Adaptive immune response-I

  1. What are APC (antigen presenting cell)
    • Dendritic cells
    • Macrophage cells
    • B-cells
  2. Antigens recognized by T
    cells  are
    • peptide
    • antigens not soluble antigens derived from
    • catabolism of proteins inside the cells.
  3. Antigens recognized by B cell
    receptors (antibody)  are
    • Proteins, polysaccharides, nucleic acid
    • of pathogens, soluble antigens
    • in
    • the extracellular spaces
  4. Where do u find the antibodies
    • Antibodies
    • do not enter cells and are ineffective against pathogens inside a cell.
  5. T cell receptors recognize
    only protein antigens derived from viruses or intracellular bacteria, internalized cytosolic proteins
  6. Distribution of APC in the lymph node
    1.Dendritic cells :
    2.Macrophages :
    3.B cells :
    • 1.found in the cortex and paracortex
    • areas
    • 2.found through out and mainly in the
    • marginal sinus, medullary cords
    • the follicles
  7. cell types function 
    Dendritic cells (DC)
    pathogens bind to TLR on immature DC-->DC sec. IL-1, TNF-α --> DC becomes mature-->B7 on DC will bind to CD28 on naive T cell --> activates naive T cell by secreting IL-12 and --> Effector T cell (TH1 cell) --> sec IFN-γ, IL-2
  8. cell types function
    Mcrophage cells
    • macrophage binds to pathogen -->binds to effector T cell --> T cell sec. INF-γ --> INF-γ  will activate the macrophage and kills the pathogen
    • cell-mediated immunity
  9. cell types function
    B cells
    • B cell binds to Virus --> binds to effector T cell to CD4 --> t-cell activates B-cell --> plasma cell--> produce antibody
    • Humoral immunity
  10. B-cell expression of class II MHC 
    constitutive increased by IL-4
  11. macrophages expression of MHC II
    low or negative; inducible by INF-γ
  12. Dendritic cells  expression of MHC II
    constitutive; increase with maturation; increase by INF-γ
  13. DC Expression of costimulators
    constitutive; inc. w maturation; induc by TLR ligands, INF-γ and T cell (CD40-CD40L interactions)
  14. macrophages Expression of costimulators
    • low, inducible by TLR ligands, INF-γ, and
    • T-cells (CD40-CD40L)
  15. B cells Expression of costimulators
    induced by T cells (CD40-CD40L), antigen receptor cross-linking
  16. Role of Dendritic
    cells as the most efficient APC
    • •Dendritic
    • cells exposed to INF gamma or TNF(from macrophage) increased expression of MHCII, CD80(B7-1) and CD86 (B7-2)
  17. Morphology and population of
    Dendritic cells
    Expression of Toll-like receptor TLR 
    1-Conentional DC
    2-plasmacytoid DC
    • 1- TLRs 4,5,8
    • 2- TLR 7,9
  18. Morphology and population of Dendritic cells
    Major cytokines production
    1-Conentional DC

    2-plasmacytoid DC
    • 1-TNF, IL-6, IL-12
    • 2-type I interferons
  19. Microbes
    transported to Peripheral lymphoid organs by
    •(mature dendritic cells) present antigen to T lymphocytes
  20. Microbes
    bind to TLR and
    dendritic cells (mature)  which  secrete
    TNF, IL-1 --> activated DC lose adhesiveness for epithelia --> express CCR7 (receptor for CCL21, CCL19)--> DC exits the epithelium --> goes to lymph node  
  21. in LN how long will it take naive T-cell w CCR7 (receptor for CCL21, CCL19) and APDC meet ?
    12-18 hrs
    • •Proteins in the cytosol of
    • any nucleated cells are
    • processed in the cytoplasm and displayed by class I MHC molecules  CD8+T Cells and  MHCI (8X1=8)
    • Extracellular
    • proteins are  internalized by APC ( dendritic, macrophages and  B cells) processed in vesicles and displayed by class II MHC molecules
    • CD4+ T Cells and MHCII (4X2=8)
  24. •What are cytosolic antigens?
    • •Microbe derived proteins produced by virus within infected host cells; phagocytosed
    • microbes; from mutated genes in tumors
  25. Deficiency
    of MHC I proteins
    and TAP, and
    MHC II cause
    Bare lymphocyte syndrome (def. MHCII)
  26. What are the steps in activation of T
    •T cell activation initiated by the interaction of  TCR-CD3 complex with a processed antigenic peptide bound to either a MHC I (CD8+ T cell) or MHC II (CD4+ T cell)
  27. T cell mediated Immunity
    pathway of CD8 and CD4
    • 1)APC -> naive CD4 T-cell -> T-cell sec. IL-2 -> IL-2R -> clonal expresion ->effecto CD4 T-cell ->activates macrophage, B-cell. other cells -> inflammation 
    • also makes memory CD4 T-cell 
    • 2)APC-> naive CD8 T-cell -> colonal expresion -> effector CD8(CTL) -> killing of infected target cell macrophage activation
    • also makes memory CD8 T-cell
  28. T cell activation
    What are the 3 signals?
    • •Signal 1: Recognition :Interaction between
    • APC+ T cell + MHC transduced by CD3 but insufficient for activation
    • Signal 2: Co-stimulation
    • by co-stimulatory molecules on APC:  B7/CD 80 & CD 86 (massively up-regulated in DC when it encounters pathogen)
    • CD 80 & CD 86 bind to CD 28
    • Signal 3: through cytokines secreted
    • by stimulated DC which would polarize the T cell response
    • •Molecules other than the antigen receptors involved in T cell response called accessory molecules. Functions: 
    • signaling and adhesion
  29. T cell activation
    What is the significance of
    • •Co-stimulators expression on APC is highly
    • increased when they encounter microbes
    • •TCR CD4+/CD8+
    • MHC peptide recognition not enough; co stimulation must to ensure that naïve T cells are activated only by microbial antigens and not by harmless
    • foreign antigens
    • •Microbial antigens only can stimulate the
    • expression of B7 on APC through cytokines
  30. what is the function of CD4 on T-cell?
    • •CD4
    • recognize phagocytized (vesicular) microbial antigens from extracellular milieu
  31. what is the function of CD8 on T-cell?
    • •CD8
    • recognize cytosol processed antigens
  32. what activates T cell
    • MHC II + TCR + CD4
    • or
    • MHC I _ TCR + CD8
  33. What makes it survive (Co-stimulation)
    • on APC: B7-1/CD80 & B7-2/CD86
    • binds to 
    • CD28 on T-cell and Cytotoxic T lymphocyte antigen 4CTLA-4 (CD152)
  34. what differentiate the T-cell
    Cytokines: IL-6, IL-12, TGFβ
  35. •TCR have weak affinity to MHC + peptide
    so how cell makes stronger bond?
    •T cell integrin= LFA-1 binds to APC ligand= ICAM-1

    •Naïve T cells have LFA-1 in low affinity; once activated by chemokines in response to infection; cluster together and bind to ICAM on APC with high affinity at sites of infection

    • •ICAM on T Cells (CD2) bind to integrin
    • (LFA-3) on APC to increase cell-cell adherence
  36. CD 28 on T cells binds to B7 on APC and triggers the transcription of what cytokines?
    •TNFα, IL-1,IL-6 from APC

    •IL-2 from T cells
  37. what is CTLA-4
  38. what is CD28
    positive co-stimulatory
  39. What is the need for Co-stimulation in
    T cell activation?
    • •TCR CD4+/CD8+
    • MHC peptide recognition not enough; co stimulation must to ensure that naïve T cells are activated only by microbial antigens and not by harmless
    • foreign antigens
  40. what is the therapeutic use of CD40-CD40L?
    • •Inhibitors
    • of CD40-CD40L in transplant
    •  rejection and treatment of chronic
    • inflammatory diseases
  41. Second co-stimulatory
    • •CD40 ligand (CD 40L) is a expressed on activated T cells and CD 40 is
    • expressed on B cells, macrophages and Dendritic cells
    • •Activated T cells  bind APC by CD40L and activate them by stimulating expression of B7 molecules and secretion of IL-12
  42. what should be used for treatment
    of Rheumatoid arthritis
    Trials for psoriasis and Crohns disease
    • Block
    • B7-1 and B7-2 binding to CD 28  using a
    • CTLA-4 Ig
  43. Best Adjuvants are
    •microbial products; convert vaccine antigens into mimic of microbial pathogen
  44. what is Clonal Anergy.
    • Naïve
    • T cells recognizing self peptides on tissue/APC 
    • lacking co-stimulatory molecules (B7) are not activated and enter a
    • state of non responsiveness 
    • this is seen in auto immune diseases this is defected
  45. what is Super antigens
    • are viral or bacterial proteins that bind simultaneously to the chain of TCR and from outside the MHC groove
  46. what types of super antigen are present?
    • •can
    • be exogenous (exotoxins which soluble proteins secreted by bacteria like Toxic shock syndrome toxin, enterotoxin )
    • or endogenous (cell membrane proteins on mammalian cells coded by
    • virus)
  47. what is the super antigen's
    • •bind
    • outside, superantigens induce non specific polyclonal stimulation of T cells and massive
    • release of cytokines (cytokine storm)
  48. IL-2 secreted by what and what is the receptor
    secreted by T-cell and binds to IL-2R/CD25 in T-cell (autocrine)
  49. does the immune system respond differently to different microbes?
    • •by
    • the cytokines they produce, cytokine receptors and adhesion molecules
  50. What are the subsets for TH0 cell
    •Three subsets:

    • •TH1 cells- Type 1 helper T cells
    • •TH2 cells- Type 2 helper T cells
    • •TH17 cells
  51. What does TH1 responsible for
    •Responsible for cell mediated, immunity, delayed hypersensitivitycytotoxic T cells

    autoimmune diseases; tissue damage associated w chronic infection
  52. How TH-1 cell produced
    • intracellular bacteria -> APC -> MHC-II to CD4-> B7 binds to CD28 -> T-cell secrets
    • INF-γ, IL-2 -> TH-1 cell then secrets IL-2,
    • IFNγ 
  53. IFNγ immune reaction
    • macrophage activation in macrophage;
    • in b-cells IgG production -> opsonization
  54. TNFβ and IFNγ mediate
  55. IL-12 which cause
    • further differentiation of TH into TH1
    • subset
  56. IL-2 and IFNγ promote
    •differentiation of CD8 into cytotoxic T cells
  57. How TH-2 cell produced
    Helminths(parasite) -> APC -> B7 to CD28 -> T-cell secretes IL-4 and IL-10 -> Th-2 then secrets IL-4,IL-5, IL-10, IL-13
  58. IL-4, IL-5 eosinophil induction
    parasitic infections
  59. IL-4 promotes class switching into and result?
    • IgG1(mouse)
    • IgG2(human) 
    • result in antibody production
  60. • in B-cell
    IL-4 promotes class switching from
    and result
    • IgM to IgE
    • result IgE : mast cell degranulation
  61. IL-4 & IL-13 --> GI what happens
    intestinal mucus secretion and peristalsis
  62. IL-5 --> eosinophiln result?
    eosinophil activation
  63. IL-4 and IL-13 --> macrophage result?
    alternative macrophage activation (enhanced fibrosis/tissue repair)
  64. IL-4 and IL-10 suppress expansion of
  65. IL-4 and IL-5:
    • •induce
    • production of IgE; allergy,
  66. IL-4,IL-5, IL-10, IL-13 immune reactions
    mast cell, eosinophil activation; IgG production; alternative macrophage activation
  67. TH-2 is responsible for
    Responsible for humoral immunity, activation of B cells, IgM, IgE, allergic reactions
  68. How TH-17 cell produced
    extracellular bacteria and fungi -> MHCII to CD4 -> T-cell secrets TGF-β, IL-6, IL-23 -> TH-17 then secrets IL-17A &F, IL-22
  69. IL-17A &F, IL-22 immune reaction
    Neutrophilic, monocytic inflammation
  70. What does TH17 responsible for r
    Autoimmune and inflammatory disease
  71. what are the diseases under TH-17 and TH-22
    • •Disease:
    • multiple sclerosis, inflammatory bowel disease, RA

    • •Bacterial
    • and fungal infections
  72. Differentiation of CD8 cells into
    cytotoxic T lymphocytes (CTL)
    CD4 binds to MHCII -> secrets IL-2 -> binds to IL-2R on CD8 after joining w infected APC (APC CD80/86 w CD28T differentiation)-> CD8 secrets INF-γ -> differentiate to CTLs
Card Set
Adaptive immune response-I
Adaptive immune response-I