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: Foreignness Chemical composition > CHONs are best immunogens, CHOs are weak; Lipids and nucleic acids: poor 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: Chemical Complexity Genetic composition of the host Method of administration and dose

HUMORAL IMMUNITY ADJUVANT: when mixed with Ag enhances duration and magnitude of the immune response by: Prolonging retention of immunogen Increasing effective size of immunogen 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: Opsonic; promote ingestion and killing by phagocytic cells Neutralize (block attachment) toxins and viruses Agglutinate bacteria; may aid in clearing 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) 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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