PBL 1 – INNATE IMMUNITY (ORAL PRESENTATION) In week 1 of the PBL, tutors will assign groups of 4 (or 5) students to the 4 topics. On week 3, each group (4 or 5 students) will give a Powerpoint presentation of 30-40 mins (7 mins per student). Although presented in a group, each talk will be marked individually so don't be concerned if a team member is absent for the final presentation. SUBJECT 1. Genetic diseases that affect phagocyte function highlight the importance of these cells in controlling bacterial infections. Outline how phagocyte function is altered by the genetic defect(s) in the diseases listed below and how this results in a defective immune response: Topic 1. Leukocyte adhesion deficiency (LAD) Starting refs: Harris et.al. Curr. Opin. Hematol. 20: 16-25 (2013); Malech and Hickstein Curr Opin Hematol 14:29-36 (2007); Etzioni and Tonetti Immun Rev 178:138 (2000) Student 1: Integrin and selectin structure Student 2: Integrin and selectin function in innate immunity Student 3: LAD type 1 - gene defects and phenotype Student 4: LAD type 2 - gene defects and phenotype Student 5: Animal models for LAD Topic 2. Chronic granulomatous disease Starting refs: Song et. al. Clin. Mol. Allergy 9:10 (2011); Malech and Hickstein Curr Opin Hematol 14:29–36 (2007); Goldblatt and Thrasher Clin Exp Immunol 122:1-9 (2000)

Student 1: Mechanisms of pathogen destruction by innate immune cells

Student 2: The respiratory burst in phagocytes Student 3: CGD gene defects Student 4: Animal models of CGD Student 5: Clinical presentation and management of CGD

SUBJECT 2. Cells of the innate immune system recognise foreign organisms through pathogen-associated molecular patterns (PAMPs). Choose one of the PAMPs below and outline how cells of the innate immune system recognise this PAMP and how this allows for cellular activation and destruction of the foreign organism:

Topic 3. Lipopolysaccharide Starting Refs: Wang and Quinn Prog. Lipid Res. 49: 97-107 (2010); Kenny and O’Neill Cytokine 43:342–349 (2008); Guha et al Cell Signalling 13: 85-94 (2001)

Student 1: Structure of LPS and lipid A Student 2: Effects of LPS on macrophages/dendritic cells/NK cells Student 3: LPS and TLR4 signalling Student 4: Pathogen destruction pathways activated by LPS Student 5: The TLR family and their ligands Topic 4. Bacterial (CpG) DNA Starting refs: Kumagai et al Advanced Drug Delivery Reviews 60: 795–804 (2008); Hacker et al Immunol:105: 245-251 (2002); Krieg Ann. Rev. Immunol. 20:709-760 (2002).

Student 1: Differences between bacterial and mammalian DNA Student 2: Effects of CpG DNA on macrophages/dendritic cells/NK cells Student 3: CpG DNA and TLR9 signalling Student 4: Therapeutic applications of CpG DNA Student 5: Delivery of stimulatory DNA into cells