Download Immune System I: Antibodies

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 (H2O2), 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-B
Anti-A
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 Creceptor, simulating…
•Actin contraction forms
phagocytic vesicle
•NADPH oxidase
reduces O2 to O2-,
which forms toxic H2O2
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