Complement and Effector Mechanisms of Adaptive Immunity

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Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

LECTURE 7: COMPLEMENT AND EFFECTOR MECHANISMS OF ADAPTIVE IMMUNITY Lecture 7 Objectives 1. To review principles of innate versus adaptive immunity 2. To learn the basic structure of antibodies 3. To learn basic principles of the complement system 4. To be able to identify components of the classical complement system 5. To learn the sequence of events that occur during activation of the classical complement pathway 6. To learn examples of genetic diseases caused by mutation of genes encoding complement components How Does an Immune System that is Evolutionarily Conserved and Slow to Change Respond to Pathogens that can Evolve Rapidly?  Nature has come up with an inventive, effective, but also dangerous solution to this problem  B cell receptors, T cell receptors, and antibodies function as adapter molecules o A part of the molecules are evolutionary conserved, and another part of these molecules can rapidly evolve to recognize pathogens T-Cell Receptor (TCR)  Recognizes peptides derived from protein antigens o Peptides must be “presented” to TCR on a MHC molecule o Peptides are small (8-12 amino acids)  TCR recognizes the peptide-MHC complex o TCR is therefore specific to one MHC allele plus peptide  Huge amount of variability in the amino acid sequences within different molecules in this variable region  Constant region on the other hand, the amino acid sequences, are relatively constant The Domains of an Immunoglobulin Molecule are Structurally Similar  Proteins form a three dimensional structure which are highly conserved – domains  Joined by linker proteins Antibody Molecules can be Cleaved into Functionally Distinct Fragments  Fab (“Fragment antigen binding”) – fragment of the antibody that retains the ability to bind to antigens o This include one light chain protein and half of the heavy chain protein  Fc (“Fragment crystallizable”) – can be crystallized, reflects the fact that amino acids are so similar in a pool of amino acids o Crystallizable because the amino acid sequence is realtively constant o In general, molecules that are highly similar can form crystal and molecules that are highly dissimilar cannot form crystals  Pepsin – cleaves molecules in a slightly different way… o Generates a number of proteolytic fragments… Epitopes and Paratopes  Epitope – also known as antigenic determinant – portion of an antigen recognized by an Ab or TCR  Paratope – unique surface topology at the ends of an Ab that is complementary to the epitope o Made up of both a heavy chain and a light chain protein – variable regions of these two working together make up the paratope – however, can be thought of as one continuous surface Antibody Effector Mechanisms  Antibodies are effector molecules because they participate in getting rid of infections  Opsonization – way of coding a pathogenic organism with molecules that allow the immune system to specifically recognize it (“planting a flag” and saying “come attack me”)  Complement activation – highly evolutionarily conserved pathway for getting rid of microorganisms o Antibodies in the complement pathway work together to form proper immune responses Complement  Component(s) of plasma that complement antibody action to kill bacteria  Participates in both innate and adaptive immune responses  A large number of proteins (about 48) that interact in a hub-like network as well as with other systems  The function of complement proteins is to o Directly kill pathogens o Opsonize pathogens to flag them for destruction o Function as a chemoattractant to recruit leukocytes to a site of damage/infection  Zymogens – proteases that themselves have to be activated by other proteases
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