| Symbol(s) | Overview |
| κ & λ | Kappa (κ) and lambda (λ) are the two light chain isotypes. Antibody light chains have a constant region (IgCL) at one end and a variable region (IgVL) at the other end. Light chain variable regions are either kappa (κ) isotype or lambda (λ) isotype. The two light chain isotypes have no known functional differences. In mammals, there is one kind of κ isotype and four kinds of λ isotype (λ1, λ2, λ3 and λ4). While an individual has both κ and λ light chains, an individual B cell only produces κ or λ. Thus, only one type of light chain is present in a typical antibody — the two light chains of an individual antibody are identical. |
| µ | µ refers to the IgM heavy chain constant region. IgM is the predominant antibody, and the membrane receptor of naïve B lymphocytes (along with IgD). However, allelic exclusion means that only one µ allele is expressed in a single lymphocyte. For example, a heterozygote with a µa allele and a µb allele will have both IgMs present, but with individual cells only expressing one or the other. Disruption of µ membrane exon reduces immunoglobulin levels by over 95%. IgM is a potent stimulator of complement. |
| Knockout | Overview |
| IL-6 | You get normal development except there are no plasma cells. IL-6 is required for plasma cell development. |
| AID | AID is an enzyme needed for somatic hypermutation (affinity maturation, and more) and also isotype switching (cytokines are needed simultaneously for isotype switching). You get normal development of B and T cells. However all of the B cells remain IgM positive; there is no isotype switching. |
| Ig-α or -β | T cell development, which does not require Igα is normal. However, B cell development is arrested in the bone marrow and mature B cells are not present in the secondary lymphoid organs. Igα is required for surface expression of the BCR. |
| RAG-1/2 | Needed for antigen specificity — but after that, not needed. Thus, they are not needed for isotype switching. Lack of RAG enzymes leads to no antibody production and no T cell maturation (arrested at DN stage). There is impaired development of both B and T cells. RAG is required for somatic assembly of both the B and T cell receptors. Without correctly assembled receptors, T and B cells do not develop.. |
| Class I MHC | CD4 cells would not be present, so no memory B cell responses, CD4 responses or CD8 responses. A + for CD8 response is OK, as some CD8 responses do not need help. There would be low levels of IgM in initial and secondary infections. |
| Class II MHC | As a result there would be no MHC II on the thymic epithelial cells, no positive selection for CD4 SP cells and consequently no CD4 SP cells. This would then cause immunodeficiency due to lack of any CD4 help to B-cells to give CD40 stimulation and promote class switching. Likewise, there would be no help for the CTL response. |
| Topic | Overview |
| Isotype Switching | T cell help through the CD40/CD40L interaction is required for isotype switching. The FLOW patterns show that expression of CD40 and CD40 L appears normal. Expression of AID is also required for isotype switching.
If there is an I region present: The defect could be in CD40 or CD40L: an interaction between them is required to isotype switch. The defect could be an overproduction of IFN-γ which blocks DNA rearrangement (switching). The defect could not be in IL-4 or its receptor since there is transcription of the unrearranged gene. If there is no I region present: then it must be AID protein (if no transcripts are formed and no Ig is present). |
| T Cell | If all you know is that T cells are not functioning — or maybe not mounting a secondary response — then a good defect candidate is CD40L. |
| No Antibodies | If they are not rearranging, that is the likely cause of no expression. If they are rearranging, there is a defect in something required for surface expression: candidates are the membrane exon of the heavy chain, Ig-α, Ig-β, or surrogate light chain; or proteins required to transport the antibody to the surface. |
| No Rearrangement | Frequently caused by lack of RAG enzymes leading to no antibody production and no T cell maturation (arrested at DN stage). |
| CD40/CD40L | Needed for isotype switching. |
| IgG1/IgE deficiency | A selective decrease in IgG1 and IgE is observed. The most likely expanation is a defect in IL-4 (or IL-4R) or possibly an increase in IFN-γ because these selectively impact these isotypes. Since IgG2 and IgG3 remain essentially unchanged it does not appear to be a general defect such as CD40 or CD40L. |
| Probe | Overview |
| Ig DNA | Unrearranged DNA shows as a single line. Rearranged DNA shows as a smear. |
| I mRNA | When T cell help ( CD40-CD40L) interaction occurs there is DNA rearrangement such that VH is joined to Cε; Iε is removed from the genome and the mRNA no longer contains it. If I mRNA is not excised, but nonfunctioning immunoglobulin is still produced, then cytokine receptors are functioning but CD40/CD40L interaction is askew. |
| Topic | Overview | ||||||||||||||||||
| Adoptive Transfer | Type of immunization involving the transfer of “sensitized” cells, serum or other components to a recipient. | ||||||||||||||||||
| Hapten-Carrier |
Haptens must be bound to carriers to induce a humoral response. The same hapten-carrier conjugate must be used to elicit a secondary response; to generate a secondary response to a hapten bound to a different carrier, the patient must first be immunized against the new carrier. T cells bind carriers; B cells bind haptens. The response of hapten-primed B cells to a hapten-carrier conjugate requires carrier-primed TH cells. Remember that CTL activity only occurs with TH help. |
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| One-Way MLR |
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| BM Chimeras | Bone marrow chimeras (aka bm chimeras) are mice which have been irradiated, thus killing their bone marrow and all bone marrow derived cells (lymphocytes) and then given bone marrow from another mouse. T cells from bone marrow chimeras do not react to the donor haplotype, and do react to the recipient haplotype (due to thymic selection) until the self-reactive self are eliminated in the periphery. Class II APCs from bone marrow chimeras will be of the donor haplotype and Class I APCs from bone marrow chimeras will be of the recipient haplotype. Bone marrow chimeras tolerate skin grafts of the donor haplotype (negative selection) and recipient haplotype (peripheral tolerance); if there is disparity at just one Class I locus there will be slow rejection — study the steps below to better understand skin graft rejection.
If you are asked whether B cells in a bone marrow chimera can respond to an extracellular bacterial infection:
If you are asked whether a bone marrow chimera can respond to an intracellular bacterial or viral infection:
When analyzing proliferation of a bone-marrow chimera responder against a stimulator:
When analyzing cytotoxicity of a bone-marrow chimera responder against a stimulator:
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| Extracellular | Extracellular bacteria induce inflammation by producing toxins. Endotoxins are bacterial cell wall components such as LPS; exotoxins are actively secreted and interfere with cell function, induce cytokine production and are cytotoxic. Extracellular bacteria can directly activate complement, with C1q directly binding the bacteria (classical pathway), mannose-binding protein binding the cell wall (lectin pathway) and/or C3b binding the cell surface (alternative pathway). Cleavage products of complement are opsonin, meaning they enhance phagocytosis. The F(c) region of IgG binds to F(c) receptors, playing a critical role in clearing extracellular bacteria (also, receptor for complement byproducts are important for clearance). | ||||||||||||||||||
| Intracellular | Intracellular bacteria are eliminated by cell-mediated immunity. The innate response consists mainly of phagocytes and NK cells; NK cells are activated either directly or by IL-12 produced by macrophages. Macrophages secrete IL-12 upon phagocytosis of bacteria, and are activated to become phagocytic by IFN-γ secreted by T cells. Also, CTLs lyse infected cells. If IL-12 and IFN-γ are present following initial pathogen exposure, the response is dominated by inflammatory thymocytes. IFN-γ and IL-12 are essential for responding to an infection by intracellular bacteria, with infected IFN-γ knockouts dying after 30 days and infected IL-12 knockouts dying after 60 days. | ||||||||||||||||||
| Viral | Viruses replicate within cells and are either cytopathic (lyse infected cells) or noncytopathic (do not lyse infected cells). Innate immunity to viruses is controlled by: interferons, produced in response to binding of dsRNAs to TLRs; and natural killer cells, which kill cells expressing stress-induced proteins and those with decreased Class I expression. Adaptive immunity to viruses is controlled by: secreted antibodies, which block extracellular virions from binding and entering cells, and which tag infected cells presenting viral particles on their cell surface; and CTLs, which eliminate infection by killing infected cells.
Antibodies are effective during the extracellular stage, preventing virions from spreading and protecting against reinfection. sIgA is a very important part of mucosal secretions, blocking viral attachment to mucosal epithelial cells. Also, antibodies may directly activate complement-mediated lysis of virion particles with lipid envelopes. However, once the virus enters a cell it is inaccessible to antibodies and infected cells must be eliminated by CTLS. CD8 T cells recognize viral antigens presented in a Class I MHC context on the surface of an infected cell. CTL activation requires co-stimulation — if the virally infected cell is not an APC, then it must be phagocytosed by a professional APC. The CD8 T cell then recognizes endogenously synthesized (synthesized within the cell) viral proteins presented in a Class I MHC context on the cell surface. Cytokines produced by CD4 T cells (TH cells) drive CD8 differentiation into effector CTLs that use antigen-specificity to locate and kill infected nucleated cells. DCs present peptides on both Class I and II MHC. T cell proliferation, indicated by H3 incorporation, indicates presentation of an immunogenic peptide on Class II while lysis indicates presentation on Class I. To mount an effective immune response against a viral infection a strong CD8 T cell response is required to kill infected cells. This requires help from CD4 T cells. Therefore, an effective vaccine requires the priming of both CD4 and CD8 T cells. Peptide 3 is presented on Class I and primes CD8 T cells against the virus while Peptide 2 primes CD4 T cells. Lysis is augmented using these peptides together because of T cell help. |
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| LCMV | LCMV is a non-cytopathic virus. Mice deficient of T cells become chronic LCMV carriers, while normal mice develop meningitis to due to CTL killing of meningeal cells. It is frequently used for experiments. | ||||||||||||||||||
| Parasites | There are many animal parasites, ranging from protozoa (unicellular eukaryote) to helminths (large worms). The principal innate response to parasites is phagocytosis, but many parasites are resistant to phagocytosis and can even replicate within macrophages. Phagocytes secrete microbicides to kill organisms too large for phagocytosis, but many helminths have thick teguments that resist neutrophil and macrophage attacks. Also, some helminths activate complement — but many of them are also resistant to lysis via complement.
Helminthic infections are eliminated by secretion of IL-4 and IL-5 by activated TH2 cells. IL-4 and IL-5 then stimulates production of sIgE that binds the worm. This IgE binds F(c)ε receptors on eosinophils, activating the eosinophils to secrete granule enzymes that destroy the parasite. Some pathogenic protozoa (such as Leishmania spp.) survive within macrophages by deactivating the macrophage. Adaptive immunity is then necessary, with TH1 cells secreting large amounts of IFN-γ to re-activate the infected macrophages. Protozoa such as malaria that replicate within and lyse host cells stimulate specific antibody and CTL responses. Another parasite, trypanosomes, change the expression of their surface antigen to evade immune response. |
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| ‘C’ Anything | If you see a chemical that starts with the letter ‘C’ (but not ‘CD’) then it is likely involved in complement. C3a, C4a and C5a are small-peptide byproducts of complement and are anaphylatoxins, binding mast-cells and basophils to induce degranulation and cause vascular permeability and smooth muscle contraction. Also, anaphylatoxins amplify the inflammatory response by inducing synthesis of pro-inflammatory cytokines. C5a is the most potent anaphylatoxin, and also is a chemoattractant and activator of white blood cells (macrophages, etc). C5a can attract white blood cells to extravasate from local capillaries and migrate into the tissue space where complement has been activated. | ||||||||||||||||||
| Phagocytes | Phagocytes have receptors which directly recognize bacteria and lead to phagocytosis, activation, microbicidal activity and cytokine secretion. | ||||||||||||||||||
| Macrophage | Tissue macrophages: trap, engulf and destroy pathogens; produce cytokines (including IL-12); induce co-stimulatory molecules; and present antigens for the adaptive immune response. Macrophages present antigens on their cell surface, they are known as antigen presenting cells (APCs). These antigens are then recognized by effector cells (B cells and T cells). Macrophages also bear CD14 (and LPS receptor), CD11b/CD18 complex (binds C3b and C4b, complement byproducts), scavenger receptor (binds sialic acid), TLR and F(c)R. F(c)R binds antigen-antibody complexes, absorbs them, degrades them in the lysosome and then presents the fragments on the cell surface. | ||||||||||||||||||
| Adaptive Immunity | Adaptive immunity is triggered when an infection eludes innate defenses and generates a threshold of antigen. Acquired immunity is effective only after several days, the time required for antigen-specific T and B cells to proliferate and differentiate into effector cells. See more at the acquired immunity overview. | ||||||||||||||||||
| T Cells | T cells do not recognize antigens floating in solution. They only recognize antigens presented by antigen-presenting cells. There are two kinds of T cells: CD4 T cells (aka helper T cells or TH cells) which respond to Class II MHC; and CD8 T cells (aka cytotoxic T cells or TC cells) which respond to Class I MHC. CD4 T cells are split into T11, TH2 and the poorly-understood TH17. CD4 cells play important roles in B cell activation and release lots of cytokines. CD8 T cells do not release as many cytokines, but eliminate virally infected and cancer cells, and are important for autograft rejection. Remember that CTL activity only occurs with TH help. | ||||||||||||||||||
| T1 vs TH2 | Naïve CD4 T cells activated in presence of IL-12 and IFN-γ are committed to TH1 lineage. Naïve CD4 T cells activated in presence of IL-4 (and especially if IL-6 is also present) are committed to TH2 lineage. These cytokines are secreted by the cells which respond appropriately to a given pathogen. TH1 and TH2 cells amplify their own populations. TH1 cells secrete IFN-γ, inhibiting TH2 proliferation. TH2 cells secrete IL-10 and TGF-β, inhibiting activation and growth of TH1 cells. | ||||||||||||||||||
| MHC Restriction | T cells only respond to self MHC molecules. MHC restriction occurs via negative selection, which is controlled by thymic dendritic cells (aka thymic stromal cells). Thymic dendritic cells are derived from bone marrow — thus, an irradiated mouse with transplanted bone marrow will tolerate the same MHC haplotypes as the donor. If the recipient mouse is MHCaa and the donor is MHCab, then the recipient mouse will then have T cells which react to MHCa and MHCb. The MHCa-reactive T cells which function normally, while the others will never be activated. However, if the recipient mouse is MHCaa and the donor is MHCbb, then then there will be no MHCa-reactive T cells in the periphery. This means there will be no T cells able to react with self MHC molecules, and the recipient will almost entirely lack an immune system. | ||||||||||||||||||
| Protective Immunity | Immunity from reinfection relies upon antibodies and armed effector T cells. Specific IgA on epithelial surfaces can neutralize a virus before it ever even enters the body. Memory B cells are responsible for antibody secretion in response to reinfection — the secondary humoral response. Compared to a response to initial infection, the 2° humoral response is characterized by a quick response of larger magnitude, with secretion of higher-affinity antibodies of different isotypes (more IgG, instead of IgM), and higher Class II MHC levels. These changes facilitate antigen uptake and presentation, allowing memory B cells interact with armed TH cells at lower antigen doses. Memory T cells are express activated cell markers (like CD44) but the CD45 isotype is different — CD45RA on naïve T cells and CD45RO on memory cells. | ||||||||||||||||||
| Tolerance | There are three mechanisms to ensure tolerance, which is selective negative immunity against self: clonal deletion, loss of certain antigen-specific cells in primary lymphoid tissues; clonal anergy, slowly-reversible induced unresponsiveness of cell population; clonal suppression, which is undone if the suppressor is removed. Clonal deletion occurs in the thymus for T cells — positive selection (kill if bind MHC too strong) on host thymic epithelium and negative selection (kill if self-reactive) on donor-derived dendritic cells. Reactivity to non-thymic self-antigens avoided via clonal anergy, which occurs when the thymocyte binds antigen (signal 1) but is no co-stimulated (signal 2). | ||||||||||||||||||
| F(ab) | The fragment antigen binding (Fab fragment) is a region on an antibody which binds to antigens. The Fab fragment is monovalent and hence would not be able to crosslink the FcεRI receptors. Crosslinking is a prerequisite for degranulation. Compare to F(c). | ||||||||||||||||||
| MHC | Class I = CD8 CTLs; Class II = CD4 THs | ||||||||||||||||||
| Lysosome | Lysosomes degrade ingested particles, sometimes presenting them via Class II MHC expression. Acidifying the lysosome renders it non-functional. | ||||||||||||||||||
| Proteaosome | Proteaosomes degrade intracellular proteins — the degraded peptides can be used for Class I MHC expression. | ||||||||||||||||||
Organs & Locations |
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| Bone Marrow | Site of B cell and macrophage maturation. | ||||||||||||||||||
| Lymph Node | B cell activation by antigens drained from tissue spaces. | ||||||||||||||||||
| Spleen | Blood-borne antigens are presented to B cells. B cell activation takes place in the spleen. | ||||||||||||||||||
Cytokines (aka monokines or lymphokines) are regulatory proteins which bind specific receptors and have pleiotropic (multiple) or redundant functions. Cytokines are important for: activation, such as stimulation proliferation of activated T cells; recruitment signals, such as brining cells to sites of inflammation; and differentiation, such as of lymphocytes in the thymus and bone marrow. There are three pathways in which cytokines operate: autocrine, where cells self-stimulate; paracrine, where cells interact with nearby cells; endocrine, where cells circulate to interact with far-away tissues.
Some cytokines are classified as chemokines. A chemokine is a small peptide released in response to injury or infection, with similarities to the antigen-binding domains of the major histocompatibility complex. Chemokines are released by macrophages, endothelial cells, keratinocytes, smooth muscle and T cells.
There are two kinds of chemokines: α chemokines, with a region bearing contiguous cysteins; and β chemokines, with conserved cysteins separated by another amino acid. α chemokines include MCAF, RANTES and MIP-1β β chemokines include IL-8 and SDF-1.
Phagocytic cells and T cells migrate towards concentrations of chemokines, following a chemokine gradient. Also, certain chemokines have multiple roles in fetal development. In addition, chemokine receptors for RANTES, MIP-1&alpha, MIP-1β and SDF-1 are accessory receptors for entry of HIV into a cell.
| Cytokine | Produced By | Immunity | Overview |
| Interleukin 1 (IL-1) | Mφs, DCs & B Cells | Innate | A lymphocyte activator, IL-1 is an endogenous pyrogen (causing fever) which works on TH and B cells to: co-stimulate activation, promoting response to antigens; stimulate differentiation and clonal expansion; and stimulate endothelial expression of adhesion molecules. |
| Interleukin 2 (IL-2) | TH1 Cells | Adaptive | A lymphocyte activator, IL-2 is a (sometimes autocrine) stimulator of natural killer cell and activated T cell proliferation. |
| Interleukin 3 (IL-3) | Eosinophil maturation, activation and proliferation. Granulocyte and macrophage proliferation and colonies. | ||
| Interleukin 4 (IL-4) | TH2 & Mast Cells | Adaptive | A macrophage activator, IL-4 stimulates phagocytic activity and MHC class II gene expression. IL-4 stimulates isotype switching by activating the promoters for Iε, and Iγ1 (the I regions for ε and γ1 heavy chain constant region genes). IL-4 is pivotal in regulating the IgE response: IgG1 and IgE account ∼2% of all antibodies secreted by splenic B cells incubated with LPS; IgG1 accounts for ∼50% and IgE accounts for ∼20% of all antibodies secreted by B cells incubated with LPS and IL-4. IL-4 knockout mice cannot mount an IgE response to parasites. Also, CD4 T cells activated in presence of IL-4 develop into TH2 cells (especially if IL-6 is also present); IL-4 and IL-10 both inhibit T cell differentiation into TH1 cells. |
| Interleukin 5 (IL-5) | TH2 Cells | Adaptive | Eosinophil maturation, activation and generation. |
| Interleukin 6 (IL-6) | Adaptive | CD4 T cells activated in presence of IL-4 develop into TH2 cells (especially if IL-6 is also present); IL-4 and IL-10 both inhibit CD4 T cell differentiation into TH1 cells. | |
| Interleukin 8 (IL-8) | An inflammatory cytokine, IL-8 stimulates inflammation and has a key role in cell migration. IL-8 alters adhesion molecules on monocytes, increasing their affinity for the endothelial adhesion protein ICAM-1. Binding to ICAM-1 helps monocytes migrate through tissues to the site of infection. | ||
| Interleukin 10 (IL-10) | TH2 Cells | A macrophage activator, IL-10 inhibits cytokine production and down-regulates MHC class II gene expression. IL-4, IL-10 and TGF-β all inhibit CD4 T cell differentiation into TH1 cells. | |
| Interleukin 12 (IL-12) | Macrophages & DCs | Innate | CD4 T cells differentiate into TH1 cells in presence of IL-12 and IFN-γ (also, IFN-γ inhibits CD4 T cell differentiation into TH2 cells). IL-12 and IFN-γ are produced by macrophages and NK cells. |
| Interleukin 13 (IL-13) | Like IL-4, IL-13 stimulates IgE production. | ||
| Interferon Alpha | Granulocytes | Innate | Interferon Alphas (IFNα) are a family of 14 closely related small proteins synthesized by granulocytes in response to a viral infection. |
| Interferon Beta | Fibroblasts & others | Innate | Interferon Betas (IFNβ) are produced by most cells of the body in response to double-stranded RNA (dsRNA indicates that a virus is present). IFNβ activates endoribonuclease (which cleaves viral RNA) and proteins inhibiting translation (thus stopping viral replication). Also, IFN-β promotes isotype switching to IgA by activating the promoter for Iα and Iγ2b (the I regions for the the IgA and IgG2b heavy chain constant region genes). |
| Interferon Gamma | TH1, CD8+ & NKs | Adaptive | Interferon Gammas (IFNγ) activate macrophages, and increase antigen presentation by stimulating expression of Class I and II MHC molecules. IFN-γ also activates isotype switching to IgG2a by activating the promoter for Iγ2a (the I region for the IgG2a heavy chain constant region gene). In addition, CD4 T cells differentiate into TH1 cells in presence of IL-12 and IFN-γ — also, IFN-γ inhibits CD4 T cell differentiation into TH2 cells, so TH1 activation amplifies itself. IL-12 and IFN-γ are produced by macrophages and NK cells, and are both absolutely critical for clearing intracellular infections (knockouts for either die from intracellular infections). IFN-γ inhibits the DNA rearrangement required to isotype switch to IgE. |
| MCAF | Macrophage chemoattractant and activating factor (MCAF) is self-explanatory. | ||
| MIP-1β | Macrophages Fibroblasts |
MIP-1β is a chemoattractant for CD8+ cells. | |
| RANTES | T cells | RANTES attracts memory CD4+ cells (aka TH cells or helper T cells). | |
| SDF-1 | Attracts cells to stromal elements. | ||
| TGF-β | Adaptive | Transforming Growth Factor Beta (TGF-β) inhibits B and T cell proliferation, and T cell and macrophage function. Along with IL-10, TGF-β inhibits activation and growth of TH1 cells — since IL-10 and TGF-β are secreted by TH2 cells, this aids amplification of TH2 cell populations. | |
| TNF-α | Innate | An inflammatory cytokine along with IL-8, tumor necrosis factor alpha (TNF-α, aka cachectin) stimulates: inflammation (heat, swelling, immunoglobulin accumulation, complement, capillary permeability and capillary widening); and expression of genes encoding adhesion molecules (thus helping recruit immune system cells to the site of inflammation). | |
| Erythropoietin | Erythropoietin induces differentiation of hematopoietic cells toward red blood cells. | ||
| G-CSF | G-CSF induces formation of granulocyte colonies. | ||
| M-CSF | TH1 & TH2 Cells | M-CSF induces formation of macrophage colonies. | |
| GM-CSF | GM-CSF induces formation of granulocyte and macrophage colonies. |
| Next Steps | Please study cytokine receptors. |
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| CD | Overview |
| CD1 | Human CD1 is encoded by five non-polymorphic and closely linked (very near each other) genes on Chromosome 1. These genes — CdD1a,b,c,d,e — have an intron/exon structure similar to MHC Class I genes and encode proteins homologous (similar) to MHC Class I and MHC Class II proteins. However, CD1 proteins are able to present non-peptide antigens to T cells, including mycobacterial cell wall lipids & glycolipids with hydrophobic lipid tails and hydrophilic heads. CD1 has a very narrow and hydrophobic binding pocket, thus suggesting that the lipid actually nestles within the pocket with just its hydrophilic head exposed. T cells specific for that hydrophilic end then bind the CD1-antigen complex, similar to T cell binding of the peptide-MHC complex. |
| CD3 | Present on all T cells. Necessary for TCR signal transduction and surface presentation. CD3 is a multicomponent signal-transducing complex accompanying the T cell receptor with function similar to the Ig-α/Ig-β B cell receptor complex. It is a complex of five invariant polypeptide chains which associate to form three dimers: a γε (gamma-epsilon) heterodimer; a δε (delta-epsilon) heterodimer; and a ζζ (zeta-zeta) homodimer or a ζη (zeta-eta) heterodimer. The ζ and η chains are encoded by the same gene, but differ at their carboxyl-terminal ends due to alternative RNA splicing.
Part of the immunoglobulin superfamily, the γ, δ and ε chains contain extracellular, transmembrane and cytoplasmic domains. The ζ chain is distinct, with shorter extracellular and longer cytoplasmic domains. All CD3 chains contain a negatively charged amino acid (aspartic or glutamic acid) which interacts with one or two positively charged transmembrane TCR residues. CD3 chains have an immunoreceptor tyrosine-based activation motif (ITAM) located in their cytoplasmic tail. Also found on the Ig-α/Ig-β heterodimer of the B cell receptor complex and IgE and IgG F(c) receptors, ITAMs interact with tyrosine kinases and are critical for signal transduction. In CD3, the γ, δ and ε chains each contain a single ITAM, while ζ and η chains contain three ITAMs. |
| CD4 | CD4 binds to Class II MHC molecules, and is a 55kD monomeric membrane glycoprotein containing: four extracellular immunoglobulin-like domains (D1, D2, D3 and D4); a hydrophobic transmembrane region; and a long cytoplasmic tail containing three serine residues that can be phosphorylated. Like CD8, the extracellular domain of CD4 binds to the conserved regions of MHC molecules on antigen-presenting cells. The membrane-distal domain (furthest from the membrane) of CD4 binds Class II MHC molecules at a hydrophobic pocket formed by the α2 and β2 domains. |
| CD5 | CD5 is a marker typically found on T cells, but also present on B-1 cells (not B-2 cells, aka conventional B cells). |
| CD8 | CD8 binds to Class I MHC molecules, and is usually a disulfide-linked αβ heterodimer or αα homodimer. The α and β chains are both 30-38kD glycoproteins with: an extracellular immunoglobulin-like domain; a stalk; a hydrophobic transmembrane region; and a cytoplasmic tail of 25 to 27 residues, several of which can be phosphorylated. Like CD4, the extracellular domain of CD8 binds to the conserved regions of MHC molecules on antigen-presenting cells. CD8 binds to Class I α2 and α3 domains, and interacts somewhat with β2-microglobulin. Upon binding CD8, the Class I α3 domain changes slightly; only a single CD8 can bind a Class I MHC molecule at a time. |
| CD11 | See CD18 |
| CD16 | An F(c)γ receptor, CD16 stimulates binding and uptake of antigens for antigen presentation. |
| CD18 | Integrins are heterodimeric, composed of a CD18 β subunit bound to a CD11a, b or c α subunit. The three integrins are: LFA-1 (CD18/CD11a), essential for adherence of T cells to APCs for T cell activation; macrophage-1 antigen (CD18/CD11b), aka integrin αMβ2, a receptor of complement byproducts on macrophages; and integrin αxβ2 (CD18/CD11c), also a complement receptor. |
| CD19 | Part of B cell coreceptor, with a long cytoplasmic tail with docking sites. Other components of the B cell coreceptor are CD21 and CD81. |
| CD21 | Aka CR2, CD21 is part of B-cell coreceptor and binds C3d, a byproduct of complement. Since B cells are part of acquired immunity and complement is part of innate immunity, this is an example of different branches of the immune system interacting together. Other components of the B cell coreceptor are CD19 and CD81. |
| CD22 | Present on the membrane of resting B cells, CD22 delivers a negative signal that makes activation of B cells more difficult. |
| CD23 | CD23, aka F(c)εRII, binds Ige. |
| CD24 | A molecule known as heat stable antigen (HSA). |
| CD25 | The α chain of the IL-2 receptor, present on pre-B cells. |
| CD28 | A co-receptor of the T cell receptor. Important for T cell activation. |
| CD32 | An F(c)γ receptor, CD16 stimulates binding and uptake of antigens for antigen presentation. |
| CD34 | Present on about 1% of hematopoietic stem cells. Not unique to stem cells, but irradiated mice (completely lacking stem cells) inoculated with an enriched population of CD34+ cells can restore hematopoiesis. |
| CD40 | A molecule on the surface of B cells which binds CD154 (aka CD40L) on the TH cell surface. CD40 is involved in the formation of a T-B conjugate. Also, CD40 is a tumor necrosis factor — a family of cell surface proteins and cytokines which regulate cell proliferation and apoptosis. Its ligand, CD40L (CD154) belongs to the TNF receptor (TNFR) family. CD40 binding to T cell CD40L is necessary for immunoglobulin gene rearrangement for a functional antibody. |
| CD40L | See CD154 |
| CD43 | Leukosialin. Only expressed on pro-B cells. |
| CD45R | Aka B220, CD45R is a protein tyrosine phosphatase found on leukocytes. As a marker unique to B cells, B220+ cells are usually assumed to be B cells. |
| CD64 | An F(c)γ receptor, CD16 stimulates binding and uptake of antigens for antigen presentation. |
| CD80 | Also known as B7-1, CD80 is a principal costimulatory molecule present on antigen presenting cells. |
| CD81 | Also known as TAPA-1, CD81 is part of the B cell coreceptor. Other components of the B cell coreceptor are CD19 and CD21. |
| CD86 | Also known as B7-2, CD86 is a principal costimulatory molecule present on antigen presenting cells. |
| CD152 | Also known as CTLA-4. |
| CD154 | Expressed on the activated TH cell membrane, CD154 (aka CD40L) is a tumor necrosis factor receptor (TNFR) protein which binds CD40 (a tumor necrosis factor) on the surface of B cells. Involved in the formation of a T-B conjugate. Toger with AID, induces isotype switching. B cell CD40 binding to T cell CD40L is necessary for immunoglobulin gene rearrangement for a functional antibody. |
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