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Immune system
Detects and inactivates foreign molecules, viruses, bacteria and microorganisms Two components with 2 strategies B Lymphocytes (humoral immune response):
Soluble antibodies (immunoglobulins) Secreted by plasma cells Recognize and bind to foreign molecules.
Immunoglobulins
The binding to the foreign molecules is:
Specific High affinity
Effector functions: biological effects that result as consequence of antigen binding like
Inactivation, degradation, lysis
Can recognize and interact with foreign molecules even if not encountered before Huge number of different kinds (~108)
Epitope
Particular site on antigen to which antibody binds Antigenic determinant
Hapten
small molecule, not an antigen Antigen if attached to macromolecule
Dinitrophenol
a small molecule
Monoclonal antibodies
One kind of antibodies Produced from clone of one single cell
Antibodies produced
Monoclonal
Large amounts
Desired specificity
Structure of antibodies
Immunoglobulin G ( IgG ) is the major class of antibodies in the plasma. 150 kDa Tetramer of
Two heavy chains 50 kDa Two light chains 25 kDa Connected by disulfide bonds
light chain
Heavy chain
IgG can bind and cross link antigens with multi binding sites
10
Classes of immunoglobulins
IgG
IgA
IgM
IgD
IgE
11
12
AA sequence H chain (multiple myeloma patients) 1- 113 vary from one patient to another 114 446 same in many patients
Variable and constant regions of light and heavy chains 3 stretches (7-12 amino acids) hypervariable VL VH CL VL CH 3 VH
13
14
Immunoglobulin fold
Pair of sheets
Each built of antiparallel strands Connected by disulfide Three loops at one end of the structure Hypervariable stretches The binding surface complementarity determining regions (CDR)
differentiated cell
VC
15
V V
V V
V V V V
V V
V V
V C
16
V 1 , V2 ,
. V40 VJ
J1, J2,
J5
VJC
17
18
Genes encoding heavy chains are present on chromosome 14 The variable gene is assembled from 3 segments
51
~27
19
20
Class switching
Proper immune response: Secreted antibodies must have appropriate effector function IgM IgG or IgA ... Specificity unchanged
Light chain unchanged VH unchanged CH is changed
Gene rearrangement: movement of VDG from a site near one C gene to a site near another C gene Shifting of the recognition domain different effector function unchanged binding specificity
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22
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C-Reacrive Protein
Undetectable in healthy individuals In patients with diverse inflammatory diseases
Acute rheumatic fever, bacterial infection, gout .. Tissue damage
Reacts with C substance ( polysaccharide in Pnumococci and molecular groups on a wide variety of bacteria
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