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134 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Lymphoid progenitor stem cells make:
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B cells, T cells, and natural killer cells
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Myeloid progenitor stem cells make:
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erythrocytes (RBCs), megakarocytes (platelets), basophils, eosinophils, granulocytes (neutrophils, monocytes), mast cells
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Primary lymphoid tissue
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bone marrow, thymus – creating B and T cells respectively
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Secondary lymphoid tissue
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spleen, tonsils, lymph nodes
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Differences between innate and adaptive immune system
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innate: primitive, pattern recognition; limited diversity of receptors germline encoded; fast acting (minutes/hours); phagocytes, NK cells; no memory; first line of defense, necessary for proper activation of adaptive.
adaptive: recent, specific epitope recognition; large diversity of receptors produced by somatic recombination of gene segments; slow acting (days); lymphocytes; has memory; activated secondarily, response enhanced by repeated infection |
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defensins
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-endogenous antibiotic peptide
-located in PMNs(neutrophils), macrophages, Paneth cells -broad spectrum antibiotic -form membrane channels or pores with their + charged AA side chains and hydrophobic AA side chains interacting with bacterial cell membranes' negatively charged phospholipid headgroups and hydrophobic FA chains |
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pseudomembranous colitis
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severe infection of the colon (intractable diarrhea), often resulting from eradication of the normal gut flora by antibiotics (clindamycin) causing C. difficile to become overpopulated b/c they are resistant to that antibiotic.
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Where do neutrophils complete maturation?
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bone marrow
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Where do monocytes complete maturation?
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tissues
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function of chemokines and who secretes them
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regulate leukocyte movement towards site of infection in tissues
secreted by infected tissues, resident leukocytes, and activated endothelium |
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chemokines
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8-10kd proteins with 20-70% homology in AA sequences
subdivided into 4 families on the basis of relative position of their cysteine residues |
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chemokine neutrophils bind to
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CXCR1 or CXCR2 on IL-8
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ARDS (acute respiratory distress syndrome)
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acute inflammatory process in lungs
leukocyte infiltrate built up: neutrophils respective chemokine: IL-8, etc |
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sarcoidosis
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leukocyte infiltrate built up: T cells and macrophages
respective chemokines: IP-10 |
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How do immune cells (leukocytes) know where to find the infection?
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chemokines
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How do the WBCs actually get from the blood to the tissues?
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diapedesis
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steps to diapedesis
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1) tethering of selectin from endothelium to WBC (movement goes from 4000 to 40um/sec); ICAM-1
2) ICAM-1 on endothelium weakly binds to LFA-1 integrin on WBC 3) chemokines released from macrophages attach to 7TM receptors and causes a change from low affinity to high affinity bond conformation change in integrin which stops the WBC on the endothelium 4) WBC can pass through tight junctions of endothelium and move to tissue side via a chemokine gradient |
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PAMPs
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pathogen-associated molecular pattern - conserved molecular motifs on surface of microbes (ex: LPS, mannose, etc)
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PRR
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pattern recognition receptor - host receptors that recognize PAMPs (ex: CD14, TLRs, NODs, etc)
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what does innate immunity depend on?
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Recognition of a PAMP by a PRR to induce signal transduction and changes in gene expression leading to inflammation and destruction of microbes through cytokine production and phagocytosis
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LPS
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lipopolysaccharide PAMP (O antigen, core, lipid A)
source = gram negative bacterial cell wall PRR = TLR, CD14 response = macrophage activation |
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mannose-rich glycans
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PAMP
source = microbial glycolipids and glycoproteins PRR = mannose receptor or plasma mannose binding lectin response = phagocytosis or complement activation respectively |
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TLR
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PRR: extracellular LRR (leucine rich repeat) domain, single TM alpha-helix, intracellular TIR domain
9 TLRs discovered which is why multiple exposures don't lead to the same outcome, some are dimers, TLR4 binds LPS |
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What happens with PAMPs and PRRs come together?
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Extracellular side: LPS + LBP binds to CD14 on cell surface – CD14 is high affinity binding molecule for LPS (LPS is PAMP which binds to LPS binding protein = LBP); This complex binds to a dimerized TLR4/MD2 complex);
Signaling across the cell membrane can now occur Cytoplasmic side:TLR4 TIR domain may or may not interact with MyD88 adapter protein; Interaction leads to downstream production of NFkB and AP1; No interaction with MyD88 leads to production of IRF 3 Nucleus: NFkB translocates (first created intracellularly) into the nucleus where is a powerful transciption factor that upregulates the production of proinflammatory gene products like cytokines |
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IL-1
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cytokine that activates vascular endothelium and lymphocytes, local tissue destruction, increases access of effector cells. produces fever and production of IL-6
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TNF-alpha
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cytokine that activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes. produces fever, mobilization of metabolites, shock
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phagocytosis
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receptors on host cell (PRRs) bind pathogen/bacteria (PAMPs).
obstinization - bacteria or pathogen is coded with certain molecules (C3B) to enhance receptor binding once inside cell, pathogens enclosed in phagosomes creating phagolysosome which will degrade material |
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oxygen-dependent intracellular killing mechanisms
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NADPH oxidase converts O2 to superoxide anion
Production of H2O2 by superoxide dismutase Myeloperoxidase + H202 = halide ions into cell walls of bacteria |
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oxygen-independent intracellular killing mechanisms
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enzymes in lysosome, acid production, cationic proteins
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rickettsiae
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intracellular bacteria that wants to be taken up by phagocytosis; can lyse the phagosome membrane with phospholypase, destroying the endosome compartment; then replicate and destroy the entire cell and can directly infect adjacent cells via injection of Factin
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lymphocyte maturation disorders
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Bruton's agammaglobulinemia
DiGeorge Syndrome Severe combined Immunodeficiency |
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Which type of immune cells are generated in the thymus?
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T cell, NK cell
dendritic cell |
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Which type of immune cells are generated in the bone marrow?
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B cell, NK cell
monocyte, megakaryocyte |
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Innate vs Adaptive/Humoral Immunity
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Innate:
-receptors - recognize pathogens are germline encoded -response - fast and nonspecific -no memory -neutrophils, macrophages, dendritic cells, NK cells, and complement adaptive: -receptors - recognize pathogens undergo V(D)J recombination during lymphocyte development -response - slow on first exposure, but memory response is faster and more robust -T cells, B cells, circulating antibody |
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Passive vs Activity Immunity
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active:
-induced after exposure to foreign antigens -slow onset -long-lasting protection (memory) passive: -based on receiving preformed antibodies from another host -rapid onset -short lifespan of antibodies -ex: IgA in breast milk |
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Adaptive Humoral Response: Primary vs Secondary Antibody response
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primary:
-lag after immunization - usually 5-10 days -peak response - smaller -antibody isotope - usually IgM>IgG -antibody affinity - lower average affinity, more variable secondary: -lag after immunization - usually 1-3 days -peak response - larger -antibody isotope - relative increase in IgG (sometimes IgA or IgE) -antibody affinity - higher average affinity (affinity maturation) |
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Steps of Lymphopoiesis
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-differentiation
-acquisition of antigen recognition (diversity, clonality, developmental checkpoints) -proliferation |
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What cell surface marker is present on all B cells up to but not including plasma cells?
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CD19 - also used as a cell-surface marker for counting B cells in clinical studies
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Describe the differentiation of B cells in primary lymphoid organs with respect to cell surface markers.
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-CLP (common lymphoid precursor) - CD19-
-proB - CD+/IgM- -preB - CD+/IgM- -immB - CD19+, low IgM -matB - CD19+/IgM+D+ |
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Describe the general antibody structure.
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-2 heavy chains with constant and variable regions (VDJ rearrangement)
-2 light chains with constant and variable regions (VJ rearrangement) |
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What leads to the diversity of the humoral response?
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Ig Heavy (5 genes, mu, delta, etc)) and Light (2 genes, kappa, lambda) chain RECOMBINATION
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Describe the differentiation of B cells with respect to gene rearrangement.
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-proB: H chain VDJ rearrangement in 1st allele; if unsuccessful, H chain VDJ rearrangment in 2nd allele; if successful ->
-preB: uRNA, u protein, pre-B receptor expression -> inhibition of further H chain rearrangements; k chain VJ and lambda chain VJ rearrangement, if successful -> -immB: k chain RNA, k protein, IgM expression or lambda chain RNA, lambda protein, IgM expression -> inhibition of further light chain gene rearrangements |
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Where does complement bind on Igs?
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CH2 for IgG
CH4 for IgM |
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Where does the Fc receptor bind on Igs and on what cells is it present and why is this important?
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Fc receptor binds to entire bottom region (Fc region) of Ig. Fc receptor is present on macrophages, dendritic cells, NK cells, neutrophils, eosinophils, other B cells. It is important so that other cells can bind the Ig once its released.
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What is the significance of the variable region on Igs?
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It can change (variable) and is the antigen binding site.
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What is essential for B cell development, promoting rearrangement?
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RAG-1, RAG-2, Tdt
- cause production of functiong k or lambda light chain that permits the expression of IgM on the cell surface. |
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What can the absence of RAG genes cause?
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SCID - affects production of B and T cells
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What is caused by B cell deficiency due to lack of B cell receptor (BCR, preB receptor or mature Ig) and Ig-alpha and Ig-beta coreceptors
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X-linked agammaglobulinemia
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What is clonality?
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A B cell can have only one Ig on its surface, but it can produce a whole bunch of identical Igs. Every cell made from progenitor cell will have same antibody that it will produce - important in fighting off antigen.
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What is receptor editing?
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immB cells sense self (negative selection) and get a chance to rearrange the LIGHT chain of IgM. If the new cell is no longer self-reactive (positive selection), can mature, if not, apoptosis.
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What is negative selection?
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The immB cell wants to get rid of the cell responsive to self. ImmB shuts down if it sees self antigen and dies if the response is very robust to self antigen, then it dies via apoptosis.
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What do mature B cells express on their cell surface?
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high levels of IgM and IgD
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What causes ADA deficiency?
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(adenosine deaminase deficiency)
-B and T cell development is affected and lymphocytes can't proliferate |
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What is caused by RAG deficiency?
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ARTEMIS or OMEMN SYNDROME
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What are causes of X-linked agammaglobulinemia?
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-can't produce Ig (problem with signal transduction)
-Btk deficiency (Bruton tyrosine kinase) - responsible for 85% of disease ZAP-70 deficiency, MHC deficiency |
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What are some secondary lymphoid organs?
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spleen, lymph nodes, Peyer's patches
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Where does B cell activation occur?
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secondary lymphoid organs
-where they come in contact with foreign antigens and become effector lymphocytes and then differentiate (effector function), proliferate (clonal expansion), and produce memory cells |
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What does B cell differentiation involve?
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-ANTIBODY SECRETION
-CLASS SWITCHING (from IgM to other classes) -AFFINITY MATURATION - better recognition -produce MEMORY B cells |
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What are the requirements of B cell activation?
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-B cell receptor cross-linking - transduces signal
-costimulatory molecules (B7 on B cells and CD28 on T cells) -T cell help (optional) |
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What is the difference between T cell dependent and independent B cell activation?
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dependent: usually proteins, can have isotype switching, has affinity maturation, and memory cells
independent: usually polymers like polysaccharides, glycoproteins, cross-link themselves, have little isotype switching (only IgG), no affinity maturation, no memory, usually B1 cells that are more broad than specific |
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How does T-dependent B cell activation occur?
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B cell presents antigen to Th cell. Once BCR and TCR with antigen as well as B7 on B cell and CD28 on T cell interact, the T cell is activated, causing it to express CD40-L and to secrete cytokines. Both interaction of CD40 on B cells and CD40-L on T cells as well as cytokines, induce B cell activation.
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What is caused by mutations in CD40L?
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X-linked hyper-IgM syndrome (no class-switching from IgM to other Igs)
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What can occur following B cell activation?
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-changes in phenotype - low levels of IgM secretion; increased expressoin of costimulators and cytokine receptors; cloning/mitosis
-acquisition of effector functions - make antibodies via class-switching -become receptive to negative regulation |
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Where do T and B cell interactions occur and what does this result in?
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secondary lymphoid tissue (lymph nodes)
-production of early antibodies -formation of germinal centers |
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What happens in germinal centers?
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-affinity maturation
-isotype switching -memory B cell generation |
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Describe affinity maturation.
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Natural selection for B cells (somatic hypermutation) occurfing in germinal center. Re-expose B cells to antigen and the B cells best at recognizing the antigen survive and become memory B cells or plasma (antibody secreting) cells and the others die. Allows for 1000x or greater improvement of affinity for antibody and antigen.
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What is IgM's function?
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pentamer that can activate complement via classical pathway
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What is IgG's function?
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-cells with Fc receptors (macrophages, dendritic cells, NK cells, B cells, neutrophils, and eosinophils) can phagocytose antigen/IgG complexes
-also activates complement -transferred across placenta to fetus |
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What's IgE's function?
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-important in immune response to helminths (parasitic worms)
-present on mast cells and when cross linked by antigen will produce mast cell degranulations and immediate hypersensitivity response |
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What is IgA's function?
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-present at mucosal surfaces (mouth, somtach, intestines, lungs)
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What are secreted antibodies effector functions?
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1) neutralization of toxins and viruses
2) complement activation via the classical pathway 3) stimulation of antibody-mediated cellular cytotoxicity 4) opsonization by macrophages via the Fcgamma (IgG) receptors 5) IgE-mediated hypersensitivity reactions by basophils and mast cells |
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What is hyper-IgM syndrome?
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-can't class-switch, no memory
-suffer from lots of infections: pneumonia, otitis media, won't live long |
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What are primary immunodeficiencies due to?
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genetic defects in the production, maturation, or function of:
B cells, T cells, SCID (T and B), or phagocytes |
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phagocyte disorders
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Chediak-Higashi Syndrome
Chronic Granulomatous Disease Leukocyte Adhesion Deficiencey (type I) |
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Bruton's Agammaglobulinemia features
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-X-linked recessive
-defect in TYROSINE KINASE GENE (BTK) -low Igs, LOW B CELLS -RECURRENT BACTERIAL INFECTIONS occuring when maternal IgG levels decline (6 months) -normal proB cells in bone marrow -treat with IV Ig replacement |
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DiGeorge Syndrome features
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-CARDIAC ANOMALIES, HYPOPLASTIC THYMUS, and HYPOCALCEMIA
-failed development of 3rd and 4th pharyngeal pouches (parathyroids) -chr 22q11 deletion -partial: most patients -complete: thymic aplasia (form of SCID) -IMPAIRED T CELL MATURATION -TETANY from hypocalcemia (low serum Ca and high serum P and low PTH) -recurrent viral and fungal infections |
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SCID features.
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-impairment of B and T cells
-RECURRENT SEVERE INFECTIONS, CHRONIC DIARRHEA, and FAILURE TO THRIVE -PERSISTENT VIRAL, FUNGAL, and BACTERIAL INFECTIONS -X-linked: mutation in gamma chain component of receptor for IL-2,7,etc; IL-7 important in T cell maturation -autosomal: 1/2 caused by ADA deficiency (involved in breakdown of purines - B and T injured by accumulation of toxic metabolites); mutations in RAG1/RAG2 -treat with hematopoietic stem cell transplantations (HSCT) |
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Chediak-Higashi Syndrome
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-autosomal recessive
-ABNORMAL FUSION of phagosomes with lysosomes resulting in a fialure to kill ingested microbes -RECURRENT PYOGENIC INFECTIONS -partial oculocutaneous ALBINISM -METALLIC HAIR, speckled hyper/hypopigmentation -progressive neurologic symptoms -GIANT CYTOPLASMIC GRANULES in leukocytes and platelets -treat: HSCT |
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Chronic Granulomatous Disease
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-lack of phagocyte NADPH OXIDASE activity
-susceptible to infection by CATALASE (+) ORGANISMS -RECURRENT BACTERIAL AND FUNGAL INFECTIONS (staph aureus, aspergillus) -test: nitroblue tetrazolium test (NBT) -superoxide reduces yellow NBT to blue usually -treat: acute infections; antimicrobial prophyalxis (trimethoprim, sulfamethoxazole, interferon-gamma) - reduces rate of infections |
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Why are patients more prone to CATALASE POSITIVE ORGANISMS when there is a defect in NADPH oxidase?
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NADPH oxidase noramlly reduces oxygen to superoxide and then superoxide is converted to H2O2 by SOD. Then H2O2 is converted to water by catalase or ROS by myeloperoxidase.
Blocking NADPH oxidation reduces H2O2 and all is shuttled to catalase side to form water and none is able to form ROS, which help phagocytes kill the organisms. |
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What is the significance of a positive result from the NBT (nitroblue tetrazolium test) test?
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A positive test means that superoxide reduced yellow NBT to blue which is normal.
Yellow means that it was unable to produce superoxide to change to blue - have NAPDH problem |
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Leukocyte Adhesion Deficiency (type I)
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-defect in INTEGRIN (selectin, ICAM1/2) on phagocytes (CD18)
-delayed separation of the UMBILICAL CORD -RECURRENT BACTERIAL INFECTIONS -skin/mucosa -absent PUS formation -impaired wound healing |
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Ataxia-telangiectasia features.
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-autosomal recessive, defect in chr11, ATM gene involved in DNA DAMAGE DETECTION
-cerebellar ATAXIA -oculomotor APRAXIA -spider angiomas (telangiectasia) -recurrnet SINOPULMONARY infections - #1 cause of death -increased risk of malignancy (ATM phophorylates p53 tumor suppressor protein) -increased ALPHA-FETOPROTEIN -REDUCED IgA and IgG -NO THERAPY CAN ALTER COURSE OF DISEASE -hypersensitive to ionizaing radiation and chemicals (reduce Xrats) |
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apraxia
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inability to coordinate head and eye movements when shifting gaze rapidly
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Wiskott-Aldrich Syndrome features
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-X-linked, mutation in WASP gene
-RECURRENT PYOGENIC INFECTIONS, THROMBOCYTOPENIC PURPURA, and ECZEMA = wIPE -bleeding due to thrombocytopenia - #1 cause of death -normal IgG, elevated IgA and IgE, decreased IgM -treat: HSCT, splenectomy |
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purpura
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small non-blanching area when pushing on discolored skin; leakage from blood vessel under skin
-defined at 0.3cm to 1cm in diameter |
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Common Variable Immunodeficiency (CVID)
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-heterogeneous group of disorders characterized by defective Ig production
-MOST PREVALENT form of severe antibody deficiency -most commonly diagnosed between mid-teens and early thirties -reduced serum IgG levels, low IgA and/or IgM -poor or absent response to immunization -absence of any other defined immunodeficiency state -Infections, Pulmonary disease, GI disease, Autoimmune disease, Malignancies = IPAM -treat: Ig replacement (no reduction in malignancies) |
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Hyper-IgM Syndrome features.
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-mutation in CD40L on CD4 Th cells leads to inability to class witch
-Xlinked -presents early in life with sever pyogenic infections -high levels of IgM, low levels of other Igs |
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What is the most common immunodeficiencey?
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CVID (common variable immunodeficiency)
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What raises suspicion for a primary immunodeficiency?
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When a child presents with RECURRENT infections, especialy if the infections are SERIOUS (pneumonia, meningitis, sepsis)
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B cell immunodeficiency histopathology/lab abnormalities and common infectious consequences.
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-absent or reduced follicles and germinal centers in lymphoid organs
-reduced serum Ig levels -pyogenic bacterial infections |
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T cell immunodeficiency histopathology/lab abnormalities and common infectious consequences.
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-may be reduced T cell zones in lymphoid organs
-reduced DTH reactions to common antigens -viral and other intracellular microbial infections and virus-associated malignancies |
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What are some "type II" autoimmune diseases and what are their mechanisms?
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-complement cascade activation: autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, Goodpasture's Syndrome
-receptor blockade: Myasthenia Gravis (auto-Ab against nACh-R) -receptor activation: Grave's disease |
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Grave's Disease features
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-Type II autoimmunity disease
-Antibodies generated to cell surface or ECM proteins leading to receptor activation -thyroid stimulating Igs activate TSH RECEPTOR on thyroid follicular cells, causing THYROID HORMONE OVERPRODUCTION |
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Goodpasture's syndrome
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-type II autoimmune disease
-Antibodies generated against glomerular and alveolar basement membrane proteins leading to COMPLEMENT CASCADE ACTIVATION causing local inflammation and tissue destruction -classically causes PULMONARY HEMORRHAGE and GLOMERULONEPHRITIS |
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systemic Lupus Erythematosus (SLE)
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-type III autoimmunity
-immune complex deposition leads to disease -auto-antibodies to cell surface, cytoplasmic, and nuclear proteins cause tissue destruction, which in turn produces soluble antigen -immune complexes form in circulation -symptoms: cuteanous vessels -> malar/butterfly rash; glomeruli -> lupus nephritis; joints -> arthritis |
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What are some "type IV" autoimmune diseases and what are their mechanims?
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-T-cell mediated tissue destruction
-type I DIABETES mellitus - destruction of pancreatic beta cell causes insulin deficiency -RHEUMATOID ARTHRITIS - destruction of synovium leads to systemic, classicaly symmetric polyarthritis -MULTIPLE SCLEROSIS - CNS demyelinating disease caused by T cell attack on MYELIN basic protein |
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What is hypersensitivity?
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OVERreaction by the adaptive immune system to an innocuous environmental stimulus in a PREVIOUSLY SENSITIZED, PREDISPOSED host
-leads to INFLAMMATION and tissue damage |
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What enzyme makes Prostaglandins?
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Cylcooxygenase (COX)
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What enzyme makes Leukotrienes?
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Lipooxygenase
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What are some chemical mediators of Acute Inflammation?
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Prostaglandins
Thromboxane A2 Leukotrienes Histamine |
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What are the primary leukocytes in acute inflammation?
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neutrophils
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What are the cardinal signs of inflammation?
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rubor (rendess) - Histamine-mediated vasodilation
calor (heat) - Histamine-mediated vasodilation tumor (swelling) - Histamine-mediated increase in vessel permeability dolor (pain) - prostaglandin E2 sensitization of bradykinin and other pain mediators |
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What are some stimuli to acute inflammation?
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infection, immune reaction, trauma, burns, radiation, necrosis, etc.
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What are the vascular events involved in acute inflammation?
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-vasoconstriction (seconds) - helpful in preventing blood loss in trauma
-VASODILATION - Histamine and other vasodilators (NO, PG) relax smooth muscle and increase blood flow -INCREASED VESSEL PERMEABILITY - also via Histamine, PG, other chemical mediators -swelling/edema - caused by net outflow of fluid from permeability that overwhelms lymphatic drainage -reduction of blood flow - interstitial pressure now > than hydrostatic pressure |
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Where do chemical mediators derive from?
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plasma, leukocytes, local tissue, bacterial products
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What is the precursor of PGs, TXs, and Leukotrienes?
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arachidonic acid (essential Fatty Acids)
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Where are prostaglandins found?
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macrophages, endothelial cells, platelets, mast cells
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What is the precursor for other prostaglandins such as PGE2, PGD2, and PGF2alpha?
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PGH2
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PGE2 features.
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-dinoprostone
-PG responsible for VASODILATION, PAIN, fever, GI protection -made in the endothelial wall -renal function |
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PGD2 features.
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-found in mast cells
-important in vasodilation, bronchoconstriction/asthma, pain ehancement |
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PGF2alpha features.
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contraction of uterus (abrotofactant)
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PGI2 features
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-prostacyclin
-VASODILATION, INHBITION of PLATELET AGGREGATION (antithrombotic), GI protection -made in endothelial wall (opposite of Thromboxane A2) |
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Thromboxane A2 features.
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-VASOCONSTRICTION, PLATELET AGGREGATION (thrombotic), bronchoconstriction, found in PLATELETS
(opposite of PGI2) |
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COX-1
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-constitutively active (always there)
-involved in fever, pain, GI protection, platelet aggregation |
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COX-2
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-involved in fever, pain, GI protection, platelet aggregation
-inducible at times of INFLAMMATION |
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x
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Eared Grebe
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A small, slender-necked, slender-billed grebe. In breeding plumage, black head and back; golden ear tufts; black crest. In winter plumage, dark gray above, white below; neck dusky. Similar in winter to Horned Grebe, but chunkier, and bill appears slightly upturned, sides of face smudged with gray, whitish patch behind ear
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Types of NSAIDs
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-Salicylates - ASPIRIN - diflunisal, sulfazaline
-Propionic Acid derivatives - IBUPROFEN, NAPROXEN -Acetic Acid derivatives - indomethacin, ketorolac -Oxicams - piroxicam, meloxicam -Fenamates -COX-2 inhibitor - celecoxib (Celebrex) |
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Clinical use of NSAIDs
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-anti-inflammatory (arthritis, lupus, etc)
-pain/analgesia (headaches, cramps) -fever (antipyretic) -cardiovascular/neurovascular protection |
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Aspirin Mechanism and Use
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-Acetylsalicylicacid (ASA)
-IRREVERSIBLE INHIBITION of BOTH COX-1 and COX-2 -inhibition of PG production reduces pain and inflammation -anti-platelet effect: TXA2 (pro-inflammatory) and PGI2 (anti-inflammatory) inhibition |
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Aspirin Toxicity
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-Gastric intolerance/ulcers (PGE2, PGI2)
-bleeding (D/c about 1 week before surgery) -renal damage -tinnitus -metabolic acidosis, hyperventilation, respiratory depression at high doses -REYE's SYNDROME in children with viral infection - FATTY LIVER change -res |
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Which NSAID acts on only COX-2 and how?
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-celecoxib (celebrex)
-REVERSIBLE INHIBITION of COX-2 -decrease in GI side effects -potential negative cardio events |
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Where are leukotrienes found?
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lung, platelets, mast cells, leukocytes
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Why are leukotrienes important in pathogenesis of asthma/allergic rhinitis?
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-LTC4, LTD4, LTE4 - increase vessel permeability, BRONCHOCONSTRICTION
-LTB4 - chemotaxis and activation of neutrophil adhesion molcules |
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what is the precursor of Luekotrienes and what enzyme is needed to make them?
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arachidonic acid
lipoxygenase (hydroxylation) |
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Zileuton (Zyflo CR)
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-blocks 5-lipooxygenase enzyme (leukotriene synthesis inhibitor)
-used in MAINTENANCE treatment of ASTHMA -oral -toxic: liver toxicity, secreted in breast milk |
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Montelukast (SINGULAIR), Zafirlukast (ACCOLATE)
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-blocks leukotriene cysLT1 receptor
-inhibits bronchoconstriction -used in MAINTENANCE treatment of ASTHMA, allergic rhinitis, exercise induced asthama prophylaxis -oral -toxic: abdominal pain, dizziness, headache, sore throat |
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Antihistamine uses and mechanism
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-conjunctivitis, hay fever, mild sleep disorders, motion sickness, pruritis, rhinitis, urticaria
-REVERSIBLE, COMPETITIVE antagonists to H1-Receptor |
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First generation antihistamines features
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-sedating (His in hypothalamus; involved in alertness; block and get sleepy)
-anticholinergic (dry mouth, constipation, blurred vision, tacycardia, urinary retention) -antiemetic -anti-motion sickness -shorter half-life |
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What are some first generation antihistamines?
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-diphenhydramine (Benadryl)
-dimenhydrinate (dramamine) -promethazine (phenergan) |
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diphenhydramine (benadryl)
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-first generation antihistamine
-useful in allergies, itching, mild sleep disorders, nausea -lasts about 4 hours |
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dimenhydrinate (dramamine)
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-first generation antihistamine
-used for motion sickness, anti-emetic, also causes sedation and anticholinergic side effects |
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promethazine (phenergan)
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-first generation antihistamine
-very useful sedative/anti-emetic -lasts 4-12 hours |
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second generation antihistamine features and examples
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-non-sedating (do NOT cross blood brain barrier)
-little or no anticholinergic side effects -ex: cetirizine (zyrtec), loratidine (claritin), fexofenadine (allegra) |
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