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Biophysical Immunology Laboratory. Thomas Vorup-Jensen. Institute for Medical Microbiology and Immunology University of Aarhus Denmark vorup-jensen@microbiology.au.dk. B-cell activation and Ab production Janeway’s Immunobiology Chapter 10 Cellular and humoral factors .

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slide1

Biophysical Immunology Laboratory

Thomas Vorup-Jensen

Institute for Medical Microbiology and Immunology

University of Aarhus

Denmark

vorup-jensen@microbiology.au.dk

slide2

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

B cells are activated in T cell dependent and independent processes

Presentation of antigens to T cells by B cells

Structure and function of antibodies

slide3

I

II

III

slide6

(CD8+ T cellsarealso

Important for clearance of virus!!)

slide17

Signalling occurs by redistribution

of kinases and phosphotases

in cell-cell contact.

slide18

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Cytokine environment is important B cell differentiation.

T cells contribute to the cytokine production. Signaling in

T cell are regulated by formation of the immunological

Synapse.

slide19

Dendriticcells: a veiledmembranethatpermitsefficientadhesion to lymphocytes?

K. Inabaet al., J. Exp. Med. (1984) 160:858

slide22

Macrophages (MØ) produce more proteases

thandendriticcellsor B lymphocytes

AEP: asparagineendopeptidase; cat:cathepsin

Delamarreet al. Science (2005) 307:1630-1634

slide30

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Lymph nodes are central in B cell differentiation. T and B cells

occupy distinct zones in this tissue

slide37

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

The antibody production is regulated with regard to isotype and

clonality in response to microbial products

slide42

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Antibodies (immunoglobulins) posses different functionalities

Antibodies are actively transported to distinct location in the body

slide47

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Antibody effectormeachnisms (I):

Antibodies may act to neutralize functions of microbial molecules

(sometimes a trouble in drug treatment!)

slide48

”Target-binding” complement proteins arelargerthan the rest….

…but why?

Tanakaet al. (2010)

35 nm

Vorup-Jensen & Boesen (2011) Adv. Drug Discov. Rev. 63:1008-19

J Infect Chemother16:383–387

slide51

Does curvature of epitope-presenting surfaces affect IgM conformation?

IgM

Variable

region

Pedersen et al.J. Immunol. (2010) 184:1931-45

slide52

S. aureus liberates PGN fragments to the culture medium during growth

EM micrographs

of sections

S. aureus T7

o/n culture

Filtration

through

0.22 mm membrane

Agarose

Embedded

filtrate

slide54

”Handedness” of epitopeswill not permitIgMavidity binding to

front-to-backrepeatingepitopes

Fab1-2

Fab9-10

Fab3-4

Fab5-6

Fab7-8

slide55

50 nm

Organization of the cellwall of S. aureus:

a nm-scaled pattern?

Touhami A et al. (2004) J. Bacteriol.186: 3286–3295.

slide56

Cell wall pattern has structural

features on par with the sizes

of MBL and IgM!

Touhami A et al. (2004) J. Bacteriol.186: 3286–3295.

slide58

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Antibody effectormeachnisms (II)

IgG and IgM Antibody isotypes mediate complement activation

Size of Ab and topology of surfaces (!) may influence complement

activation.

slide65

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

Antibody effectormeachnisms (III)

Fc receptors are important for phagocytic uptake and leukocyte

responses

slide66

B-cellactivation and Ab production

Janeway’sImmunobiologyChapter10

Cellular and humoral factors

Important messanges:

B cells are activated in T cell dependent and independent processes

Cytokine environment is important B cell differentiation.

T cells contribute to the cytokine production. Signaling in

T cell are regulated by formation of the immunological

Synapse.

Lymph nodes are central in B cell differentiation. T and B cells

occupy distinct zones in this tissue

slide67

Structure and function of antibodies

The antibody production is regulated with regard to isotype and

clonality in response to microbial products

Antibody isotypes mediate different types of immunity, depending

specificity, tissue distribution, and size (!).