Pathology exam study guide.pdf

Pro-inflammatory Cytokines IL-1 -Produced by macrophages IL-6 -Produced by macrophages -Induces fat and muscle cells to metabolize IL-17 -Protects from fungal infections. -Psoriasis, MS, asthma, IBD, periodontitis -Involved in massive inflammatory response TNFα IFNɣ PRR IL-4 -Both drives the develop...

Pro-inflammatory Cytokines IL-1 -Produced by macrophages IL-6 -Produced by macrophages -Induces fat and muscle cells to metabolize IL-17 -Protects from fungal infections. -Psoriasis, MS, asthma, IBD, periodontitis -Involved in massive inflammatory response TNFα IFNɣ PRR IL-4 -Both drives the development of Th2 cells and is synthesized by Th2 cells -Induce B cells to produce IgE -Helps mast cells, eosinophils IL-10 -Treg function: suppression TGFβ -Produced by macrophages -During sepsis → DIC → fever -Increases vascular permeability -Transforming Growth Factor -Treg function -Inhibits macrophage activation -Inhibits cytotoxic T cell function CCR7 -Produced and activated by T cells and NK cells -Secreted by TH-1 -Signal 1 -*Activates macrophages* -Can both be expressed by DC and T cells -Helps migration to lymph nodes -binding to only two ligands: CCL19/CCL21 CD40 -CD40 signaling of B cells promotes germinal center formation -Important for proliferation C4b2a → C3 convertase -Catalyzes the cleavage of C3 into C3a and C3b. This is the most important step in the complement pathways. IL-12 -NKC activated by IL-12 -Induces differentiation of CD4 cells into Th1 cells IL-2 -Produced by T cells -*Critical for T cell proliferation* IL-2Rα -Upregulation -High affinity receptor LFA-1 -Key T cell integrin -Adhesion to ICAM-1 facilitates firm endothelium adhesion -Pattern Recognition Receptors -Cellular receptors that recognize PAMPS/DAMPS -TLRs, Lectin, NLR’s PAMPS -Pathogen associated DAMPS -Necrotic cells -Damage associated APCS -Antigen Presenting Cell -Express MHC II -DCs, Macrophages, B cells Toll-like Receptors ↳ A class of PRR’S ↳(10 in humans) TLR4 TLR3 Anti-inflammatory Cytokines -Extracellular -MyD88 receptor -LPS (endotoxin) → TLR4 -Intracellular -*Recognizes dSRNA → found in viruses* -TLR3 recruits TRIF and triggers IFNα/β production C3a C4a C5a -Anaphylatoxins:C5a >C3a> C4a -Causes inflammation -C5a: powerful chemoattractant, but not structurally related to other chemokines C3b -*Main effector molecule in the complement pathways* -Cleaved by factor I into C3d CD3 -Signal transduction -(TCR) HEV Th1 Th2 Th17 M- Cell -Mucosal lymphoid tissues -Peyer's patches CD4 -Helper cells -Recognize extracellular pathogens -Need antigen presenting cells -MHC class II (β2) -Transcription factor = IL-4, GATA-3 -Activated by IFNɣ CD8 -Cytotoxic → *Perforin & Granzymes* -MHC class I (αβ) -Intracellular pathogen -Recognize any nucleated cells -High Endothelial Venules -Naive lymphocytes -No specific antigen -Express: CCR7, CCL21, CCL19 -CD4 T cell -*Activated macrophages* -Secretes IFNɣ and CD40L -Signal 1= IFNɣ -Signal 2= CD40L -Tuberculoid Leprosy -Cytokines = IFNɣ and IL-2 -CD4 T cell -Allergen specific -*Response to parasite* -Mediates worm elimination -Eosinophil activation -Lepromatous Leprosy -Cytokines = IL-4, IL-5 IL-13 -Enhances neutrophil response -Autoimmunity -Differentiation occurs when IL-6 is present -Cytokines = IL-6, IL-17 TFH -Activates B cells -Cytokine = IL-21 TREG -Suppresses other effector T cells -Cytokines = IL–10, TGF-β DAF -Membrane bound regulator -Binds to C3b or C4b -Dissociation of C3 convertase Lectins ↳Carb binding PRRs C-type -Calcium dependent -Recognizes PAMPS -mediates phagocytosis Dectin-1 -Cytokine production MBL -Mannan-binding lectin -Binds mannose -Activated lectin pathway MASP -MBL associated serine proteases -Cleaves C2 and C4 components of complement NLRs -Family of intracellular receptors -Responsible for inflammatory response activation: -Caspase-1 activation -Cleavage of pro-IL1β and secretion of IL-1β -NOD1 / NOD2 ↳senses gram (+) and gram (-) bacteria Dendritic Cells -Antigen specific immune response -Link innate and adaptive immune response -Activate naive T cells -Role in defense against viruses -Binds dSRNA via TLR3 Innate Immunity -Natural (first to happen) -Primitive -Exists prior to infection -Non antigen specific -RAPID -Phagocytes Adaptive immunity -Specific/ acquired -Evolved -In response to infection -Antigen specific -SLOW -Lymphocytes MHC I MHC II Polymorphic α chain associated with β2 microglobulin Polymorphic α and β chains Cell types All nucleated cells APC’s and thymic epithelial cells Peptide source Endogenous Exogenous Peptide size 8-10 13-17 T cells CD8+ CD4+ Loading site E.R. Endosome Enzymes Cytosolic proteasome Endosomal/lysos omal proteases Binding TAP CLIP/ Invariant chain Structure BCR TCR -Recognizes different types of molecules -Recognizes peptides only -No need of MHC -Needs MHC -Diff. Shapes of epitopes ↳tertiary conformation -Linear peptides ↳primary conformation -Two pairs of heavy and light chains -One α and one β chain -Two antigen binding sites -One antigen binding site -Igα and Igβ -CD3 Immunoglobulins IgM -(“Macro”) -Largest and first antibody -Involved in activation of classical pathway -Pentamer → 10 binding sites IgG -(“General”) -Most common; in blood -Neutralization of microbes and toxins -Opsonization of antigens for phagocytosis -Involved in activation of classical pathway -ADCC -Monomer → 2 binding sites IgE -(“Sneeze”) -Allergic reactions -Eosinophil and mast cell mediated defense against helminths -Monomer → 2 binding sites IgA -(“Airway”) -Found in respiratory tracts and other mucosa -Breast milk -Dimer → 4 binding sites IgD -Marker to define mature B cells