Humoral Immunity Lecture (2)

HUMORAL IMMUNITYHUMORAL IMMUNITY

Antibody mediatedAntibody mediated Part of Specific immunity along with cell-Part of Specific immunity along with cell-

mediated typemediated type When Nonspecific immunity fails, tissue When Nonspecific immunity fails, tissue

macrophages take up the organismsmacrophages take up the organisms

specific immune responses activated specific immune responses activated Antibody is synthesizedAntibody is synthesized

HUMORAL IMMUNITYHUMORAL IMMUNITY Primary molecular component: antibodyPrimary molecular component: antibody Ab is made by B-cells and plasma cells in Ab is made by B-cells and plasma cells in

response to Ag challengeresponse to Ag challenge Ab: protection vs rechallengeAb: protection vs rechallenge

block spread of agent in bloodblock spread of agent in blood

facilitate elimination of infectious agentfacilitate elimination of infectious agent Ab must also interact with host cells (macrophage, Ab must also interact with host cells (macrophage,

complement)complement) Ab also serve as B-cell receptors to stimulate Ab also serve as B-cell receptors to stimulate

plasma cell growth and produce more Absplasma cell growth and produce more Abs


General Properties of an Antigen:General Properties of an Antigen:1.1. ForeignnessForeignness2.2. Chemical compositionChemical composition > CHONs are best immunogens, CHOs are> CHONs are best immunogens, CHOs are weak; Lipids and nucleic acids: poorweak; Lipids and nucleic acids: poor3.3. Molecular sizeMolecular size 500-1000 Da= min size for immunogenicity500-1000 Da= min size for immunogenicity <10,000 Da = weak immunogen<10,000 Da = weak immunogen >10,000 Da = strong immunogen >10,000 Da = strong immunogen


General Properties of an Antigen:General Properties of an Antigen:

4.4. Chemical ComplexityChemical Complexity

Response to Ag may vary according to:Response to Ag may vary according to:

1.1. Genetic composition of the hostGenetic composition of the host

2.2. Method of administration and doseMethod of administration and dose

HUMORAL IMMUNITYHUMORAL IMMUNITYADJUVANT:ADJUVANT: when mixed with Ag enhances when mixed with Ag enhances

duration and magnitude of the immune duration and magnitude of the immune response by:response by:

1.1. Prolonging retention of immunogenProlonging retention of immunogen

2.2. Increasing effective size of immunogenIncreasing effective size of immunogen

3.3. Stimulating local influx of macrophages and/or Stimulating local influx of macrophages and/or other immune cell types to the injection site.other immune cell types to the injection site.

Ex. Freund’s adjuvant, liposomes, bacterial cell wall Ex. Freund’s adjuvant, liposomes, bacterial cell wall components, molecular cages for Ag and polymeric components, molecular cages for Ag and polymeric surfactant, E.coli, cholera toxin surfactant, E.coli, cholera toxin


ImmunogenImmunogen = substance capable of eliciting = substance capable of eliciting an immune responsean immune response

AntigenAntigen = substance recognized by immune = substance recognized by immune responseresponse

EpitopeEpitope = Molecular structure recognized by = Molecular structure recognized by immune responseimmune response

HaptenHapten = incomplete immunogen that cannot = incomplete immunogen that cannot initiate response but that can be initiate response but that can be recognized by Abrecognized by Ab


Carrier Carrier = protein modified by hapten to elicit = protein modified by hapten to elicit responseresponse

AdjuvantAdjuvant = substance that promotes immune = substance that promotes immune response to an Agresponse to an Ag

T-independent AgsT-independent Ags = Ags with large repetitive = Ags with large repetitive structures (e.g., bacteria, flagellin, structures (e.g., bacteria, flagellin, lipopolysaccharide, polysaccharide)lipopolysaccharide, polysaccharide)

T-dependent AgsT-dependent Ags = Ags that must be = Ags that must be presented to T and B cells for Ab presented to T and B cells for Ab productionproduction


Immune Component: Immune Component: Fc ReceptorFc Receptor

Interaction: macrophage (opsonization)Interaction: macrophage (opsonization)

PMNs (opsonization)PMNs (opsonization)

T cells (activation)T cells (activation)

NK cells, ADCC (killing)NK cells, ADCC (killing)

Mast cells for IgE (allergic Mast cells for IgE (allergic

reactions, anti-parasitic)reactions, anti-parasitic)


Immune Component: Immune Component: ComplementComplement

Interaction: Complement systemInteraction: Complement system

Function: OpsonizationFunction: Opsonization

Killing (especially bacteria)Killing (especially bacteria)


Antimicrobial Action of Antibodies:Antimicrobial Action of Antibodies:

1.1. Opsonic; promote ingestion and killing by Opsonic; promote ingestion and killing by phagocytic cellsphagocytic cells

2.2. Neutralize (block attachment) toxins and Neutralize (block attachment) toxins and virusesviruses

3.3. Agglutinate bacteria; may aid in clearingAgglutinate bacteria; may aid in clearing

4.4. Render motile organisms nonmotileRender motile organisms nonmotile


Antimicrobial Action of Antibodies:Antimicrobial Action of Antibodies:

5.5. Combine with Ags on the microbial surface, Combine with Ags on the microbial surface, activate complement cascade, thus activate complement cascade, thus inducing an inflammatory response, inducing an inflammatory response, bringing fresh phagocytes and serum Abs bringing fresh phagocytes and serum Abs into the siteinto the site

6.6. Combine with Ags on the microbial surface, Combine with Ags on the microbial surface, activate complement cascade, anchor the activate complement cascade, anchor the membrane attack complex (C5b to C9) membrane attack complex (C5b to C9)


Immuneglobulins (Antibodies)Immuneglobulins (Antibodies)

1. 1. IgDIgD

> exists primarily as membrane/surface IgD > exists primarily as membrane/surface IgD on B-cell, along with IgM they are the only on B-cell, along with IgM they are the only isotypes expressed by the same cellisotypes expressed by the same cell

> no known biologic function> no known biologic function

> less than 1% of serum Igs> less than 1% of serum Igs

> 185 kDa molecular mass> 185 kDa molecular mass



2. 2. IgMIgM

> first Ab produced versus Ag challenge> first Ab produced versus Ag challenge

> can be produced in T-independent manner> can be produced in T-independent manner

> 5-10% of total Igs in the adult> 5-10% of total Igs in the adult

> half life 5 days> half life 5 days

> pentameric: 5 units joined by disulfide > pentameric: 5 units joined by disulfide bonds and the J chain (900 kDa)bonds and the J chain (900 kDa)


Immuneglobulins (Antibodies)Immuneglobulins (Antibodies)2. 2. IgMIgM > theoretically has 10 Ag binding sites;> theoretically has 10 Ag binding sites; > binds complement the best (1 pentamer > binds complement the best (1 pentamer

activates the classic pathway)activates the classic pathway) > Monomeric IgM is with IgD on surface of B > Monomeric IgM is with IgD on surface of B

cellscells > cannot go from blood to tissue because of > cannot go from blood to tissue because of

size size



2. 2. IgMIgM

> immunity vs polysaccharide Ags (capsules)> immunity vs polysaccharide Ags (capsules)

> promotes phagocytosis and bacteriolysis > promotes phagocytosis and bacteriolysis through complement activationthrough complement activation

> major component of rheumatoid factors> major component of rheumatoid factors


Immuneglobulins (Antibodies)Immuneglobulins (Antibodies)3. 3. IgGIgG > about 85% of all Igs in the adult> about 85% of all Igs in the adult > half life of 23 days (longest)> half life of 23 days (longest) > molecular mass of 184 kDa> molecular mass of 184 kDa > 2 L chains of 22,000 Da and 2 H chains of > 2 L chains of 22,000 Da and 2 H chains of

55,000 Da each55,000 Da each > 4 subclasses: IgG 1-4, diff structure, relative > 4 subclasses: IgG 1-4, diff structure, relative

concentration and functionconcentration and function



3. 3. IgGIgG

> production is T-cell dependent; can cross > production is T-cell dependent; can cross the placentathe placenta

> principal Ig in booster and anamnestic > principal Ig in booster and anamnestic responseresponse

> high binding capacity for Ags, fixes > high binding capacity for Ags, fixes complement, stimulates chemotaxis and complement, stimulates chemotaxis and acts as opsonin acts as opsonin

Cross-reactive antibodiesCross-reactive antibodies

May react with more than 1 microorganism May react with more than 1 microorganism when they share similar Ag’ic determinantswhen they share similar Ag’ic determinants

Historically called Natural antibodiesHistorically called Natural antibodies Immune properties well documented in lab Immune properties well documented in lab

animalsanimals Often directed against polysaccharides with Often directed against polysaccharides with

similar structures across different species, similar structures across different species, genera and familiesgenera and families


Immuneglobulins (Antibodies)Immuneglobulins (Antibodies)4. 4. IgAIgA > 5-15% of all Igs in the adult> 5-15% of all Igs in the adult > half life of 6 days> half life of 6 days > molecular mass of 160 kDa, basic 4-chain > molecular mass of 160 kDa, basic 4-chain

monomer, but can occur as dimers, trimers monomer, but can occur as dimers, trimers or multimers thru the J chainor multimers thru the J chain

> > Secretory IgaSecretory Iga = appears in body secretions = appears in body secretions for local immunityfor local immunity


Immuneglobulins (Antibodies)Immuneglobulins (Antibodies)4. 4. IgAIgA > production requires T-cell help and mucosal > production requires T-cell help and mucosal

stimulation by adjuvants like cholera toxin stimulation by adjuvants like cholera toxin and attenuated salmonellaand attenuated salmonella

> binds to poly-Ig receptors on epithelial cells > binds to poly-Ig receptors on epithelial cells for transport across cellsfor transport across cells

> remains bound to IgA and cleaved to > remains bound to IgA and cleaved to become become Secretory Component Secretory Component once once secretory IgA is secretedsecretory IgA is secreted



4. 4. IgAIgA

> about 2 gms of IgA/day secreted by adults> about 2 gms of IgA/day secreted by adults

> appears in colostrum, intestinal and > appears in colostrum, intestinal and respiratory secretions, saliva, tears and respiratory secretions, saliva, tears and other secretionsother secretions

> IgA-deficient persons have more frequent > IgA-deficient persons have more frequent respiratory tract infectionsrespiratory tract infections

Pneumonia in IgA DeficiencyPneumonia in IgA Deficiency

HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)5. 5. IgEIgE > less than 1% of total serum Igs in adults> less than 1% of total serum Igs in adults > half life of about 2.5 days> half life of about 2.5 days > most are bound to Fc receptors on mast > most are bound to Fc receptors on mast

cells and serve as receptors for allergens cells and serve as receptors for allergens and parasite Agsand parasite Ags

> once Ige is bound by Ag, mast cells release > once Ige is bound by Ag, mast cells release histamine, prostaglandin, platelet activating histamine, prostaglandin, platelet activating factors and cytokinesfactors and cytokines

HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)

5. 5. IgEIgE

> serve as protection versus parasitic > serve as protection versus parasitic infectionsinfections

> responsible for the manifestations of > responsible for the manifestations of anaphylactic (Type 1) hypersensitivityanaphylactic (Type 1) hypersensitivity

Anaphylactic shockAnaphylactic shock

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Humoral Immunity Lecture (2)