combined strength of antibody– antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination interactions (as the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination can have multiple epitopes Epitopes Sites on an antigen that interact with specific antibodies. Vaccination) and is dependent on the:
    • Number of antibody antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-binding sites in antibody (antibody valency)
    • Affinity of the binding sites for antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
    • Structural arrangement of interacting parts of antibody– antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination

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Functions

General functions

  • Neutralization of toxins and the infectivity of pathogens: 
    • Bacterial toxins are neutralized and effects are inactivated.
    • Neutralizing antibodies use the Fab (which forms highly specific binding to the target attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology sites or receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors) → prevents pathogen adherence 
    • Some Igs cause organisms to aggregate (IgA → agglutination → entrapment in mucus)
    • After attachment Attachment The binding of virus particles to virus receptors on the host cell surface, facilitating virus entry into the cell. Virology, fusion with host membranes can be inhibited.
  • Complement activation Complement Activation The sequential activation of serum complement proteins to create the complement membrane attack complex. Factors initiating complement activation include antigen-antibody complexes, microbial antigens, or cell surface polysaccharides. Systemic Lupus Erythematosus and generation of membrane attack complex Membrane attack complex A product of complement activation cascade, regardless of the pathways, that forms transmembrane channels causing disruption of the target cell membrane and cell lysis. It is formed by the sequential assembly of terminal complement components (complement C5b; complement C6; complement C7; complement C8; and complement C9) into the target membrane. The resultant C5b-8-poly-c9 is the ‘membrane attack complex’ or MAC. Type II Hypersensitivity Reaction (MAC) causing cell lysis and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Antibodies (primarily IgM and IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis) activate the complement system Complement system Serum glycoproteins participating in the host defense mechanism of complement activation that creates the complement membrane attack complex. Included are glycoproteins in the various pathways of complement activation (classical complement pathway; alternative complement pathway; and lectin complement pathway). Innate Immunity: Barriers, Complement, and Cytokines.
    • MAC: 
      • Activated complement components are C5b, C6, C7, C8, and C9.
      • Introduces large pores on the pathogen surface, leading to pathogen death
  • Opsonization (with or without complement) for phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation
    • Involves coating of pathogens by molecules that enhance phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation
    • Antibodies, especially IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, can function as opsonins (like C3b).
  • Antibody-dependent cellular cytotoxicity ( ADCC ADCC The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface immunoglobulin G whose Fc portion is intact. The effector cell is a ‘killer’ cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. Humoral Adaptive Immunity):
    • Involves Fc-bearing immune cells (e.g., natural killer cells Natural killer cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D antigen. Lymphocytes: Histology) able to produce toxic molecules
    • These cells are stimulated through Fc receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors by Igs (particularly IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis). 
    • Activation of the immune cell releases toxic molecules, causing lysis of target cell.
    • IgE also triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) ADCC ADCC The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface immunoglobulin G whose Fc portion is intact. The effector cell is a ‘killer’ cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. Humoral Adaptive Immunity:
      • The eosinophil (with the Fc receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors) recognizes IgE.
      • Helminth-bound IgE stimulates eosinophil degranulation, and the cytotoxic Cytotoxic Parvovirus B19 granules kill parasites that are too large to be phagocytosed.
  • Clearance of immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency:
    • Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–antibody complexes activate the complement system Complement system Serum glycoproteins participating in the host defense mechanism of complement activation that creates the complement membrane attack complex. Included are glycoproteins in the various pathways of complement activation (classical complement pathway; alternative complement pathway; and lectin complement pathway). Innate Immunity: Barriers, Complement, and Cytokines: 
      • Antibody Fc regions in IgM and IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis bind BIND Hyperbilirubinemia of the Newborn C1q.
      • Immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency are opsonized with C3b fragments.
    • Immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency, bearing C3b fragments, bind BIND Hyperbilirubinemia of the Newborn to complement receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors 1 (CR1) on RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology. 
    • RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology then take the immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency to the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy, where macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation phagocytose the complexes.

Functions of the different Ig Ig X-linked Agammaglobulinemia classes

  • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis:
    • Main antibody in secondary immune response Secondary immune response Humoral Adaptive Immunity
    • Functions are affected by subclass, but, in general, IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis:
      • Fixes complement
      • Participates in ADCC ADCC The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface immunoglobulin G whose Fc portion is intact. The effector cell is a ‘killer’ cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. Humoral Adaptive Immunity (binding Fc receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors)
      • Enhances phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation (opsonin)
    • Ability to cross the placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity, mediated by receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on placental cells for IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis Fc.
      • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis antibodies produced in the mother against pathogens she encounters are passed to the fetus.
      • Maternal IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis levels in newborns wane 6–12 months after birth.
  • IgM
    • Monomer form serves as a B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( BCR BCR Lymphocytes: Histology) in naive B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions.
    • Facilitates activation of the B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions by binding to helper T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions
    • Produced in the primary immune response Primary immune response Humoral Adaptive Immunity
    • Fixes complement, leading to lysis of microorganisms
    • Agglutinin: can agglutinate pathogens, thus facilitating pathogen elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy
  • IgA: 
    • A secretory component is added, allowing transport of IgA across mucosal membranes.
    • The secretory form (dimer) prevents bacterial colonization Colonization Bacteriology of mucosal surfaces.
    • Major Ig Ig X-linked Agammaglobulinemia in secretions: tears, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy, colostrum Colostrum The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. Breastfeeding/breast milk, and mucus
  • IgE: 
    • Binding of allergen to IgE triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of inflammatory mediators from mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation and basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation (allergic response)
    • Important in elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of parasites ( eosinophils Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Innate Immunity: Phagocytes and Antigen Presentation bind BIND Hyperbilirubinemia of the Newborn to IgE-coated helminths Helminths Commonly known as parasitic worms, this group includes the acanthocephala; nematoda; and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. Anthelmintic Drugs, leading to killing of the parasite) 
  • IgD:
    • Together with IgM, constitutes the BCR BCR Lymphocytes: Histology of naive B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions

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Clinical Relevance

  • X-linked agammaglobulinemia X-linked agammaglobulinemia X-linked agammaglobulinemia, also known as Bruton’s agammaglobulinemia or Bruton’s disease, is a rare, recessive genetic disorder characterized by the improper development of B cells, leading to a lack of mature B cells capable of responding to stimulation by cell-mediated immune responses or certain antigen-presenting cells. X-linked Agammaglobulinemia: results from mutations in the X- chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics encoding for Bruton tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase (BTK), which is essential for B-cell development and maturation. The disease is characterized by the absence of B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions, leading to recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID), primarily by encapsulated Encapsulated Klebsiella bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology and viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology and involving the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, sinuses, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions as well as the CNS. Treatment involves administration of immune globulin.
  • Common variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables immunodeficiency Immunodeficiency ChĂ©diak-Higashi Syndrome ( CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID)): also known as humoral immunodeficiency Immunodeficiency ChĂ©diak-Higashi Syndrome. Common variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables immunodeficiency Immunodeficiency ChĂ©diak-Higashi Syndrome is a disorder of the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs characterized by reduced serum levels of IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA, and IgM.  The underlying causes of CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID) are largely unknown. Individuals with this condition are prone to infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in the GI and the upper and lower respiratory tracts. CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID) is also associated with a higher risk of developing autoimmune disorders, granulomatous diseases Granulomatous diseases A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern. Type IV Hypersensitivity Reaction, and malignancy Malignancy Hemothorax. The treatment is immune globulin replacement therapy.
  • Hyper-IgM syndrome Hyper-IgM syndrome The hyperimmunoglobulin M (hyper-IgM) syndrome, is a group of rare inherited immunodeficiency disorders characterized by low or absent serum levels of IgA, IgG, and IgE and normal or elevated levels of IgM. Hyper-IgM syndrome is most commonly caused by X-linked mutations in the CD40 ligand gene, which results in abnormal signaling between B and T lymphocytes. Hyper-IgM Syndrome: characterized by normal or elevated levels of IgM with decreased or absent levels of other Igs. There are X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) and autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance types of hyper-IgM syndrome Hyper-IgM syndrome The hyperimmunoglobulin M (hyper-IgM) syndrome, is a group of rare inherited immunodeficiency disorders characterized by low or absent serum levels of IgA, IgG, and IgE and normal or elevated levels of IgM. Hyper-IgM syndrome is most commonly caused by X-linked mutations in the CD40 ligand gene, which results in abnormal signaling between B and T lymphocytes. Hyper-IgM Syndrome. The syndrome presents with recurrent sinopulmonary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, and lymphoid hyperplasia Lymphoid hyperplasia Common Variable Immunodeficiency (CVID). The diagnosis is verified by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Treatment includes Ig Ig X-linked Agammaglobulinemia replacement therapy and prophylactic antibiotics. Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation is another option. 
  • IgA deficiency IgA deficiency A dysgammaglobulinemia characterized by a deficiency of immunoglobulin a. Selective IgA Deficiency: characterized by low levels of IgA with normal IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis and IgM levels. IgA deficiency IgA deficiency A dysgammaglobulinemia characterized by a deficiency of immunoglobulin a. Selective IgA Deficiency is the most common primary immunodeficiency Immunodeficiency ChĂ©diak-Higashi Syndrome. Many individuals are asymptomatic; however, there is a potential for recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID) as well as autoimmune disease. Individuals may be prone to anaphylactic transfusion reactions Transfusion reactions Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions because of the presence of IgA in blood products. Some of these cases eventually progress to CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID). The treatment involves prophylactic antibiotics and avoidance of blood products that contain IgA.

References

  1. Forthal, D.N. (2014) Functions of antibodies. Microbiology Spectrum 2(4):1–17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159104
  2. Matthews, A.J., Zheng, S., DiMenna, L.J., Chaudhuri, J. (2014). Regulation of immunoglobulin class-switch recombination: choreography of noncoding transcription, targeted DNA deamination, and long-range DNA repair. Advances in Immunology 122:1–57. https://doi.org/10.1016/B978-0-12-800267-4.00001-8
  3. Riedel, S., Hobden, J.A., Miller, S., Morse, S.A., Mietzner, T.A., Detrick, B., Mitchell, T.G., Sakanari, J.A., Hotez, P., Mejia, R. (Eds.). (2019). Immunology. Chapter 8 of Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2629&sectionid=217769996
  4. Schroeder, H.W., Jr., Cavacini, L. (2010). Structure and function of immunoglobulins. Journal of Allergy and Clinical Immunology 125(2 Suppl 2):S41–S52. https://doi.org/10.1016/j.jaci.2009.09.046

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