Exam 2: Antibodies, BCR, B cell Development, B cell immunity

central tolerance

training B cells during development to be self-tolerant

true

During development, the BCRs of B cells are tested to make sure they are not reactive to self proteins. true or false

false

Follicular dendritic cells are professional antigen presenting cells that activate both B and T cells. true or false

true

Germinal centers are structures within secondary lymphoid tissue that contain activated B cells that are undergoing proliferation. true or false

receptor editing

Process by which B cells with that bind self are edited; RAG gene expression allows light chain editing. Can undergo this process until all V and J segments have been used.

somatic hypermutation, affinity maturation, isotype switching

What are the three processes that occur in the germinal enter that diversify antibodies?

Ig-alpha/beta

mu heavy chain on pro-B cells has to interact with signaling protein chains, ________and send a signal to be considered functional. If not functional, try again on other chromosome. If still not function, die.

opsonins

Antibodies can be ______, molecules that enhance phagocytosis The Fc portiosn of antibodies bound to a microbe will bind the Fcy receptors on phagocytes, stimulating them to ingest the microbe spleen is important site for clearing opsonized bacteria

antigen

B cell activation is a result of ___ binding membrane immunogen B cells internalize, process, and present the ______ via receptor mediated endocytosis

false

B cell development is dependent upon the success of DNA rearrangment to make the MHC genes. true or false

activated

B cell primary function: secrete antibodies, antibodies perform effector function B cell secondary function: bind and internalize antigen, process it for presentation to T cells To perform any functions, a B cell must be ______________.

T cells

B cells are msot strongly activated by antigen and contact with _____ (T-dependent antigen activation (TD))

false

B cells are phagocytic. true or false

false

B cells can only be activated through ligand binding of their BCR. true or false

bone marrow

B cells complete most of their development in the ___ before migrating to secondary lymphoid tissues

false

B cells complete their final developmental stage in the bone marrow. true or false

true

B cells have to interact with stromal bone marrow cells to recieve signals that allow them to move from one developmental stage to another. true or false

IgD, IgM

B cells in the periphery express ___ and become mature B cells. Once activated, they stop secreting that and start secreting ___

stromal cells

Bone marrow ______ play important role in B cell maturation; make physical interactions with developing B cells and secrete proteins that promote growth and survival

constant

Class switching results in loss of ___ region DNA Switch regions (not RAG and RSS) regulate the recombination

true

Cytokines produced by T cells influence class swithcing in B cells - determine which Ig isotype that B cell produce. true or false

RAG-1/2

Enzymes that cut and recombine V(D)J segments of Ab DNA in somatic recombination recognizes RSS around each gene segment

linear epitope

Epitope of a protein recognized by antibody that consists of a linear sequence of amino acids within the protein's primary structure. T CELLS

CD34

Hematopoietic stem cell surface protein

secreted

If an IgM has NO hydrophobic tail at the end of its constant region, is it secreted or transmembrane?

transmembrane

If an IgM has a hydrophobic tail at the end of its constant region, is it secreted or transmembrane?

somatic recombination

Ig Genes are assembled by recombination events at the DNA level VJ or VDJ gene segments splice together to form the variable regions these events are the only known site-specific DNA rearrangements in vertebrates

complement activation

IgM is the best, IgG can do it when bound to antigen...can bind the activating protein of the complement cascade (C1qrs complex) and inititate the classical complement pathway activatino by IgG requires two or more IgG monomers the structure of IgM allows for easy C1qrs binding

true

Immunoglobulins can be membrane-bound or secreted. true or false

heavy chain

In Ig gene rearrangements, which chain is made first?

linked recognition

In TD activation, T cells and B cells are activated by the same antigen but different epitopes

variable

In heavy chain rearrangements, segments making up the ____ region will determine antigen specificity this is the most varied and unique part of the gene because it codes for the variable and hypovariable portion of the protein that will bind unique epitopes

constant

In heavy chain rearrangements, the ___ region contains all the genes that can be used t make a specific antibody class/isotype

kappa or lambda

In light chain rearrangements, the constant region can either be ________________

functional light chain

In order for a pre-B cell to become an immature B cell, it must have a..........

functional heavy chain

In order for a pro-B cell to become a pre-B cell, it must have a ............

CD19

Pan B cell marker - glycoprotein found exclusively on B cells

DiGeorgeSyndrome

Patients with __ lack a thymus and have almsot no T cells. ALthough they have normal numbers of B cells, they fail to make antibodies to most antigens, but can produce low affinity IgM antibodies specific for a few microbial antigens (T independent antigen activation (TI))

1. antigen binding 2. costimulation (C40/CD40L) 3. cytokines

SIgnals required for activation of B cells via TD antigens

hinge

Some antibodies (IgG, IgD, IgA) have movable arms due to a flexible _____, which allows the antigen binding at a variety of angles

allelic exclusion

Successful rearrangements of DNA on both chromosomes could result in two heavy chains, which would mean two heavy chain specificity....... After we have a working heavy chain, we need to turn off heavy chain rearrangement locus on the other heavy chain.

T-independent antigen (TI)

TI-1 Polyclonal activators that bind surface proteins (like TLRs) other than the BCR, so antigen specificity isn't required (often microbial cell wall components (LPS) , also called mitogens TI-2 bind multiple BCRs simultaneously due to repetitive epitopes and multivalency molecule that activates T/B cell non-specifically through receptors other than B cell

co-receptor

The BCR and_______ works together to activate B cells to surface and soluble antigens ___ contains CR2 (complement receptor), CD19 (pan B cell marker), and CD81 engagement of ____ by complement coated antigens sends additional activation signals which ensures protection of IgM and initiates proliferation

signaling

The BCR requires membrane-bound antibody AND the association of two ____ proteins Igalpha, Igbeta) BCR binds antigen ONLY Igalpha and Igbeta are responsible for transmitting signals

true

The enzymes RAG-1 and RAG-2 are required for somatic recombination (the joining of specific V, D and J gene segments). true or false

Passive immunity

Via the FcRn, IgG crosses the placenta to provide antibody protection for the fetus IgA in mother's milk is transferred to newborns

multiple

There is only one way to activate T cells, but ____ ways to activate B cells, each way being a different levels of activation

true

To make the B cell receptor, B cells first have to splice the DNA to make a unique B cell receptor gene. true or false

RSS

Two forms, 12 and 23 RAG always lands on 12 and 23, binds, comes together and cleaves at this point hint: recombination signal sequence

IgM and IgD

What two antibodies can a B cell produce at the same time? This is because these two are made as one RNA transcript, and simoltaneously expressed. Mature naive B cells express both

c

Which of the following is NOT true of antibodies? A. Antibodies are proteins. B. Each antibody has 2 heavy chains. C. Each antibody has 1 light chain. D. Antibodies have a variable region that binds antigen.

D

Which of the following is a function of antibodies? A. Recognize and bind pathogen. B. Flag pathogens so that other immune components can phagocytose or kill them. C. Lyse cells directly. D. A and B

post-B

Which of the following is not a stage in B cell development? Pro-B Immature Mature Post-B Pre-B

allelic exclusion

While there are many mechanisms to generate diversity in antigen specificity utilizing the gene segments inherited from mom & dad, these mechanisms are tightly regulated so that a single B cell finally expresses *only one heavy chain and one light chain* this ensures that each individual B cell is specific for only one antigenic epitope/determinant

FcR

___ bind the Fc portion of antibodies IgG, IgA, IgE and mediate their functions of opsonization, antibody-dependent cellular cytotoxicity, mast cell degranulation

IgA

___ forms dimers. the end of the constant region has a tailpiece of 18 amin acids that are necessary for polymerization

IgM

___ forms pentamers. region has a tailpiece of 18 amin acids that are necessary for polymerization

IgG

___ is the workhorse of the systemic humoral immune system 4 subclasses that binda variety of FcRs and have flexible hinge regions, IgG can perform almost all antibody functions

heavy

____ chain isotypes (M, G, A, D, E) are functionally different have 1 variable region and 3-4 constant regions the constant regions determine the type of antibody

IgE

____ provides a mechanism for rapid ejection of pathogen from body by binding to ___ Fc receptors on mast cells. When multiple ___ antibodies are cross-linked by antigen, this triggers degranulation by mast cells

light

_____ chain isotypes (kappa and lambda) are functionally the same with some structural variation has one variable region and one constant region

follicular dendritic cells (FDCs)

________ interactiosn are necessary for the survival of naive B cells passing through lymphoid tissue, but also for improving the receptor (BCR) specificity of activated B cells via affinity maturation ___ bind intact opsonized antigens and preserve it for interaction with B cell

hydrophobic tail

________________ at the end of the constant region on an antibody determines if it is secreted or membrane bound

immunogen

a stimulus that elicits an immune response

lymphoid tissue

activation of B cells via TD antigens is dependent on interactions that occur in ________

T-dependent antigen (TD)

additional activation signals are provided by T cells proteins because they have to be recgnized by both B and T cells

VLA-4 and VCAM-1

adhesion molecules used for B cell maturation --lymphoid progenitor cell

CDR (complementarity determining region)

aka hypervariable region = 3 loop regions of hyper-variability (CDR 1,2,3) found at tip of each arm on Ab that form antigen binding site (determine complementarity). Other portions of variable region are called the *framework regions*.

agglutination

antibodies clump insoluble antigens in a special form of neutralization makes it easier for immune system to recognize and clear IgM does this

true

antibodies themselves are not toxic or destructive to the pathogen... they just bind tightly to the pathogen true or false

antibody-dependent cellular cytotoxicity

antibody function Fc receptors are surface proteins that bind the Fc portion of antibodies ANtibodies bind target cells by their Fab fragment, leaving their Fc portion free to interact with cells having Fc receptors ie NK cells can attack host cells that have self reactive antibodies

IgD

antibody that Has no known function in a secreted form.

IgA

antibody that can exist as a dimer or a monomer

IgE

antibody that is Is required for the degranulation of mast cells.

IgM

antibody that is Is the best at activating complement.

IgA

antibody that is Most abundant in secretions and mucosal surfaces.

IgG

antibody that is Most predominant in the blood serum and extracellular fluid.

IgG

antibody that is predominant in the blood and tissues has a RcRn (neonatal) receptor that transports ____ from the bloodstream into the extracellular space via transcytosis

IgA

antibody that is present in secretions (tears, saliva, milk, intestinal fluid) transcytosis via poly-Ig receptor in association with J-chain

IgM

antibody that only exists as a pentamer

reversible, non-covalent

antigen-antibody interactions are ___________ & _______________

immunoglobulin (Ig)

antigen-binding protein made by B-cells when it is on the surface- BCR when it is secreted- antibody

TdT

best source of junctional diversity! enzyme that randomly fills in with nucleotides at joints

AID

enzyme used in class switching to cleave loop once you switch classes, you cannot go back because the DNA is looped out and degraded

discontinuous epitope

epitope of a protein recognized by antibody that consists of a discontinuous sequence of amino acids within the protein

degranulation of mast cells

function of antibody IgE granules contain histamine and other inflammatory mediators which act on smooth muscle cells to generate violent reactions such as sneezing, coughing, vomiting, or diarrhea to forcibly eject pathogens or toxins natural target of degranulation is parasitic infection but these reactions can be elicited by harmless antigens causing allergic reactions

antibody

function: recognize and bind antigen target the bound antigen to other immune system components

Ka and SCF

growth signals used for B cell maturation --pro-B cell

somatic recombination

joining together of V, D, J, and constant regions; requires enzymes RAG1 and RAG2 RANDOM PROCESS

class (isotype) switching

occurs in secondary lymphoid tissue after B cell activation-NOT a change in antigen epitope specificity different signals can induce B cells to switch isotypes (change the constant region so IgM can beome IgG/IgA etc.) this happens by attaching the VDJ region to a new constant region

Fc receptor-mediate functions

opsonization (IgG) antibody-dependent cellular cytotoxicity (IgG) IgE-mediated mast cell degranulation, rapid pathogen expulsion

variable region

part of the antibody that binds antigen and greatly differs between different antibodies recognizes and allows antibody binding of specific epitopes within antigens

constant region

part of the antibody that is responsible for effector functions, does not differ between different antibodies

AAA

polyadenilation determines where to splice RNA

IgG

present in secretions of the nose, lower respiratory tract, and urogenital tract plasma cells in the lamina propria secrete ____ and it is transported in the blood and mucosal tissues via FcRn

B1 cell

primitive B cell found in pleura and peritoneum that only secretes IgM that reacts to bacterial glycoproteins (some cross react to A and B antigens on RBCs) beneficial for complement self-renewing no memory no DNA rearrangement, no class switching

somatic hypermutation

process in the germinal body that diversifies antibodies point mutations in the variable region of the heavy and light chains ---does not change antigen specificty but changes the affinity of the BCR for its antigen

isotype switching

process in the germinal body that diversifies antibodies the change in the antibody isotype/class due to a change in heavy chain constant region. This changes the range of function so fthe antibody ---does not alter antigen specificity

affinity maturation

process in the germinal body that diversifies antibodies the selection of B cells producing antibodies with more specific/greater affinity for antibody-antigen binding

selection

process of making sure newly formed IgM's are not strongly reactive to host proteins

F(ab)2

proteases cleave antibodies into distinct fragments ___ is the antigen binding fragment

Fc

proteases cleave antibodies into distinct fragments ___ is the crystallization fragment

CR2

protein found on co-receptor, complement receptor

immature B cell

stage in B cell development IgM heavy and light chain expressed on surface

pre-B

stage in B cell development undergoing light chain rearrangement

pro-B

stage in B cell development undergoing heavy chain rearrangement

J chain

structure that catalyzes polymeric structures of IgM and IgA

IL-7

survival signal used for B cell maturation --pro-B cell

plasma cell

terminally differentiated B cell that is no longer activated by antigen, but rather secretes large amounts of antibody specific for the last antigen that activated the B cell

cross reactivity

when an antibody binds to a similar epitope that is not its cognate epitope (ie binds to host protein)...can result in disease BAD

neutralization

when antibodies bind to surface protein on microbes and coat the microbe, preventing it from binding to other receptors or cell surfaces antibodies can bind toxins as well, very small molecules often secreted by microbes IgA is the best IgG and IgM can also do this

naive

word used to describe B cells that have never encountered an antigen, never been activated