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Chapter 7 – HumoralImmune Responses

Dr. Hafez Sumairi

Learning outcomes

1.How are receptor-expressing naive B lymphocytesactivated and converted to antibody-secretingcells?

2.How is the process of B cell activation regulatedso that the most useful types of antibodies areproduced in response to different types ofmicrobes?

Phases and types of humoral immune responses

1. Naive Blymphocytes

• Membranebound receptors

• IgM and IgD

2. Clonal expansion

3. Differentiation

4. Heavy-chain isotype(or class) switching

5. Affinity maturation

Different subsets of B cells respond preferentially to proteinand nonprotein antigens1. Follicular B cells

• Reside in and circulate through the folliclesof lymphoid organs

• The bulk of T-dependent• Class-switched• High-affinity antibody responses to protein

antigens• Give rise to long-lived plasma cells

2. Marginal-zone B cells• Located in the peripheral region of the

splenic white pulp• Respond to blood-borne polysaccharide

antigens

3. B-1 cells• Respond to nonprotein antigens• In the mucosal tissues and peritoneum.

Antibody responses to the first and subsequent exposuresto an antigen, called primary and secondary responses,differ quantitatively and qualitatively

Stimulation of B lymphocytes by antigen

• Humoral immune responses are initiated when antigen-specific Blymphocytes in the spleen, lymph nodes, and mucosal lymphoidtissues recognize antigens.

Antigen-inducedsignaling in B cells• Antigen-induced clustering

of membrane Ig receptorstriggers biochemical signalsthat are transduced byreceptor-associatedsignaling molecules

• B cell receptor (BCR)complex, analogous to theT cell receptor (TCR)complex of T lymphocytes

Role of complement proteinsand other innate immunesignals in B cell activation• B lymphocytes express a

receptor for a protein of thecomplement system that providessignals for the activation of thesecells

• B lymphocytes expresscomplement receptor type 2(CR2, or CD21), which bindsC3d.

Functionalconsequences of B cellactivation by antigen• B cell activation by

antigen (and othersignals) initiates theproliferation anddifferentiation of thecells and prepares them tointeract with helper Tlymphocytes, if theantigen is a protein

Function of helper T lymphocytes in humoral immuneresponses to protein antigens

Germinal center, sonamed because thesecentral lightlystaining regions oflymphoid folliclesare sites whereactivated Blymphocytes divideand give rise toprogeny with alteredB cell receptors.

Heavy-chain isotype(class) switching•

Helper T cells stimulate the progeny ofIgM and IgD–expressing B lymphocytesto produce antibodies of different heavychain isotypes (classes)

• Affinity maturation occurs in thegerminal centers of lymphoid follicles andis the result of somatic hypermutation ofIg genes in dividing B cells, followed bythe selection of high-affinity B cells byantigen

• Antibody-secreting cells that areproduced in the germinal centers havealso been called plasmablasts becausethey are not fully differentiated.

Antibody responsesto T-independentantigens

Regulation of humoralimmune responses:antibody feedbackAntibody feedback

• Fc receptor expressed on Bcells (as well as on manymyeloid cells) calledFcγRIIB delivers inhibitorysignals that shut off antigenreceptor–induced signals,thereby terminating B cellresponses. This process, inwhich antibody bound toantigen inhibits furtherantibody production

Thank you

Title

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Chapter 8 – EffectorMechanisms of

Humoral Immunity

Dr. Hafez Sumairi

The complementsystem• It is a collection of circulating and cell

membrane proteins that play importantroles in host defense against microbes andin antibody-mediated tissue injury.

• Of the three major pathways ofcomplement activation, two, called thealternative and lectin pathways, areinitiated by microbes in the absence ofantibody, and the third, called theclassical pathway, is initiated by certainisotypes of antibodies attached to antigens

• The classical pathway of complementactivation is triggered when IgM orcertain subclasses of IgG (IgG1, IgG2,and IgG3 in humans)

The complement system

The complement systemThe late steps of complement activation

Functions of thecomplement system• The complement system plays an

important role in the elimination ofmicrobes during innate and adaptiveimmune 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