Transcript Slide 1

HUMORAL IMMUNITY
 Primary molecular component: antibody
 Ab is made by B-cells and plasma cells in
response to Ag challenge
 Ab: protection vs rechallenge
block spread of agent in blood
facilitate elimination of infectious agent
 Ab must also interact with host cells (macrophage,
complement)
 Ab also serve as B-cell receptors to stimulate
plasma cell growth and produce more Abs
HUMORAL IMMUNITY
General Properties of an Antigen:
1. Foreignness
2. Chemical composition
> CHONs are best immunogens, CHOs are
weak; Lipids and nucleic acids: poor
3. Molecular size
500-1000 Da= min size for immunogenicity
<10,000 Da = weak immunogen
>10,000 Da = strong immunogen
HUMORAL IMMUNITY
General Properties of an Antigen:
4. Chemical Complexity
5. Genetic composition of the host
6. Method of administration and dose
HUMORAL IMMUNITY
ADJUVANT: when mixed with Ag enhances
duration and magnitude of the immune
response by:
1. Prolonging retention of immunogen
2. Increasing effective size of immunogen
3. Stimulating local influx of macrophages
and/or other immune cell types to the
injection site.
HUMORAL IMMUNITY
Immunogen = substance capable of eliciting
an immune response
Antigen = substance recognized by immune
response
Epitope = Molecular structure recognized by
immune response
Hapten = incomplete immunogen that cannot
initiate response but that can be
recognized by Ab
HUMORAL IMMUNITY
Carrier = protein modified by hapten to elicit
response
Adjuvant = substance that promotes immune
response to an Ag
T-independent Ags = Ags with large repetitive
structures (e.g., bacteria, flagellin,
lipopolysaccharide, polysaccharide)
T-dependent Ags = Ags that must be
presented to T and B cells for Ab production
HUMORAL IMMUNITY
Immune Component: Fc Receptor
Interaction: macrophage (opsonization)
PMNs (opsonization)
T cells (activation)
NK cells, ADCC (killing)
Mast cells for IgE (allergic
reactions, anti-parasitic)
HUMORAL IMMUNITY
Immune Component: Complement
Interaction: Complement system
Function: Opsonization
Killing (especially bacteria)
HUMORAL IMMUNITY
Antimicrobial Action of Antibodies:
1. Opsonic; promote ingestion and killing by
phagocytic cells
2. Neutralize (block attachment) toxins and
viruses
3. Agglutinate bacteria; may aid in clearing
4. Render motile organisms nonmotile
HUMORAL IMMUNITY
Antimicrobial Action of Antibodies:
5. Combine with Ags on the microbial surface,
activate complement cascade, thus
inducing an inflammatory response,
bringing fresh pahagocytes and serum Abs
into the site
6. Combine with Ags on the microbial surface,
activate complement cascade, anchor the
membrane attack complex (C5b to C9)
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
1. IgD
> exists primarily as membrane IgD on B-cell,
along with IgM they are the only isotypes
expressed by the same cell
> less than 1% of serum Igs
> 185 kDa molecular mass
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
2. IgM
> first Ab produced versus Ab challenge
> can be produced in T-independent manner
> 5-10% of total Igs in the adult
> half life 5 days
> pentameric: 5 units joined by disulfide
bonds and the J chain (900 kDa)
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
2. IgM
> theoretically has 10 Ag binding sites;
> binds complement the best (1 pentamer
activates the classic pathway)
> Monomeric IgM is with IgD on surface of B
cells
> cannot go from blood to tissue because of
size
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
2. IgM
> immunity vs polysaccharide Ags (capsules)
> promotes phagocytosis and bacteriolysis
through complement activation
> major component of rheumatoid factors
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
3. IgG
> about 85% of all Igs in the adult
> half life of 23 days (longest)
> molecular mass of 184 kDa
> 2 L chains of 22,000 Da and 2 H chains of
55,000 Da each
> 4 subclasses: IgG 1-4, diff structure, relative
concentration and function
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
3. IgG
> production is T-cell dependent; can cross
the placenta
> principal Ig in booster and anamnestic
response
> high binding capacity for Ags, fixes
complement, stimulates chemotaxis and
acts as opsonin
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
4. IgA
> 5-15% of all Igs in the adult
> half life of 6 days
> molecular mass of 160 kDa, basic 4-chain
monomer, but can occur as dimers, trimers
or multimers thru the J chain
> Secretory Iga = appears in body secretions
for local immunity
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
4. IgA
> production requires T-cell help and mucosal
stimulation by adjuvants like cholera toxin
and attenuated salmonella
> binds to poly-Ig receptors on epithelial cells
for transport across cells
> remains bound to IgA and cleaved to
become Secretory Component once
secretory IgA is secreted
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
4. IgA
> about 2 gms of IgA/day secreted by adults
> appears in colostrum, intestinal and
respiratory secretions, saliva, tears and
other secretions
> IgA-deficient persons have more frequent
respiratory tract infections
Pneumonia in IgA Deficiency
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
5. IgE
> less than 1% of total serum Igs in adults
> half life of about 2.5 days
> most are bound to Fc receptors on mast
cells and serve as receptors for allergens
and parasite Ags
> once Ige is bound by Ag, mast cells release
histamine, prostaglandin, platelet activating
factors and cytokines
HUMORAL IMMUNITY
Immuneglobulins (Antibodies)
5. IgE
> serve as protection versus parasitic
infections
> responsible for the manifestations of
anaphylactic (Type 1) hypersensitivity
Anaphylactic shock
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