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145 Cards in this Set

  • Front
  • Back
Nitric Oxide
-Released during phagocytosis.
-Innate immunity.
-Induce phagocyte recruitment, activation, and microbial killing.
-Type 1 hypersensitivity: SMC relaxation, increased vascular permeability and dilation.
NK cell functions
-Secrete perforin and granzymes.
-Induce apoptosis via Fas-FasL.
-Principle mediators of ADCC by recognizing IgG on infected cells (have Fc-gamma-RIII).
-Release IFN-gamma to stimulate adaptive immunity.
-Kill cells lacking MHC1.
NK cell activation
IFN-alpha
IFN-beta
IL-12
NKT cells
-Lipid-CD1 restricted.
-CD3+ and CD8-
-Induce cytolysis.
-Express classical T-cell receptors (alpha/beta).
Selectin
-Bind carbohydrates.
-Mediate weak binding and rolling of WBC's on endothelium.
-Naive T-cells express L-selectin, which binds the ligand on the HEV.
-Mature T-cells lose E-selectin (to inhibit trafficking back to lymphoid tissue) and express ligand for E- and P-selectins, which are on endothelium.
-P-selectin is also on platelets.
Integrin
-alpha and beta subunits
-Mediate strong adhesion of WBC's to endothelium.
-Integrin on WBC surface, integrin ligand on endothelium.
-Switch from low- to high-affinity state via chemokines.
-Also called LFA.
-Bind CAM's & ECM.
TNF
-Involved in innate immunity.
-Mainly from macrophage, signaled by TLR.
-Also from T, NK, and mast cells.
-High level indicates autoimmune disease or bacterial infection (gram negative).
-Binds TNFR1 & 2, activates TRAF, induce transcription via NF-kappa-B.
-Systemic effects of severe infections.
-See 'biological effects' card.
IL-1
-Involved in innate immunity.
-From macrophage, signaled by TLR.
-Also from endothelial cells.
-See 'biological effects' card.
PECAM-1
-Platelet Endothelial Cell Adhesion Molecule
-On WBC and endothelium.
-Induces stable adhesion and migration of WBC into tissue.
TLR/PRR
-Toll-Like Receptor/Patter Recognition Receptor
-WBC's: surface & interior.
-Recognize PAMPS & target phagocytosis.
-Encoded in germline, so no somatic gene recombination, so limited adaptability.
PAMP's
-On microbes, not host cells.
-Bacterial lipopolysaccharide, flagella proteins, mannose, dsRNA, CpG DNA.
Genes activated by TLR's
-Cytokines: TNF, IL-1, IL-12.
IL-12
-Involved in innate immunity.
-From macrophages, signaled by TLR. Also from DC's.
-Effect on NK and T-cells: activation, IFN-gamma release, increased cytotoxicity.
-Induces Th1 differentiation.
IFN-alpha
-From DC's and macrophages.
-Activate NK cells (antiviral).
-Type 1 IFN.
-Increase MCH1 expression in all cells.
IFN-beta
-From fibroblasts.
-Activate NK cells (antiviral)
-Type 1 IFN.
-Increase MCH1 expression in all cells.
IFN-gamma
-From NK cells and T-cells.
-Involved in innate and adaptive immunity.
-High level indicates viral infection.
-Induces macrophage activation.
-Stimulates some antibody responses.
-Induces expression of LMP's and MECL (replacement beta subunits of proteasome).
IL-2
-Involved in adaptive immunity.
-From active T-cells (CD4 & CD8).
-Self-stimulatory, induces T-cell proliferation.
IL-4
-Involved in adaptive immunity.
-From Th2 cells.
-Induces differentiation of active T-cell to Th2 cell.
-Enhances B-cell antibody production.
-Inhibits macrophage activation.
IL-5
-Involved in adaptive immunity.
-From Th2 cells.
-Causes eosinophil activation (to hypodense phenotype) & production in marrow.
-Enhances B-cell antibody production.
Corticosteroids
-Inhibit innate immunity cytokines.
Remicade
-Humanized antibody to TNF.
Enbrel
-Inhibits TNF action.
-Fusion of soluble TNFR with human IgG.
Biological effects of TNF
-Endothelium: activation(express more selectins, integrin ligands, and chemokines), inflammation, coagulation.
-Neutrophil activation.
-Hypothalamus: fever.
-Liver: acute phase protein synthesis.
-Muscle & fat catabolism
-Apoptosis of many cell types.
Biological effects of IL-1.
-Endothelium: activation (express more selectins, integrin ligands, and chemokines), inflammation, coagulation.
-Hypothalamus: fever.
-Liver: acute phase protein synthesis.
-T-cells: Th17 differentiation.
Chemokines
-From macrophages, DC's, endothelial cells, T-cells, fibroblasts, and platelets.
-Effects on WBC's: activation, chemotaxis, increased integrin affinity.
IL-10
-From macrophages, DC's, and Th2 cells.
-Effects on macrophages and DC's: inhibit IL-12 production, reduce expression of costimulators and MHC2 (inhibits macrophage activation).
IL-6
-From macrophages, endothelial cells, and T-cells.
-Effect on liver: acute phase protein synthesis.
-Effect on B-cells: proliferation of Ab-producing cells.
-Effect on T-cells: Th17 differentiation.
TGF-beta
-From many cell types.
-Inhibition of inflammation.
-Induces differentiation of Th17 and regulatory T-cells.
-In mucosa, induces class switching to make IgA in MALT.
Chemokine receptors
-G-protein coupled 7-transmembrane receptor family.
-Important in devo, vascularization, cancer metastasis, and HIV.
-Drugs: receptor antagonists to block HIV entry and mobilize stem cells during transplant.
Eicosanoids
-Innate immunity.
-From phagocytes.
-Induce phagocyte recruitment, activation, and microbe killing.
ROI's
-Innate immunity.
-From phagocytes.
-Induce phagocyte recruitment, activation, and microbe killing.
Defensin
-Innate immunity.
-From phagocytes.
-Small cationic peptides capable of lysing microbes.
Acute Phase Proteins
-Innate immunity.
-C-reactive protein & serum amyloid A.
-Produced in liver via IL-6.
-Bind microbes to enhance phagocytosis.
-Induce phagocyte recruitment and activation.
-Circulating levels increase much during infection.
Lactoferrin
-Innate immune component.
Lysozyme
-Innate immune component.
2nd signals for B- and T-cell activation
-Provided by innate immune response.
-Examples: costimulator molecules, cytokines like IL-12, complement proteins.
B7
-2nd signal for T-cell activation.
-Provided by innate immune system (on APC surface).
-Recognized by CD28 receptor on T-cell.
-Expressed by macrophage after phagocytosis.
CD28
-Receptor on T-cell for the B7 ligand.
-2nd signal for T-cell activation.
CR2
-Type 2 complement receptor that recognizes Cd3 on microbe.
-On B-cell surface.
-Integral membrane protein.
-Part of 2nd signal (along with ITAM) for B-cell activation.
Proteasome proteases
-In the proteasome's beta subunits.
-Trypsin-like: cleaves to the right of basic amino acids.
-Caspase-like: cleaves to the right of acidic amino acids.
-Chymotrypsin-like: cleaves to the right of hydrophobic amino acids.
LMP & MECL
-Expression is induced by IFN-gamma.
-Replacements for beta subunits of proteasome.
-Encoded in MHC gene.
-Turns the proteasome into the "immunoproteasome."
TAP
-Transporter associated with Antigen Processing.
-Transports peptides (ending in hydrophobic amino acids and of size 6-15 amino acids) into ER.
-Encoded in MHC gene.
-Integral membrane protein on ER.
Tapasin
-Located in ER.
-Tethers newly-synthesized MCH1 to TAP so that incoming peptides can bind.
beta-2-m
-beta-2-microglobulin
-Light chain of MHC1, with Ig domain.
-Once it associates with MHC1 heavy chain in ER, the molecule is stable.
-Does not span membrane.
-Non-polymorphic.
MHC1 structure
-1 heavy chain + beta-2-m
-heavy chain domains: alpha-1, -2, & -3. Alpha-1 & -2 form peptide-binding groove, and there are polymorphisms on both domains.
MHC2 structure
-2 heavy chains (alpha and beta).
-Heavy chain domains: alpha-1 & -2. Beta-1 & -2.
-peptide-binding groove is made by alpha-1 and beta-1 domains.
-Can hold longer peptide antigens than MHC1.
-Polymorphic residues on beta chain.
Cathepsin
-Protease in lysosome, present in mM amounts.
Ii
-Invariant chain.
-3 functions: scaffold & stabilizer for MHC2, barrier to peptides in ER, zip code for MHC2 transport to lysosome.
-Prevents peptides in the ER that are destined for MCH1 from binding to MHC2.
-Integral membrane protein in ER, becomes CLIP in lysosome.
CLIP
-Class 2 Invariant chain Peptide
-Short peptide fragment derived from Ii, located in MHC2 groove while in lysosome.
-Kicked out of MHC2 by HLA-DM.
HLA-DM
-In lysosome, catalyzes the exchange of CLIP for antigen in MCH2 groove.
-Resembles MCH2 but lacks a peptide-binding groove.
CD1
-An antigen presentation molecule (on APC's) similar to MHC.
-1 heavy chain + beta-2-m.
-Present lipid antigen to NKT cells.
-Not encoded in MHC gene, not very polymorphic.
-Travels with Ii like MHC2.
-Unclear mechanism of attaining lipid antigen.
MHC genetic locus
-Chromosome 6, 200 genes
-MHC1: 3 classical gene products, HLA-A, -B, & -C (heavy chains).
-MCH2: 6 classical gene products, heterodimers HLA-DR, -DQ, & -DP (alpha and beta chains).
-Polymorphic.
-Codominant.
-Polygenic.
Ankylosing Spondylitis
-Inflammatory disease of vertebral joints.
-93% of patients have HLA-B27.
-Activating agent is a bacterium.
BCR
-Membrane-bound antibody (IgD or IgM) + 2 additional membrane-bound Ig domains (Ig-alpha and Ig-beta).
CD3
-Associated with the TCR on all T-cells (marker).
-No ligand.
IgG
-Subtypes: 1, 2, 3, 4
-Secreted because of 'tail piece'
-Opsonization, complement activation, ADCC, neonatal immunity, feedback inhibition of B-cells.
-Most commonly found Ig after secondary response.
IgM
-Initiate B-cell response.
-Membrane-bound monomer, secreted pentamer.
-Naive B-cell antigen receptor, complement activation.
-Predominant Ig early in immune response.
CDR
-Complimentary Determining Region.
-3 hypervariable regions in the variable part of Ig heavy and light chains and TCR.
-CDR3 is the most variable, located at the junction of V and C regions. Contributes most to antigen binding.
TCR
-1 alpha chain + 1 beta chain, each with Ig domains.
-Each chain has V and C regions.
-Do not undergo glass switching or affinity maturation.
-Do not mediate effector functions, just recognize MHC + peptide.
-Coreceptors for TCR are CD4 & CD8.
IgA
-Subtypes: 1 & 2
-Secreted as a dimer after binding Poly-Ig receptor at basolateral side of epithelial cell.
-Mucosal immunity, neonatal passive immunity (mother's milk is IgA-rich).
-Produced in MALT, 60-70% of total daily Ig production.
-Made in MALT b/c TGF-beta induces class-switching.
-Neutralizes pathogen in lumen.
IgD
-Not secreted.
-Naive B-cell antigen receptor.
IgE
-Intermediate hypersensitivity, allergies.
-Bind surfaces of mast and basophilic cells.
Ig isotypes
-Differ in heavy chain.
Ig allotypes
-Differ in polymorphic domain of the constant part of heavy chain.
Ig idiotypes
-Differ in polymorphic domain of V region of heavy and light chains.
Positive Selection of T-cells
-Immature T-cells with receptors reactive to self-MHC + peptide are selected to live and proceed to next step.
-Occurs in thymus cortex.
Negative Selection of T-cells
-Immature T-cells with high affinity receptors for self peptides are removed.
-Occurs in cortical-medullary junction of thymus.
E-selectin
-On endothelium.
-Bound by skin-homing lymphocytes.
MAdCAM
-Mucosal-Addressing Cell Adhesion Molecule.
-On endothelium.
-Bound by gut-homing lymphocytes.
CAM/ICAM
-Cell Adhesion Molecule.
-On endothelial cell.
-Binds integrin on WBC
Dendritic Cell Costimulatory Molecules
-B7-1 & B7-2
-Expressed by mature DC after differentiation of immature DC.
-Costimulatory molecule for T-cells.
IL-2R
-T-cell receptor for IL-2.
-On CD4+ and CD8+ cells.
-Resting T-cell has beta and gamma chains (no alpha). Low affinity state.
-The alpha chain is expressed upon recognition of antigen by T-cell. This high affinity state induces T-cell proliferation.
Th1 cells
-CD4+
-Recognize MHC2.
-Activates macrophages to kill intracellular bacteria by producing IFN-gamma.
-Stimulate antibody production to bind APC Fc receptors.
-Activate complement production.
-Stimulates costimulatory molecule expression.
CD40
-Expressed on APC (including B-cell).
-Binds CD40 ligand of CD4+ T-cells.
-Amplification signal to maintain immune response (i.e. not an activation signal-- signals 1 and 2 have already occurred).
Th2 cells
-CD4+
-Recognize MCH2.
-Activate B-cells to become plasma cells and secrete antibody.
-Release cytokines that inhibit macrophage activation.
-Produce IL-4, -5, & -10.
-Involved with allergies and parasites, eosinophilic inflammation.
CTL
-CD8+ T-cell, cytotoxic.
-Recognizes MCH1.
-Activated directly (antigen + presenting cell) or indirectly (antigen + Th1 help).
-Secretes perforin & granzyme.
-Expresses Fas Ligand to induce apoptosis of target cells, which have Fas Receptor.
Fas
-Fas Ligand on CTL's binds the Fas Receptor on target cell to induce apoptosis.
-"Death Receptor"
Proteoglycans
-Located on endothelial surface.
-Bind chemokines.
CCR7
-Cell marker on mature DC's and other cells, targeting them for migration back into lymphoid tissue for presentation to T-cells.
TS1
-PSGL1-Ig: Humanized recombinant antibody to human PSGL-1 glycoprotein (ligand for P-selectin).
-Drug to prevent WBC's from adhering to endothelium and causing inappropriate inflammation & thrombosis.
Raptiva
-Humanized monoclonal antibody that blocks LFA-1 interactions with ICAM-1 on APC.
-Drug for severe plaque psoriasis.
-Blocks T-cell activation and binding/trafficking into the dermis.
Alicaforsen
-Drug for ulcerative colitis.
-Antisense oligonucleotide that blocks ICAM-1 transcription to inhibit binding and migration of WBC's into tissue.
SCID
-50% cases: X-linked defect in common gamma chain of the IL-2 receptor.
-Lack T- & NK cells; B-cells non-functional.
-Opportunistic infections, diarrhea, failure to thrive.
-100% mortality without BMT.
-Diagnosis: CBC, lymphopenia, lymphocyte enumeration (will have low naive T-cell levels).
Toxic Shock Syndrome
-Bacterial superantigens (TSST-1) cause excessive stimulation of T-cells and macrophages.
-Massive & unregulated cytokine production (IL-1, TNF-alpha, IL-2, IFN-gamma).
-Poor antibody response to TSST-1.
Acute Infectious Mononucleosis
-CTL mediate killing of EBV-infected B-cells.
ITAM
-activating motif on Ig-alpha and Ig-beta chains of BCR
-Become phosphorylated to activate transcription factors.
-2nd signal for B-cell activation, along with CR2 (1st is antigen recognition).
ITIM
-inhibitory motive on Fc receptor on B-cell surface.
-Phosphorylates things to shut down ITAM's function.
-Fc receptor is upregulated upon B-cell activation= negative feedback.
CD5
-Cell marker on B-1 B-cells.
B-1 B-cell
-Has CD5 cell marker & IgM on surface.
-Present in mucosal tissues & peritoneal cavity.
-Recognize polysaccharides, lipids, etc. (T-cell independent).
-Become short-lived plasma cells that secrete mainly IgM.
Marginal zone B-cell
-Located in spleen & other lymphoid organs.
-Recognize polysaccharides, lipids, etc. (T-cell independent).
-Become short-lived plasma cells that secrete mainly IgM.
Follicular B-cell
-Located in spleen & other lymphoid organs.
-Recognize protein antigen (T-cell dependent).
-Become long-lived plasma cells that secrete IgG, IgA, and IgE (isotype-swiching, affinity maturation occur).
ADCC
-Antibody-Dependent Cellular Cytotoxicity.
-IgG coats host cells displaying antigen, then NK cells bind at Fc region and crosslink Fc-gamma-RIII's to kill the cell.
-IgE coats parasites, eosinophil binds at Fc region with Fc-epsilon-RI and kills parasite.
C1
-Initiates classical complement pathway.
-Binds 2 Fc regions of IgG or IgM (crosslinking) that is bound to specific antigen on microbe surface.
-Stabilized by crosslinking and activated for enzymatic cleavage of C4 & C2.
C3
-Initiates alternative complement pathway.
-Spontaneously or enzymatically cleaved by hydrolysis into C3a and C3b.
-Present in very high concentration (mg amounts).
C3b
-Cleavage product of C3.
-Covalently binds microbe surface (non-specific), becomes stable.
-Acts as an opsonin and as a component of C3 & C5 convertases.
-A substrate for Factor B, then binds Bb.
C3a
-Cleavage product of C3.
-Stimulates inflammation, activates macrophages.
C3 convertase
-Alternative: C3b + Bb
-Classical: C4b + 2b
-Cleaves C3 in addition to spontaneous hydrolysis.
C5 convertase
-Alternative: C3b + Bb + C3b
-Classical: C4b + 2b + C3b
C4
-Classical complement pathway.
-Cleaved by C1 into C4b & C4a.
C4a
-Cleavage product of C4.
-Stimulates inflammation.
C4b
-Cleavage product of C4.
-Covalently binds microbe where IgG is present and C1 is bound.
-Binds C2 for cleavage by C1.
C2
-Classical complement pathway.
-Cleaved by C1 after binding C4b.
-Cleavage product acts as the enzyme component of C3 & C5 convertases.
Factor B
-Alternative complement pathway.
-Cleaved by C3b.
-Cleavage product Bb acts as the enzyme component of C3 & C5 convertases.
MBL
-Mannose-Binding Lectin.
-Lectin complement pathway.
-Binds & crosslinds mannose on microbe surface (similar structure to C1), then activates the classical pathway just like C1.
C5
-Cleaved by C5 convertase into C5a & C5b.
-C5a induces inflammation by binding macrophages.
-C5b initiates MAC formation.
MAC formation
-Membrane Attack Complex.
1. C6 binds C5b.
2. C7 binds C5b & C6, inserts into microbe membrane.
3. C8 binds C5b, C6, & C7.
4. C9 binds C5b, C6, C7, & C8.
5. C9 polymerizes to Poly-9 ring pore.
C1 Inhibitor (C1 INH)
-Inhibits C1 serine protease activity.
-Inhibits classical complement cascade.
Factor I
-Proteolytically cleaves C3b and C4b.
-Inhibits classical and alternative complement cascades.
Factor H
-Causes dissociation of (alternative pathway) C3 convertase subunits.
-Cofactor for Factor I.
-Inhibits alternative complement pathway.
DAF
-Decay Accelerating Factor.
-Located on blood cells and endo/epithelial cells.
-Causes dissociation of C3 convertase subunits.
-Inhibits alternative and classical complement cascades.
C2 or C4 Deficiency
-Minimal disease, often asymptomatic, but most common.
-Autosomal recessive, deletions.
-Increased autoimmune-like disorders (lupus-like).
-Suggests classical complement pathway is not essential.
-Recurrent bacteremia.
C9 or MAC Deficiency
-Increased susceptibility to Neisseria infection.
C3 Deficiency
-Increased susceptibility to infections.
-Fatal in early life.
C1 INH Deficiency
-Causes hereditary angioneurotic edema.
-Excessive complement activation leads to edema in larynx and other tissues.
Poly-Ig Receptor
-Binds J chain of IgM or IgA.
-Located on basolateral side of epithelial cell.
-Secreted as a complex with the Ig into lumen.
FcRn
-Neonatal FcR.
-Located on epithelial cell surface to transport maternal IgG's to the neonate.
-Also expressed by placenta to uptake IgG.
Conjugate Vaccine
-Microbial polysaccharide + protein.
-Stimulates both humoral & cell-mediated immunity.
Infections with impaired cellular immunity
-Opportunistic infections (fungi, viruses, bacteria, protozoa).
Infections with impaired antibody production
-Encapsulated bacteria, M. pneumonia, giardiasis.
Infections with impaired complement system
-Encapsulated bacteria, recurrent meningococcal infections
XLA
-X-linked Agammaglobulinemia.
-80% of all agammaglobulinemias.
-Resp. tract infections with encapsulated bacteria, otitis.
-Low IgG AND low IgA or IgM, B-cells are extremely low (<1%), but normal T-cell # and function.
-Mutation in Btk.
-Treat with IV or sc gammaglobulin.
CVID
-Common Variable Immunodeficiency.
-Defect in B-cells.
-Resp. tract infections with encapsulated bacteria, bronchiectasis, GI infections, autoimmunity.
-Diagnosis: Low IgG low IgA OR IgM (decrease in 2 of 3 major isotypes), poor response to vaccines.
-Treatment: Ig replacement.
DiGeorge Syndrome
-Defect in pharyngeal pouches 1-6 (including thymus).
-Low T-cell and antibody count.
-Microdeletion in chromosome 22, Tbx1 gene.
-Abnormal facies, lymphpenia, thrush, recurrent sinopulmonary infections, cleft palate, cardiac abnormaliities, hypocalcemia.
-Diagnosis: FISH & microarray chip.
CGD
-Defect in NADPH oxidase of phagocytes.
-Causes: X-linked (76%) or autosomal recessive.
-Recurrent abcesses, lymphadenitits, esophageal stricture by granuloma.
-Diagnosis: DHR test.
-Treatment: antibiotics, IFN-gamma, BMT.
Common gamma chain
-Shared component of many IL receptors (IL-2, -4, -7, -15, -21)
TREC's
-T-cell Receptor Excision Circles.
-Circular pieces of DNA generated with T-cell maturation, from VDJ joining.
-Surrogate marker for # of normal naive T-cells.
-Screening for SCID: low TREC's.
Agammaglobulinemia
-Pre-BCR checkpoint defects.
-Decrease in all Ig subtypes, low # B-cells.
-Many causes: autosomal recessive or X-linked.
-Same clinical phenotype.
Btk
-Kinase that phosphorylates PLC-gamma-2, works with BLNK.
-Mutation=no Btk protein=XLA
Hypogammaglobulinemia
-Ig isotype defects.
C5-9 Deficiency
-Recurrent meningococcal infection.
-No association with autoimmune disease.
-Autosomal recessive.
MyD88 & IRAK-4 Mutations
-Pyogenic bacterial infections & defects in TLR signaling (TLR depends on these kinases).
-Diagnosis: standard immune screens are normal and not helpful. Decreased inflammatory cytokine production in vitro in response to IL-1 & TLR agonist.
Type 1 hypersensitivity
-IgE-mediated "immediate type"
-IgE coats antigen, activates mast cells & basophils, other inflammatory cells recruited.
-Early (histamine) and late (eosinophils: leukotrienes, prostaglandins, kinins) stages.
-No complement involved.
-Allergies (rhinitis, nasal and ocular pruritis), asthma, anaphylaxis, urticaria.
Type 2 hypersensitivity
-ADCC (cytotoxic type).
-Nonsoluble antigen, tumor cells.
-Autoimmune hemolytic anemia, erythroblastosis fetalis, Goodpasture syndrome, drugs bound to RBC & platelets (penicillin), myasthenia gravis, Grave's disease, rheumatic fever, blisters.
-IgG & IgM bind antigen, phagocytosis or lysis (by C8/9 or NK cell) of cell.
Type 3 hypersensitivity
-Immune complex mediated.
-Soluble antigen.
-Arthus rxn, serum sickness, SLE, acute glomerulonephritis, Farmer's lung.
-Antigen/IgG complexes deposit in low flow sites, activate complement, attract PMN's, release lysosomal enzymes.
Type 4 hypersensitivity
-Delayed type cell-mediated (no Ig involvement).
-Antigen enters skin, binds self protein, complex is phagocytosed, T-cell response (Th1 & CD8)- cytokines or cytotoxicity.
-Antigen is soluble (Th1) or cell-associated (CD8).
-Contact/Rhus dermatitis, TB, transplant rejection.
H1 & H2
-Histamine receptors, type 1 hypersensitivity.
-H1: SMC contraction, increased vascular permeability.
-H2: increased vascular permeability, stomach acid release.
-Both: vasodilation, pruritis.
Tryptase
-Type 1 hypersensitivity.
-Released from mast cell in early phase.
-alpha-tryptase: constitutively released.
-beta-tryptase: only released with mast cell activation.
-Induces remodeling of connective tissue matrix.
Mast cell products
-Early phase (stored in granules): enzymes- tryptase, chymase, cathepsin G, and carboxypeptidase.
-Late phase (synthesized): cytokines- IL-3, -4, -5, & -13, GM-CSF, and TNF. Also chemokines- MIP-1-alpha, RANTES, Eotaxin. Also lipid mediators- leukotrienes C4, D4, & E4, and PAF.
MIP-1-alpha
-Released by mast cell.
-Late phase of Type 1 hypersensitivity.
-Chemokine for monocytes, macrophages, PMN's, T-cells, eosinophils.
RANTES & Eotaxin
-Released by mast cell.
-Late phase of Type 1 hypersensitivity.
-Chemokine for T-cells and eosinophils (eosinophils have the only receptor for eotaxin).
Leukotrienes C4, D4, and E4
-Lipid mediators released by mast cells in late phase Type 1 hypersensitivity.
-Eosinophil migration, SMC contraction, vascular permeability & dilation, mucus hypersecretion.
PAF
-Platelet Activating Factor
-Lipid mediator released by mast cells in late phase Type 1 hypersensitivity.
-Attracts eosinophils & other WBC's, activates eosinophils, PMN's, and platelets, increases production of lipid mediators.
Conditions of elevated eosinophil count
Mnemonic: NAACP.
-Neoplasia
-Asthma
-Allergy (atopic disease & drug allergy).
-Connective tissue disease.
-Parasitic disease.
Steroid treatment of Type 1 hypersensitivity
-Rapid eosinophil apoptosis.
-Inhibit IL-5 production, leading to decreased eosinophil release from marrow and more apoptosis.
-Steroid binds GR-alpha, inhibiting AP-1 and NF-kappa-B.
Products of eosinophils
-Released from crystalloid granules with core MBP.
-Lysophospholipase, major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), PAF, LTC4 (leukotriene).