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Immunology Review Notes [1.24.05] Lecture 1 Innate Immunity 1. Anatomical barriers a. Skin i. 15 layers of cells are dead/maintained @ low pH 3-5 which is inhibitory to pathogens (2 sq meters) b. Mucous membranes i. All openings are lined w/ membrane (400 sq meters) ii. Saliva, tears, and mucous secretions act to wash away potential invaders and also contain antibacterial or antiviral substances 2. Physiological barriers a. Gastric acidity i. An innate physiologic barrier to infection b/c very few ingested microorganisms can survive the low pH of the stomach contents b. Soluble factors: i. Lysozyme 1. chews up cell walls of gram +; in tears 2. an enzyme present in tear, saliva, and mucous secretions that digests mucopeptides in bacterial cell walls and thus functions as a nonspecific antibacterial agent. It has frequently been used as a target antigen in immunological studies ii. complement proteins 1. a group of serum proteins that participates in an enzymatic cascade, ultimately generating the cytolytic membraneattack complex iii. mannose-binding lectins iv. interferons 1. (IFNs) several glycoprotein cytokines produced and secreted by certain cells that induce an antiviral state in other cells and also help to regulate the <a href="/keyword/immune-response/" >immune response</a> 3. Cell barriers a. Blood monocytes and tissue macrophages b. Dendritic cells i. Bone-marrow-derived cells that descend through the myeloid and lymphophoid lineages and are specialized for antigen presentation to helper T cells c. Neutrophils, eosinophils, and basophils i. Neutrophils a circulating, phagocytic granulocyte involved early in the inflammatory response. It expresses Fc receptors and can participate in antibody-dependent cell-mediated cytotoxicity. They are the most numerous white blood cells in the circulation ii. Eosinophils motile, somewhat phagocytic granulocytes that can migrate from blood to tissue spaces. They have large numbers of 1 IgE receptors and are highly granular. They are thought to play a role in the defense against parasitic organisms such as roundworms iii. Basophils a nonphagocytic granulocyte that expresses Fc receptors for IgE. Antigen-mediated cross-linkage of bound IgE induces degranulation of basophils d. Natural Killer cells i. A class of large granular cytotoxic lymphocytes that don t have Tor B-cell receptors. They are antibody-independent killers of tumor cells and also can participate in antibody-dependent cell-mediated cytotoxicity 4. Inflammatory barriers indication: pain, redness, heat, swelling - inflammatory responses to tissue damage and/or tissue invasion a. Vasodilation of capillaries (arteries) causes redness &amp; heat b. Increase in capillary permeability gets water net out of the capillaries; swelling c. Phagocytosis causes the pain; squeeze to kill causing the pus to damage tissue; pain i. As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested material, and fluid forms a substance celled pus Cells and Soluble Factors of the Immune System Innate Immune System Adaptive Immune System Resistance Not improved by repeated infection Improved by repeated infection Soluble Factors - lysozyme - antibody - complement proteins - mannose-binding lectin - interferons - T lymphocytes Cells - Macrophage/monocytes - B lymphocytes (plasma cells) - major white blood cells - produce antibodies - Neutrophils, eosinophils, and - only cells to produce them basophils - Natural Killer cells Cell-associated Receptors Toll-like receptors on macrophages - T-cell antigen receptor (TCR) that recognizes LPS on gram (-) - B-cell antigen receptor (BCR) bacteria Time Course Immediate: 0-4 hrs Late: &gt; 96 hrs Early induced response: 4-96 hrs 2 Introduction to immunology and the <a href="/keyword/immune-responses/" ><a href="/keyword/immune-response/" >immune response</a> s</a> Innate and Adaptive immunity (Pg 1-23) [Intro.] - Smallpox o Variolation the crude form like smallpox; vaccination first by the Chinese o Edward Jenner Intrigued by the milkmaids who contracted the mild disease of cowpox were subsequently immune to smallpox Jenner reasoned that introducing fluid from a cowpox pustule into people might protect them from smallpox o Pasteur Made 1st vaccination - Lymphoid o Spleen All blood move thru spleen; filter Secondary lymphoid organ where old erythrocytes are destroyed and blood-borne antigens are trapped and presented to lymphocytes in the PALS and marginal zone o MALT (mucosal-associated lymphoid tissue) Lymphoid tissue located along the mucous membranes that line the digestive, respiratory and urogential tracts o Bone marrow Some of the long bones The living tissue found w/in the hard exterior of bone o Lymph nodes A small secondary lymphoid organ that contains lymphocytes, macrophages, and dendritic cells and serves as a site for filtration of foreign antigen and for activation and proliferation of lymphocytes o Thymus gland Related to lymphocytes A primary lymphoid organ, located in the thoracic cavity, where Tcell maturation takes place - Blood is liquid and cells - White blood cells o 4/5 is innate o 1/5 is adaptive (lymphocytes) - Humoral immunity o In blood, you have antibody o Mediated by antibody o B cells/plasma cells o Memory B cells o Graph: 3 - Cell-mediated <a href="/keyword/immune-response/" >immune response</a> o Mediated by T-cells o Active T-cells o Make memory T-cells o T-cell antigen o Graph of skin transplant [1.26.05] Lecture 2 Characteristic of adaptive <a href="/keyword/immune-response/" >immune response</a> (humoral &amp; cell-mediated) o 1. Highly specific of enzyme-substrate o 2. Memory o 3. Self-nonself discrimination No primary if from like human but response if from cows o 4. Diversity Has possibility to response to all antigens Antigens, Haptens, Epitopes, Paratopes, and Adjuvants Antigens o Substances that can be recognized by the immunoglobulin receptor of B cells, or by the T-cell receptor when complexed w/ MHC o TCR &amp; BCR If your positively activate TCR leads to the cell-mediated response If your positively activate BCR leads to the B cell response o Tolerance Complete antigen o Induces a humoral and/or cell-mediated <a href="/keyword/immune-response/" >immune response</a> and interacts w/ the products of the response o Aka immunogen A substance capable of eliciting an <a href="/keyword/immune-response/" >immune response</a> . All immunogens are antigens, but some antigens (ex haptens) are not immunogens o Immunogenicity The capacity of a substance to induce an <a href="/keyword/immune-response/" >immune response</a> under a given set of conditions o Antigenicity The ability to combine specifically w/ the final products of the above responses Ex. Antibodies and/or cell-surface receptors Incomplete antigen o Can t induce <a href="/keyword/immune-response/" >immune response</a> by itself; can function as an antigen o Some small molecules called haptens, are antigenic but incapable, by themselves, of inducing a specific <a href="/keyword/immune-response/" >immune response</a> o Haptens Lack immunogenicity - - - 4 - Karl Landsteiner chemically defined system for studying the binding of and individual antibody to a unique epitope on a complex protein antigen Small organic molecules that are antigenic but not immunogenic Chemical coupling of a hapten to a large protein (like <a href="/keyword/bovine-serum-albumin/" ><a href="/keyword/bovine-serum/" >bovine serum</a> albumin</a> ), called a carrier, yields an immunogenic haptencarrier But when multiple molecules of a single hapten are coupled to a carrier protein, the hapten becomes accessible to the immune system and can function as an immunogen Ex: rushiol Found in poison ivy and oak that contain hapten Essential features of immunogens o Organic macromolecules No organic macromolecules will activate the TCR or BCR o Chemical complexity The most efficient antigen is protein The more aromatic the amino acid, the better the antigen Not restricted to natural occurring proteins (D-amino acids) Polysaccharides are the less antigenic than protein In solution probably not antigenic If attached to biological membrane can make it antigenic Pure lipids are not antigenic If have lipoprotein can become antigenic Lipids acts as haptens For the stimulation of B-cell responses, lipids are used as haptens and attached to suitable carrier molecules such as the proteins keyhole limpet hemocyanin or <a href="/keyword/bovine-serum-albumin/" ><a href="/keyword/bovine-serum/" >bovine serum</a> albumin</a> Pure nucleonic acids are incapable of activating either responses DNA &amp; RNA act as haptens o Foreign To prevent from attack self-cells The response can be specific as to a single amino acid Higher response if similar in protein like primates and humans bovine albumin serum o Susceptibility to antigen processing and presentation The development of both humoral and cell-mediated <a href="/keyword/immune-responses/" ><a href="/keyword/immune-response/" >immune response</a> s</a> requires interaction of T cells w/ antigen that has been processed and presented together w/ MCH molecules Macromolecules that can t be degraded &amp; presented w/ MHC molecule are poor immunogens Ex: using polymers of D-amino acids for a L-amino acids enzymes 5 Humoral response: Breaks the antigens &amp; presents to get Thelper cell for the B cells Cell-mediated response: If it can t present it &amp; process it; it can t act as an antigen o Side notes: Major histocompatibility complex (MHC) Class I: present on the surface of all cells w/ a nucleus Class II: present mainly on professional antigen presenting cells Dendritic cells B-cells Macrophages - Epitopes and paratopes o Epitope Def: The portion of an antigen that is recognized and bound by an antibody or TCR/MHC combination; also called antigenic determinant Shape on the antigen that is recognized by Tc cell or antibody Can be recognized by TCR Small antigens have revealed that B &amp; T cells recognize different epitopes on the same antigenic molecule The recognition of antigens by T cells and B cells is fundamentally different B cells recognized soluble antigen when it binds to their membrane-bound antibody Most T cells recognize only peptides combined w/ MHC molecules on the surface of antigen-presenting cells and altered self-cells; T-cell epitopes, as a rule, can t be considered apart from their associated MHC molecules [Table 3-4] Comparison of antigen recognition by T cells and B cells Characteristic B cells T cells Interaction w/ antigen Involves binary complex of Involves ternary complex of T-cell membrane Ig and Ag receptor, Ag, and MHC molecule Binding of soluble antigen Yes No Involvement of MHC None required Required to display processed molecules antigen Chemical nature of antigens Protein, polysaccharide, lipid Mostly proteins, but some lipids and glycolipids presented on MHC-like molecules Epitope properties Accessible, hydrophilic, mobile Internal linear peptides produced by peptides contained sequential or processing of antigen and bound to nonsequential amino acids MHC molecules 6 - o Paratope Def: The site in the variable (V) domain of an antibody or T-cell receptor that binds to an epitope on an antigen o Ex. ag-ab or TCR Epitope paratope highly specific Adjudvants o Def: A substance (e.g., Freund s adjuvant, alum, bacterial LPS) that nonspecifically enhances the <a href="/keyword/immune-response/" >immune response</a> to an antigen o The macromolecule s ability to induce an <a href="/keyword/immune-response/" >immune response</a> will depend on certain properties of the biological sys that the antigen encounters. Properties such as genotype of the recipient, the dose and route of antigen administration, and the administration of substances that increase <a href="/keyword/immune-response/" >immune response</a> o Adjuvants are often used to boost the <a href="/keyword/immune-response/" >immune response</a> when an antigen has low immunogenicity or when only small amounts of an antigen are available o BSA can be increased fivefoldsor more if the BSA is administered w/ an adjuvant o Characteristics Antigen persistence is prolonged Co-stimulatory signals are enhanced Local inflammation is increased The nonspecific proliferation of lymphocytes is stimulated o Freund s adjuvant water-in-oil adju. also prolong the persistence of antigen o Ex. Aluminum potassium sulfate (only one approved by FDA) [1.31.05] Lecture 3 - Duel Systems o Myebid system carry out one or two phagocytosis &amp; then die Fast and can t sustain The three are considered granulocytes 1) Neutrophils Multi-lobed nucleus Most abundant in white blood (12-14 nm) 50-70% in white blood cell Immature o Well develop of the rough ER, golgi apparatus, &amp; lyzosomes Mature o Barely any rough ER or golgi apparatus, but plenty of lyzosomes o Considered in terminal differentiated state After 1st response (used up all lyzosome) then renders useless Forms, matures, differentiates, &amp; stays in the bone marrow 7 Produces 7 million cells per minute Once released in 2-3 days, if not functioned, then die by apoptosis When infection/damaged tissue occurs, neutrophils rush in where inflammation is Neutrophils employ both oxygen-dependent &amp; oxygenindependent pathways to generate antimicrobial substances More likely than macrophages to kill ingested microorganisms They exhibit a larger respiratory burst than macrophages and are able to generate more reactive oxygen intermediates and reactive nitrogen intermediates 2) Eosinophils Bi-lobed nucleus and granulated cytoplasm 1) Leave the bone marrow at immature stage 2) Go by bloodstream then into the spleen to mature 3) Leave the spleen to circulate in the bloodstream (30 mins) 4) Then go into the tissue 1-3% in blood Having parasitic &amp; allergic reactions will increase eosinophil Can function as phagocytosis but not considered as them o More considered for parasitic o And carrying out exocytosis Promote inflammation by migrating to the parasitic side then releasing lyzosome Initial response by the respiratory burst They use bromine to form hypobromite while neutrophils uses hypocholorite Play a role in the defense against parasitic organisms 3) Basophils Lobed nucleus and heavily granulated cytoplasm IN BLOOD About 0.2% in blood (&lt; 1) Found in circulation In inflammation Mast Cells o Virtually indistinguishable to basophils o (IN TISSUE) o Not found in circulation o Released in blood as undifferentiated cells; they don t differentiate until they leave the blood &amp; enter the tissue 8 - o Found in a wide variety of tissues, including skin, connective tissues of various organs, and mucosal epithelial tissues of the respiratory, genitourinary and digestive tracts Substances play a major role in certain allergic responses Both neutrophils &amp; eosinophils are phagocytic, whereas basophils aren t o Mononuclear-phagocytic system Macrophages in tissues Eliminate pathogens, virus-infected cells, and tumor cells Activated macrophages also express higher levels of class II MHC molecules, allowing them to function more effectively as antigen-presenting cells Macrophages and TH cells facilitate each other s activation during the <a href="/keyword/immune-response/" >immune response</a> Monocytes in blood Longer and sustainable Carry out phagocytosis everyday See as monocyte/macrophage Come by bone marrow Released in blood immature macrophages (monocytes) About 5% in blood Matures in the tissue macrophage Has a nice rounded nucleus Histiocyte Def: an immobilized ( tissue fixed ) macrophage found in loose connective tissue If a monocyte migrates into a connective tissue &amp; matures there If mature: In lungs alveolar macrophages In liver Kupffer cell In connective tissue histiocytes In kidney mesangial cells In brain microglial cells In bone osteoclasts They phagocytosizes dead/dying RBC There are more rough ER, golgi apparatus, and lyzosomes Extra notes: Phagocytosis consists of neutrophils and macrophages Stages of Phagocytosis Chemotaxis o 1st step in phagocytosis, macrophages are attracted by and move toward a variety of substances generated in an <a href="/keyword/immune-response/" >immune response</a> chemotaxis o Neutrophil chemotactic factors (NCF) 9 Endogenous Def: Originating w/in the organism or cell Chemokines o Def: Any of several secreted low-molecular-weight polypeptides that mediate chemotaxis for different leukocytes and regulate the expression and/or adhesiveness of leukocyte integrins o They selectively, and often specifically, control the adhesion, chemotaxis, and activation of many types of leukocyte populations and subpopulations o Chemokines cause leukocytes to move into various tissue sites by inducing the adherence of these cells to the vascular endothelium o w/in seconds, the addition of an appropriate chemokine to leukocytes causes abrupt and extensive change in shape, the promotion of greater adhesiveness to endothelial walls by activation of leukocyte integrins, and the generation of microbicidal oxygen radical in phagocytes Ex: IL-8 &amp; MIP-1B Exogenous Def: Originating outside of the organism or cell o Extravasation Def: Movement of blood cells through an unruptured vessel wall into the surrounding tissue, particularly at sites of inflammation movement of circulating neutrophils into tissues Endothelial cells express leukocyte-specific cell-adhesion molecules (CAMs) Some are expressed constitutively or by local concentration of cytokines Extravasation in Neutrophils Neutrophils are generally the first cell type to bind to inflamed endothelium and extravasate into the tissues 1st step, neutrophils attach loosely to the endothelium by a low-affinity selectin-carbohydrate interaction This interaction tethers the neutrophil briefly to the endothelial cell, but the shear force of the circulating blood soon detaches the neutrophil. Selectin molecules on another endothelial cell again tether the neutrophil; this process is repeated so that the neutrophil tumbles end-over-end alone the endothelium rolling Margination Def: accumulation of lymphocytes at the wall of blood vessels as an early result of inflammation 10 Selectins The selectin family of membrane gylcoproteins has a distal lectin-like domain that enables these molecules to bind to specific carbohydrate groups Selectin molecules are responsible for the initial stickiness of leukocytes to vascular endothelium Mucins A group of serine- and threonine-rich proteins that are heavily glycosylated Integrins Heterodimeric proteins (consists of an and a chain) that are expressed by leukocytes and facilitate both adherence to the vascular endothelium and other cell-to-cell interactions ICAMs Several adhesion molecules contain a variable number of immunoglobulin-like domains and thus are classified in the immunoglobulin superfamily Attachment o Opsonization Def: Deposition of opsonins on an antigen, thereby promoting a stable adhesive contact w/ an appropriate phagocytic cell The rate of phagocytosis of an antigen was higher in the presence of specific antibody oto the antigen than in its absence A molecule that binds to both antigen and macrophage and enhances phagocytosis Opsonins proteins that have the ability to enhance phagocytosis Ex: immunoglobulins &amp; complement proteins The promotion of phagocytosis of antigens by macrophages and neutrophils Ingestion o Phagosome Def: intracellular vacuole containing ingested particulate materials; formed b the fusion of pseudopodia around a particle undergoing phagocytosis The digested contents of the phagolysosome are then eliminated in a process called exocytosis Digestion o Oxygen-independent killing mechanisms Lysozyme and various hydrolytic enzymes Defensins Def: Cysteine-rich, positively charged, antimicrobial peptides that contain 25 to 35 amino acids and are found in macrophages and neutrophils Activated macrophages produce a group of antimicrobial and cytotoxic peptides Used to kill bacteria like S. aureus, S. pneumoniae, E.coli 11 - - Also activated macrophages also secrete tumor necrosis factor (TNF- ), a cytokine that has a variety of effects and is cytotoxic for some tumor cells Mainly against Gram (-) bacteria, fungi, &amp; envel. viruses o Oxygen-dependent killing mechanisms Respiratory burst Def: A metabolic process in activated phagocytes in which the rapid uptake of oxygen is used to produce reactive oxygen intermediates that are toxic to ingested microoganisms Process results in the activation of a membrane-bound oxidase that catalyzes the reduction of oxygen to superoxide anion NADPH-dependent oxidases attaches to the lysosomal membranes project into the lumen of the phagosome after degranulation NADPH + 2O2 (NADPH oxidase) superoxide ion (spontaneous) hydrogen peroxide (myeloperoxidase) hypochlorite L-arginine + O2 + NADPH (nitric acid synthetase) nitric oxide + L-citrulline + NADP The Functions of Macrophages Phagocytosis o Macrophage mannose receptor only on macrophages o CD14 on monocytes and macrophages As secretory cells o Important for macrophages to release cytokines and other mediators to tell the others about the site of inflammation o Some factors secreted by macrophages Lipid mediators Prostaglndins, leukotrienes, &amp; platelet-activating factor Cytokines IL-1 activates endothelium &amp; lymphocytes, causes fever IL-6 activates lymphocytes, causes fever IL-8 attracts neutrophils, basophils, &amp; T cells to site of infection IL-12 activates Natural Killer cells TNF-alpha activates endothelium &amp; increases vascular permeability, causes fever &amp; septic shock Acute-phase proteins Induced by IL-1, IL-6, &amp; TNF-alpha C-reactive protein Mannan-binding lectin Tissue healing &amp; repair - 12 - Antigen processing and presentation o Antigen-presenting cells (APC) Macrophages Dendritic cells B cells o Two pathways for processing antigen Class I Endogenous antigens Eliminated by cytotoxic T cells CD8 cell-surface molecule Cytosolic pathway In cytoplasm or contiguous nucleus Class II Exogenous antigens Presented to T helper cells CD4 cell-surface molecule Endocytic pathway In vesicular compartments Basic Structure of Immunoglobulins History o 1890: Emil von Fischer describe the stuff in serum: antibodies o 1930: Heidelberger showed that antibodies are proteins o 1939: Tiselius &amp; Kabat antibodies are associated &amp; indistinguishable from the gamma-globulin fraction of serum The gamma-globulin fraction was identified as containing serum antibodies immunoglobulins Graph of Electrophoresis of serum - o 1950s &amp; 1960 s Porter 150,000 bivalent (binds 2 ags) IgG (papain) 2 x 45,000 monoval Fab fragments + 1 50,000 Fc fragment o Papain Enzyme that won t hydrolyze the nonglobular region (such as praline) o Fab: fragment, antigen binding 13 o Fc: fragment crystallizable 150,000 bival IgG (pepsin) 100,000 bival F(ab )2 fragment (mercaptoethanol) 2 x 50,000 monoval Fab fragments Observed that Igs prepared to Fab reacted w/ both H and L chains whereas Igs to Fc reacted only w/ H chains Pepsin digestion breaks into F(ab )2 &amp; Fc fragments Papain digestion 2 Fab &amp; 1 Fc Mercaptoethanol 2 H-chain &amp; 2 L-chain Edelman 150,000 bival IgG (mercaptoethanol) 2 x 50,000 polypeptides (Heavy chains) +2 x 25,000 polypeptide (Light chains) Light &amp; Heavy Chain Structure Fig 4-2 - - Variable Regions o the first 110 or so amino acids of the amino-terminal region of a light or heavy chain varies greatly among antibodies of different specificity V regions: VL &amp; VH Complementarity-determining regions (CDRs) They on both light and heavy chains constitute the antigenbinding site of the antibody molecule o In general, more residues in the heavy-chain CDRs appear to contact antigen than in the light-chain CDRs. Thus the VH domain often contributes more to antigen binding than the VL domain o The CDR3 is the most variable of the CDRs Constant Regions o The sites of attachment for carbohydrates are restricted to the constant region 14 - - o CH1 &amp; CL domains may contribute to antibody diversity by allowing more random association between VH &amp; VL domains than would occur if this association were driven by the VH/VL interaction alone Hinge Region o Is rich in praline residues and is flexible, giving IgG, IgD, and IgA segmental flexibility o Two prominent amino acids in the hinge region are praline and cysteine Other constant-region domains IgA, IgD, IgG IgE, IgM (G.A.D) (M.E) CH1/CH1 CH1/CH1 Hinge region CH2/CH2 CH2/CH2 CH3/CH3 CH3/CH3 CH4/CH4 o The 5 classes of antibody and there subclasses can be expressed either as secreted immunoglobulin (sIg) or as membrane immunoglobulin (mIg) o Secreted immunoglobulin has a hydrophilic amino acid sequence of various lengths at the carboxyl-terminal end o The membrane-bound immunoglobulin, the carboxyl-terminal domain contains three regions Extracellular hydrophilic spacer sequence composed of 26 amino acids residues Hydrophobic transmembrane sequence A short cytoplasmic tail o A memory B cell can express mIgM, mIgG, mIgA, or mIgE L chain structure Based on: o L chain amino acid sequencing From 100-110 amino acids was found to be the variable region The carboxyl terminal half of the molecule was constant region Two light chain types Kappa ( ): 60% in human light chain Lambda ( ): 40% in human light chain A single antibody molecule contains only one light chain type, either or , never both Framework regions (FR) Def: a relatively conserved sequence of amino acids located on either side of the hypervariable regions in the variable domains of immunoglobulin heavy and light chains Forms the beta-sheets that provide the structural framework of the domain w/ the CDRs forming 3 loops at one edge of each sheet o X-ray diffraction of L chains Ig superfamily H chain structure 15 - - - Based on: o H chain amino acid sequencing The remaining part of the protein revealed five basic sequence patterns, corresponding to 5 different heavy-chain constant (C) regions (). Each of these 5 different heavy chains is called an isotype The heavy chains of a given antibody molecule determine the class of that antibody: IgM( ), IgG( ), IgA( ), IgD( ), or IgE( ) o X-ray diffraction of H chains Immunoglobulin fine structure o The secondary structure is formed by folding of the extended polypeptide chain back and forth upon itself into an antiparallel pleated sheet Notes on Multiple Myeloma Patients Multiple myeloma o A cancer of antibody-producing plasma o A clone of plasma cells in an individual w/ multiple myeloma has escaped normal controls on their life span and proliferation and aren t end-stage cells; rather, they divide over and over in an unregulated way w/o requiring any activation by antigen to induce proliferation o The myeloma cells secrete excessive amounts of light chains discovered in the urine of patients then called Bence-Jones proteins Abnormal amount of normal protein o Myeloma protein Abnormal amount of normal antibody molecules Immunoglobulin Isotypes and Subisotypes IgG o Structure H2L2 MW ~146 kd ~75% of total serum Subclasses 1, 2, 3, 4 &gt;95% Homology w/ difference in hinge region #1 in the body o Effector function Activation of the complement system IgG3 &gt; IgG1 Opsonization by IgG for enhanced phagocytosis (IgG1 = IgG3) &gt; IgG4 Neonatal immunity mediated by maternal IgG Only IgG can cross the placenta barrier IgG1 &gt; IgG3 &gt; IgG4 Antibody-depended cell-mediated cytotoxicity (ADCC) - - 16 Capable of lysing targeting cells (like Neutrophils, eosinophils, macrophages, NK cells) But b/4 they can lyse, the IgG must be bind IgG is the major Ig isotype produced in the 2 humoral <a href="/keyword/immune-response/" >immune response</a> Can be taken into the lumen of the infants into the blood IgM o Structure Pentameric H2L2 w/ additional Joining chain the monomers are joined by disulfide bridges &amp; J chain MW ~970 kd ~8% of total serum Subclasses None #3 in the body o Effector function 1st isotype to be synthesized in the 1 humoral <a href="/keyword/immune-response/" >immune response</a> &amp; by neonates Activation of the complement system in serum BETTER THAN THE IgG Neutralization of virions in the serum Monomeric IgM (H2L2) is membrane bound &amp; functions as the antigen receptor on the surface of B cells While IgG contains a pair of paratope, IgM has 10 paratopes sites; thus making it more efficient Fc fragment towards the inner Serum IgA o Structure 80% H2L2 monomer 20% dimer, trimer, tetramer, &amp; pentamer (held by J chain) MW ~160 kd 15-20% in total serum Subclasses 1, 2 w/ 90% homology o Effector function No known, unique defense mechanism Secretory IgA o Structure Consists of: 2 IgA monomers 1 J chain 1 secretory complement (SC) piece MW ~390 kd SC piece 17 - - - - To wrap around the Fc region of IgA &amp; IgM molecules to cover sites of susceptible to cleavage by proteolytic enzymes and thus protect the Igs from the proteases that are abundant in the mucosal environment o Effector function Mucosal immunity is mediated by secretory IgA Can t cross blood barrier IgD o Structure H2L2 monomer MW 175-185 kd Subclasses None Usually degraded (proteolysis) by serum plasmin: difficult to isolate (very little in blood) o Effector function No antibody activity is associated w/ IgD On membrane of B cells; co-expressed w/ IgM, indicating the differentiation of an immature into the a mature B cell IgM &amp; IgD function as antigen receptor for B cells The B cell 1st expresses IgM (still immature) Then IgD and IgM are expressed (mature plasma cell) IgE o Structure H2L2 monomer MW ~190 kd Subclasses None Normal IgE occurs in the serum at the lowest concentration VERY LITTLE IN BLOOD o Effector function Immediate-type hypersensitivity is triggered by IgE IgE and IgD can t activate the immune system alone IgG, IgA, IgM can activate the immune system - 18 ... 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