Immuno Quiz 2

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Immuno Quiz 2
2012-09-18 02:18:20

Immuno Quiz 2
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  1. Primary (generative) tissues
    Development and maturation of B and T lymphocytes

    include: bone marrow and the thymus
  2. Secondary (Peripheral) tissues
    where immune responses to microbes take place (activation)

    include: lymph nodes, spleen, mucosal/cutaneous lymphoid tissues
  3. Hematopoetic Stem Cell


    Multipotential Progenitor Cell which divides into
    Common Lymphoid and Myeloid progenitor
  4. B cell development in the bone marrow
    MPP > Common lymphoid progenitor > early pro-B cell > late pro-B cell > pre-B cell> immature B cell.
  5. B cell development (continued)
    as the B cell "rolls along" the thymus, it gets modified by rearranging its immunoglobulin genes and removing those reactive to self-antigens (positive-negative selection)
  6. Once Developed,
    B cells go into peripheral lymphoid organs to get activated
  7. Development of T cell progenitors in the bone marrow
    MPP> common lymphoid progenitor > migration from bone marrow to thymus> T cell development in the thymus
  8. medulla of thymus
    where final stages of T cell receptors rearranged. moved from cortex. self reactive T cells are terminated
  9. positive negative selection
    T cells that recognize self MHC molecules receive signals for survival. those that interact strongly against self antigen are eliminated
  10. Secondary lymphoid tissues
    the anatomy of secondary lymphoid tissues enables trapping of antigens and concentrates lymphocytes/APCs (coming from infection site)

    where adaptive immune responses are developed
  11. major secondary lymphoid tissues include:
    • lymph nodes
    • spleen ("blood filter" RBC and antigens go thru here)
    • mucosal-associated lymphoid tissues (MALT)
    • gut-associated lymphoid tissues
    • bronchial associated lymphoid tissues
  12. gut-associated lymphoid tissues
    • tonsils (mostly B cell)
    • adenoids
    • peyer's patches (small intestine)
  13. two critical antigen filters
    both collect antigen by the lymphatic system or spleen

    without infection, 5 million lymphocytes leave the blood and enter secondary lymphoid tissues per min.
  14. lymph nodes
    fluid from epithelia, connective tissues and most parenchymal organs that are drained by lymphatics (which transport lymph to lymph nodes)
  15. lymph passes thru lymph nodes and MALT
    where antigens and lymphocytes are concentrated to increase probability to have rare angien-specific.

    lymph nodes are important for immune responses to lymph-borne pathogens
  16. lymph node morphology (cortex)
    cortex: have follicles where mature but naive/inactivated B cells meet with follicular dendritic cells (FDC) to become activated then they migrate to wherever
  17. lymph node morphology (paracortex)
    T cells in the lymph nodes are concentrated in the paracortex, which also contains dendritic cells that present antigens to T cells

    T cells constantly move around the lymphatics to look for dendritic cells
  18. Spleen
    blood passes thru spleen where antigen and lymphocytes are concentrated to increase probability to have rare antigen specific lymph cells to see antigen in the blood.

    crucial for blood-borne pathogens 
  19. spleen morphology
    • white pulp: secondary lymphoid tissue
    • red pulp: RBC

    spleen does NOT drain into the lymph
  20. spleen morphology (cont'd)
    red pulp is a marginal zone where T and B cells react better.

    both zones have DC and macrophage.

    blood enters thru network of channels called (sinusoids) where blood-borne antigens are trapped and concentrated by DC and macrophage
  21. chemokines
    chemoattract cytokines.

    large family of small cytokines that stimulate migration of lymphocytes

    cytokines are secreted proteins that mediate immune response
  22. chemokines orchestrate the development of secondary lymphoid tissues (1)
    stromal cells and high endothelial venules (HEV) secrete CCL21
  23. chemokines orchestration (2)
    dendritic cells are receptieve to CCL21 and then migrate into the developing lymph node thru lymphatics
  24. chemokines orchestration (3)
    DC secrete CCL18, 19 which attract T cells to the developing lymph node
  25. chemokines orchestration (4)
    B cells are attracted to the developig lymph node via the CCL 18, 19.
  26. after activation, lymphocytes alter expression of chemokine receptors
    B and T cells migrate toward each other and meet at the edge of follicles where helper T cells interact and help B cells mature and differentiate into antibody producing PLASMA cells
  27. activated lymphocytes
    exit lymph nodes thru efferent lymphatic vessels and leave the spleen thru veins
  28. lymphocyte recirculation and migration into tissues
    naive T cells migrate from the thymus to lymph nodes. enter via high endothelial venules into thymus. T cells express specific adhesion molecules and chemokine receptors (L-selectin CD62L, CCR7 which binds to HEV)
  29. lymphocyte recirculation and migration into tissues (2)
    naive lymphocytes constantly recirculate betwen blood and peripheral lymphoid organs, where they may be activated by antigens to become effector cells.

    effector cells to sites of infeciton
  30. Homing of naive T cells to lymph nodes is controlled by specific adhesion molecules and chemokine receptors
    CD62L (L-selectin) and CCR7
  31. CD62L
    the interaction of this cytokine promotes adherence and rolling of T cells.
  32. CCR7 ligands
    chemokines CCL19 and CCL21 made by HEVs of lymph nodes and Peyer's patches. also produced by stroma of T cell zone in the spleen
  33. T cells that recognize specific antigens are activated
    during activation, T cells reduce the expression of adhesion molecules and chemokine receptors that attracted them to lymph nodes.

    also increase expression of receptors for phospholipid sphingosine 1-phosphate

    the concentration of sphingosine is higher in the blood than in lymph nodes and activated T cells enter the circulation and to infection sites
  34. circulation of activated and memory B cells
    the activated B cells leave the germinal center and the plasma cells (terminally differentiated) go to the bone marrow
  35. activated and memory B cells
    both may remain in the lymph node or migrate to bone marrow
  36. circulation of activated and moemory B cells (2)
    active, ongoing process. new naive B and T cells constantly generated.
  37. Innate immunity characteristics
    • intrinsic mech for host protection
    • first line of defense against microbial infections
    • triggered by damaged host cells
    • instructs adaptive IS to become active
  38. Principal components of innate immunity
    • epithelial barriers
    • cells in circulation and in tissues (phagocytes)
    • natural killer cells, dendritic cells, intraepithelial lymphocytes and plasma proteins (complements)
  39. epithelial barriers
    • physical barrier to infection: physical protection for common portals of entry (skin, GI tract, respiratory tract)
    • chemical barrier: (kills microbes by locally produced antibiotics i.e. sweat)
    • immune barrier: kills microbes and infected cells by intraepithelial lymphocytes
  40. Cells of immune system
    in circulation and in tissues

    • phagocytic cels: neutrophils, monocytes, macrophages
    • dendritic cells
    • natural killer cells
    • Intraepithelial lymphocytes
  41. phagocytic cells: neutrophils
    • most abundant lymphocyte
    • first cells to respond to infections in the blood
    • new cells produced rapidly in response to infection
    • ingest microbes in circulation and migrates to infection cites in tissues
    • dies after the job
  42. phagocytic cells: monocytes/macrophages
    • ingests microbes in blood/tissues
    • monocytes are in circulation but less abundant than neutrophils
    • etner and reside in tissues as macrophages
    • macrophages are found in connective tissue and also every organ of the body
  43. maturation stages of mononuclear phagocytes
    • bone marrow stem cell> blood monocyte> tissue macrophage>
    • can differentiate into microglia, kupffer cells, alveolar macrophages, osteoclasts. (histiocytes)
    • can be activated into a macrophage. (sinusoidal cells, peritoneal macrophages)
  44. neutrophils and monocytes
    • monocytes do not have phagocytic function. have to mature. live on tissues as macrophages
    • monocytes participate in inflammation. initial inflammation is good to alert and immobilize area but may become dangerous leading to disease
    • ingest microbes in circulation
    • express selectin receptors and integrins, enabling migration to tissues
  45. Microbe recognition
    • cells express receptors that recognize microbial pathogen-associated molecular patterns (PAMPs) shared by microbes of the same type among bacteria, fungi, viruses
    • examples of recognized substance: bacteial LPS, terminal mannose residues, ds-RNA, unmethylated CpG oligonucleotides
    • microbes cannot mutate for protection against innate immunity b/c target structures are ESSENTIAL for survival
  46. innate immune system recognizing antigens
    • the macrophages have limited diversity but they have TLR to recognize something that is commonly found in many microbes
    • such as ds RNA, LPS, etc
    • innate recognition are nonclonal receptors: identical receptors for all cells of the same lineage
  47. adaptive immune system recognizing antigen
    • not broad. look for detail of microbial molecules
    • encoded by genes produced thru somatic recombination of gene segments, resulting in greater diversity
    • clonal distribution. clones of lymphocytes with distinct specificities express different receptors
  48. cellular location of receptors of innate immune system
    • present in cell surface, endosomes (where the eaten microbes are chilling), and cytoplasm. 
    • present in phagocytes, DC, endo/epithelial cells
  49. TLRs are specific for different components of microbes
    • signals generated upon engagement of TLRs activate transcription factors, stimulating expression of cytokines, enzymes, and other proteins involved in antimocrobial functions of activated phagocytes and DC. 
    • two Interferon regulatory factors are NFkB (transcription factor that activates cytokines, endothelial adhesion molecs) and IRF-3 (make interferons that block viral replication)
  50. common TLR pathways taken for signal transduction
    happens quickly and numerous ways exist. something can break signal and initiate disease due to the complexity
  51. recognition of microbes (innate)
    • recognition via receptors: encoded in the germline (pattern recognition receptors) limited diversity
    • specificity: recognizes umbrella of molecular patterns shared by microbes
    • distribution of receptors: nonclonal, ID receptors expressed on all cells of a particular type
    • response: same each time. no improvement
    • hard for microbes to escape
  52. how leukocytes (neutrophils, monocytes, and activated T cells) migrate from blood into infected T cells
    • macrophages in tissues recognize antigens and produce TNF and IL-1.
    • these stimulate leukocytes to get close
    • selectin helps bring them in to tether and roll and integrin causes firm adhesion
    • then chemoknes help the leukocyte to come thru the tissue
  53. chemokines role on leukocyte migration from blood to infected tissues
    chemokines increase affinity of integrin binding of phagocytes to vascular endothelium, stimulate motility, and create a chemoattractant gradient for attracting phagocytes to infection sites 
  54. killing of microbe 
    • macrophage expresses receptors for many bacterial constituents: LPS, mannose, scavenger, TLR 4, glucan
    • bacteria binds to one of these and the macrophage releases cytokines and lipid mediators of inflammation
    • then the bacteria gets swallowed into phagosome, which combines with lysosome to become phagolysosome
  55. phagocytosis (intrcellular killing of microbes)
    • after microbe is enveloped, the phagolysosome dissolves cell wall and then toxic substances such as NO, reactive oxygen species, inducible nitric oxide synthase which are lethal are released
    • the DNA of bacteria is severely damaged
  56. chemokines, lipid mediators , N-formylmethionyl peptides are recognized by alpha helical transmembrane receptors
    this causes increased integrin avidity and cytoskeletal changes leading into migration into tissues 
  57. microbeial characteristics such as LPS are recognized by toll-like receptors
    this creates production of cytokines and reactive oxygen intermediate which kills microbes 
  58. mannose receptors detects mannose from bacteria
    then the phagocytosis of microbe into phagosome and eventual killing of bacteria follows 
  59. cytokines released (TNF, IL-12)
    • causes inflammation and enhanced adaptive immunity. 
    • microbes are eliminated in the first 24. if infection goes on, inflammation is initiated regardless of microbes being killed 
    • make the wound look bad but tissue starts remodeling due to fibroblast growth factors, angiogenic factors, metalloproteinases.