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BIOL 107 Exam 2
Immunology
206
Biology
Undergraduate 4
03/05/2013

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Term
Antigen
Definition
molecular structures recognized by cells of adaptive immune system

substance that binds to the products of the adaptive immune response (Ab, T cell) (antigenic).
Term
Ag of B cell
Definition
Native structure of protein or polysaccharide
Area of recognition on an Ag - epitope
Linear
Conformational
Term
Ag of T cell
Definition
Processed peptide that binds to MHC on APC (antigen presenting cell)
Term
Immunogen
Definition
substance that induces the adaptive immune response (immunogenic)
Term
Immunogenic is always antigenic
Antigenic is not always immunogenic
*Memorize this concept
Definition
Term
B cell recognizes specific Ag via
Definition
B cell receptor (BCR)
Term
Over view of B cell response in secondary lymphoid tissues
(4 main steps)
Definition
1. B cell recognizes specific Ag via B cell receptor (BCR)
2. B cell activation
2a. B cell interact with CD4 Th cells
via Immunological synapse, lymphokines
3. B cell proliferation
differentiation
3a. Undergo somatic hypermutation
Ag class switch in LN.
Become plasma cells that produce
(IgG, IgA or IgE)
3b. IgM plasma cell
4. Generation of memory B cell
Term
Antibody structure
Definition
Y shaped molecule.
2 identical sub-units (light and heavy chain) linked together by disulfide bond
2 light chains, 2 heavy chains
Flexible hinge region
Term
Dual functions of Ab
Definition
1. Antigen binding site – N-terminal- variable region.

Genetically diverse
Each individual Ab recognize a specific Ag.(clonal)

2. Effector site – C-terminal, - constant region

Interacts other cells and soluble proteins to perform Ab function.
Effector cells (macrophage, neutrophil, NK cell etc.
Effector molecules (complements)
Term
variable domain (VL or VH)
Definition
The first N-terminus domain. Ag binding domain.
Term
constant domains (CL, CH1-3)
Definition
C – terminus domains. Less variable.
Term
The flexible region between CH1 and CH2 is
Definition
the hinge region (disulfide bond)
Term
Molecules with structure similar to Ig (repeated domain) is belong to...
Definition
the immunoglobulin super family) (remember ICAM-1?)
Term
Two forms of Immunoglobulin
Definition
1. Membrane bound Ig – B cell receptor (BCR)
2. Secreted Ig – Antibody (Ab).
Term
Membrane bound Ig – B cell receptor (BCR)
Definition
Extra transmembrane region for membrane anchoring.
For binding specific Ag and initiating B cell activation.
Naïve B cell has BCR but does not produce secreted Ab.
Term
Secreted Ig – Antibody (Ab).
Definition
No-transmembrane region
Produced by antigen activated and differentiated B cells – plasma blasts and plasma cells.
Plasma cell (terminally differentiated B cell) produces Ab but does not express BCR on cell surface
Term
Structure of Ig domain
L chain as example
Definition
A domain consists of 2 beta sheets hold together by disulfide bond and forms beta barrel.

Variable domain has bigger beta sheet with extra loops.

Some loops in VARIABLE domain are the actual Ag binding areas.
Term
The aa sequence viability in V region is..
Definition
....not evenly distributed
Term
Hyper variable region (HV)
Definition
Sequences in some loops at the tip of the V domain that are highly variable. contributes to antibody diversity and antigen binding specificity
Term
framework region (FR)
Definition
Regions between hyper variable region (HV) that are relatively constant.
FR corresponds to the beta sheet and other loops.
Term
Both light and heavy variable domains have __ HV and __ FR regions
Definition
3 HV and 4 FR regions
Term
Antibody’s antigen binding site is formed by variable regions from...
Definition
both hyper variable region (HV) of light and heavy chains from V region (VL and VH)
Term
Antibody diversity is determined by...
Definition
HV from both light and heavy chains.
Term
The HV regions is also called
Definition
complementarity–determining-region (CDR).
Term
Ig can be enzymetically cleaved into:
Definition
Fab (fragment antigen binding) or F(ab’)2


Fc (fregment crystalizable). – confer the binding to effector molecules or cells.
Term
Fab and F(ab’)2 can bind to antigen without _____ function
Definition
effector function (such as opsonin to induce phagocytosis, antibody-dependent cell-mediated cytotoxity (ADCC), and complement activation.)
Term
IgM is secreted as a _____ connected by ______ and _____
Definition
IgM secreted as pentamer connected by disulfide bond and J chain (joining chain)
Term
3 things IgM pentamer does for antigens:
Definition
increases Ag binding site, Ag binding strength (avidity), and better complement activation.
Term
Which Ig can be either monomeric or dimeric?
Definition
IgA
Term
Dimeric IgA is also called ....
Definition
...secretory IgA since it can be transcytosed through mucosal epithelial cells into the musocal surface.
Term
Monomeric IgA are mainly found where?
Definition
circulating in blood
Term
antibody (immunoglobulin) repertoire
Definition
The total number of antibody (immunoglobulin) specificity
Term
Each B cell produces one clone of antibody that recognizes only one specific
Definition
epitope
Term
Antibody repertoire is made of ...
Definition
the combined antibody specificity from all B cells in an individual.
Term
Antibody gene in B cell undergo
Definition
somatic recombination
Term
Light chain V domain is made of....
Definition
V-J segments
Term
Light chain V region consists of a ____ segment and a ____ segment
Definition
1. larger (~100 aa) variable (V) gene segment
2.small (~10 aa) joining (J) gene segment.
Term
heavy chain V region consists of ___,___, and ___ segment
Definition
1. variable V segment
2. diversity D segment
3. joining J segment
Term
Which chain and which region of immunoglobulin rearranges first?
Definition
H chain V region genes are rearranged first.
Term
VH (variable heavy) domain is made up of....
Definition
VDJ segments. After D-J recombination, V segment rearranges with the D-J to form VDJ.
Term
Are L chain V region genes rearranged before or after H chain V region?
Definition
L chain V region genes are rearranged AFTER H chain V region.
Term
VL (variable light) domain is made up of...
Definition
VJ segments. One V and one J segment out of many are rearranged (V-J-recombination)
Term
VL (variable light) domain is made up of...
Definition
VJ segments. One V and one J segment out of many are rearranged (V-J-recombination)
Term
recombination signal sequences (RSS)
Definition
sequences that flank V,D, J gene segments. RSS arrangement: heptamer – spacer – nonamer. Heptamer is always adjacent to coding sequence.
Term
Two kinds of RSS
Definition
23 base-pair spacer, 12 base-pair spacer
Term
Immunoglobulin gene rearrangement occurs only between segments with RSS of
Definition
12 spacer and 23 spacer (12/23 rule). This rule ensure rearrangement only between V(D)J.
Term
Ig gene rearrangement is a multiple step process involving lymphocyte specific recombinases....
Definition
RAG-1 and RAG-2 (recombinant activating gene)
Term
1. RAG1/RAG2 complex binds to RSS of __ and __ segments.

2. Afterwards, what is the process that RAG1/RAG2 follows?
Definition
1. V and J

2.
a) brings two RSS together
b) cleave at the end of heptamer
c) loop out sequence between two RSSs
Term
Cellular DNA repair enzymes join DNA ends to create....
Definition
signal joint and coding joint.
Term
Cellular DNA repair enzymes are involved for gene rearrangement for....
Definition
....both immunoglobulin and T cell receptor.
Term
severe combined immune deficiency (SCID)
Definition
When deficiency in genes involving in the gene rearrangement results in the deficiency in both B cells and T cells
Term
After Ig gene rearrangement, do B cells have MORE or LESS DNA than cells with germline DNA?
Definition
Less DNA
Term
What additional immunoglobulin gene can be created at the coding joint?
Definition
Diversity gene
Term
What type of nucleotides are added to the VJ or VDJ junction sites?
Definition
P-nucleotides and N-nucleotides
Term
1. P-nucleotides (palindromic nucleotides)
2. N-nucleotides (Nontemplated nucleotides)
Definition
1. generated by open hairpins at a random site
2. generated by randomly adding nucleotides by TdT
Term
junctional diversity
Definition
The diversity created at junction site due to additional nucleotides, it significantly increases the total diversity
Term
TdT
Definition
terminal deoxynucleotidyl transferase
Term
The immunoglobulin gene diversity is generated by 3 ways during rearrangement:
Definition
1. V region genetic rearrangements (recombination) – combinatorial diversity
2. At V-D-J or V-J joints - Junctional diversity
3. Ag binding site is formed by combining VL and VH.
Term
CDR1,2 are in...
Definition
V segments
Term
CDR3 is formed at...
Definition
VJ or VDJ joint regions.
Term
Once V(D)J rearrangement is completed, will V region undergo further rearrangement?
Definition
Nope.
Term
After V region rearrangement the light and heavy chains of Ig DNA are organized as:
Definition
L – V (D)J – C (L or H)
Term
4 Steps that occur during immunoglobulin expression
Definition
1. Primary RNA for H or L chain is transcribed.
2. Processed mRNA with removed introns, added poly A tail is ready to be translated to Ig L or H chain proteins.
3. L (leader peptide) is cleaved after translation,
4. Disulfide bond is formed to hold 2 H/L chains together
Term
Alternative RNA processing produces
Definition
IgM and IgD mRNA – NOT DNA rearrangement
Term
Naïve B cells express which Igs?
Definition
IgM and IgD
Term
Primary RNA transcripts for H chain contains C region for...
Definition
both IgM and IgG
Term
Which two Igs are the only Igs that can be co-expressed?
Definition
IgM and IgD
Term
1. MC stands for....
2. pAmm or pAdm stands for...
2. SC stands for....
Definition
1. membrane coding
2. site for cleavage and polyadenylation
3. secretion code
Term
Each Ig H chain (IgM for example) has ___ sequence for transmembrane region of membrane bound IgM and ___ sequence for secreted IgM
Definition
MC sequence and SC sequence
Term
Primary IgM RNA transcript contains
Definition
both SC and MC
Term
Alternative RNA processing cleaves at ____ or ____ and produces mRNA for either ____ IgM or _____ IgM
Definition
Alternative RNA processing cleaves at either pAmm and pAm and produces mRNA for either membrane IgM or secreted IgM.
Term
There are five isotypes of antibody, which are determined by constant regions of ____
Definition
H chain
Term
Each isotype of Ab have distinctive....
Definition
...tissue distribution and functions along with antibody functions
Term
IgM is primarily in found____, with one exception, which is....
Definition
Found mainly in blood circulation and can exit blood vessels to enter tissues during inflammation
Term
Which two Igs are both found in blood circulation and tissue interstitial fluids?
Definition
IgG and monomeric IgA
Term
Which Ig can be transported from placenta to fetus?
Definition
IgG
Term
Which Ig is secreted by B cells in mucosal tissues transcytosed through epithelial cells to ____ surface and be secreted from mammary gland to milk?
Definition
Dimeric IgA Dimeric IgA is secreted by B cells in mucosal tissues and can be transcytosed through epithelial cells to MUCOSAL surface and be secreted from mammary gland to milk..
Term
Which Ig binds tightly to FceRI and where are these FceRI receptors found? (found on three types of cells)
Definition
IgE binds tightly to FceRI (Fc receptor for IgE) on MAST CELLS, BASOPHILS, and ACTIVATED EOSINOPHILS
Term
Where are these mast cell, basophils, or activated eosinophils located when IgE binds tightly to their FceRI receptors?
Definition
1. mast cells: distribute in connective tissue under epithelial cell layer (skin, mucosal surface)
2. basophils: blood circulation
3. activated eosinophils: mucosal surface
Term
Fc receptor FcRn facilitates ....
Definition
...IgG entry to tissue interstitial and placenta
Term
IgG transport through endothelial cells is aimed by...
Definition
...FcRn
Term
FcRn is a ____ molecule that protects IgG from ___ and increases IgG _____
Definition
FcRn is a MHC class I like molecule that protects IgG from degradation and increases IgG half-life
Term
Dimeric IgA is transported to mucosal surface by ...
Definition
....active transcytosis
Term
Poly-Ig receptor on basolateral membrane of mucosal epithelial cells binds ___ chain of which Ig and then transports that particular Ig to the apical surface of the cell.
Definition
Poly-Ig receptor on basolateral membrane of mucosal epithelial cells binds J chain of dimeric IgA (also called secretory IgA, sIgA) and transports sIgA to the apical surface of the cell.
Term
secretory component
Definition
Portion of the receptor remaining on sIgA after poly-Ig receptor is cleaved
Term
sIgA protects....
Definition
....the mucosal surfaces of the body by resisting the proteases on the musosal surfaces including intestinal surface.
Term
Epitope
Definition
part of antigen that antibody binds, also called antigenic determinant
Term
Multivalent antigen
Definition
a complex molecule or a whole pathogen has many epitopes on it.

1. Multiple distinct epitopes – binding of many different Ab

2. Repeated epitopes. – multiple identical molecules or molecular structures on pathogen such as polysaccharides which bind to the same Ab molecules
Term
Linear epitope:
Definition
Linear sequence, epitope will not disappear when protein is denatured.
Term
Conformational/discontinuous epitope:
Definition
Epitope will disappear when protein is denatured.
Term
Three modes of neutralization
Definition
1. Ab binds to virus surface proteins and blocks virus attachment and entry to cells – kills virus by terminate virus replication cycle and prevents virus from continuous spreading between cells.

2. Ab binds to bacteria surface protein and prevents bacteria attachment to cell – prevents invasion.

3. Ab binds to toxin and prevents toxin binding to cellular receptor – abrogates toxin effects.
Term
Which two Igs have the strongest neutralizing activity?
Definition
IgG, IgA
Term
Can Ab neutralize without Fc portion?
Definition
Yes, and Ab neutralizing activities have been used to block bio-active molecules in research and treatments.
Term
Antibody effector functions:
(there are five of them)
Definition
1. Neutralization
2. complement activation
3. opsonization
4. Antibody-dependent cell-mediated cytotoxicity - (ADCC)
5. sensitizing of mast cells - IgE
Term
Soluble pentameric IgM is in ___ form that can not activate classic pathway of complement activation.
Definition
planar
Term
IgM binding to Ag induces conformation change to ____ form that can activate complement
Definition
staple
Term
_____are required for complement activation. (Single Ag bound IgG can not activate complement)
Definition
Multiple Ag bound IgG (at least 2)
Term
The binding of what two molecules causes an immune complex in blood circulation that can further activate complements resulting in C3b binding in immune complex?
Definition
Antibody (IgG) binding of soluble Ag such as toxin or pathogen fragments
Term
Which receptor on erythrocytes binds C3b on the immune complex and brings the complex to liver or spleen?
Definition
Complement receptor 1 (CR1)
Term
The mechanism of immune complex removal:
Definition
Macrophages, which have CR1 and Fc receptor can remove immune complexes from erythrocytes and digest them
Term
Failure to clear the immune complex will result in....
Definition
...deposit of large amount of immune complex on basal membrane of small blood vessel in organs such as kidney, causing diseases such as nephritis.
Term
During opsonization, IgG1 and IgG3 bind to pathogens and interact with...
Definition
...Fc receptor (FcyRI) on phagocytes.
Term
Which Ig has very little opsonization activity?
Definition
IgM
Term
During antibody-dependent cell-mediated cytotoxicity, which Igs bind to antigens expressed on surface of target cell?
Definition
IgG1, G3
Term
During antibody-dependent cell-mediated cytotoxicity, Fc portion of IgG interacts with which Fc receptor on NK cell?
Definition
FcyRIII
Term
IgE binds to high affinity FceRI on....
Definition
mast cells, basophils and activated eosinophils
Term
degranulation
Definition
IgE on cell surface will bind to parasites and trigger mast cells and others to release granule contents
Term
Granules of mast cell, basophil and eosinophil contain histamine and other inflammatory mediators that cause ....
Definition
smooth muscle contraction, blood vessel permeability increase that function to attack and expel parasites from body.
Term
Describe IgG1 in the following:

1. Hinge region flexibility
2. Susceptible to proteolysis
3. Activate complement
4. Specific functions
Definition
1. intermediate
2. low
3. good
4. abundant, general purpose IgG
Term
Describe IgG2 in the following:

1. Hinge region flexibility
2. Susceptible to proteolysis
3. Activate complement
4. Specific functions
Definition
1. low, rigid
2. low
3. OK
4. specific for repeat epitope on bacterial polysaccharide
Term
Describe IgG3 in the following:

1. Hinge region flexibility
2. Susceptible to proteolysis
3. Activate complement
4. Specific functions
Definition
1. high
2. high
3. very good
4. better Ab cross-linking, good for COMPLEMENT activation
Term
Describe IgG4 in the following:

1. Hinge region flexibility
2. Susceptible to proteolysis
3. Activate complement
4. Specific functions
Definition
1. intermediate
2. low
3. poor
4. antagonize IgE, anti-inflammatory and anti-allergic, NO complement activation
Term
functional monovalent Ag
Definition
When IgG4 switch H and L chain
Term
FcyRI: Binds to which Ig and what function does it have?
Definition
1. IgG1, 3

2. Activate phagocytes
Term
FcyRIIB1: Binds to which Ig and what function does it have?
Definition
1. IgG1, 3

2. Inhibit naïve B cell activation
Term
FcyRIII: Binds to which Ig and what function does it have?
Definition
1. IgG1, 3

2. Activating NK cell, mediate ADCC
Term
FceRI: Binds to which Ig and what function does it have?
Definition
1. IgE

2. Bind IgE to the surfaces of mast cells, basophil, activated eosinophil and sensitize them. Activate these cells for degranulation during parasitic infection and allergic reaction.
Term
FcaRI: Binds to which Ig and what function does it have?
Definition
1. IgA

2. Fc receptor for IgA
Term
FcRn: Binds to which Ig and what function does it have?
Definition
1. IgG

2. Bind to IgG for transporting through endothelial cells and placenta – not a real Fc receptor
Term
B cell receptor (BCR)
Definition
membrane bound immunoglobulin (Ig) that recognizes specific antigen.
Term
BCR associates with ___ and ___, which are the signal transduction molecules for BCR.
Definition
Iga and Igb
Term
B cell receptor complex
Definition
Membrane Ig + Iga and Igb
Term
1. Iga and Igb extracellular domains
2. Iga and Igb cytoplasmic domain
Definition
1. Iga and Igb extracellular domains are Ig like and are linked by a disulfide bond.

2. Iga and Igb cytoplasmic domain each contains an immunoreceptor tyrosine-based activation motifs (ITAM), which is important in BCR signal transduction after Ag binding
Term
B cell co-receptor consists of: (3 things)
Definition
1. CR2 (CD21) binding to iC3b or C3d on pathogen.

2. CD19: signal transduction, increase BCR signaling strength.

3. CD81: function unclear.
Term
B cells have ___ that bind to C3b C3b and facilitate cleavage of C3b to ____ then to ____ by factor I
Definition
CR1, iC3b, C3d
Term
How does B cell brings co-receptor complex close to BCR?
Definition
Binding C3d by CD21 (CR2
Term
B cell can be activated by cross-linking B cell receptors (BCR) with ....
Definition
multivalent antigens on pathogen
Term
BCR cross-linking activates....
Definition
Iga and Igb and B cell signal transduction pathway.
Term
Signaling pathway 1 (BCR complex):
Definition
After Ag cross-linking of BCR...

Src-family protein tyrosine kinases such as Blk, Fyn or Lyn phosphorylate and activate ITAM of Igα and Igβ.

Activated ITAM recruits another tyrosine kinase Syk that binds to ITAM on Igβ.
Term
Signaling pathway 2 (BCR co-receptor)
Definition
Binding CD21 (CR2) to C3d on Ag brings BCR co-receptor close to BCR.

BCR associated kinases phosphorylate and activate CD19.

Activated CD19 recruits Src family tyrosine kinase such as Lyn to activate signal transduction pathway.

BCR co-receptor mediated signaling pathway augments the B cell activation signaling pathway
Term
Cognate CD4+ helper T cell
Definition
CD4 T cell recognizes processed peptide Ag derived from the same protein Ag that B cell recognizes
Term
Primed helper T cell
Definition
When CD4 T cell becomes activated (primed) by peptide Ag presented by DC.
Term
To get help from T cell, B cell needs to... (2 things)
Definition
1. Present Ag to cognate T cell - B cell binds protein Ag via BCR, internalizes Ag, process protein Ag to be peptide Ag, and presents peptide Ag on MHC class II molecule to cognate CD4 T cell.

2. Establish physical contact with cognate helper T cell.
Term
Basic steps of T cell help of B cell activation, proliferation and differentiation (6 steps)
Definition
1. CD4 helper T cell is activated by DC – primed helper T cells.
2. B cell receptor binds to protein Ag and activated
-BCR – Ag cross-linking,
-BCR co-receptor – C3d.

3. B cell internalizes protein Ag, processes peptide Ag and presents on MHC class II.

4. Primed cognate CD4 helper T cell recognize peptide Ag presented by B cell.

5. B cell establishes physical interaction with cognate T cell. Interaction augments B cell activation

6. T cell secrete cytokines to drive B cell activation, proliferation and differentiation to become Ab producing plasma cells.
Term
immunological synapse (list what parts of B cell link to T cell during physical interaction)
Definition
Interaction of primed cognate CD4 T cells and B cells.

1. TCR--Ag + Class II MHC (Ag binding)
2. CD4--Class II MHC (T cell co-receptor)
3. CD40L--CD40 (Co-stimulatory molecules)
4. LFA-1--ICAM-1 (Adhesion molecules)
Term
Cognate T cells secret cytokines IL4, IL5, and IL6. What are their functions?
Definition
IL4 – secreted early, for B cell activation, proliferation, differentiation.

IL5, IL6 – secreted later, for B cell differentiation, Ab production
Term
Two signals for B cell activation to T dependent antigen:
Definition
1. Signal from antigen binding to BCR

2. Signal from Th cell and B cell interaction
Term
linked recognition
Definition
B cell can only receive help from helper T cell that recognizes the same antigen
Term
Haptens
Definition
small non-immunogenic molecules– can bind to Ig (antigenic) but can not elicit B cell and T cell responses

No antibody response
Term
In order to produce antibody against hapten, hapten is fist linked to...
Definition
protein carrier (hapten-carrier link).
Term
DC processes the hapten-carrier linked molecule and presents peptide Ag derived from protein to stimulate T cell. This t-cell is now called a..
Definition
primed peptide Ag specific T cell
Term
Hapten specific B cell can be activated by binding to...
Definition
hapten on linked molecule.
Term
Example of hapten and carrier phenomenon
Definition
Linking bacteria polysaccharide with a protein carrier, tetanus toxoid, to elicite Ab against polysaccaride
Term
Some of the pathogens are transported to secondary lymphoid tissues and taken up by specialized.....
Definition
subcapsular sinus macrophage (SCS MΦ) and follicular DC (FDC).
Term
SCS MΦ and FDC
Definition
These cells trap pathogen Ag with complement receptor (CR1 or CR2) to complement components (C3b or C3d) on pathogens.

Displays bound antigen on their cell surface.
Term
FDC originate from
Definition
stromal cells or fibroblasts
Term
How do FDC display complement coated pathogen and pathogen antigens for B cells to recognize?
Definition
FDC use complement receptors.

CR1 – C3b
CR2 – iC3b, C3d.
Term
Both activated T and B cells down regulate the expression of what chemokine and why?
Definition
S1P (sphingosine-1-phosphate) receptor.
S1P is the chemokine that attracts lymphocytes exit from LN.
Term
After T and B cell interaction, these cells move to _____ to form _____
Definition
These cells then move to medullary cords for further proliferation to form primary focus
Term
Some of B cells in primary focus differentiate to be...
Definition
plasmablasts, which are plasma cells that produce IgM as quick Ab response to pathogen.
Term
Some of these B cells in primary focus move back to follicle with T cells to form...
Definition
germinal center (GC) or secondary focus.
Term
Tfh
Definition
Helper T cells in GC are called follicular helper T cells (Tfh)
Term
mantle zone
Definition
Zone where resident resting B cells are pushed to the edge of GC
Term
Activated B cells in GC form dark and light zones.

B cells in dark zone are called centroblasts. What are the functions of centroblasts?
Definition
Large, intense proliferation.
Express low BCR
Undergo somatic hypermutation
Term
Activated B cells in GC form dark and light zones.

B cells in light zone are called centrocyte. What are the functions of centrocytes?
Definition
Small, low proliferation
BCR re-expression
Undergo affinity maturation
Term
somatic hypermutation
Definition
Ag activated B cells undergo mutation in V region during proliferation

Centroblasts undergo somatic hypermutation, move to light zone and become centrocytes.
Term
somatic hypermutation is mediated by...
Definition
activation-induced cytidine deaminase (AID), which is expressed only in proliferating B cells (centroblasts).
Term
Function of AID
Definition
AID randomly converts DNA cytosine to uracil, which can be converted to a random base by DNA repair enzymes, error-prone translesion DNA polymerase – induced random point mutation in V region.
Term
affinity maturation
Definition
B cells undergo somatic hypermutation will be selected to survive based on Ig affinity to Ag.
Term
Two places centrocyes migrate to after surviving Ig affinity test:
Definition
1. Some of high affinity centrocytes may differentiate to be plasma cells or memory B cells and exit LN.
2. Plasma cells enter bone marrow for long-term production of Ab.
Term
tingible body macrophage.
Definition
MΦs that ingest dead cells
Term
Ab class switch is regulated by ____ and mediated by ___ and ____
Definition
Ab class switch is regulated by T cell cytokines and mediated by switch sequence (switch region) and AID (activation-induced cytidine deaminase).
Term
During Antibody class switch:

Switch sequence is located at
Definition
5’ of every C region except (Cd) - IgD so that IgD cannot be expressed alone
Term
During Antibody class switch:

Th1 response produces...
Definition
IFN-g and stimulates IgG2a, IgG3 (mice), IgG1 (human) for better opsonization, phagocyte and NK cell activation against intracellular pathogen..
Term
During Antibody class switch:

Th2 response produces...
Definition
IL4, IL5 and TGF-b (transforming growth factor b)and stimulates IgG1, IgG2b (mice), IgG2, IgG4 (human) and IgA and IgE.
Term
BLIMP-1
What process does BLIMP-1 regulate?
Definition
transcriptional repressor that turns off genes that are responsible for B cell proliferation and differentiation.

BLIMP-1 functions:
Converting B cells to plasma cells that produce large amount of Ab.
Term
Two places plasma cells migrate to:
Definition
1. medullary cords to be short-live plasma cells

2. bone marrow becoming long-lived plasma cells.
Term
3 things Plasma cells do:
Definition
1. down-regulate surface BCR

2. stop differentiation

3. produce large amount of secreted Ig - antibody.
Term
Characteristics of Memory B cells:
Definition
1. Memory B cells have increased frequency to specific Ag (proliferation)
2. They have increased affinity (affinity maturation) to Ag
3. Produces more functional Ab (Ig class switch)
Term
Memory B cells are found in...
Definition
blood and secondary lymphoid tissues
Term
Human memory B cells express special markers such as ____ and higher levels of ____ and other _____ for more efficient interaction with T cells
Definition
Human memory B cells express special markers such as CD27 and higher levels of MHC class II and other co-stimulatory molecules for more efficient interaction with T cells..
Term
FcgRIIB1 has ITIM which stands for
Definition
Immunoreceptor tyrosine-based inhibitory motif
Term
* Concept to remember:

Secondary antibody response is limited to antigen epitopes present during the primary B cell response because only memory B cells are re-activated.
Definition
Term
Antibody response to protein Ag requires ____
Definition
helper T cells (TD Ag)
Term
TI Ag
Definition
athymic

TI Ag can not be processed by B cells to present to T cell
Term
early protective response
Definition
Antibody response against TI antigen occurs rapidly after pathogen infection
Term
two classes of TI Ag.
Definition
1. TI-1 Ag:
Lipopolysaccharide (LPS) or bacteria CpG DNA, which has intrinsic function to directly activate B cells.

2. TI-2 Ag:
Polysaccharide on encapsulated bacteria – Streptococcus pneumoniae.
Form repeated units and activate Ag specific B cells by extensively cross-linking of BCR and co-receptors.
Term
B cell response to thymus independent type 1 Ag (TI-1)
Definition
TI-1 Ag activates B cell by:

TI-1 Ag will:

1. Bind to BCR and co-receptor
2. Bind to Toll like receptors (TLRs)
Term
No T cell help in TI-1 antibody response means:
Definition
1. Ab response to TI-1 Ag (especially to extracellular pathogen) develops more rapidly than Ab response to TD antigens.

2. lack of somatic hypermutation, no affinity maturation – low affinity Ab

3. little Ab class switch and memory response because no T cell help – mostly IgM Ab.
Term
Two types of B cell responses to thymus independent type 1 Ag (TI-1)
Definition
1. In high concentration, TI-1 Ag can activate both Ag specific and non-specific B cells – polyclonal activation.

non-BCR receptors such as TLR mediate activation of Ag non-specific B cell.

2. In low concentration, (in most situations during early infection), TI-1 Ag activate only Ag specific B cells.

Antigen-specific BCR, co-receptor and TLR mediate this activation.
Term
B cell mitogens
Definition
polyclonal B cell activation, proliferation induced by TI-1 Ag
Term
B cell response to thymus independent type 2 Ag (TI-2)
Definition
TI-2 Ag activates B cells by extensive cross-linking of BCR and co-receptors.

TI-2 Ag can activate B cell to produce IgM by cross-linking BCR.
Term
B cell activating factor (BAFF)
Definition
B cell activating factor (BAFF) from activated DC can drive B cell undergo class switching to produce IgG Ab
Term
TI-2 Ag stimulates two unique subsets of B cells:
Definition
B1 cells and marginal zone B cells (MZ B cells).
Term
Regular B cells are also called
Definition
follicle B cells or B2 cells
Term
Common characteristics of B1 and MZ B cells:
Definition
1. limited Ag repertoire, low circulation, self renew, recognize common pathogen components such in polysaccharides of encapsulated bacteria.

2. These B cells react to pathogen infection and produce quick protective Ab response.
Term
B1 cells
Definition
developed early in fetal liver
located in peritoneal cavity
produce Ab to protect body cavity
Term
Marginal zone B cells (MZ B cell)
Definition
locate in marginal zone of spleen
produce Ab to bloodborne pathogens, .
Term
natural antibodies
Definition
B1 cells contribute large portions of IgM in blood of non-immunized individual
Term
B1 and MZ B cell are similar to innate immune cells because:
Definition
B1 and MZ B cell are the cells that recognize common pathogen pattern instead of specific diverse Ag (similar to innate immune cells).
Term
The polysaccharide capsule of encapsulated bacteria prevents:
Definition
prevent phagocytosis and T cell response
Term
young children are susceptible encapsulated bacterial infection because....
Definition
Functions of B1 and MZ B cell are not fully developed in young children and cannot develop Ab response to carbohydrate Ag
Term
To vaccine these children without B1 and MZ B cells...
Definition
polysaccharide Ag is conjugated to a carrier protein to induce T dependent Ab response to polysaccharides (hepton – carrier phenomenon).
Term
Immunization is process of using _____ Ag stimulate the body immune response to produce antibody
Definition
exogenous Ag (immunogen)
Term
hyperimmunization
Definition
strong antibody response stimulated by repeated injections of antigen (immunogen)
Term
antiserum or hyperimmune serum
Definition
Blood collected from these animals with high titers of antibody specific to the immunogen
Term
Polyclonal antibody production:

Subcutaneous (sc) and Intradermal (id)
Definition
most efficient because many DCs can present Ag and induce adaptive immune response.
Term
Myeloma cells lack
Definition
HGPRT
Term
Fuse spleen cell and myeloma cell using
Definition
PEG
Term
De novo pathway
Salvage pathway
Definition
1. De novo pathway: able to synthesize its own nucleotides

2. Salvage pathway: dependent on HGPRT to form new nucleotides. This pathway is blocked by aminopterin found in HAT media.
Term
Hybridoma cells
Definition
myeloma cells that obtain HGPRT and Ab genes from spleen cells
Term
limiting dilution
Definition
common cloning method to make monoclonal antibodies
Term
Transcriptional factors that regulate B cell development
Definition
E2A, EBF or Pax5
Term
B cell development can be divided in several stages based on two things:
Definition
Ig V region rearrangement and the generation of B cell receptor .
Term
Pick the right selection:
V region of H chain is rearranged (first/second) at (pro-B cell or pre-B cell stage)
Definition
V region of H chain is rearranged first at pro-B cell stage.
Term
Pick the right selection:
V region of L chain is rearranged (first/second) at (pro-B cell or pre-B cell stage)
Definition
V region of L chain is rearranged at pre-B cell stage.
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