IMMUNITY AND ANTIBODIES
Stem cells in bone marrow differentiate into various blood cells
Phagocytes attack alien cells
A non-specific reaction Mast cells release histamine Histamine dilates capillaries, which leak complement proteins (serum enzymes)
A non-specific reaction Complement proteins attract phagocytes Phagocytes move out of capillary
A non-specific reaction Phagocytes engulf bacteria and other dead cells Phagocytes produce chemical toxins (H 2 O 2 ), which kills the bacteria (and the phagocytes)
How do cells know when there is an invasion? A signal cascade Signals: Fragment of bacterial or fungal cell wall binds CD14 Toll receptor activated Protein kinase cascade phosphorylates NF-kB NF-kB activates transcription
Specific immune reactions Discovery: anti-bacterial or anti-viral effect! Example: smallpox infection produces severe (often fatal) fever! Cowpox followed by smallpox infection usually not successful (Jenner, 1796)! Resistance transferred with serum ("humor") Agglutination of cells Precipitation of molecules Opsonization (stimulation of phagocytosis) Activation of complement
Lymphocytes are involved in defenses against specific invaders
Agglutination! Inject vertebrate with foreign red blood cells (rbcs), e.g. sheep cells into rabbits! Serum (blood minus clot) contains factors that agglutinate the foreign rbcs
Analysis! Rbcs are antigens! The serum factors are antibodies! Agglutination is explained by hypothesis that antibodies are proteins with!2 binding sites, specific for the antigen
Transfusion reactions! Carbohydrates A, B on cell surfaces are antigens, elicit antibodies! O cells lack both A and B! Serum has antibodies to A and B antigens that are not present on its own cells. Cells: O A B AB Serum: anti-a anti-b Anti-A none anti-b
Transfusion reactions! Anti-A-type antibodies in O and B-type sera agglutinate A (and AB) rbcs! Anti-B-type antibodies in O and A-type sera agglutinate B (and AB) rbcs! AB sera contain no antibodies (universal recipient)! Nothing agglutinates O rbcs (universal donor) Anti-A Anti-B Anti-A Anti-B
Antigens Viruses Bacteria Other pathogens Foreign proteins Foreign, complex carbohydrates Some organic small molecules (if attached to macromolecules) Foreign Complex Large
Antibodies Proteins Light and heavy chains Constant regions Variable regions Antigen binding sites The binding sites of any one antibody molecule have the same specificity, but different antibodies differ in the specificity of their binding sites
There are also different classes of antibodies with different constant regions
Precipitation of molecules! Reaction of antibodies with large molecules! Formation of large aggregate (precipitate) from proper ratio of antigen and antibody
Opsonization (stimulation of phagocytosis)! Antibody-binding to bacteria (and other antigens) stimulates their uptake into phagocytes
Phagocyte reactions Antigen binds to C- receptor, simulating Actin contraction forms phagocytic vesicle NADPH oxidase reduces O 2 to O 2-, which forms toxic H 2 O 2 NADP+ NADPH
Complement Antiserum + (foreign) red blood cell: agglutination Antiserum + (foreign) red blood cell + fresh plasma: lysis Complement: plasma proteins acting in sequence Starts with antibody aggregate Attracts phagocytes Ends with lytic enzyme
Summary Non-specific defenses are the first line of defense against pathogens. Cell damage and bacterial fragments serve as signals to activate the defense process. Mast cells, complement, neutrophils, and macrophages are the major players in nonspecific defense against pathogens Antibodies--induced serum proteins-- provide specific recognition of foreign invaders and stimulate phagocytosis