Immunology

antigen

An antigen is any molecule that stimulates an immune response. Most antigens are proteins or polysaccharides, though small molecules coupled to carrier proteins (haptens) can also be antigenic. The segment of an antigenic molecule to which its cognate antibody binds is termed an epitope or antigenic determinant.

allergen : allergic reactions : antigenic determinant : autoantigenic : autoimmune disorders : class I histocompatibility molecule (MHC I) : class II histocompatibility molecule (MHC II) : immunogen : endogenous : epitope : exogenous : lipid Ag : pathogen-associated molecular pattern (PAMP) : pattern-recognition receptor (PRR) : polysaccharide Ag : T-dependent : T-independent : tolerogen : Toll-like receptor (TLR) : tumor antigens : tumor-associated antigen (TAA) : tumor-specific antigen (TSA) ▼

Antigens are classified by immune activity as immunogens, tolerogens, or allergens according to whether the molecule in question activates the immune response, is tolerated by the immune system, or elicits an allergic response, respectively. Allergic reactions are exaggerated immune responses to molecules (allergens) that would otherwise not prove harmful. Antigens may also be classified according to their source as exogenous, endogenous, autoantigenic, or tumor antigens.

Exogenous antigens are foreign molecules that are ingested (endo-, phagocytosis) by antigen presenting cells on which the fragmented and extruded antigens are then carried on class II histocompatibility molecules (MHC II) for presentation to CD4+ Th cells. Pathogen-associated molecular patterns (PAMPs ) are small molecular sequences consistently found on pathogens that are recognized by Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs). Pattern recognition receptors (PRR) are a class of innate immune response-expressed protein receptors that respond to PAMPs.

Endogenous antigens are internally generated molecules that become presented on the cell surface in the complex with class I histocompatibility molecules (MHC I). Endogenous antigens may result from exogeneous viral or bacterial infections that have altered the host cell.

In autoimmune disorders, endogenous, self-molecules induce autimmune attack by CD8+ Tc/CTLs that have escaped negative selection in the thymus.

Tumor-specific antigens (TSAs) typically result from a tumor specific mutation and are targetted for non-self attack when displayed on class I histocompatibility molecules. Tumor-associated antigens (TAAs) are more common than TSAs, and are presented both by tumor cells and by normal cells. Tumor antigens may elicit targetting by CTLs before the tumor cells can successfully proliferate and metastasize. Unfortunately, tumors employ a variety of mechanisms to evade the immune system.

Protein antigens are T dependent in that they require T cell co-operation to induce antibody responses in B cells. Non-protein antigens, such as polysaccharides and lipids can elicit T-independent antibody responses. Such T-independent antigens are typically polymeric, so it is believed that they are able to cross-link BCR-surface-Ig sufficiently strongly to activate B cells without T cell costimulation. These T-independent polymeric antigens elicit IgM antibodies and do not demonstrate affinity maturation. However, a subclass of T cells are specialized to present lipid and glycolipid antigens – γδ T cells recognize foreign nonpeptide antigens presented by CD1 proteins, which are MHC-like-molecules specialized for the presentation of lipids.

ф activation ф anergy ф antibodies ф antigen presenting cells (APCs) ф autoimmunity ф basophils ¤ cancercell-cycle control ф class-switch recombination ф clonal selection ф dendritic cells o-o endogenous vs exogenous ф eosinophils ф granulocytes ~ growth factors ф immune cytokines ф immune response ф immune tolerance ф inflammatory response ф interferons ф isotype switching ф leukocytes ф lymphocytes ф lymphokines ф lymphoid system ф macrophages ф MHC ф monocytes ф pathogens ф pattern-recognition receptors ф phagocyte ф plasma cells ¤ proliferation ф receptorsregulation of gene expression ф secondary antibody diversification ф signaling ф surface receptors ф vaccines

Tables  Fc receptors  Immune Cytokines  Immunoglobulins  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers 

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dendritic cells

Dendritic cells and their immature counterparts, Langerhans cells (LC), are highly specialized, professional antigen-presenting cells (APC) located in the skin, mucosa, and lymphoid tissues.

adhesion : APC activities : clonal expansion B cells : cytokines : DC types : disorders : ectopic FDC-formation : follicular dendritic cells (FDC) : FDC networks : generating germinal centers : germinal centers : immature dendritic cells : immune regulators : immunological synapse : interferon producing cells : lymphoid dendritic cells : maturation : morphology : myeloid dendritic cells : pDC : plasmacytoid dendritic cells (PDC, IPC) : precursor dendritic cells : regulators : Th1 and Th2 stimulation : TLRs : types of DC : veiled cells

Immune dendritic cells are named for their morphology (long surface projections), and bear no relationship to neurons. Immature dendritic cells are also called 'veiled cells' because they display large cytoplasmic 'veils' rather than dendrites. DC and LC play a key role in the induction phase of contact allergenicity.

As key regulators of immune responses, dendritic cells (DC) stimulate lymphocytes to perform cell-mediated and humoral immune responses against pathogens and tumor cells. DCs can also educate T cells to tolerate self-antigens, thereby minimizing autoimmune reactions.

Types of dendritic cell
follicular dendritic cells (origin?) – FDC
lymphoid dendritic cells (lymphopoiesis) –
myeloid dendritic cells (monocytopoiesis) – MDC1, MDC2
plasmacytoid dendritic cells – PDC, IPC – the major producers of type I interferon (IFN)

Immature, precursor dendritic cells (pDC) circulate throughout the body, migrating to lymphocyte rich tissues (such as spleen and lymph nodes) upon stimulating encounter with antigen. The dendritic cells internalize the antigen, then digest, and externalize the fragmented antigen that they present to lymphocytes in MHC-peptide complexes, expressing markers that stimulate lymphocyte activation. Dendritic cells are the most effective antigen presenting cells. Follicular dendritic cells stimulate differentiation of B cells, monocytopoietic lineages (pDC1) stimulate differentiation of Th1 cells, lymphopoietic dendritic cells (pDC2) induce differentiation of Th2 cells. Plasmacytoid cells produce type 1 interferon (IFN-α, β, Ω) and can mature into dendritic cells that link innate and adaptive immune responses.

A variety of factors operate in antigen recognition and processing by immature (precursor) dendritic cells and in the maturation of immature cells. Toll-like receptors on the surfaces of precurson dendritic cells recognize microbial components and induce the differentiation of dendritic cell precursors. GM-CSF and IL-4 stimulate the maturation of monocytopoietic pDC1, while IL-3 stimulates the differentiation of pDC2. The transition to mature dendritic cells down-regulates those factors that were involved in antigen internalization, while up-regulating the expression of MHC, costimulatory molecules that participate in lymphocyte activation, adhesion molecules, and specific cytokines and chemokines.

Adhesion molecules enhance direct interactions between T cells and dendritic cells (immunological synapse). Dendritic cell stimulation of formation of Th1 and Th2 cells appears to be regulated by negative feedback. Th1 production of interferon-γ blocks the further stimulation of Th1 differentiation by DC1 cells. Th2 production of IL-4 kills the dendritic cell precursors that contribute to Th2 cell creation. Thus, although IL-4 stimulates Th2 differentiation, the promotion of Th2 cell formation by DC2 cells does not appear to involve IL-4. Costimulatory receptors CD80 and CD86 expressed by mature dendritic cells activate T cells in concert with the recognition of antigen/MHC by the T cell receptor. The secretion of IL-12 by dendritic cells stimulates T cell responses, in particular the differentiation of Th1 cells, which produce interferon-γ and other inflammatory cytokines.

Follicular dendritic cells are stromal cells unique to primary and secondary lymphoid follicles. FDCs express all three types of complement receptors as well as Ig-Fc receptors, through which antigen-antibody immune complexes are retained. FDCs present native antigens to potential memory B cells, of which only those coated with high affinity B cell receptors (BCR) are able to bind.

Recirculating resting B cells migrate through the FDC networks. Antigen-activated B cells undergo clonal expansion within the FDC networks in a T cell-dependent fashion, generating germinal centers. Evidence suggests the presence of two types of dendritic cells within human germinal centers: (i) the classic FDCs that express DRC-1, KiM4, and 7D6 antigens represent stromal cells; and (ii) the newly identified CD3-CD4-CD11c- germinal center dendritic cells (GCDC) represent hematopoietic cells that may be analogous to antigen-transporting cells of mice.

Within germinal centers, B cells undergo somatic hypermutation, positive and negative clonal selection, isotype switching and differentiation into high-affinity plasma cells and memory B cells. Adhesion between FDCs and B cells is mediated by ICAM-1 (CD54)-LFA-1(CD11a) and VCAM-VLA-4. T cells may interact with FDCs in a CD40/CD40-ligand-dependent fashion.

Ectopic FDC-formation is found in a number of autoimmune diseases and/or chronic inflammatory situations, suggesting that FDC development is not restricted to secondary lymphoid organs, but rather that local conditions drives a precursor cell type into FDC-maturation. The precursor of FDCs has presently not been identified, but data suggests a close relation to fibroblast-like cells. [s] It was initially believed that all DCs were of myeloid origin until several recent studies demonstrated that some DCs could also be efficiently generated from lymphoid-restricted precursors. FDCs appear to be involved in the growth of follicular lymphomas and in the pathogenesis of HIV infection.[pm]

Lymphoid dendritic cells are of lymphopoietic origin, and IL-3 stimulates the differentiation of pDC2 cells into DC2 cells, which stimulates differentiation of Th2 cells, which secrete the lymphokine interleukins 4, 5, 10, and 13. (IL-4, IL-5, IL-10, IL-13)

Myeloid dendritic cells are of monocytopoietic origin, and the maturation of precursor cells (pDC1) is stimulated by GM-CSF, and IL-4. Mature DC1 cells secrete interleukin 12 (IL-12), which acts through the JAK-STAT pathway to induce Th1 cells to secrete TNF-β (lymphotoxin) and IFN-γ. MDC-1 is the more common subtype, and is a major stimulator of Th1 cell differentiation. MDC-2 is rare, and may function in response to wound infection.

Plasmacytoid dendritic cells (pDC=IPC) are the major producers of type I interferon (IFN) and exhibit the unique ability to link innate and adaptive immune responses, by differentiating into DC capable of stimulating naive T cells and modulating the adaptive immune response. Human plasmacytoid DCs (PDCs) can induce either Th1- or Th2-type immune responses upon exposure to viruses or IL-3, respectively.

Plasmacytoid dendritic cell precursors (pDC) are type 1 interferon-(α, β, Ω)-producing cells (IPCs) that comprise 0.2%-0.8% of peripheral blood mononuclear cells (humans, mice). IPCs display plasma cell morphology, selectively express Toll-like receptor (TLR)-7 and TLR9, and rapidly secrete massive amounts of type 1 interferon following viral stimulation. IPCs promote the function of natural killer cells, B cells, T cells, and myeloid DCs through type 1 interferons (IFN) during an antiviral immune response. Later in viral infection, IPCs differentiate into a unique type of mature dendritic cell, which directly regulates the function of T cells and thus links innate and adaptive immune responses. [s, ] [fft]

images [] sem dendritic cell and T cell [] micrograph Langerhans cells [] PKC bII signaling in dendritic cells [] micrograph gallery dendritic cells [] photomicrograph dendritic cells interacting with yeast (lilac) [] photomicrograph Human Dendritic cell (labelled with anti MHC class-I FITC) presenting Influenza antigens to T-lymphocytes.
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ф activation ф affinity maturation ф anergy ф antibodies ф antigen ф APCs ф autoimmunity ф B cells ф bloodbone marrow ф CD ф cellular response ф class-switch recombination ф clonal selection ф complement system ф costimulation ф helper T cell ф hematopoiesis ф humoral immunity ф immune cytokines ф immune response ф immune tolerance ф inflammatory response ф interferons ф isotype switching ф killer T cells ф lymphocytes ф lymphokines ф lymphoid system ф lymphopoiesis ф macrophages ф MHC ф monocytopoiesis ф pattern-recognition receptors ф phagocyte ф plasma cells ф receptors ф signaling ф somatic hypermutation ф surface receptors ф T cells ф thymus

Tables  Complement Receptors  Cytokines  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors

IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. [Annu Rev Immunol. 2005]
Plasmacytoid dendritic cell precursors/type I interferon-producing cells sense viral infection by Toll-like receptor (TLR) 7 and TLR9. [Springer Semin Immunopathol. 2005] PMID: 15592841 [Free Full Text]
Natural type I interferon-producing cells as a link between innate and adaptive immunity. [Hum Immunol. 2002] PMID: 12480256
Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. [Blood. 2004] PMID: 14670916
Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. [J Exp Med. 2003] PMID: 12515817
Roles of toll-like receptors in natural interferon-producing cells as sensors in immune surveillance. [Hum Immunol. 2002]

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pattern-recognition receptors

Pattern recognition receptors (PRR) are a class of innate immune response-expressed proteins that respond to pathogen-associated molecular patterns (PAMP) and endogenous stress signals termed danger-associated molecular patterns (DAMP).

adaptive : adaptor proteins : alarmins : CARD domain : CATERPILLER : collectin : complement receptors : damage-associated molecular patterns : DAMP : helicases : innate : LGP2 : lipid transferases : Mal : Mda5 : multicellular animals : MyD88 : NALP : NLR : NOD : PAMP : pathogen-associated molecular patterns : pattern recognition receptors : pentraxin : PGR : plant R : PRR : RIG-I : RNA helicases : SARM : SARM action : TIR : TLR : TLR-1 : TLR-3 : Toll-like receptors : TRAM : TRIF

Adaptive immunity employs clonally distributed B and T lymphocytes that are coated by millions of lymphoid cell-surface receptors, which are generated by complex VDJ recombination rearrangements so as to specifically recognize an enormous variety of antigens (specificity and memory). Evolutionarily more ancient, the innate immune system relies on a much smaller number of receptors, called pattern recognition receptors (PRRs).

Multicellular animals employ pattern recognition receptors to recognize pathogen-associated molecular patterns (PAMPs) in order to detect pathogens. However, cellular stressors are another causative agent of cell and tissue damage. Cells recognize both stressors and their associated tissue damage via receptor-mediated detection of intracellular proteins ("alarmins") released by the lysed cells.

Pattern recognition receptors (PRR) are a class of innate immune response-expressed proteins that respond to pathogen-associated molecular patterns (PAMP) and endogenous stress signals termed danger-associated molecular patterns (DAMP). The evolutionarily more recent adaptive immune response employs diverse surface receptors that display decremental binding affinities for epitope stimuli.

Pattern recognition receptors (PRRs) include:
Membrane-associated PRR
_____Toll-like receptors (TLR) sense pathogen-associated or danger-associated molecular patterns extracellularly or in endosomes and receptors may link innate and adaptive immune responses (Drosophila signaling Fig).
Cytoplasmic PRR of the CATERPILLER family (also known as NACHT–leucine-rich repeat (NLR) proteins):
_____ ● Nucleotide-binding oligomerization domain proteins (NODs) recognize intracellular MDP (muramyl dipeptide) and transduce signals via NF-κB and MAP kinase pathways through the serine/threonine kinase RIP2. The nucleotide-binding oligomerization domain binds nucleotide triphosphate. NODs signal via N-terminal caspase recruitment (CARD) domains to activate downstream gene induction events.
_____ ● Pyrin domain–containing proteins (NALPs) contain contain a nucleotide binding site (NBS) for nucleotide triphosphates plus C-terminal leucine-rich repeats (LRRs), which appear to act as a regulatory domain and may be involved in the recognition of microbial pathogens. NALPs appear to recognize endogenous or microbial molecules or stress responses and to form oligomers with caspase-1, which cleave IL-1 into its active form.
_____RNA helicasesLGP2 acts as a dominant-negative inhibitor, and RIG-I and Mda5 activate antiviral signaling. These RNA Helicases recruit factors via twin N-terminal CARD domains, activate antiviral gene programs.
_____ ● plant R proteins that share structural and functional similarity with PRRs found in higher animals.
Secreted PRR
_____Complement receptors
_____Collectins
_____Pentraxin proteins, such as serum amyloid P component (SAP), acute-phase C-reactive protein (CRP), cytokine-modulated PTX3 . Pentraxins utilize calcium dependant ligand binding and display a distinctive flattened β-jellyroll structure comprising five monomers with radial symmetry that form a ring approximately 95Å across and 35Å deep.
_____Lipid transferases
_____Peptidoglycan recognition proteins (PGRs) are most critical for insect immunity, and are less well characterized in mammals.

PAMPs are small molecular sequences consistently found on pathogens that are recognized by Toll-like receptors (TLRs) and other pattern recognition receptors (PRRs). PAMPs include bacterial lipopolysaccharide "endotoxin" (LPS→TLR4), bacterial flagellin, lipoteichoic acid, lipoproteins and peptidoglycan (→TLR1,-2,-6), mannose residues, N-formylmethionine, fungal glucans, endogenous heat shock proteins, extracellular matrix molecules, and nucleic acid variants associated with viruses (vRNA→TLR3, unmethylated cytosin-guanosin dinucleotide (CpG islands)→TLR9, dsRNA) and bacteria (bacterial DNA, unmethylated cytosin-guanosin dinucleotide (CpG)→TLR9).

DAMPs – Effector cells of innate and adaptive immunity employ nonclassical pathways to secrete alarmins when they are activated by PAMPs or other alarmins. Endogenous alarmins and exogenous PAMPs therefore elicit similar responses, and can be considered subgroups of a larger set, the damage-associated molecular patterns (DAMPs).

Toll-like receptors (TLRs) appear to be one of the most ancient, conserved components of the immune system, and are the basic signaling receptors of the innate immune system. TLRs (TLR1-TLR11) show homology with the Drosophila Toll protein and the human interleukin-1 receptor family, and are transmembrane proteins that recognize extracellular or endosomal pathogen-associated molecular patterns. The TLR family is characterized by the presence of leucine-rich repeats, which mediate ligand binding, and the Toll/interleukin-1 receptor-like domain (TIR), which mediate interaction with intracellular signaling proteins. TLRs function as homo- and heterodimers with different ligand-binding specificity, and rely upon TIR co-receptors for effective ligand sensitivity. Thus, the specificity of Toll-like receptor signaling is due to adaptor proteins containing Toll–interleukin 1 receptor (TIR) domains. Five TIR adaptors display activating functions: MyD88, Mal, TRIF, TRAM, and SARM. The adaptor proteins activate intracellular molecules, including protein kinases (IRAK1, IRAK4, TBK1, and IKKi) that amplify the signal, ultimately inducting or suppressing genes that orchestrate the inflammatory response. Thousands of genes are thus activated by TLR signaling, making TLRs one of the most important gateways for gene modulation.

TLRs are activated by molecules associated with pathogens (PAMPs) or with injured host cells/tissue (DAMPs). Most identified TLR ligands are either conserved microbial products that signal the presence of an infection, or endogenous ligands resulting from other danger conditions. TLRs trigger signals evoking synthesis and secretion of cytokines and activation of host defenses through NF-κB, MAP kinases, and costimulatory molecules.

To avoid excessive inflammatory responses, TLR signalling must be tightly regulated. MAPK phosphatase 1 (MKP1) is a key negative regulator of Toll-like receptor (TLR)-induced inflammation in vivo. Phosphorylation of MAPK p38 — which is associated with the modulation of cytokine production — is considerably increased and prolonged in the absence of MKP1. [MKP1]
Table  Toll-like Receptors

Toll-like receptor-1 (TLR-1) displays homology to the receptor for interleukin-1 (IL-1) by virtue of similar cytoplasmic portions.

Toll-like receptor–3 (TLR-3) responds to double-stranded (ds) RNA, which is a viral replication intermediary for many viruses. TLR-3 activation transduces its signal into an intracellular transduction pathway, leading to activation of JNK, p38 MAPK, and NF-κB.

NF-κBs, Nuclear Factor kappa Bs, are ubiquitous transcription factors involved in responses to cellular stressors such as cytokines, bacterial antigens, and viral antigens. Free NF-κB translocates to the nucleus where it binds to specific κB sequences in DNA, initiating transcription of related genes, including those for immunoreceptors, cytokines, and its own inhibitor, IκB. Inhibitor of kappa B (IκB, IkappaBalpha) inactivates NF-κB by sequestering NF-κB dimers within the cytoplasm. Physiological activities mediated by NF-κB include cellular proliferation, and inflammatory, immune, and cellular survival responses.
[] signaling pathways []

The specificity of Toll-like receptor signaling is due to adaptor proteins containing Toll–interleukin 1 receptor (TIR) domains. Five TIR adaptors display activating functions: MyD88, Mal, TRIF, TRAM, and SARM.

SARM is a negative regulator of TRIF-dependent Toll-like receptor signaling, which blocks gene induction 'downstream' of TRIF but not of MyD88. The association fo SARM with TRIF, and the 'knockdown' of endogenous SARM expression by interfering RNA leads to enhanced TRIF-dependent cytokine and chemokine induction.[r]

adaptive ф adaptive : adaptor proteins § adaptor protein : alarmins : allograft rejection : CARD domain § CARD domains : CATERPILLER ~ cellular stress response ~ chemokine : collectin : complement receptors ф complement system ф costimulatory molecules ~ cytokines : damage-associated molecular patterns : DAMP : graft rejection ~ heat shock proteins : helicases ~ helicases : innate ф innate ф immune response ф inflammatory response : LGP2 : lipid transferases : MalMAPKsMAP kinases : Mda5 : multicellular animals : MyD88 : NALP : § NF-κB : NLR : NOD : PAMP ф pathogens : pathogen-associated molecular patterns : pattern recognition receptors : pentraxin : PGR : plant R : PRR : RIG-I : RNA helicases : SARM : SARM actionserine/threonine kinases ф signaling ф surface receptors : TIR : TLR : TLR-1 : TLR-3 : Toll-like receptors : TRAM : TRIF ф VDJ recombination ▲ф

Tables  Complement Receptors  Cytokines  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors 

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[pdf review]

See TOLLing away in Brazil. Mitchell JA, Fitzgerald KA, Coyle A, Silverman N, Cartwright N. [Free Full Text] Nat Immunol. 2006 Jul;7(7):675-9.

Toll, A New Piece in the Puzzle of Innate Immunity. Wright SD. [Free Full Text Article] J Exp Med. 1999 Feb 15;189(4):605-9.

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receptors

The functionality of cells of the immune system is particularly dependent on signal pathways, and the various lymphoid cell types sport an array of receptors.

antigenic determinant : APC costimulation : BCR: complement receptors : cytokines : epitope : FcR : Ig-Fc : IgG : opsonins : pathogen associated molecular patterns : pattern recognition receptors : phagocyte receptors : respiratory burst complement : respiratory burst Fc : : scavenger receptors : TCR : TLR : Toll-like receptors : VDJ recombination

Phagocytes

Phagocytic cells detect infectious agents that bind to a variety of receptors on the phagocytes cell membranes, including:

Fc receptors (FcR, Ig-Fc) – the constant region (Fc) of IgG on bacterial surfaces can bind to the Fc receptor on phagocytes. Such binding to the Fc receptor requires prior antibody-antigen interaction. The binding of IgG-coated bacteria to phagocytic Fc receptors stimulates both metabolic activity in the phagocytes (respiratory burst) and phagocytic activity. Fc receptors include the clusters of differentiation, CD16 (Fcγ RIII), CD32 (Fcγ RII-A, Fcγ RII-B2, Fcγ RII-B1), and CD64 (Fcγ RI), Fcε RI, and Fcα RI. All FcR are stimulatory except inhibitory Fcγ RII-B1 and B2, which contain immunoreceptor tyrosine based inhibition motifs (ITIMs) in their cytoplasmic tail. Table  Fc receptors

Complement receptors – Phagocytic cells possess a receptor for the C3b complement opsonins, and binding of C3b-coated bacteria to this receptor stimulates enhanced phagocytosis and the respiratory burst. Table  Complement Receptors.

Scavenger receptors bind a variety of polyanions on bacterial surfaces, stimulating phagocytosis of the polyanion-coated bacteria. Macrophage scavenger receptors appear to mediate important, conserved functions, so it was likely pattern-recognition receptors that arose early in the evolution of host-defense mechanisms. Table  Scavenger Receptors

Toll-like receptors are a variety of pattern recognition receptors (PRR) that recognize pathogen associated molecular patterns (PAMP) on infectious agents. Binding of the infectious agents to Toll-like receptors stimulates phagocytosis and the release of inflammatory cytokines (IL-1, TNF-α, IL-6) from the phagocytes. Table  Toll-like Receptors

Tables  Complement Receptors  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Scavenger Receptors  Toll-like Receptors .

Lymphocytes

The surfaces of B cells and T cells are coated with thousands of identical copies of different integral membrane receptors (BCRs, TCRs), each capable of binding with a different antigen.

Receptor characteristics
● thousands of copies of integral membrane proteins with unique antigen binding sites
● encoded by genes assembled by VDJ recombination produced without antigen encounter
● the antigen binding site recognizes an antigenic determinant or epitope on the antigen
● binding, by non-covalent forces, is based on complementarity of the surface of the receptor and the surface of the epitope

Binding of receptor to epitope, when accompanied by APC-costimulation, leads to:
stimulation of the B or T cell to leave the G0 phase and enter the cell cycle
● repeated mitosis generates a clone of cells of identical specificity, each coated with an identical antigen receptor.

Cytokine receptors:
Hematopoietin family receptors are dimers or trimers with conserved cysteines in their extracellular domains and a conserved Trp-Ser-X-Trp-Ser sequence. The two subunits are i) cytokine-specific, and ii) signal transducing. Examples are receptors for IL-2 through IL-7 and GM-CSF.
___Colony-stimulating factors (CSFs) are glycoprotein molecules that support growth of hematopoietic colonies. Examples are receptors for interleukin 3 (IL-3), G-CSF, GM-CSF, M-CSF.

Interferon family receptors
Interferons are immune cytokines that are classified, as type I, II, or III, according to the receptors through which they signal. Interferon (INF) family receptors have conserved cysteine residues and include the receptors for IFNα, IFNβ, and IFNγ.

Tumor Necrosis Factor family receptors possess four extracellular domains. Examples are receptors for TNFα, TNFβ (lymphotoxin β, LT), CD40, CD27, CD30, and Fas.

Chemokine family receptors have seven transmembrane helices (serpentine, GRCRs) and interact with G protein. This family includes receptors for IL-8, MIP-1, MCP (monocyte chemoattractant protein), and RANTES (regulated upon activation normal T cell expressed and secreted). Chemokine receptors CCR5 and CXCR4 are used by HIV to preferentially enter either macrophages or T cells.

Tables  Complement Receptors  Fc receptors  Immune Cytokines  Immunoglobulins  Interferons  Cell Adhesion Molecules  Cell signaling  Receptor Tyrosine Kinases (RTKs)  Receptor Signal Transduction  Second Messengers  Scavenger Receptors  Toll-like Receptors 

▲ф ф antibodies ф antigen : antigenic determinant ф APCs : APC costimulation : BCR ф BCR ф B cells ф CD ф cellular response ф clonal selection ф complement system : complement receptors ф complement system ф costimulation : cytokines ~ cytokines ф dendritic cells : epitope : FcR  Fc receptors ф granulocytes ф helper T cell ф hematopoiesis ф humoral immunity : Ig-Fc : IgG  Immune Cytokines  Immunoglobulins □□ Immunology ~ immunoglobulins ф inflammatory response ф immune cytokines ф immune response ф lymphocytes ф lymphoid system ф macrophages ф MHC : opsonins ф pathogens : pathogen associated molecular patterns (PAMP) : pattern recognition receptors (PRR) ф pattern-recognition receptors : phagocyte receptors ф phagocyte ф plasma cells : respiratory burst complement ››› respiratory burst : respiratory burst Fc : scavenger receptors ф signaling ф surface receptors : TCR ф TCR ф T cells : TLR : Toll-like receptors : VDJ recombination ▲ф

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