Chapter 8 – effector mechanisms of humoral immunity lecture 8

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Chapter 8 – EffectorMechanisms of

Humoral Immunity

Dr. Hafez Sumairi

Learning outcomes

1.What are the mechanisms used by secreted antibodiesto combat different types of infectious agents andtheir toxins?

2.What is the role of the complement system in defenseagainst microbes?

3.How do antibodies combat microbes that enter throughthe gastrointestinal and respiratory tracts?

4.How do antibodies protect the fetus and newbornfrom infections?

Properties of antibodies that determineeffector function

Properties of antibodiesthat determineeffector function• Switching to the IgG

isotype prolongs theduration an antibodylasts in the blood andtherefore increases thefunctional activity ofthe antibody

• Neonatal Fc receptor(FcRn)

Neutralization ofmicrobes andmicrobial toxinsAntibodies bind toand block, orneutralize, theinfectivity ofmicrobes and theinteractions ofmicrobial toxinswith host cells

Opsonization andphagocytosisThe process of coating particles forsubsequent phagocytosis is calledopsonization, and the molecules that coatmicrobes and enhance their phagocytosis arecalled opsonins.

Antibody-dependentcellular cytotoxicity• Antibody-dependent cellular cytotoxicity

(ADCC)

• ADCC is also one of the mechanisms bywhich therapeutic antibodies used to treatcancers eliminate tumor cells.

Immunoglobulin E–and eosinophil/ mastcell–mediated reactionsIgE antibodies may also bind to and activatemast cells, which secrete cytokines, includingchemokines, that attract more leukocytes thatfunction to destroy the helminths.

The complementsystem• It is a collection of circulating and cell

membrane proteins that play important rolesin host defense against microbes and inantibody-mediated tissue injury.

• Alternative and lectin pathways, areinitiated by microbes in the absence ofantibody

• Classical pathway, is initiated by certainisotypes of antibodies attached to antigens

• The classical pathway of complementactivation is triggered when IgM or certainsubclasses of IgG (IgG1, IgG2, and IgG3 inhumans)

The complement system

The complement systemThe late steps of complement activation

Functions of thecomplement system• In innate and adaptive immune responses

• In addition to its antimicrobial effectorfunctions, the complement systemprovides stimuli for the development ofhumoral immune responses

• Inherited deficiencies of complementproteins are the cause of human diseases.

• Lacking C2 and C4 associated with anincreased incidence of systemic lupuserythematosus

• Deficiencies of C9 and MAC formationresult in increased susceptibility toNeisseria infections

Regulation ofcomplementactivation• Mammalian cells express regulatory

proteins that inhibit complementactivation, thus preventing complement-mediated damage to host cells

• Hereditary angioneurotic edema inwhich excessive C1 activation and theproduction of vasoactive proteinfragments lead to leakage of fluid(edema) in the larynx and many othertissues

• Deficiency of C1 INH

• Paroxysmal nocturnal hemoglobinuria• Deficiency of DAF

Functions ofantibodies at specialanatomic sitesMucosal Immunity

• Immunoglobulin A is produced inmucosal lymphoid tissues, transportedacross epithelia, and binds to andneutralizes microbes in the lumens of themucosal organs

• Poly-Ig receptor

Neonatal Immunity

• Maternal antibodies are activelytransported across the placenta to thefetus and across the gut epithelium ofneonates,

• Neonatal Fc receptor (FcRn)

Evasion of humoralimmunityby microbes

VaccinationVaccination is the process of stimulatingprotective adaptive immune responsesagainst microbes by exposure tononpathogenic forms or components of themicrobes.

Thank you