Chapter 9: Immunity Medited By B Cells And Antibodies

Question 1

B cell activation requires…

Answer 1

• cross-linking of surface immunoglobulin

- cross-linking of antigen receptors is the first step in B-cell activation

Question 2

B-cell receptors (BCR) on B cells are physically cross-linked by the repetitive epitopes of antigens (Ag) on the surface of a bacterial cell

Answer 2

• the BCR on a mature, naive B cell is composed of surface IgM, which binds antigen, and associated Ig-alpha and Ig-beta chains, which provide the intracellular signaling capacity

Question 3

B cell activation requires signals from the B-cell _________

Answer 3

• co-receptor
• cross-linking is not sufficient enough for activation
• signals generated from the B-cell receptor and co-receptor synergize in B cell activation

Question 4

What is the B-cell co-receptor?

Answer 4

• the B-cell co-receptor is composed of 3 polypeptide chains CD19, CD81, and CR2 (complement receptor)
• CR2 binds to complement on pathogen surfaces
• CD19 is the signaling component
• CD81 function is not known

Question 5

How does it work?

Answer 5

• binding of CR2 to C3d fragments deposited on the surface of a pathogen brings together the B-cell co-receptor complex with the B-cell receptor
• this causes them to cluster together on the B-cell surface and send two signals for B-cell activation in a synergistic way

Question 6

The antibody response to certain antigens does not require T-cell help.

Answer 6

• thymus-independent (TI)-1 antigens activate B cells without T-cells help by activating additional signals
• Lipopolysacharides ia a TI-1 antigen
• TI-1 antigens can only produce an IgM response

Question 7

TI-1 antigens can only produce an IgM response because…

Answer 7

• there is not T-cell cytokine help to isotype switch

Question 8

What is this additional signal that replaces the T-cell help to even produce IgM?

Answer 8

• innate immunity and the TLR (toll-like receptor activation)

Question 9

Thymus-independent (TI)-2 antigen can also activate B-cells without T-cell help

Answer 9

• these are repetitive carbohydrate or protein epitopes on pathogens, such as polysaccharides of the pneumoccocus
• unlike T1-1 antigens, T1-2 antigens do not activate additional signaling pathways but densely cross-link B-cell receptors and co-receptors to generate a signal above the level required to stimulate B-cell proliferation and differentiation

Question 10

Activation of naive B cells by most antigens require help from CD4 T cells

Answer 10

• antigen-stimulated B cells become trapped in the T-cell zone, where they meet effector helper T cells
• recirculating naive T cells enter the T cell zone of a lymph node draining a bacterial infection from the blood through high endothelial venules (HEX)
• T cells that encounter specific antigen on a dendritic cell proliferate and differentiate to become helper TH2 cells
• circulating naive B cells similarly enter the T-cell zone of the lymph node. B cells that encounter their specific antigen become trapped in the T-cell zone, where they process and present peptides from this antigen on MHC class 2 molecules
• helper TH2 cells and B cells specific for antigens on the same bacterium form conjugate pairs in which the T cells begin to activate the B cells
• this type of interaction between a T cell and a B cell that recognize different epitopes on the same antigen is called a cognate interaction

Question 11

B cell activation in response to thymus-dependent antigens requires cognate T-cell help.

Answer 11

• the first signal required for B-cell activation is delivered through the antigen receptor
• with thymus-dependent antigens the second signal, is delivered by a cognate helper T cell that recognizes a peptide fragment of the antigen bound to MHC class 2 molecules on the B-cell surface

Question 12

Two signals together drive B cell proliferation and differentiation into plasma cells

Answer 12

• IL-4, IL-5, IL-6

- CD40L/CD40 interaction

Question 13

After B cell activation, some B cells leave the _________ _________ to produce IgM antibodies in the ____________ ____________, and other leave the primary focus and go to the __________ _________ of the B cell zones to isotype switch and hyper mutate.

Answer 13

• primary focus
• medullary cords
• primary follicles

Question 14

What is the primary focus?

Answer 14

• is clonal expansion in the medullary cords produces plasma cells secreting IgM under the influence of IL-5 and IL-6
• this period of cellular proliferation can last several days

Question 15

Selection of ______________ by antigen in the germinal center drives affinity maturation of the B cell response.

Answer 15

• centrocytes
• after activation, proliferation, and differentiation of B cell in the germinal center, somatic hypermutation produces centrocytes with a diversity of BCR
• competition between centrocytes for the antigen drives affinity maturation
• centrocytes that can’t bind with a high affinity undergo apoptosis

Question 16

The cytokines made by helper T cells determine how B cells switch their immunoglobulin isotype

Answer 16

• individual cytokines can either induce (green), augment (yellow), or inhibit (red) the switching of immunoglobulin synthesis to a particular isotype

Question 17

Cytokines made by helper T cells determine the differentiation of antigen-activated B cells into plasma cells or memory cells

Answer 17

• once centrocytes leave the germinal center, IL-10 helps them differentiate into antibody producing plasma cells
• in the latter stages of immune response, as the infection subsides, centrocytes differentiate into memory B cells under the influence of IL-4

Question 18

Isotype switching diversifies antibody function by changing the HC constant region

Answer 18

• IgM, IgG and monomeric IgA protect the internal tissues of the body

Question 19

IgM has pentameric form and enters the blood to go to the site of infection, inflammation and tissue damage throughout the body

Answer 19

• pentameric form allow for strong binding to antigen

Question 20

After isotype switching, affinity maturation produces _____ and monomeric _____ that is as good as a pentameric IgM in neutralization.

Answer 20

• IgG and IgA
• there are receptor that carry IgG into the extracellular spaces
• IgG and IgA also prevent blood-borne infection

Question 21

Dimeric IgA protects the…

Answer 21

• mucosal surfaces of the body
• these epithelial surfaces of the body include the linings of the gastrointestinal tracts, eyes, nose, throat, respiratory, urinary and genital tracks, and mammary glands
• the poly-Ig receptor binds to the DIMERIC IgA (and pentameric IgM) and carries the IgA in an endocytic vesicles to the other side of the cells (apical face of the epithelial cell)

Question 22

IgE provides a mechanism for the rapid ejection of pathogens from the body

Answer 22

• as soon as IgE is made, it is quickly bound with high affinity to mast cells by an Fc receptor (FcER1 on mast cells) in the connective tissues
• this receptor is also found on circulating basophils and activated eosinophils present in mucosal tissues
• when a pathogen binds IgE coated mast cells, it activates the mast cells to produce mediators that act on smooth muscle to cause violent reactions such as sneezing, coughing, vomiting, and diarrhea that forcible eject the pathogens from the respiratory and gastrointestinal tracks

Question 23

Mothers provide protective antibodies to young, both before and after birth

Answer 23

• during pregnancy, IgG is transported to placenta to fetus
• after birth, the baby has protection… only in blood/tissue
• also baby gets dimeric IgA through mother’s milk for protection of mucosal surfaces

Question 24

High affinity neutralizing antibodies prevent viruses and bacteria from infecting cells

Answer 24

• viral infections can be blocked by neutralizing antibodies
• viral proteins can agglutinate when bound with antibodies
• disease causing bacterial infections at mucosal surfaces can be prevented by neutralizing antibodies

Question 25

High affinity IgG and IgA antibodies are used to neutralize microbial toxins and animal venoms

Answer 25

• many common diseases are caused by bacterial toxins
• antibodies that bind to the toxins can neutralize a toxin
• toxoids are used for incorporation into vaccines

Question 26

IgG and IgM are great act activating…

Answer 26

• complement

- binding of IgM to antigen on a pathgen’s surface activates complement by the classical pathway

Question 27

Complement activation (classical pathway) by IgG requires the participation of two or more IgG molecules

Answer 27

• at least two molecules of IgG bound to pathogens or soluble antigens are required to activate the complement cascade

Question 28

Erythrocytes facilitate the removal of immune complexes from the circulation

Answer 28

• disposal of immune complexes is crucial in the defense and protection of tissues
• red blood cell CR1 helps to clear immune complexes from the circulation
• small soluble immune complexes bind to CR1 on erythrocytes
• erythrocytes then transport them to the liver and spleen
• in the spleen and liver they are transferred to the CR1 of macrophages and taken up for degredation

Question 29

Fc receptors enable hematopoietic cells to bind and be activated by IgG bound to pathogens

Answer 29

• Fc receptors on phagocytes trigger the uptake and breakdown of antibody coated pathogens
• signals from the Fc receptors enhance phagocytosis of bacterium and the fusion of lysosomes containing degradative enzymes with phagosomes
• antibody-coated target cells can be killed by NK in antibody-dependent cell mediated cytotoxicity ADDC

Question 30

IgE binds to high-affinity Fc receptors on mast cells, basophils, and activated eosinophils

Answer 30

• the FcER1 receptor for IgE on mast cells, basophils, and activated eosinophils has an affinity for the Fc region of IgE that is 100 fold higher than that of the IgG receptor
• IgE molecules are tightly bound in the absence of antigen on mast cells

Question 31

The cytoplasm of many resting mast cell is filled with ___________ containing _________ and other molecules that contribute to ______________

Answer 31

• granules
• histamines
• inflammation
• inflammatory mediators secreted into the tissue by activate mast cells, basophils, and eosinophils, increase the permeability of the local blood vessels enabling other cells to come into the tissue
• inflammation is swelling reddening and pain

Question 32

Mast cells response to antigen is a very fast mechanism

Answer 32

• some people make IgE in response to relatively innocuous substances like pollen and shellfish
• causes allergic reactions and asthma
• in extreme cases, can cause life-threatening systemic inflammatory response called anaphylaxis