BIO 343 Lecture Notes - Lecture 4: Immunogenicity, Antiserum, Fragment Crystallizable Region
Immunology Chapter 4: Adaptive Immunity
Hayden Casassa
• B Cell Reeptors BCR’s ad atiodies
o Specifically bind one or a limited number of extracellular antigens
o Antibody repertoire is the total number of different (1016) specific Abs that a person can make
▪ Number is actually closer to 109
o Stimulated B cell gives rise to antibody-secreting plasma cells with same Ag specificity as
original BCR
• Antibodies are glycoproteins with variable and constant regions
o Four polypeptides joined together by disulfide bonds.
o 2 heavy chains that are ~150 kDa and 2 light chains that are ~25 kDa each
o This leads to 2 identical Ag binding sites
o Greatest AA variability is between different Abs is in the N-terminal variable region
• Flexible hinge region of IgG allows binding to many different arrangements of antigens
o Following cleavage with a protease and a reducing agent, the Ab can be dissected into 3 pieces:
2 Fab fragments and 1 Fc fragment
o Stem of Ab is called the Fc region. Some cells express Fc receptors that bind this region (CD16 in
ADCC on NK cells)
• 5 Isotypes or Classes of Human Antibodies by differences in heavy chain region
o gamma (g), mu (m), delta (d), alpha (a), and epsilon (e) chains
• Light chains either have Kappa (k) or lambda chains
• All 5 antibody types could bind to the same pathogen, but once it binds how that it is dealt with differs
on type of antibody that it is bound to.
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o IgG can be passed to offspring through bloodstream
o IgE can bind to mast cells due to constant region
• Heavy and light chain are folded into series of compact and stable Immunoglobulin (Ig) domains
o There are 12 domains of IgG
▪ 3 Constant domains and 1 variable region for each heavy chain
▪ The light chain has 1 variable and 1 constant region
▪ Annotated VH→CH1→CH2→CH3 or VL and CL
▪ Each domain consists of 2 Beta-pleated sheets
• Be able to name domains of antigen binding site or whole IgG molecule
• Immunoglobulin Superfamily
o Large group of cell surface and soluble proteins that contain one or more Ig-like domains
• Antigen Binding Site
o One Ag binding site consists of hypervariable regions (HVs) also known as Complementarity-
Determining Regions (CDRs) present in the six loops from the VH and VL domain
o 3 loops in each CDR for the 4 variable regions meaning 12 Variable regions in every Antibody
▪ 6 per antigen binding site
▪ The loops are’t idetial
o Framework region has little difference (Yellow), but the Red HV region is where the Ag binds
• An antigen is any molecule that can be bound by a B cell receptor (BCR) or antibody, or by the T cell
receptor (TCR) when it is complexed with and MHC molecule
o TCR’s ol reogize peptide fragets of protei Ags that hae ee degraded ad displaed
by other cells expressing MHC molecules
▪ In other words, only way T cell can recognize is when a human cell when the fragment is
attached to MHC molecule
• Immunogenicity is the ability of a substance to induce a B cell and/or T cell adaptive response.
o Typically, the bigger and more diverse then the better they elicit an immune response
o AA (worst)→ Haptens→ Lipids→ Steroids→ Carbs→Proteins (best)
• Properties of Immunogens and Antigens (What makes a good antigen)
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Document Summary
2 fab fragments and 1 fc fragment: stem of ab is called the fc region. Some cells express fc receptors that bind this region (cd16 in. Igg can be passed to offspring through bloodstream. Immunoglobulin superfamily: large group of cell surface and soluble proteins that contain one or more ig-like domains, antigen binding site, one ag binding site consists of hypervariable regions (hvs) also known as complementarity- In other words, only way t cell can recognize is when a human cell when the fragment is attached to mhc molecule. Good: humanized are entirely human with only the hv region (cdr) being of mouse origin. Best: antibodies are encoded by gene segments spread along chromosomes, they are brought together randomly to form a rearranged functional gene by somatic. Recombination: somatic recombination occurs only during b cell development in the bone marrow before.