Ephantus Njagi
Mechanisms of Humoral Immunity
Background
 Mechanisms of humoral immunity are accomplished after
interaction of:
 B cells
 Antibody production
 antigen binding
Interaction of antigen with B cells
 Each antibody binds to a specific antigen
similar to a lock and key through:
 Noncovalent bonds or Intermolecular forces.
 Hydrogen bonds
 Electrostatic bonds
 Van derWaal forces
 Hydrophobic bonds
 An immune complex is formed from the
integral binding of an antibody to a soluble
antigen.
 The bound antigen acting as a specific
epitope, bound to an antibody is referred to
as a singular immune complex.
B-cell Activation and Differentiation
Clonal expansion and Differentiation
B cells mediated immune response
Humoral immunity(HI) or antibody mediated
immunity:
The total immunological reaction that B cells recognize antigen,
then activate, proliferate, differentiate into plasma cells and
produce Ab.
 B2 cells mediated immune response toTD-Ag
 B1 cells mediated immune response toTI-Ag
PartⅠ: Immune response of B2 cell to TD-Ag
Characteristics ofTD-Ag:
 PossessT cell epitope and B cell epitope
 NeedTh cells participation
 Both CMI and HI
 Produce several types of antibodies: IgG
 Produce immune memory
1. B cells recognize antigen
BCR directly recognize the conformational
determinant, capture Ag and present Ag signal to
Th cells
No APC , no MHC restriction
Specificity
conformational
linear
Clonal Selection
B-cells Antibody on Surface
Antigens
Only B-cells that bind antigen
are selected
Clonal Expansion
B-cells Antibody on Surface Proliferation of selected
B-cell
Somatic Mutation
B-cells Antibody on Surface Improved Antibody Binding
By Genetic Rearrangement
Somatic
Mutation
2. B cells activation, proliferation and
differentiation
(1) B cell activation: double signals
 First signal : antigen signal
BCR--conformational determinant on the surface of Ag
Igα/Igβtransduct first signal
CD19/CD21 (co-receptor) binds to C3d on Ag
 Second signal: co-stimulatory signal
The CD40 on B cells binds to CD40L on activatedT cells
CD40
Immunoglobulin
receptor
MHC II
Antigen
Cytokine
receptor
B
cell
B7
B7 CD28
TCR
TCR
T helper
cell
1. Antigen presentation to
Th cell
2. B7 expressed
B
cell
3. Th cell is
activated
and expresses
CD40 ligand,
Cytokines
secreted
CD40
ligand
Cytokine
B
cell
T helper
cell
B
cell
B
cell
B
cell
5. B cell activated
6. B cells proliferate, differentiate, secrete Ig
Interaction between Th cell and B
cell
 B cells act onT helper cells:
 B cells present Ag toTh cells
 B cells provide B7 forTh cells
 T helper cells act on B cells:
 ActivatedTh cells provide co-stimulatory molecule for B cells:
CD40L-D40
 ActivatedTh produce Cytokines to help B cells proliferate and
differentiate
 Activated B cells express receptors of cytokines
 ActivatedTh2 secrete cytokines IL-4, IL-5, IL-6 to enhance
proliferation and differentiation of B cells
 B cells differentiate into plasma cells (antibody forming cells)-
produce Ab, some activated B cells become memory B cells
Interactions between B cell and Th cell
B cell
activation
B cell Th cell
Ag processing
Th cell
activation
Cytokines affect proliferation and
Class switch of B cells
3. Stage of effect----the function of Ab
1. Neutralization-Ab covers up sites on toxic molecule/virus.
2. Opsonization-Ab-mediated phagocytosis.
3. Complement fixation-cascade reacts to ag-ab complexes.
4. Agglutination/precipitation-Cross-link ags into
complexes-aids phagocytosis.
5. Immobilization-Abs bind to flagella etc. & prevent escape
macrophage death.
6. ADCC-NK, macrophage
7. Participate in hypersensitivity-I,II,III
1. Neutralization:
* to neutralize microbial toxins and animal venoms
* to prevent viruses and bacteria from infecting cells
2. ADCC—NK
Antibody-coated target cells can be killed by natural killer cells(NK cell) in
antibody-dependent cell-mediated cytotoxicity, that is called ADCC.
3.Opsonization – macrophage
Fc receptors on phagocytes trigger the uptake of antibody-coated bacteria.
As a result, this action enhance phagocytosis of the bacterium.
Complement proteins bind to antibodies.
4.Activation of complement
Complement can be activated to directly lyse bacteria by the presence of
antibodies bound to the bacteria.
5. Participate in hypersensitivity
IgE binds to high-affinity Fc receptors on mast cells and basophils, and leads to
the rapid release of granules containing inflammatory mediators into
surrounding tissue, cause hypersensitivity
Primary and secondary antibody responses to protein
antigens differ qualitatively and quantitatively

Humoral Immunity

  • 1.
  • 2.
    Background  Mechanisms ofhumoral immunity are accomplished after interaction of:  B cells  Antibody production  antigen binding
  • 3.
    Interaction of antigenwith B cells  Each antibody binds to a specific antigen similar to a lock and key through:  Noncovalent bonds or Intermolecular forces.  Hydrogen bonds  Electrostatic bonds  Van derWaal forces  Hydrophobic bonds  An immune complex is formed from the integral binding of an antibody to a soluble antigen.  The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex.
  • 4.
    B-cell Activation andDifferentiation
  • 5.
    Clonal expansion andDifferentiation
  • 6.
    B cells mediatedimmune response Humoral immunity(HI) or antibody mediated immunity: The total immunological reaction that B cells recognize antigen, then activate, proliferate, differentiate into plasma cells and produce Ab.  B2 cells mediated immune response toTD-Ag  B1 cells mediated immune response toTI-Ag
  • 7.
    PartⅠ: Immune responseof B2 cell to TD-Ag Characteristics ofTD-Ag:  PossessT cell epitope and B cell epitope  NeedTh cells participation  Both CMI and HI  Produce several types of antibodies: IgG  Produce immune memory
  • 8.
    1. B cellsrecognize antigen BCR directly recognize the conformational determinant, capture Ag and present Ag signal to Th cells No APC , no MHC restriction Specificity
  • 9.
  • 10.
    Clonal Selection B-cells Antibodyon Surface Antigens Only B-cells that bind antigen are selected
  • 11.
    Clonal Expansion B-cells Antibodyon Surface Proliferation of selected B-cell
  • 12.
    Somatic Mutation B-cells Antibodyon Surface Improved Antibody Binding By Genetic Rearrangement Somatic Mutation
  • 13.
    2. B cellsactivation, proliferation and differentiation (1) B cell activation: double signals  First signal : antigen signal BCR--conformational determinant on the surface of Ag Igα/Igβtransduct first signal CD19/CD21 (co-receptor) binds to C3d on Ag  Second signal: co-stimulatory signal The CD40 on B cells binds to CD40L on activatedT cells
  • 14.
    CD40 Immunoglobulin receptor MHC II Antigen Cytokine receptor B cell B7 B7 CD28 TCR TCR Thelper cell 1. Antigen presentation to Th cell 2. B7 expressed B cell 3. Th cell is activated and expresses CD40 ligand, Cytokines secreted CD40 ligand Cytokine B cell T helper cell B cell B cell B cell 5. B cell activated 6. B cells proliferate, differentiate, secrete Ig
  • 15.
    Interaction between Thcell and B cell  B cells act onT helper cells:  B cells present Ag toTh cells  B cells provide B7 forTh cells  T helper cells act on B cells:  ActivatedTh cells provide co-stimulatory molecule for B cells: CD40L-D40  ActivatedTh produce Cytokines to help B cells proliferate and differentiate  Activated B cells express receptors of cytokines  ActivatedTh2 secrete cytokines IL-4, IL-5, IL-6 to enhance proliferation and differentiation of B cells  B cells differentiate into plasma cells (antibody forming cells)- produce Ab, some activated B cells become memory B cells
  • 16.
    Interactions between Bcell and Th cell B cell activation B cell Th cell Ag processing Th cell activation
  • 17.
    Cytokines affect proliferationand Class switch of B cells
  • 20.
    3. Stage ofeffect----the function of Ab 1. Neutralization-Ab covers up sites on toxic molecule/virus. 2. Opsonization-Ab-mediated phagocytosis. 3. Complement fixation-cascade reacts to ag-ab complexes. 4. Agglutination/precipitation-Cross-link ags into complexes-aids phagocytosis. 5. Immobilization-Abs bind to flagella etc. & prevent escape macrophage death. 6. ADCC-NK, macrophage 7. Participate in hypersensitivity-I,II,III
  • 21.
    1. Neutralization: * toneutralize microbial toxins and animal venoms * to prevent viruses and bacteria from infecting cells
  • 22.
    2. ADCC—NK Antibody-coated targetcells can be killed by natural killer cells(NK cell) in antibody-dependent cell-mediated cytotoxicity, that is called ADCC.
  • 23.
    3.Opsonization – macrophage Fcreceptors on phagocytes trigger the uptake of antibody-coated bacteria. As a result, this action enhance phagocytosis of the bacterium.
  • 24.
    Complement proteins bindto antibodies. 4.Activation of complement Complement can be activated to directly lyse bacteria by the presence of antibodies bound to the bacteria.
  • 25.
    5. Participate inhypersensitivity IgE binds to high-affinity Fc receptors on mast cells and basophils, and leads to the rapid release of granules containing inflammatory mediators into surrounding tissue, cause hypersensitivity
  • 30.
    Primary and secondaryantibody responses to protein antigens differ qualitatively and quantitatively