humoral immunity
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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 - PowerPoint PPT PresentationTRANSCRIPT
HUMORAL IMMUNITYHUMORAL IMMUNITY Primary molecular component: antibodyPrimary molecular component: antibody Ab is made by B-cells and plasma cells in response Ab is made by B-cells and plasma cells in response
to Ag challengeto 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
HUMORAL IMMUNITYHUMORAL IMMUNITYGeneral 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
HUMORAL IMMUNITYHUMORAL IMMUNITY
General Properties of an Antigen:General Properties of an Antigen:
4.4. Chemical ComplexityChemical Complexity5.5. Genetic composition of the hostGenetic composition of the host6.6. 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 immunogen2.2. Increasing effective size of immunogenIncreasing effective size of immunogen3.3. Stimulating local influx of macrophages Stimulating local influx of macrophages
and/or other immune cell types to the and/or other immune cell types to the injection site. injection site.
HUMORAL IMMUNITYHUMORAL IMMUNITYImmunogenImmunogen = substance capable of eliciting = substance capable of eliciting
an immune responsean immune responseAntigenAntigen = substance recognized by immune = substance recognized by immune
responseresponseEpitopeEpitope = Molecular structure recognized by = Molecular structure recognized by
immune responseimmune responseHaptenHapten = 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
HUMORAL IMMUNITYHUMORAL IMMUNITYCarrier Carrier = protein modified by hapten to elicit = protein modified by hapten to elicit
responseresponseAdjuvantAdjuvant = substance that promotes immune = substance that promotes immune
response to an Agresponse to an AgT-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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmune 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)
HUMORAL IMMUNITYHUMORAL IMMUNITY
Immune Component: Immune Component: ComplementComplement Interaction: Complement systemInteraction: Complement system Function: OpsonizationFunction: Opsonization Killing (especially bacteria)Killing (especially bacteria)
HUMORAL IMMUNITYHUMORAL IMMUNITYAntimicrobial Action of Antibodies:Antimicrobial Action of Antibodies:1.1. Opsonic; promote ingestion and killing by Opsonic; promote ingestion and killing by
phagocytic cellsphagocytic cells2.2. Neutralize (block attachment) toxins and Neutralize (block attachment) toxins and
virusesviruses3.3. Agglutinate bacteria; may aid in clearingAgglutinate bacteria; may aid in clearing4.4. Render motile organisms nonmotileRender motile organisms nonmotile
HUMORAL IMMUNITYHUMORAL IMMUNITYAntimicrobial Action of Antibodies:Antimicrobial Action of Antibodies:5. Combine with Ags on the microbial surface, 5. 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 pahagocytes and serum Abs bringing fresh pahagocytes and serum Abs into the siteinto the site
6. Combine with Ags on the microbial surface, 6. 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)
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)1.1. IgDIgD > exists primarily as membrane IgD on B-cell, > exists primarily as membrane IgD on B-cell,
along with IgM they are the only isotypes along with IgM they are the only isotypes expressed by the same cellexpressed by the same cell
> less than 1% of serum Igs> less than 1% of serum Igs > 185 kDa molecular mass> 185 kDa molecular mass
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)2. 2. IgMIgM > first Ab produced versus Ab challenge> first Ab produced versus Ab 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)
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (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
HUMORAL IMMUNITYHUMORAL IMMUNITYImmuneglobulins (Antibodies)Immuneglobulins (Antibodies)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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