MMG 451 Assignment 4 (25 possible points) Due: June 26th, 2017 at 11:59 pmInstructions: This exercise is meant to help you prepare for the final exam. In your own words, please fill in the grey boxes in the table below regarding the various immune conditions. Please note, some conditions may have more than one type of immune disease. For full credit, under the column for the type of immune disease, please specify the type of hypersensitivity (type I-IV) or immunodeficiency (congenital or acquired), if applicable. In the Pathogenesis/Effect on Immune System/Clinical Manifestation column, please provide a short description of the effect/manifestation. Each box is worth 1 pt.You may work individually or in a group on this assignment (to a maximum of 4 students) however, everyone must submit their own sheet. Late assignments will not be accepted. Immune Condition Associated Defect or Mutation Target of the immune system (what do the components of the immune system target?)Pathogenesis/Effect on Immune System/Clinical Manifestations Type of Immune Disease (autoimmunity, hypersensitivity, or immunodeficiency)Leukocyte adhesiondeficiency (LAD)Genetic mutations for various cell adhesion molecules or cell signaling moleculesDefective leukocyte adhesion to endothelial cells or defective leukocyte rolling. Both lead to defective migration into tissues. Congenital immunodeficiencyBare Lymphocyte Syndrome Decreased expression of MHC II molecules due to defects in transcription factors Defects in helper T cell functions related to cell mediated and humoral immunityCongenital immunodeficiencyHuman Immunodeficiency Virus (HIV)Retrovirus that infects CD4+ T cells and takesover its gene machinery causing a depletion of CD4+ T cells Infects CD4+T cells using the CXCR4/CCR5 chemokine receptorsAcquired Immunodeficiency Chronic granulomatous diseaseMutation in phagocyte oxidaseDefective production of reactive oxygen species by phagocytes; recurrent intracellular bacterial infectionCongenital immunodeficiencyHyper-IgM syndrome(X-linked)Genetic mutation in CD40LDefects in helper T cell functions,isotype switching, and cell mediated immunityCongenital immunodeficiencyDiGeorge syndromeNo thymus Lack of T cell production resultingin a decreased immune responseCongenital immunodeficiencySCID – X-linked Mutations in cytokine receptor common y chain. Defective T cell development in absence of IL-7 signalsHigh risk of infections due to a severe deficiency in the immune systemCongenital immunodeficiencyWiskott-Aldrich syndrome Mutations in WAS Inability to activate T cells due to signaling defects in T cell cytoskeletal rearrangementCongenital immunodeficiencyX-linked (Bruton’s) AgammaglobulinemiaPre-B receptor checkpoint defect, Btk mutationDecrease in all serum Ig isotypes, reduced number of B cellsCongenital immunodeficiencyCrohn’s disease Inflammation mediated by Th1 and Th17 cytokines Intestinal bacteria stimulate inflammation within the wall of the GI tractType IV hypersensitivity, Autoimmunity Chediak-Higashi syndromeDefect in fusion of endosomes with lysosomes in various phagocytic cellsDefects in phagocytic cells of lysosome function and inability toexocytose granules Congenital immunodeficiencyRheumatoid arthritisCollagenCitrullinated self proteinImmune complex deposition in small joints, Inflammation as a result of the release of TH1 and TH17 cytokinesAutoimmunity, type IV hypersensitivityAllergies (ie. pollen) Mast Cell activation which leads to an increase and excessive immune responseType I hypersensitivityGraves’ Disease TSH receptor Stimulation of TSH receptors on thyroid follicular cells by autoreactive antibodiesType II hypersensitivityAcute rheumatic feverStreptococcal antigen looks like myocardial antigen resulting in antibody cross-reactivityAutoreactive IgG antibodies bound to self-antigen on host tissues stimulate inflammation and macrophage activationAutoimmunity, type II hypersensitivitySystemic lupus erythematosus (SLE, Lupus)DNA and other nuclear proteinsNephritis, arthritis, vasculitis Type III hypersensitivity Type I Diabetes Antigens of β cells in the islets of LangerhansThe pancreas is unable to produce insulin or produces a very small amount Autoimmunity, hypersensitivityContact dermatitis (ie. poison ivy)Targets self-protein modifying it to look foreign (Neoantigen) Th1 cells stimulate inflammation by the release of proinflammatorycytokines such as IFN-γType IV