Micro ch 15

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  1. adaptive immunity
    • protection provided by immune responses that mature throughout life
    • involved B cells and T cells
  2. lymphocytes
    the primary participants in the adaptive immune responses
  3. primary repsonse
    • the first response to a particular antigen
    • As a result of initial encounter, adaptive immune system "remembers" the mechanism that proved effective against specific antigen
  4. secondary response
    refers to the stronger antigen-specific immune response that results when an antigen is encountered again later in life (after a primary repsonse)
  5. 2 basic strategies for countering foreign material used by adaptive immune response
    • humoral immunity
    • CMI (cell-mediated immunity) or cellular immunity
    • *both are powerful and, if misdirected, can damage the body's own tissues
  6. humoral immunity
    • works to eliminate extracellular antigens
    • Ex:  bacteria, toxins, or viruses in bloodstream or in tissue fluids
  7. CMI
    deals with antigens residing within a host cell, such as a virus infecting a cell
  8. B cells
    • b lymphocytes
    • responsible for humoral immunity
    • develop in bone marrow
    • programmed to make antibodies
    • *In response to extracellular antigens, B cells may be triggered to proliferate and then differentiate into plasma cells
  9. Plasma cells
    function as factories that produce Y-shaped proteins called antibodies
  10. Antibodies
    • Y shaped proteins
    • bind to antigens, highly specific
    • protect host by both direct and indirect mechanisms
    • Have 2 functional regions: 2 identical arms & the stem
  11. What do the arms do on antibodies
    • Arm bind to specific molecules
    • the amino acid sequence of the end of the arms varies among antibodies, providing the basis for their specificity
  12. What do the stems do on antibodies
    • function as a "red flag"
    • tagging antigen bound by antibodies and enlisting other immune system components to eliminate molecule
  13. How do antibodies protect both directly and indirectly
    • Direct effort is due to their ability to bind antigens. Simply by binding, coat antigen & prevent it from attaching to host cell
    • Indirect protective effect is "red flag" tagging for elimination
  14. B cell receptor (BCR)
    a membrane-bound version of specific antibody the B cell is programmed to make
  15. How does a naive B cell know when to respond
    • B-cell surface has numerous copies of BCR
    • If naive B cell encounters an antigen that it's BCR binds, cell is triggered to multiply
    • Some of resulting clones eventually differentiate, becoming plasma cells
    • *Before it can multiply, however, generally needs to be activated by another type of lymphocyte - a Tcell- which also must recognize antigen and confirm danger
  16. T cells
    • T lymphocytes - are cell mediated immunity
    • name reflects they mature in thymus
    • 2 subsets help eliminate antigen: cytotoxic T cells and helper T cells
    • Both have multiple copies of surface molecule T-cell receptor
    • Also includes 3rd T-cell subset: regulatory T cells
  17. Cytotoxic T cell
    Type of lymphocyte programmed to destroy infected or cancerous "self" cells
  18. Helper T cells
    Type of lymphocyte programmed to activate B cells and macrophages, and assist other parts of the adaptive immune response
  19. T-cell receptor (TCR)
    • functionally analogous to BCR
    • allows cell to bind a specific antigen
    • However, unlike BCR, does not recognize free antigen
    • Instead, the antigen must be presented by one of body's own cells
  20. regulatory T cells
    • help prevent the immune system from mounting a response against "self" molecules
    • failure to do this results in autoimmune diseases
  21. Just like B cells, naive helper T cells and naive cytotoxic T cells must be activated. How are they activated?
    • Dendritic cells are responsible for T-cell activation
    • *recall T cell part of innate immunity. Once activated, T cell proliferates and then differentiates to form effector T cells, armed to perform distinct protective roles
  22. TH cells
    • Effector helper T cells
    • help orchestrate various responses of humoral and cell-mediated immunity
    • Activate B cells and macrophages
    • produce cytokines that direct and support T cells
  23. Tcells
    • respond to intracellular antigens
    • when they find antigen, induce the "self" cell that harbor it to undergo apoptosis
  24. lymphatic system
    • collection of tissues and organs that bring the population of B cells and T cells into contact with antigens
    • Each lymphocyte recognizes only one or a few different antigens
  25. lymphatics
    • lymphatic vessels
    • where flow of lymphatic system takes place
    • Carries lymph
  26. lymph
    a fluid that forms as a result of the body's circulatory system
  27. secondary lymphoid organs
    • sites where lymphocytes gather to contact the various antigens
    • Ex: lymph nodes, spleen, tonsils, adenoids, and appendix
  28. Peyer's patches
    • tissues in the intestinal walls that inspect samples of intestinal contents
    • Have specialized epithelial cells (M cells) which transfer material from intestinal lumen to Peyer's patches
    • Dendritic cells in and near patches also reach throu epithelial layer and grab intestinal stuff to present to lymphocytes
  29. MALT
    • Mucosa-associated lymphoid tissue
    • Lymphoid tissue present in the mucosa of the respiratory, gastrointestinal and genitourinary tracts
    • Includes Peter's patches
  30. mucosal immunity
    • the immune response that prevents microbes from invading the body via mucous membranes
    • Involves MALT
  31. SALT
    • skin-associated lymphoid tissue
    • Lymphoid tissues under the skin
  32. Primary lymphoid organs
    • include the bone marrow and thymus
    • Bone marrow is where hematopoietic stem cells reside.
    • B cells and T cell originate in bone marrow, but ONLY B cells mature there
    • Immature T cells migrate to thymus and mature there
    • Once mature, lymphocytes gather in secondary lymphoid organs and await to encounter antigen
  33. immunogen
    used when referring specifically to an antigen that elicits an immune response in a given situation
  34. 2 categories of antigens
    • *Antigens include an enormous variety of materials, from invading microbes and their products to plan pollens
    • But all fall into 2 categories:
    • T-dependent antigens
    • T-independent antigens
  35. T-dependent antigens
    • The responding B cell requires assistance from the TH cell in order to become activated
    • characteristically have a protein component
  36. T-independent antigens
    • can activate B cells without Tcell help
    • include lipopolysaccharide (LPS) and molecules with repeating subunits, such as carbs
  37. antigenic
    • term used interchangeably with immunogenic to describe the ability of an antigen to elicit an immune response
    • Various antigen differ in effectiveness to stimulate immune response. Proteins generally induce strong response as lipids often do not
  38. epitopes
    • discrete regions of an antigen molecule recognized by the adaptive immune system
    • Some are stretches of 10 or so amino acids where as others are 3D shapes
  39. Fab regions
    • the two identical arms of antibody
    • bind antigen
  40. Fc region
    the stem of the antibody
  41. Heavy chain vs light chain (on antibody)
    • *recall all antibodies have same basic Y-shaped structure, called antibody monomer
    • Consists of 2 copies of a high-molecular weight polypeptide chain, called the heavy chain, and two copies of a lower molecular-weight polypeptide chain, called the light chain
    • (See pg 360)

    • Amino acids in the chains fold into domains, referred to as immunoglobulin domains:
    • light chains have two domains each
    • Most heavy chains have 4
  42. How is light chain linked to heavy chain, & how are two heavy chains linked together
    • by a disulfide bond
    • the fork of the Y is a flexible stretch called the hinge region where one or more disulfide bonds link the two heavy chains
  43. Variable region
    • the portion at the ends of the Fab regions (the top sections of the arms)
    • accounts for the antigen-binding specificity
  44. antigen-binding site
    • part of the variable region
    • the portion that attaches to a specific epitope (btwn the 2 fingers of the top portion of arms)
    • fit needs to be precise, as interaction depends on numerous non-covalent bonds to keep molecules together
    • Is reversible
  45. Constant region
    • includes the entire Fc region, as well as part of two fab region (the lower 2 sections of arms)
    • Allows other components of immune system to recognize the otherwise diverse antibody molecules
  46. 5 general types of constant regions, and those corresponding to major classes of immunoglobulin (Ig) molecules
    • IgM
    • IgG
    • IgA
    • IgD
    • IgE
    • All have same basic monomeric structure, but each class has different constant portion of heavy chain
  47. Protective outcomes of antibody-antigen binding
    • Neutralization
    • Opsonization
    • Complement system activation
    • Immobilization and prevention of adherence
    • Cross-linking
    • Antibody-dependent cellular cytotoxicity
  48. Protective outcomes of antibody-antigen binding:
    Neutralization
    • Toxins/viruses must bind specific molecules on cell surface before they can damage cell
    • If they are covered in antibodies, can't attach to cells and is said to be neutralized
  49. Protective outcomes of antibody-antigen binding:
    Opsonization
    Phagocytic cells have receptors for Fc region of IgG, making it easier for phagocyte to engulf antibody-coated antigens
  50. Protective outcomes of antibody-antigen binding:
    Complement system activation
    • Antigen-antibody complexes can trigger complement system
    • When multiple molecules of certain antibody classes bond to cell surface, a specific complement system protein attaches to their Fregions, initiating the cascade
  51. Protective outcomes of antibody-antigen binding:
    Immobilization and prevention of adherence
    • Binding of antibodies to flagella interferes with microbe's ability to move
    • binding to pili prevents it from attaching to surfaces
  52. Protective outcomes of antibody-antigen binding:
    Cross-linking
    • The 2 arms of antibody can bind separate but identical antigen molecules, linking them
    • Overall effect is that large antigen-antibody complexes form, creating big "mouthfuls" of antigens for phagocytic cells to engulf
  53. Protective outcomes of antibody-antigen binding:
    Antibody-dependent cellular cytotoxicity
    • (ADCC) 
    • When multiple IgG molecules bind to a virally infected cell or a tumor cell, becomes target for destruction by natural killer cells (NK)


    NK cells attach to Fregions of IgG and once attached, kills the target cell by delivering compounds directly to it
  54. IgM
    • 970,000 daltons in cellular weight
    • Structure is a pentamer (pentagon), large size prevents it from crossing from bloodstream into tissues, so primary role is control of bloodstream infections

    • Accounts for 5% to 13% of circulating antibodies
    • Half-life in serum is 10 days
    • Is first class produced during primary response 
    • Is principal class produced in response to some T-independent antigens
    • Direct protection by neutralizing, immobilizing, preventing adherence to cell surfaces, and cross-linking
    • Binding leads to activation of complement system
  55. IgG
    • 146,000 daltons in cellular weight
    • Structure is typical Y antibody
    • Accounts for 80% - 85% of total serum immunoglobulin (as serum is liquid part of blood)
    • Most abundant class in blood and tissue fluids
    • Provides longest term protection as half life is 21 days
    • Transports across placenta & protects fetus; long 1/2 life extends protection through first several months after birth
    • Provides direct protection by neutralizing, immobilizing, preventing adherence, and cross-linking
    • Binding facilitates phagocytosis, leads to activation of complement system, and allows antibody-dependent cellular cytotoxicity
  56. IgA monomer form
    • 160,000 molecular weight
    • Accounts for 10-13% of antibodies in serum
    • However, most IgA is secretory IgA
  57. sIgA
    • Secretory IgA
    • *recall monomeric for accounts for 10-13%. Most IgA is secreted form, a dimer called sIgA
    • 390,000 molecular weight
    • Most abundant class produced, but majority secreted into mucus, tears, and saliva providing mucosal immunity

    • Half life is 6 days
    • Also found in breast milk, protecting infant intestine tract
    • Protects by neutralizing, immobilizing, and preventing attachment
  58. IgD
    • 184,000 molecular weight
    • typical Y structure
    • <1% of all serum immunoglobulins
    • Half life 3 days
    • involved in development and maturation of antibody response
    • Functions in blood not well understood
  59. IgE
    • 188,000 molecular weight
    • typical Y structue
    • <0.01% , barely detectable in blood
    • Half life is 2 days
    • Binds to the Fregion to mast cells and basophils
    • Bound IgE allows cells to detect parasites & other antigens & respond by releasing granule contents
    • Involved in many allergic reactions; unfortunately, basophils and mast cells also release chemicals when IgE binds to normally harmless materials such as foods, dust, pollen... leading to immediate reactions
  60. Clonal selection
    • theory that describes how the immune system is capable of making an array of antibody specificities
    • Each B cell is programmed to make only a single specificity of antibody
    • When antigen is introduced, only B cells capable of making appropriate antibody can bind to antigen
    • Critical theme in adaptive immune response, pertaining to both B cells and T cells
  61. Summarize what happens with clonal selection
    • When an antigen enters a secondary lymphoid organ, only the lymphocytes that specifically recognize that antigen will respond
    • the antigen receptor they carry on their surface governs this recognition
    • Lymphocytes may be immature, naive, activated, effector, or memory cells
  62. Immature lymphocytes
    These have not fully developed their antigen-specific receptors
  63. Naive lymphocytes
    These have antigen receptors, but have not yet encountered the antigen to which they are programmed to respond
  64. Activated lymphocytes
    • These are able to proliferate
    • have bound antigen via their antigen receptor and have received the required accessory signals from another cell, confirming that the antigen merits a response
  65. effector lymphocytes
    • Are descendants of activated lymphocytes, armed with ability to produce specific cytokines or other protective substances
    • Plasma cells are effector B cells
    • Tc cells are effector cytotoxic T cells
    • Tcells are effector helper T cells
  66. memory lymphocytes
    • long-lived descendants of activated lymphocytes
    • can quickly become activated when antigen is encountered again
    • responsible for speed and effectiveness of secondary response
  67. T-dependent antigens
    • recall most antigens are T-dependent
    • meaning B cells that recognize them require help from TH cells
  68. B-cell activation
    • Naive B cells gather in secondary lymphoid organs to encounter antigens
    • When B cell's antigen receptor binds to a T-depend antigen, B cell takes antigen in by endocytosis, enclosing within an endosome. There, antigen is degraded into peptide fragments & delivered to structures called MHC class II molecules
  69. MHC class II molecules
    These molecules move the peptide fragments to the B-cell surface and "present" them for inspection by TH cells
  70. Antigen presentation
    Process by which pieces of antigen are presented on B-cell surface for TH cells to inspect
  71. What does TH cell do when it scans B-cell
    • Scans naive B cells in secondary lymphoid organs to determine if any have encountered any antigen they recognize
    • If TH antigen receptor binds one of the peptide fragments presented by B cell, then that T cell activates the B cell by delivering cytokines to B cell & initiating process of clonal expansion of that particular B cell
  72. What if no TH cells recognize the peptides presented by B cell
    • That B cell may become anergic (unresponsive to future exposure to antigen)
    • Results in tolerance to that antigen
  73. Characteristics of Primary response
    • Takes about 10 - 14 days for substantial amounts of antibodies to accumulate
    • During delay, person may experience s/s of infection
    • Immune system is actively responding though
  74. Affinity maturation
    • Form of natural selection among proliferating B cells
    • As activated B cells multiply, spontaneous mutation commonly occur in certain regions of antibody genes
    • Some result in slight changes in antigen-binding site of antibody ( and therefore B-cell receptor)
    • B cells that bind antigen for longest duration are most likely to proliferate
  75. Class switching
    • All B cells are initially programmed to differentiate into plasma cells that secrete IgM
    • Cytokines produced by TH cells induce some activated B cells to switch that genetic program, causing them to differentiate into plasma cells that secrete other antibody classes
    • B cells in lymph nodes most commonly switch to IgG production
    • B cells in mucosa generally switch to IgA production
    • *After class switching, some B cells become memory B cells
  76. secondary reponse
    • significantly faster and more effective than primary- repeat invaders generally are eliminated before they cause noticeable harm
    • Vaccination takes advantage of this naturally occurring phenomenon 
    • Memory B cells are responsible
  77. Explain Memory B cells in secondary response
    • Responsible for efficiency of 2nd response
    • There are more cells - memory B cells & memory T helper cells - that can respond to specific antigen
    • Memory B cells are able to scavenge even low concentrations of antigen cause receptors have been fine tuned through affinity maturation
  78. T-independent Antigens
    • T-indep antigens can activate B cells without aid of TH cells
    • One type of T-indep antigens are polysaccharides & others have numerous identical evenly spaced epitopes
    • Because of the arrangement of epitopes, clusters of B-cell receptors bind to antigen simultaneously, leading to activation of that B cell w/o involvement of helper T cells
  79. Role of T cells
    • Different from B cells in that T cells never produce antibodies
    • Instead, effector T cell directly interact with other cells - target cells - to cause distinct changes in those cells
  80. Structure of T cell receptor
    • Has two polypeptide chains (set of either alpha and beta or gamma and delta), each with variable and constant region
    • See pg 369
  81. TCR
    • T-Cell receptor
    • *Recall T cells have multiple copies of T-cell receptor on surface that recognizes specific epitope
    • Receptor does not interact with free antigen, must be presented by another host cell
    • Host cell does this partly by degrading antigen & presenting peptides of antigens proteins via MHC molecules
    • When T cell recognizes antigen, actually recognizing both peptide & MHC molecule
  82. MHC molecules
    • Major histocompatibility complex molecules
    • 2 types: MHC class I and class II
    • Both shaped like elongated bun and hold peptide lengthwise, like bun holds hot dog
  83. MHC class I vs MHC class II
    MHC class I molecules present endogenous antigens (antigens made within cell)

    MHC class II molecules present exogenous antigens (antigens taken up by cell)

    *All nucleated cells produce MHC class I, but only specialized cell types make class II
  84. What cell types make MHC class II molecules
    What are they referred to as
    Referred to as APCs (antigen-presenting cells)

    Includes dendritic cells, B cells and macrophages
  85. As Cytotoxic T cells and Helper T cells are involved in eliminating antigens, how do they differ in their roles and how they recognize antigens
    Cytotoxic T cells (TC) recognize antigen presented on MHC class I molecules & respond to endogenous antigens

    Helper T cells (TH) recognize antigen presented on MHC class II molecules & respond to exogenous antigens
  86. cluster of differentiation (CD) markers
    • *As cytotoxic and helper T cells are identical microscopically, scientists distinguish them based on presence of surface proteins called CD markers
    • Most Cytotoxic T cells have CD8 marker
    • Most Helper T cells carry CD4 marker
  87. Explain T cell activation
    • dendritic cells play crucial role in activation
    • Immature dendritic cells reside in peripheral tissues, particularly under skin & mucosa, gathering materials
    • They use both phagocytosis and Pinocytosis 
    • En route to secondary lymphoid organs, dendritic cells mature into form that presents antigen to naive T cells
    • Cells that detected pathogens produce co-stimulatory molecules
  88. Co-stimulatory molecules
    • Surface proteins produced by dendritic cells that detected pathogens
    • function as emergency lights for T cell, communicating danger
  89. What happens when Naive T cells recognize antigen by dendritic cells:
    displaying co-stimulatory molecules
    not displaying co-stimulatory molecules
    If the T cells recognize antigen presented by dendritic cells DISPLAYING costimulatory molecules, can become activated T cell

    If T cell recognize antigen presented by dendritic cell NOT DISPLAYING co-stimulatory molecules, become anergic (can't respond) and eventually undergo apoptosis
  90. Effector Functions of TC (CD8) cells
    • Induce apoptosis in infected "self" cells
    • also destroy cancerous "self" cells
    • Tc cells distinguish infected/cancerous cells from normal by proteins produced in nucleus of cell. These are inspected by T cells through MHC class I molecules
    • Is protein not recognized as self, cell will be targeted for lethal effector functions of Tc cells
    • T cell will also release cytokines that alert neighboring cells
  91. What do function of TH cells
    • they orchestrate the immune response
    • activate B cells and macrophages and T cells
  92. Effector Functions of TH (CD4) cells
    • TH cells activate cells that present peptides they recognize on MHC class II
    • Various cytokines are released, depending on subset of responding Tcell
    • Macrophages and B cells present peptides from exogenous proteins in the groove of MHC class II molecules
  93. Subsets of dendritic cells and T cells
    Direct immune system to an appropriate response
  94. conjugate vaccine
    A vaccine composed of a polysaccharide antigen covalently attached to a large protein molecule, thereby converting what would be a T-independent antigen into a T-dependant antigen
  95. hapten
    • a molecule that binds to a B-cell receptor yet does not normally elicit antibody production
    • Ex is how people develop allergies to penicillin
  96. NK cells
    • recall they lack antigen specific receptors
    • induce apoptosis in antibody-bound "self" cells - they can do this because they have Fc receptors for IgG on surface (recall Fc is red flag)
    • Attach and delivers perforin and protease containing granules directly into cell
    • They can also initiate apoptosis in stressed "self" cell that lacks MHC class I molecules
  97. In gene arrangement, how many segments are there for B cell
    • 3 segments, one each from DNA regions called:
    • V - variable  (40 different segments)
    • D - Diversity (25 )
    • J - Joining    (6)
  98. Imprecise joining
    • occurs when nucleotides get deleted or added btwn sections
    • changes reading frame of encoded protein
  99. Combinatorial association
    • refers to specific groups of light chains and heavy chains that make up antibody molecule
    • Both acquire diversity through gene rearrangement and imprecise joining
  100. Negative selection of self-reactive B cell
    • Once B cells is developed antigen receptor, it passes through rigorous checkpoints in bone marrow
    • Most important is negative selection, which eliminates any B cell that binds "self"
    • Most B cells fail and induced to undergo apoptosis
    • If cell weren't eliminated, immune system may attack "self" by mistake
  101. Pos and Neg selection of self-reactive T cells
    • Fate of developing T cells rests on 2 phases of trials = pos & neg selection
    • Positive only permits those T cells that recognize MHC to develop further
    • If passes positive, must then go through neg = T cell that recognize "self" peptides presented on MHC are eliminated
    • Pos & neg selection so strict, over 95% developing T cells undergo apoptosis in thymus

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Micro ch 15
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2016-06-14 04:27:54
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micro ch 15
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