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2011-05-11 15:29:34
Immunology MS1

Immunology Lecture 3 Syllabus complete
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  1. lipopolysaccharide (LPS)
    • major inflammatory stimulus found in gram negative bacteria
    • aka endotoxin
    • elicits septic shock via TLR4
  2. gram staining
    • gram +: purple
    • gram -: pink
    • based on thickness of peptidoglycan on cell wall
  3. bacteria lipoproteins signal through which receptor?
  4. Composition of bacterial lipoprotein
    diacylglycerol moiety bound to cysteine through thioester linkage
  5. 4 Toxin producing bacterial diseases
    • cholera (vibrio cholerae): bacteria stays in gut lumen and secretes toxins
    • tetanus (clostridium tetani): secretes very low amounts of potent neurotoxin that's undetected by immune response
    • diphtheria (corynebacterium diphtheria): transmitted via respiratory secretions, toxins kill epithelium and form pseudomembrane leading to airway swelling
    • toxic shock (staphylococcus aureus): produces superantigens that activate many T cells to develop shock
  6. Viral life cycle
    • attach to host surface receptor
    • internalization in endocytic vesicle
    • uncoating of protein shell
    • nucleic acid is used to synthesize viral mRNA
    • mRNA directs synthesis of viral proteins
    • viral particle sself assemble and exits infected cell
  7. cellular tropism
    each type of virus can only infect a narrow range of eukaryotic host cells
  8. Herpes simplex viruses
    • infect neuronal cells
    • exists in nucleus as an episomal element (plasmid-like)
    • periodic release of virus results in recurrent outbreak
  9. 2 major differences betwee human and fungal cells
    • carbohydrate polymer cell wall
    • surrounding matrix of manoproteins/mannans
  10. What are mannoproteins?
    • conjugates of peptides with long polymers consisting of mainly mannose
    • initiate immunity via TLR
  11. 2 morphological forms of fungi
    • Yeast: single cell, reproduce asexually via budding
    • Mould: complex filamentous form
  12. Where do fungi grow?
    • soil
    • extracellulary inside host
  13. Candida cause disease under these 4 circumstances
    • antibiotic treatment reduces normal bacterial flora
    • chemotherapy reduce # of neutrophils
    • AIDS
    • other immunodeficient syndromes
  14. What disease is caused by cryptococcus neoformans?
    • inhalation of this yeast causes pneumonia
    • can cause meningitis in AIDS patients
  15. How does cryptococcus neoformans escape phagocytosis by neutrophils and macrophages?
    polysaccharide capsules
  16. Defect in which part of the immune system is especially detremental in a histoplasma capsulatum infection?
    • Cell mediated immunity
    • this yeast can avoid killing and proliferate within macrophages, so they must be controlled by cell mediated immunity
  17. Characteristics of asperguillus
    • opportunistic pathogen mould
    • inhaled spores usually stay dormant unless host has low PML and macrophage counts
    • causes pneumonia
  18. Disease caused by entamoeba histolytica
    lives in the intestine, can cuause ulcers and bloody diarrhea
  19. What are helminths?
  20. Response and result to helminth infection
    • local inflammation with plasma cells, eosinophils, and mast cells
    • histamine release
    • chronic inflammation may lead to fibrosis
  21. Disease caused by trypanosoma
    African Sleeping Sickness
  22. TLR family receptors is part of the ___ immune system?
  23. pathogen-associated molecular patterns (PAMPs)
    innate immune system uses PAMPs to sense presence of pathogenic microbes
  24. pattern recognition receptors (PRRs)
    receptors used by innate immune system to recognize PAMPs
  25. What is mannose-binding lectin (MLB)?
    • soluble component of innate immune system
    • targets bacteria for phagocytosis
  26. Mechanism of MBL action
    • MBL= mannose binding lectin
    • localizes on bacterial cell wall by binding specific spatial pattern of mannose and fructose residues
  27. 2 most common causes cold
    • Rhinoviruses (30%)
    • Coronavirus (15%)
  28. Pathway of common cold infection
    • viruses attach to nasopharynx via ICAM1
    • viral replication within cell then spread to upper respiratory tract
  29. Timeline of common cold infections
    Infection occurs 2-3d prior to development of symptoms, and usually resolves 7-10d later
  30. 1st step of innate immune response to viral infection
    activate type 1 interferons in infected cell
  31. RIG1 and MDA5 localization and function
    • - PRR sensors that are expressed in cytoplasm/cytosol of most cells
    • - recognizes dsRNA
  32. pathway of innate immune system in a viral infection
    • PRR sensors (RIG1 and MDA5) recognize viral dsRNA
    • activate transcription factors (IRF3, IRF7)
    • initiate production of type 1 interferons
  33. 4 pathways initated by tyep 1 interferon
    • induce resistance to viral replication in all cells
    • increase MHC class I expression and antigen presentation in all cells
    • activate dendritic cells and macrophages
    • activate NK cells to kill virus-infected cells
  34. Function of MHC class I molecules
    enhance recognition and killing of virally infected cells by cytotoxic T cells
  35. Function of dendritic cells
    promote initiation of adaptive resonse in local lymph nodes
  36. Function of macrophages
    promote secretion of inflammatory cytokines
  37. What is the most immediate innate response to viral infection?
    NK cell activation target production of virus by infected cell
  38. Development of NK cells (location, lineage)
    • produced in bone marrow
    • circulates in blood
    • lymphoid
  39. What activates NK cells?
    • type 1 interferon
    • other macrophage-induced inflammatory cytokines
  40. How is NK cell killing regulated?
    • NK cell inhibitory receptors block killing of cells with normal amoutns of MHC class I molecules
    • downregulation of MHC class I molecules in virally infected cells will be lysed
  41. Basic responsibility of MHC class I molecules
    presenting pieces of intracellular pathogens to CD8+ T cells
  42. Evolution of NK cells
    • MHC class I molecules present intracellular pathogens to CD8+ T cells
    • some viruses evolve to downregulate MHC class I molecules in infected host to evade CD8+ T cells
    • innate immune system develops NK cells which lyse cells lacking MHC class I molecules
  43. 4 primary responsibilities of the innate immune system
    • prevent infections into sterile tissues
    • detecting infections in sterile tissues
    • mounting an immediate, nonspecific response to clear pathogen
    • transporting antigens to lymph node to elicit adaptie response
  44. 3 ways to breach simple mechanical barriers (epithelial tight junction)
    • microscopic trauma
    • major trauma
    • introduced by arthropod vectors
  45. 9 types of innate immune barriers
    • epithelium with tight junction
    • longitudinal air/fluid flow
    • movement of mucus by cilia
    • fatty acids
    • low pH
    • pepsin (enzyme)
    • lysosozyme (salivary enzymes)
    • defensins (antibacterial peptides)
    • normal flora
  46. 5 cellular processes of innate imune system
    • phagocytosis
    • inflammation
    • recognition of extraellular pathogens
    • recognition of intracellular (viral) infections
    • recognition and kiling of viral infected cells by NK cells
  47. 4 pro-inflammatory cytokines
    • IL1
    • IL4
    • IL6
    • TNF-alpha
  48. local and systematic effects of IL-1beta
    • activate vascular endothelium
    • activate lymphocytes
    • local tissue destruction increases access of effector cells

    systemic: fever, IL6 production
  49. local and systemic effects of TNF-alpha
    • activate vascular endothelium and vascular permeability
    • increases entry of IgG, complement and cells
    • increases fluid drainage to lymph nodes

    systemic: fever, shock, mobilize metabolites
  50. local and systematic effects of IL6
    • lymphocyte activation
    • increased antibody production

    systematic:fever, acute phase protein production by hepatocytes
  51. effects of Cxcl8
    chemotactic factor recruits neutrophils, basophils,a nd t cells to site of infection
  52. effects of IL12
    • activates NK cells
    • induces differentiation of CD4 T cells into Th1 cells
  53. Effects of IL1beta/IL6/TNF-alpha on LIVER
    • acute phase proteins (mannose binding lectin)
    • activation of complement opsonization
  54. Effects of IL1beta/IL6/TNF-alpha on BONE MARROW ENDOTHELIUM
    • Neutrophil mobilization
    • phagocytosis
  55. Effects of IL1beta/IL6/TNF-alpha on HYPOTHALAMUS
    • increased body temperature
    • decreased viral and bacterial replication
    • increased antigen processing
    • increased specific immune response
  56. Effects of IL1beta/IL6/TNF-alpha on FAT/MUSCLE
    protein and energy mobilization to increase body temperature
  57. Effects of TNF-alpha on DENDRITIC CELLS
    • migration to lymph nodes and maturation
    • initiates adaptive immune response