immuno lect 7

b cells originate and mature in

bone marrow

b cells are activated after

exposure to antigens

b cells are usually activated in

lymphoid follicles

b cells become

plasma cell or memory B cell

b cells undergo

class-switching to other antibody types

b cells affinity of

antibodies increases (somatic to affinity maturation)

antibodies are proteins produced by b lymphocytes in response to

specific foreign antigens, including microorganisms and toxins

2 regions of antibody structure

fab region, Fc region

fab region contains the

antigen binding site

antigen binding site binds only

specific epitope

fab region is highly

variable

Fc region determines the

class

Fc region is responsible for

effector/immune responses

as with TCRs, diversity is vast with

heavy chain, light chain

heavy chain refers to what recombination

VDJ recombination

light chain refers to what recombination

VJ recombination

antigen binding site diversity is generated during maturation in the

bone marrow

bone marrow stroma signals the B cell to rearrange

H and L chains

1st step of heavy chain rearrangement

random d segment joins a random J segment

2nd step of heavy chain rearrangement

DJ randomly joins w/a V segment to make VDJ

what enzymes cut the DNA during VDJ recombination

RAG enzymes

which chain is rearranged first, heavy or light

heavy

What happens if the B cell fails to make a functional heavy chain?

it gets a second change, additional heavy chain rearrangement begins on the other allele

what triggers light chain rearrangement

successful expression of a functional heavy chain, plus a signal from the stroma

What happens if the light chain rearrangement fails?

further light chain rearrangement occurs

H and L chain associate and form

b cell receptor (BCR or antigen receptor)

if no BCR, then the cell

dies

if self-reactive BCR, rearrangement

occurs, and if still self-reactive, cell dies

if BCR reacts w/soluble protein such as serum albumin, there is no

cross-linking of receptors, and B cells becomes anergic

each antigen binding site has how many complementarity determining regions

6

complementarity determining regions are also called

hypervariable regions

where are the complementarity determining regions on the chains

3 on heavy, 3 on light

b cells make what while still in the bone marrow

membrane-bound antibodies (BCRs)

b cell antibodies are initially only

membrane-bound

which immunoglobulin isotypes are found on naive b cells

IgM, IgD

b cell receptors are

membrane-bound immunoglobulin on the b cell surface, together with its associated signaling proteins

2 signaling proteins of the BCR-complex

Ig-alpha, Ig-beta

all naive b cells coming from the bone marrow express

membrane-bound IgM and membrane IgD

after activation of a b cell in secondary lymphoid organ, the antibody production shifts from

membrane-bound to secreted antibody, occurring via alternative splicing of primary transcript

if the heavy chain is gamma, the class is

IgG

if the heavy chain is mu, the class is

IgM

if the heavy chain is alpha, the chain class is

IgA

if the heavy chain is omega, the class is

IgD

if the heavy chain is epsilon, the class is

IgE

class switching occurs only

after activation

class switching occurs if b cell encounters

antigen and adequate co-stimulatory molecules

class switching involves deleting

parts of the heavy chain gene from the constant portion

(class switching) What mechanism removes the unwanted constant region genes?

Looping-out deletion: the DNA loops out and is cut away

(class switching) recombinase excises the

intervening DNA

(class switching) cytokine profile of the T_h cell determines the

antibody class produced

IgA concentration is highest at

mucosa

IgA is secreted at mucosal surfaces in which organs

respiratory, GI, urinary, skin, mammary gland, eye

dimeric IgA is actively

secreted across mucosal surfaces

dimeric IgA is formed by linking

2 IgA molecules by the J chain

dimer IgA binds to

polymeric immunoglobulin receptor

polymeric immunoglobulin receptor is the

secretory component

dimeric IgA is endocytosed by

mucosal epithelial cell and transported to luminal side of cell

dimeric IgA is secreted into

GI lumen

(dimeric IgA) secretory component remains on IgA and protects from

intestinal proteases

activation of b cells can occur with or without

t cells

b cell activation with a t cell required an

activated t cell

(b cells interact w/t helper cells) b cells display antigen on

MHC 2, bind to helper t cell

(b cells interact w/t helper cells) b cells are influenced by

cytokines secreted by the helper t cell

strong activation of t cell interacting with b cell,

clonal expansion occurs (b cells become plasma cells or memory b cells)

2 pathways of b cell activation without t cells

thymus-independent antigen TI-1, thymus-independent antigen TI-2

thymus-independent antigen TI-1 activates

BCR and co-recpetor simultaneously

thymus-independent antigen TI-2 contains a strong

crosslinking of BCR

example of thymus-independent antigen TI-1

LPS, TLR

thymus-independent antigen TI-2 example

repetitive proteins or polysaccharides

b cell activation

b-cell activation without T cells create a weaker

signal than if the B-cell is activated with t cell help

thymus independent B cell activation has no

t cell involvement, class-switching, somatic hypermutation, affinity maturation

What 3 things does thymus-dependent B cell activation require?

A very specific antigen, an activated Th cell, and co-stimulatory molecule binding

What does the activated Th cell release to help the B cell?

cytokines

What 3 outcomes does thymus-dependent activation produce?

Isotype switching, somatic hypermutation, and affinity maturation

when b cells are activated with t cell help, what occur

class switching and somatic hypermutation occur

class switching switch the type of

antibody plasma cells secrete

class switching can never revert

to other Ig types b/c DNA was excised

serum levels of different immunoglobulin types will change

after the initial exposure to antigen

What are the 4 features of antibody production after a second exposure to antigen?

A faster response, a bigger response, different antibody classes, and higher-affinity antibodies

How do antibody classes change after a second exposure?

They shift from IgM to other classes

What is the increase in antibody affinity after repeated exposure called?

Affinity maturation

What are the 6 antibody functions listed?

B cell activation (as part of the BCR), acting as an opsonin, inactivating toxins, mast cell degranulation, activating complement, and activating ADCC

How do antibodies contribute to B cell activation?

As part of the BCR

What does ADCC stand for?

Antibody-dependent cellular cytotoxicity

Which cells carry out ADCC?

NK cells

Which complement pathway do antibodies activate?

The classical pathway

Which antibody sits on the mast cell surface?

IgE

What triggers mast cell degranulation?

Antigen binding and cross-linking IgE on the mast cell surface

How do antibodies neutralize toxins?

By binding them and directly blocking their effects

Name 2 examples of toxins antibodies can block

Bacterial toxins and venom