Term
|
Definition
|
|
Term
| Three compliment pathways that ultimately activate C3 |
|
Definition
| Classic, lectin, alternative |
|
|
Term
| Classical pathway: overview |
|
Definition
| Antibody-dependent and independent recognition of danger |
|
|
Term
|
Definition
| Antibody-independent recognition of danger via sugar residue patterns |
|
|
Term
| Alternative pathway: overview |
|
Definition
| Default activation (can happen on any surface). 1st pathway evolutionarily |
|
|
Term
| Major site of production for complement proteins |
|
Definition
|
|
Term
| When does complment production increase 3-50 fold |
|
Definition
|
|
Term
| Examples of immunologic events that can be triggered by the complement cascade (4) |
|
Definition
| Membrane attack complex (MAC) lysis of microbes; opsonization of microbes leading to phagocytic uptake; solubilization/removal of immune complexes; proteolytic events produce inflammatory mediators |
|
|
Term
| Classical pathway: 1st factor to bind? |
|
Definition
|
|
Term
| Classical pathway: Ability of Ig types to activate compliment (4) |
|
Definition
|
|
Term
| Classical Pathway: Antibody-dependent activation |
|
Definition
| Traditionally, C1q binds to two close-together Ab-bound antigens on a pathogen surface. C1q --> C1r --> C1s |
|
|
Term
| Classical Pathway: Antibody-independent example |
|
Definition
| C1 can also bind to C-reactive proteins, which is antibody-independent. C-RP is acute phase and can increase 1000 fold in sepsis/inflammation |
|
|
Term
| Classical Pathway: Activated C1 cleaves |
|
Definition
| Cleaves C3 --> C4a and C4b, and cleaves C2 --> C2a and C2b |
|
|
Term
| Classical Pathway: C3 Convertase |
|
Definition
| C4b covalently binds to pathogen surface; C2b joins to form C3 Convertase. Proteolytic site is on C2b |
|
|
Term
| Classical Pathway: C3 Convertase cleaves |
|
Definition
| C3 --> C3a and C3b. C3a is a chemotactic agent; C3b is an opsonizing agent, binding to the pathogen's surface |
|
|
Term
| Classical Pathway: C5 Convertase |
|
Definition
| C3b + [C4b + C2b] = C5 Convertase |
|
|
Term
| Systemic lupus erythematosus (SLE) |
|
Definition
| Susceptible to bacterial infection, can be due to a deficiency of C1q and early classical pathway components |
|
|
Term
| Lectin Pathway: Recognition Step, Mannin-Binding Lectin (MBL) |
|
Definition
| MBL - like C1, except it binds carbohydrates on pathogen surface instead of antibodies. Thus, Lectin pathway is Ab-independent |
|
|
Term
| Lectin Pathway: MBL-Associated Serine Proteases (MASPs) |
|
Definition
| MASP-2 handles the cleavage steps: C4 --> C4a + C4b; C2 --> C2a + C2b |
|
|
Term
| Lectin Pathway: Subsequent steps |
|
Definition
| Same as classical pathway. After MASP-2 cleaves C4 and C2, C3 convertase forms from C4b+C2b… then C5 convertase forms from C4b+C2b+C3b. |
|
|
Term
|
Definition
| Leads to increased susceptibility to bacterial infections, especially in infants and the immunocompromised |
|
|
Term
| Alternate Pathway: Soluble C3 convertase formation |
|
Definition
| C3 --> iC3 (C3-H2O) by spontaneous hydrolysis. Factor B binds to iC3. Factor D cleaves Factor B into Ba+Bb; only Bb stays bound. iC3+Bb = Soluble C3 Convertase |
|
|
Term
| Alternate Pathway: Membrane-Bound C3 Convertase formation |
|
Definition
| C3 convertase cleaves C3 --> C3a+C3b; C3b binds/opsinizes membrane. This C3b is bound by Factor B. Factor D cleaves B as before, leaving C3b+Bb. Properdin is a stabilizer for the membrane bound form. Properdin + C3b + Bb = Membrane-Bound C3 Convertase |
|
|
Term
| Alternate Pathway: Amplification |
|
Definition
| Since C3 convertase produces C3b, and C3b is the source for membrane-bound C3 convertase, there is positive feedback and amplification very close to the membrane surface |
|
|
Term
| Alternate Pathway: Membrane-Bound C5 Convertase |
|
Definition
| Properdin + Bb + C3b + another C3b = Mem Bd C5 Convertase |
|
|
Term
| Alternate Pathway Regulation: Factor H, and 2 modes of regulation |
|
Definition
| Factor H can bind to C3b to stop the alternative pathway, and requires nearby host molecules (polyanion) to do so. Two modes: 1)Factor H accelerates the decay of Membrane-Bound C3 Convertase. 2) Factor H + Factor I turns C3b into IC3b, an inactive form. |
|
|
Term
| Alternate Pathway Regulation: Other membrane-bound regulatory proteins (4) |
|
Definition
| DAF, CR1 (Decay acceleration), MCP, CR1 (Cofactor with Factor I inactivation). These are common to all pathways |
|
|
Term
| Alternate Pathway: Requirements for a surface to be activating |
|
Definition
| The AP can deposit C3b on all surfaces. A surface is only ACTIVATING if the surface CANNOT bind Factor H OR the surface DOES NOT have membrane-bound regulators like DAF, CR1, and MCP. |
|
|
Term
| Decay Acceleration/Cofactor for Factor I in Classical and Lectin pathways does not use Factor H. Instead, it relies on |
|
Definition
| Soluble C4 Binding Protein |
|
|
Term
| Terminal Complement Components: C5 --> end |
|
Definition
| C5 convertase produces soluble C5b --> C6 binds --> C7 binds (makes membrane-bound) --> C8 binds (inserts into membrane) --> 10-16x C9 polymerize to form a membrane pore = Membrane Attack Complex (MAC) |
|
|
Term
| Deficiency of C5, C6, C7, C8, C9 |
|
Definition
| Trouble forming MAC pore. Increased susceptibility to Neisserial infections |
|
|
Term
| Four groups of complement functions |
|
Definition
| Host Defense/Pathogen Control; Generation of Pro-Inflammatory Mediators; Humoral/Cellular Adaptive Immunity; Housekeeping |
|
|
Term
| Complement Functions: Host Defense |
|
Definition
| Direct killing of pathogens (MAC), neutralization of viruses (C1q, C4b, C3b interferes with virus activity), opsonization of pathogens --> phagocytosis |
|
|
Term
| Receptors on macrophages that recognize C3b |
|
Definition
|
|
Term
| Complement Functions: Generation of Proinflammatory Mediators |
|
Definition
| C3a, C4a, C5a (soluble byproducts from coag. Cascade) --> smooth muscle contraction, increase in vascular permeability, degranulation of mast cells & basophils |
|
|
Term
| Proinflammatory mediators: Anaphylatoxins in order of potency |
|
Definition
| C5a > C3a >> C4a. C5a is a strong chemotactic agent, C3a is weak, C4a is not chemotactic |
|
|
Term
| Complement Functions: Adaptive Immune Response - B cell activation |
|
Definition
| C3d is a ligand for CR2, which makes B cell activation more efficient together with Ab recognition |
|
|
Term
| Complement Functions: Housekeeping - clearance of immune complexes from circulation |
|
Definition
| Erythrocytes bind C3b via CR1 receptor, carries immune complexes to liver or spleen |
|
|
Term
| Failure to clear waste (early classical pathway deficiencies) leads to (2) |
|
Definition
| Autoimmune disease (since autoantigens from dead cells have not been cleared) and immune complex disease (SLE) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Soluble, short-lived polypeptide hormones produced by different cells that regulate the immune system |
|
|
Term
| Paracrine, autocrine, endocrine |
|
Definition
|
|
Term
| Group 1: Acute Inflammatory Response Cytokines (3) |
|
Definition
|
|
Term
|
Definition
| Produced by macrophages mainly (also lymphoid, mast, endothelial cells, cardiac myocytes, fibroblasts, neuronal cells). |
|
|
Term
| TNF-a: Receptor types (2) |
|
Definition
| Type 1 - found on many tissues. Type 2 - found on immune cells only. |
|
|
Term
| TNF-a: Local/systemic effects |
|
Definition
| Local: Microbes trigger m-phages to make TNF-a for acute inflammation; this recruits neutrophils/macrophages by stimulating endothelial cells to produce chemotactic factors. Systemic: Acts on hypothalamus, pituitary, fibroblasts, endothelial cells, tissue repair |
|
|
Term
|
Definition
| Macrophages, monocytes, dendritic cells |
|
|
Term
|
Definition
| Type 1 = inflammatory. Type 2 = suppressor |
|
|
Term
|
Definition
| Increases expression of adhesion molecules, raises body temperature, regulates hematopoeisis |
|
|
Term
| IL-1: Local/systemic effects |
|
Definition
| Local: Similar to TNF-a. Systemic: Fibroblasts, endothelial cells, bone marrow, tissue repair |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Pro and anti-inflammatory effects; inhibits TNF-a and IL-1. Chief cytokine involved in fever |
|
|
Term
| IL-6: Local/systemic effects |
|
Definition
| Local: Inflammation. Systemic: B-cell differentiation, hepatocytes, neuronal, mesangial, osteoclast |
|
|
Term
| Pathogen associated molecular patterns (PAMPS) |
|
Definition
| PAMPS bind to toll-like receptors on macrophages to trigger release of IL-6 |
|
|
Term
| Acute phase response feeds back to brain and ultimately to adrenals to produce compliment-activating factors (2): |
|
Definition
| Mannose binding lectin (MBL), C-reactive protein (CRP) |
|
|
Term
|
Definition
| Anti-TNF-a monoclonal antibody used for treatment in rheumatoid arthritis and inflammatory bowel disease |
|
|
Term
| Group 2: Inflammatory interferons |
|
Definition
| Type I: IFN-a, IFN-b. Type II: IFN-gamma |
|
|
Term
|
Definition
| Lymphocytes, macrophages, fibroblasts, endothelial cells, osteoblasts |
|
|
Term
|
Definition
| Antiviral, stimulating macrophages + NK cells. Induces clas I MHC expression |
|
|
Term
|
Definition
| IFNAR1/2, can be found on multiple immune + non-immune cells |
|
|
Term
|
Definition
| T cells - TH1 and cytotoxic T; dendritic cells, NK cells |
|
|
Term
|
Definition
| Anti-viral, lowers TH2 activity, induces class II MHC expression |
|
|
Term
|
Definition
| IFNGR1/2, on immune cells only |
|
|
Term
|
Definition
| Inflammation of liver; treated with IFN-a-2b |
|
|
Term
| IFN-g receptor deficiency |
|
Definition
| Genetic defect in IFNGR1 --> impairs ability to fight mycobacterium, leisteria, leishmania, salmonella with macrophages. IL-12 and IL-12 receptor mutations would also cause |
|
|
Term
| Group 3: Cytokines in Hematopoiesis (3) |
|
Definition
| Erythropoietin (EPO), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| lungs, muscles, macrophages |
|
|
Term
|
Definition
| Regulate many cell functions (differentiation, survival, induction, proliferation) and guides development to granulocyte, macrophage, eosinophil, megakaryocyte, RBC. Necessary for neutrophil function |
|
|
Term
|
Definition
| multiple tissues, or locally displayed by membrane |
|
|
Term
| Chronic myeloproliferative disorders |
|
Definition
| Receptors for cytokines including EPO, G-CSF involve Jak Stat cascade. Mutation of Val 617 --> Phe in Jak2 of the receptor causes hypersensitivity to these factors. Presentation: Polycythemia, thrombocythemia, exaggerated erythropoiesis and megakaryocytopoiesis |
|
|
Term
| Group 4: Cytokines regulating T and B cells (3 important, 6 total) |
|
Definition
| IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 |
|
|
Term
| Interleukin receptor structure: |
|
Definition
| Alpha, beta, and gamma chains. Gamma chain common among all 6 of these Ils. Beta chain same for 2 and 15. All alpha chains unique |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Produces Abs, stimulates Th2, inhibits TH1 cells |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| X-linked severe combined immunodeficiency: deficiencies that can cause (4) |
|
Definition
| Common gamma chain**, Jak3, IL-7Ra chain, ZAP70 |
|
|
Term
| SCID from mutations in purine degradation enzymes (2) |
|
Definition
| These mutations cause accumulation of substances that are toxic to developing T cells. Adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) deficiency |
|
|
Term
|
Definition
| SCID from RAG1/RAG2, or Artemis (necessary RAG helper protein) deficiencies |
|
|
Term
| Hyper IgE syndrome: mutation in |
|
Definition
| Stat3 gene; decreased level of IL-17A-expressing Th17 cells |
|
|
Term
|
Definition
| Two immune responses, Th1 (IFN-g, IL-2, cytotoxic T cell) and Th2 (IL-4, IL-5, IL-10). The Th2 response is much more severe |
|
|
