BIOL 1104 Lecture Notes - Hapten, Hyperbola, Histocompatibility

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Published on 30 Jan 2013
Department
Course
Professor
IMMUNOLOGY
L4/p.1
Molecular Basis of Humoral Immunity: Ab Structure and Fxn
-Innate Immunity is ineffective against viruses!!
Bacteria can evade Innate Immunity 1.Shielding Targets (encapsulation)
2. Evolution (variation of surface components.
ADAPTIVE IMMUNITY
-Mediated by T and B lymphocytes-carry receptors for specific antigens
-B cells differentiate into Ab (Ig-recognition element) secreting plasma cells.
2 forms of Antibodies 1. Soluble (circulates, scavenges) 2. Membrane bound (receptor for antigen)
Soluble Ig mediation of host defense (detect free antigen)
1. Neutralization of viruses and bacterial toxins
-Ab prevents bacterial adherence or uncoating (neutralizes usual receptor mediated fxn of
antigen)
2. Opsonization-facilitation of phagocytosis
-Since capsule can evade detection. Ab can coat cell or make capsule more rigid to help the
phags.
3. Complement Activation
Complement: augments phagocytosis, B cell responsiveness, and microbial killing by Ab
(a) enhances opsonization (b)lysis bacteria
Membrane bound Ig
1. Triggers Lymphocyte Activation (w/ 2nd signal from T cells)
2. Mediates antigen uptake for presentation to reactive T cells
TCR is only surface bound. Not secreted!!! (can detect antigen expressed inside cell )
CLONAL SELECTION
1. Each lymphocyte has receptor w/ unique binding features generated at random (generator of
diversity)
2. Antigen binding triggers clonal expansion (proliferation) and differentiation
3. Cells made by clonal expansion have antigenic specificities identical to parent cell
4. Self-reactive cells are deleted (fail safe mechanism)
ANTIBODIES
-in all vertebrates but not in invertebrates. Present in serum and body fluids
-Serum: albumin>immunoglubulins>fibrinogen>C1-C4
Immunogen-molecule that elicits an Ab response
1° response = 2-4wks later specific antibodies appear
Time lag = clonal expansion and differentiation of B cells to plasma cells (Ab secreting)
2° response = more rapid, specific, and intense due to immunologic memory
-direct result of clonal expansion (higher affinity to antigen)
Different immunogen-again delayed and lower titer primary response specificity
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Structural Organization of Abs
1.Immunoglobulins are a family of related glycoproteins
-each class has distinct structure and function but similar principles
-2 light chains (қ mainly and λ) and distinctive heavy chain
Five classes of Ab: IgM, IgD, IgG, IgA, IgE sizes: 1,000,000MW – 150,000MW
Variable region-recognize foreign molecules (“generator of antigen receptor diversity)
Constant region-engage various effector functions to dispose of bound material
L4/p.2
Subunit structure of IgG (most abundant class in serum)
-Y shaped
-Heavy chains and light chains linked by interchain disulfide bonds.
-Papain 2Fab (antigen binding [valence of 1]) + Fc (crystallizable)
-Pepsin F(ab’)2 (valence of 2) + Fc (degraded)
Primary Structure of IgG
1. B cell tumors provide source of homogenous Ab
-immune response usually activates many B cell clones heterogeneous antibodies
-Multiple Myeloma (cancer of Ab secreting cells that crowd out other cells of the
marrow)homogenous Ab
Monoclonal Ab=derived from progeny of single B cell so homogenous sequence.
=highly specific inexhaustible biochemical reagents
Making clones of Ab secreting cells (Monoclonal Ab)
1. Infect animal with antigen.
2. Fuse spleen cells (make Ab) with immortal myeloma cells hybridomas
-genetically tag myeloma cells so they won’t grow in specific media
3. Transfer to HAT medium (selects against genetically tagged cells and unfused spleen cells)
-only cells that survive are immortal hybridomas (myeloma fused with Ab producing cells)
4. Select hybridomas that make Ab specific for antigen A (how????)
5. Clone hybridoma
2. Domain structure of Ig polypeptide chains
-Amino Terminal of light chains (variability VL) Carboxyl terminal (identical for given type of
light chain(CL)
VH CH
-Antigen binding sites = VH and VL (highly variable globular domain)
Elbow domain = between variable and constant domainsFlexible (50 degrees flexion
-Hinge = between Fab and Fc (btw CH1 and CH2)Very Flexible (180 degrees rotation and flexion)
-has cysteine residues for inter HC dS bonds
-CH2 = complement binding site CH3 = Fc receptor binding site
Proof of Flexibility
1. Immunize rabbit with DNP and isolate anti-DP antibodies
2. React antibodies with divalent ligand and examine by electron microscopy
3. Found cyclic structures with 3, 4, or more sides observed (small Fc projections)
also observed globular domains (VH/VL) (CH1/CL)(CH2/CH3)
Distinguishing features of Ig classes
Isotype-particular class of Ig chain (different properties are from differences in their heavy chains)
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