What are the 3 properties of the immune system (vertebrates)
- SPECIFIC recognition of foreign molecules
- Ability to DESTORY foreign parasite
- MEMORY mechanism, rapid response to second infection
4 examples of antigens
Antigens are molecules being recognized
- Bacteria
- Viruses
- Other Parasites
4, Foreign molecules
-> Non-self
What are the 2 types of the human immune system? Describe the main components of each
- Non-specific (Innate)
a) Barriers
- (skin, stomach acid etc…)
b) Inflammation
- (phagocytes –white blood cells/leukocytes) - Specific (adaptive)
a) Lymphocytes
- B-lymphocytes
Humoral response
b) T lymphocytes
- Cellular response - Thelper cells
- Tcytotoxic cells
Compare the humeral vs. cellular response
- Humeral (B cells from Bone-marrow))
- Abs
- works OUTSIDE the cell
- causes proteolysis - Cellular (T cells from Thymus)
- works INSIDE infected cell
- Tissue rejection
- Virus infected cells
- Cancer cells
- causes proteolysis
Similar immunoglobulin molecules involved
Compare proteins of the humoral and cellular immune response using a diagram
Slide 7
- Common evolutionary origin
- Gene duplication + diversification of function
- Soluble IgG, B cell, Killer T cell, MHC class I, MHC class II
Describe and label the immunoglobulin domain structure
Slide 8
Each immunoglobulin monomer is made up of 4 polypeptide chains: 2 light chains, (23 KDa), 2 heavy chains (53 KDa), which are bound by disulfide bonds
Draw the following Ig and describe the fxn
Slide 9
1. IgM: Early response to microorganisms, Only in bloodstream (pentamer), J- poly peptide
- IgG: (g-globulin) most abundant of circulating Ab, transverse blood vessel walls, crosses the placenta
- IgA: monomer or dimer, J polypeptide body secretions, lines the surface of cells
- IgD: Little is known about its function
- IgE: Associated with allergic reactions, Constant regions interact with mast cells.
Draw an IgG, labelling each part. What is the fxn of the constant domains of the heavy chains
Slide 10
- Signal macrophages to attack particle
- Identify Ig type for delivery to diff tissues or secretion
What is the Fc fragment?
fragment that crytallizes easily
What is the Fab fragment?
fragment with antigen binding
2 reasons why its difficult to work with full length Ab?
- Abs are very flexible (Flexible linker)
2. Divalent, cause aggregation and precipitation
Describe the attack of a foreign molecule from many angles
When a foreign molecule is found in the blood, many different antibodies may bind to it, attacking at different angles. Three different antibodies that bind to the protein lysozyme (in green at the center) are shown here. The crystal structures (PDB entries 1fdl , 3hfl , and 3hfm ) each include only one arm of the antibody (termed “Fab” for “antigen-binding fragment”), which has been separated from the antibody for ease in study. The rest of the antibody is indicated extending from the edges of the illustration. Notice that the antibodies pick entirely different binding sites on the small lysozyme molecule.
IgG mainly has what kind of protein domain
Beta sandwich/Beta sheets
Both the constant and variable domains of the light and heavy chains have a similar structure called _____
the immunoglobulin fold
What is the immunoglobulin fold?
- Found in many proteins involved in cell recognition
- 2 antiparallel b-sheets packed tightly against each other
Describe the constant domain of Abs. Draw it as a greek key motif and boxing the greek key motif
- Compressed antiparallel “b-barrel”
- 7 b-strands (4 + 3)
- Joined by a disulfide bond
- Short loops
Describe the variable domain of Abs.
- 9 b-strands
- C’ and C’’ contains the Hypervariable region CDR2
- Hypervariable regions on the same side of the barrel
- Disulfide btwn B and F
- CDR3 and CDR2: hairpin turns
- CDR1: crossover turn
- Loops from the 5 stranded b-sheet contributes more residues to the Ag binding site
- Another example of the importance
of loops in protein function
The antigen-binding site is formed from close association of the hypervariable regions from ______
both heavy and light chains
Draw parts of Fab fragment
Slide 19
Describe packing of the 4-stranded sheets in CONSTANT domains of an Fab fragment (CH1 and CL)
- 4-stranded beta sheets are ~90 degrees (rare in domain-domain interactions)
- Hydrophobic interactions
Another name for hypervariable region
CDR (complementarity determining regions)
- CDR1 (~28 AAs), CDR2 (~50 AAs), CD3 (~95 AA’s)
Describe the packing of the 5 stranded b-sheets in the variable domains (VH and VL)
- Variable domains are close to parallel, so HV regions are close. C’’ not involved in the packing
- 4 out of the 5 strands pack to form a barrel from the variable domains
The hypervariable region join to form an ________
extended Ag-binding surface
Describe the interaction btwn antigen and Ab
- Complementarities in shape
- INTERmolecular NON-COVALENT bonding
