B cell Flashcards

Question

Variable regions function which structure forms antigen-binding site

Answer 1

Ag binding VL and VH forms antigen-binding site (2 identical sites per antibody)

Answer 2

1. neutralization 2. other functions (will see in a future lecture)

Answer 3

involved in Complement activation (C1q → classical pathway) Constant region (Fc) can bind to Fc receptors on phagocytes and other cell types (eg. mast cells, eosinophils) results -phagocytosis -secrete histamines -kill antigen (granulocytes)

Answer 4

-Two Fab fragments per antibody -Each has **antigen-binding domain** AND part of the **constant H and L chains** -Fab = fragment antigen binding

Answer 5

one Fc fragment Fc= fragment crystalizable constant region of the heavy chain receptors that bind antibodies recognize the Fc region

Answer 6

* Two heavy chains (variable and constant regions) * Two light chains (variable and constant regions) * **Held together by intra-/interchain disulfide covalent bonds** * Both the constant and variable regions are folded in complex three dimensional structures, including beta strands

Answer 7

CDR * hypervariable loops (greatest variability in the antibody sequence) * in the antigen-binding site * 3 per variable domain * not part of the beta strands * at the extremities of the antibody * directly react with antigen 12 CDRs/antibody

Answer 8

non-covalent bonding between Ig and the Ag epitope * Hydrogen bonds * van der Waals * Hydrophobic * Ionic

Answer 9

* Lock and key specificity * Extremities of the antibody are responsible for this interaction * Size variability of what’s being recognized by the antibody * Variation in the antibody itself – CDR varies in length * Location of epitopes can be anywhere on the antigen

Answer 10

5 classes Different number of Ig-like domains differences in the length of the constant region of the heavy chain (constant region) -heavy chain is what differentiates the different antibody -Fc fragment of each Ig is different each class performs different functions during immune responses

Answer 11

Pentameric 5 antibodies linked together via disulphide bonds Heavy chain: one variable region and 4 constant regions (4 Ig-like domains for the heavy chain) J chain: polypeptide that links the disulphide bond Mature naïve B cells express transmembrane IgM prior to activation IgM is part of first wave of secreted antibodies Most effective initiator of complement cascade

Answer 12

Heavy chain: one variable region and 3 constant regions IgD is part of first wave of secreted antibodies

Answer 13

Most abundant in plasma. most abundant in your blood Heavy chain: one variable region and 3 constant region The most abundant in plasma 4 subclasses in humans-IgG1, 2, 3, 4 Produced following differentiation in the Germinal Center (class switching only happen in the germinal center)

Answer 14

Heavy chain: one variable region and 4 constant regions Produced primarily in response to Helminth infections Recall role of IgE in TH2 response

Answer 15

Heavy chain: one variable region and 3 constant regions **Monomer in plasma** **Dimer in mucous secretions through the J chain** (primarily found in mucous surface) Important for mucosal immunity Two subclasses: IgA1 and IgA2.

Answer 16

also called primary diversification through the process of **somatic recombination** **1.combinational diversity** **2.junctional diversity**

Answer 17

on seperate chronmosomes

Answer 18

use **groups of segments** of genes to create different possible antibodies using **somatic recombination** tightly regulated machinary controls the recombination processes and many of **DNA repair proteins (enzymes)** are envolved in

Answer 19

process that segments rearranged

Answer 20

Variable, joining, constant region gene segments 2 different loci on seperate chromosomes, with different constant regions -k chain -lamda chain each loci includes many different V and J segments when one of the chain is expressed, the other will be silenced = only one the chain will expressed

Answer 21

variable, diversity, joining, constant rejoin gene segments D is heavy chain only one locus many different constant regions represent the different isotypes (different constant regions are corresponds to different Ab) -Cdelta: IgD -Cgamma: IgG -Cepsilon: IgE -Calpha: IgA

Answer 22

CDR 1 and 2: encoded in the V segments of light and heavy chain CDR 3: encoded in the joining of V-J segments of light chain adn V, D, J gene segments of heavy chain **CDR 3 is the most variable CDR**

Answer 23

inherited all the segments but during B cell development, V (D) J recombination occurs to choose one of each to make up the variable region

Answer 24

light chain: VJ join together, then join with C heavy chain: DJ first join together, then join V, then join C

Answer 25

Diversity that is the result of different combinations of V, D, and J regions

Answer 26

RSSs: recombination signal sequences

Answer 27

recombinase enzymes

Answer 28

RSS are on both side of the gene segment each has **conserved nonamer (9bp) and heptamer (7bp)** （一个在一端）+ either **12 or 23 bp spacer sequence** between the nonamer and hte heptamer **12/23 Rule** The spacing and arrangement dictate that a 12-bp RSS must pair with a 23-bp RSS for recombination to occur

Answer 29

RSS regions are brought together, creating a loop in the DNA RAG-1 and RAG-2 are enzymes that necessary for recombination: responsible for recognizing and cutting DNA at the immunoglobulin-encoding regions and RSS **RAG covalently closed DNA hairpin ends** RAG: recombination activating gene loop: **signal joint** -get excised and deleted coding region of selected V and J regions remain: **coding joint**

Answer 30

During recombination, nucleotides may be added or removed at the junctions between V and DJ; D and J; (or the V and J for the light chain)

Answer 31

Signal joint is ligated together and discarded Coding joint: hairpin cleavage Repair proteins bind the hairpin at the coding ends **Artemis**: an endonuclease, opens the DNA hairpins in 1 of the 3 possible ways 1. 3' get cut a bit (overhang) 2. blunt end 3. 5' get cut a bit

Answer 32

Happens mainly in light chain P nucleotides are added to the overhangs to make complementory strands to blunt end then get ligated togather

Answer 33

Happens mainly in heavy chain **Exonuclease activity** may remove nucleotides on each side of the coding joint **Terminal Deoxynucleotidyl Transferase (TdT)** can add up to 20 N-nucleotides (non- template-encoded) to the cleaved strands----reason for why CDRs vary in length **Repair enzymes** then trim off nonmatching nucleotides, fill in remaining single-stranded gaps and ligate the new DNA

Answer 34

exonuclease

Answer 35

**1. Multiple gene segments** -which gene segments are put together **-Combinatorial diversity** **2. Recombination of segments in Heavy chain/light chain** **-Junctional diversity** **3. P nucleotide addition** -templated nucleotide addition between joints, resulting from asymmetrical cleaving of hairpin structures **4. Exonuclease trimming** -sometimes occurs at junctions, losing nucleotides **5. Nontemplated N nucleotide addition** -mediated by TdT activity, adding in random nucleotides between joints

Answer 36

alpha and beta chain each has a variable and a constant region on each variable region there is an antigen binding site

Answer 37

alpha chain locus has multiple V and J segments beta chain locus has multiple V, D and J segments Somatic recombination takes place in the thymus irreversible

Answer 38

alpha chain: VJ beta chain: DJ recombination occur first, and then V-DJ recombination then combination of alpha and beta chain

Answer 39

**similar mechanism to BCR** - V, D, and J segments are flanked by RSS - RAG-1/2 recognize these sequences - Artemis cuts the DNA hairpins, creating the signal and coding joint - TdT adds non-coded nucleotides in the joining regions **Difference with BCR** - Ig heavy chain → D segment is surrounded by two RSS, **both with 12-bp spacing** - TCR beta chain → D segments have a **5’ 12 bp RSS and a 3’ 23 bp RSS**

Answer 40

3 CDR per chain sites with most diversity CDR3 is the most diverse one CDR1 and 2 are encoded within the V segments of alpha and beta chains CDR 3 is encoded in the D and J segments of the beta chain and between the V and J segments of the alpha chain

Answer 41

ensures that each B cell synthesizes only one allele for a heavy and one allele for a light chain each B cells might express different antibodies but on one B cell express the same one once BCR is expressed on the surface of the developing cell, it will send a signal to silence the part of the gene that codes for the other chromosome (through methylation and inaccessible to transcription machinery) Genomic silencing of the other chromosome ensures each B cell will only express the same copy of BCRs that have the same specificity

Answer 42

IgM and IgD are the first wave of secreted antibodies initially, newly formed B cell express IgM (primary b cell receptors) later some B cells switch to expressing IgD ->IgM and IgD being co-expressed on B cell surface activation by signal 1and 2, some form primary focus and become plasmablast=capable for secreting Ab

Answer 43

**alternative RNA splicing** B cell produce a long primary mRNA transcript that is differentially spliced to yield either of two distinct mRNA molecules secreted and transmembrane mRNA are the result of RNA splicing too

Answer 44

M: mu D: delta G: gama A: alpha E: epsilon

Answer 45

occur in germinal center (after receive signal 1 and 2 again) **Somatic hypermutation**: higher affinity for antigen, specificity remains the same **Class Switching**: a process that replaces one heavy chain constant region with one of a different isotype act on already rearranged Ig genes: V(D)J recombination has occurred in the variable region

Answer 46

Operates on activated B cells in peripheral lymphoid organs (in the germinal center of lymph nodes) - Somatic hypermutation mainly occurs in the CDR loops of the V regions - B cells that can bind, process, and present more Ag to T cells for cytokine assistance survive→ Affinity maturation High rate of point mutation in the V gene sequence that improve Ag binding random, can increase or decrease the affinity **Affiinity maturation**: selects for the survival of mutated B cells that have a high affinity for the antigen also occurs during secondary or tertiary responses (get higher and higher affinity antibodies) - Increased antibody affinity with increased exposure

Answer 47

only occur after B cell activation within the germinal center after antigen contact (signal 2 a second time, must receive CD40 to engage in CSR) irreversible **recombination guided by switch regoins upstream of each C gene** - one after the VDJ region - one upstream of the constant region to be recombined cytokines secreted by Tfh in germinal center will inform class switching - transcription is activated upstream of constant region - DNA accessible to AID (only worked on ssDNA) to make nicks on both strands of DNA - double stranded (DS) breaks in DNA upstream of constant region will be recombined - DSbreak repair machinery repairs break by cutting out the intervening DNA - selected region now adjacent to VDJ region - the constant region after the recombined C constant region is not translated type 2 response cytokine IL-4 induces IgE

Answer 48

HLA molecules: polymorphism and polygene TCRs: combinatorial diversity junctional diversity pairing (alpha and beta chain) BCR/Ig: primary diversification - combinatorial diversity - junctional diversity - combination of H and L chains secondary diversification - somatic hypermutation - class switching

Answer 49

dark zone and light zone **light zone** follicular helper T cells follicular dendritic cells (FDCs) retain Ag in the light zone primary site of plasma and memory cell differentiation **dark zone** B cells dark zone thought to be site of somatic hypermutation

Answer 50

B cells that first enter germinal center: - have already encounter Ag (signal 1) and have been activated by a T cell at the B-T border (Signal 2 and proliferated) - Have the ability to produce IgM/IgD of a baseline affinity (tranmembrane) In the germinal center: -B cell in the dark zone undergo somatic hypermutation - increase affinity -then B cell migrate to light zone where they compete to bind antigen trapped on FDCs - higher affinity B cells will bind Ag, to receive signal 1 again, then internalize the ag:BCR and then go through affinity maturation - lower affinity B cells fail to bind Ag, do not receive signal 1 and die by apoptosis -B cell that process Ag and present it on MHC II can interact with TFH (linked recognition) -signal received via CD40 (part of signal 2) -B cell receive cytokines from Tfh, class switching -class switching from IgM/IgD to IgG or IgA or IgE The Ag specificity is still the same B cells can then re-enter dark zone and undergo additional somatic hypermutation

Answer 51

follicular dendritic cells (FDCs) serve as Ag concentration site for future selection and differentiation interaction of B cells with follicular helper T cells provides conditions for differentiation memory cell production and class switching

Answer 52

Plasma cells: -thye stop expressing high levels of BCR -secrete Ig of the same secificity as the BCR of their progenitor B cell -should bind Ag with higher affinity -secreted Ig can be IgG, IgA, IgE Memory B cells: express high levels of BCR BCR has same specificity as progenitor B cell BCR should have higher affinity

Answer 53

AID: activation-induced cytidine deaminase - protein responsible for somatic mutations - deaminate cytidine residues in ssDNA - cytidine change to uridine which is then removed mismatch repair pathway + error-prone polymerase activity will give incorporate any nucleotide into the nick produces individual point mutations in Ig heavy and light chian variable regions some of these changes are non-productive

Answer 54

Early reinfection handled by pre-formed Abs/effector T cells from primary the previous response late reinfection handled by immune memory B/T cells (faster and better)

Answer 55

Ability of the immune system to respond more rapidly and more effectively on a second encounter with an antigen – Dependent on adaptive immune mechanisms: * Ag-specific * Memory responses occur after primary response (secondary, tertiary, etc.) by lymphocytes initially generated late in the primary response * Long-lived In practical terms, memory leads to resistance to a particular infectious disease upon re-exposure only after having had that disease once before – Or after being vaccinated

Answer 56

– More Abs, more cells – Different Abs (higher affinity), different lymphocyte features

Answer 57

* Easier to detect/monitor for B cells than T cells – Antibodies can be measured in serum – Memory T cells reside in tissues * Mediated by a small and steady number of memory cells: – Some of them proliferating at a given time (another infection)

Answer 58

most IgM-producing cells (some IgD) come from primary focus some B cells will go to germinal center where they will undergo somatic hypermutation and class switching late in the response

Answer 59

some memory B cells make IgM most memory B cells express IgG (some IgA and IgE), undergo further somatic hypermutation IgG concentration and affinity both dramatic increase in later response

Answer 60

**increasing affinity of Abs** due to somatic hypermutation: b cells can re-enter the germinal center Memory B cells also express class-switching surface ig istoype (**IgG**-bearing memory B cells) Memory B cells express higher levels of MHC class II, CD40 and receptors for survival and proliferation than naïve B cells - helps to acquire and present antigens more efficiently to Tfh than naïve B cells - increases antibody production Memmory B cells circulate through the blood and take up residece in the spleen an lymph node

Answer 61

At least 90% of effector cells die by apoptosis after pathogen is cleared, leaving behind antigen-specific memory T cells use surface markers to distinguish different types of T cells memory T cells phenotypically close to effector T cells - less requirement for activation - express unique set of receptor - different surface adhesion molecules, costimulatory receptors - have large expression of CD28 - no need for strong co-stimulatory signal or cytokines - still require contact with p:MHC but more sensitive to stimulation and respond more quickly memory T cells become effector T cell upon reactivation

Answer 62

Tcm cells Tem cells Trm cells and other memory T cells subtypes

Answer 63

**central memory T cells** - leave the thymus and then become a memory T cell directly -**Reside in/travel between secondary lymphoid tissues** - Are **rapidly reactivated by second Ag exposure** - Can differentiate into several subset types depending on cytokine environment (**Th1, Th2, Th17**)

Answer 64

**effector memory T cells** - **Travel to/between tertiary tissues** - Contribute better to first-line defenses – can interact with local APCs! - Shift right back into effector functions on second Ag exposure (**convert back to their previous T cell type**)

Answer 65

**permanent residents of previously infected tissue** - respond upon infection - CD8+ T rm found in multiple tissues

Answer 66

cytokines: IL-7, IL-15 protein: Notch 1 strength of antigen interaction: determine whether T cell can become a memory T cell or not

Answer 67

pro-survival cytokine, lead to increased expression of Bcl-2 Bcl-2: anti-apoptotic factor expression of IL-7Ralpha is down-regulated during effector T cell differentiation but is retained or reacquired by those cells destined to become memory T cells IL-7Ralpha: important indicators of a memory CD8+ positive T cells

Answer 68

Memory CD8+ T cells are more abundant than memory CD4+ T cells - because they are faster at proliferating and differentiating, they only have one outcomes Memory CD8+ T cells still require the help of CD4+ T cells for longevity

Answer 69

Make someone or an animal resistant to a particular infectious disease or pathogen

Answer 70

Temporary adaptive immunity conferred by the transfer of immune products, such as antibody (antiserum), from an immune individual to a nonimmune one no self immune response

Answer 71

adaptive immunity that induced by natural exposure to a pathogen or by vaccination

Answer 72

delivery of pre-foremed antibody 应用场景： - immune deficiency - toxin or venom exposure with immediate threat of life - exposure to pathogens that can cause death faster than an effective immune response can develop does not activate host immune response no memory response generate, not permanent protection 应用案例：埃博拉病毒

Answer 73

passive transfer of ab to nonimmunized animal prevents activation of naïve B cells (early childhood won't give vaccine injection, because the baby has antibodies from the mom) **original antigenic sin** once have effective response, memory cells are involved in rather than activating new naïve cells that target new epitopes

Answer 74

active immunization induce immunity and memory can be achieved by natural exposure to infectious agent or acquired artificially (vaccines) lead to B and T cells response

Answer 75

Specific immune response (with memory) is induced on purpose by exposing a person to an altered and non-dangerous form or component of the infectious agent

Answer 76

whole vaccines: have the whole part of virus - inactivated - live-attenuated component vaccines: only have part of the pathogen - protein subunit (macromolecule) - virus like particles - DNA/RNA based - non-replicated - relicating vital vector that carried in another virus

Answer 77

included in vaccine to enhance the immune response to a vaccine - **Promoting some inflammation can recruit more immune cells** to the area, enhancing effectiveness - **Slowing down Ag release can promote longer interactions**, enhancing effectiveness

Answer 78

- Virus has multiple mutations that prevent it from causing a productive infection in immunocompetent humans - These vaccines have “built in内置” adjuvant → PAMPs from virus trigger immune response

Answer 79

When the majority of the population is immune to an infectious agent, thus significantly reducing the pathogen reservoir due to the low chance of a susceptible individual contacting an infected individual

Answer 80

1. virus and toxin neutralizaiton--prevent pathogen host binding 2. opsonization--phagocytosis 3. complement fixation--phagocytosis, lysis, inflammation 4. antibody dependent cell mediated cytotoxicity (ADCC)--NK-induced apoptosis 5. bind Fc receptors on granulocyte (mast, eosinophils, basophils)--ag binding to Ab triggers degranulation 6. transport--get transported to exert function

Answer 81

Family of cell surface (transmembrane) receptors that bind to the Fc portion of Igs very wide range of cell: macrophages, granulocytes, DCs, mast cells, B cells, epithelial cells, NK cells, etc. Bind igs in a class specific manner Fc gamma RI: bind IgG Fc epsilon RI: bind IgE Fc alpha RI: bind IgA FcR mediate many effector functions of atibodies crosslinking FcRs are important for triggering signalling (FcR bind antibody bind antigen) using FcRs allows non-specific immune cells to take advantage of antigen-specific antibodies

Answer 82

1. degranulation (by crosslink) 2. opsonization 3. transportation and maintenance of serum levels 4. ADCC

Answer 83

promotes and/or enhances the engulfment of antigens by phagocytes **mainly IgG** Free IgG doesn't crosslink FcRs, aggregation of binding can allow crosslinking of FcRs and then triggger intracellullar signaling

Answer 84

Include several subclasses, each with distinct effector capabilities - Some IgG subclasses are effective at complement fixation - Some IgG subclasses are good at mediating ADCC by NK cells **All IgG variants bind to Fc receptors, enhancing phagocytosis by macrophages → opsonization**

Answer 85

activates the killing activity of several types of cytotoxic cells, for ex, NK cells NK can release granules through 2 different pathway: ADCC and Innate pathways -ADCC * NK cells have **Fc gamma Rs** * They can recognize the Fc region of **IgG** antibodies * If these FcRs bind to antibodies on a cell → crosslinking triggers signaling → NK cell * releases toxic granules → target cell dies by apoptosis -Innate MHC class I binding

Answer 86

Antibody-Dependent Degranulation from granulocytes (Some place this in the same category as ADCC) **by IgE, Th2 response** * TH2 cytokines activate eosinophils & mast cells * Mast cell granules contain histamine and other molecules * Eosinophils & mast cells express receptors that recognize the Fc portion of IgE → eosinophils & mast cells can then specifically target pathogen and degranulate mast cells has baseline binding of IgE

Answer 87

Best known for role in **allergy and asthma** Also play a role in protection against parasitic helminths (worms) and protozoa **Made in very small quantities, but induce potent effects** - **Degranulation of eosinophils/basophils** - Release of molecules such as histamine to damage large pathogens

Answer 88

protects against viral or bacteria infection, or against the damaging effects of toxins targets: toxins, viruses, bacteria Binding of antibodies to toxins or pathogen (anti- ) to prevent them from binding their targets and exerting their effects **IgG and IgA** antibodies most important for neutralization

Answer 89

Major isotype found in secretions - Mucus in gut - Milk from mammary glands - Tears - Saliva

Answer 90

results in the generation of the membrane attack complex (MAC), inflammation and/or opsonization **IgM and IgG** (IgM is most effective) **classical pathway** C1q binds pathogen surface – Can bind pathogen directly – Can bind antibodies that are bound to pathogen surface **connect adaptive to innate** Once C1q binds – Triggers signaling cascade on pathogen surface – C3 convertase is generated – C3 cleaved → C3a and C3b

Answer 91

* First Ab produced in a primary response * **Tend to be lower affinity** * Pentavalent (10 total Ag binding sites) * Very good at activating complement cascade * Also efficient at forming dense Ab-pathogen complexes that are efficiently engulfed by macrophage

Answer 92

Different Ig classes in different parts of the body FcRs allow the targeting of different Ig classes to different parts of the body * IgA selectively found in mucosal tissues * IgE found near epithelial surfaces * IgM found in blood * IgG is widely distributed → including to developing fetus

Answer 93

have maternal IgG in circulation also get some IgA through breast milk example of passive immunity antibodies remain for 4-6 months

Answer 94

FcR that can transport IgA dimer across barriers

Answer 95

IgD is a minor component of blood (0.2% of circulating antibodies) but is **present at higher levels in secretions of the upper respiratory tract** **Bind basophils and mast cells, prompting them to release antimicrobial peptides (AMPs), cytokines and chemokines.** Some researchers state that the IgD function is not well understood

Answer 96

**ensures that the immune system avoids destroying host tissue** Many of the random rearrangements used to create B and T cell receptors could be self-reactive Tolerance helps to keep these self-reactive recognition molecules/cells from circulating in the bloodstream

Answer 97

T cells develop initially in the bone marrow (very early stages), but then migrate to the thymus to achieve full maturity **Developing T cells are known as thymocytes** Undergo rigorous selection → mature naïve T cells

Answer 98

**Cortex and medulla**: cortex, outside layer * Cortical epithelial cells * Medullary epithelial cells * Thymocytes * Macrophages * Cortical DCs

Answer 99

**T cell precursors enter thymus as double negative (DN) cells** (don’t express CD4 OR CD8) 3 stages of T cells in thymus 1.double negative (no CD4 and CD8) 2.double positive (both CD4 and CD8) 3.single positive (CD4 or CD8)

Answer 100

positive selection and negative selection

Answer 101

Selects thymocytes bearing receptors capable of binding self-MHC molecules, resulting in **MHC restriction** Cortical epithelial cells express high levels of MHC class I and II DP T cells can browse peptide MHC on the surface of these cells * If TCRs can’t bind →cells die by neglect 90-96% die, need macrophages to clear up * If TCRs bind too strongly → cells die (too strong means specific to that self peptide) TCRs bind low to “just right” (only specific to the self MHC not the peptide)→positive selection to single-positive stage occurs - If binding occurs to MHC II with CD4 → T cell becomes a SP CD4+ T cell - If binding occurs to MHC I with CD8 → T cell becomes a SP CD8+ T cell

Answer 102

Selects against thymocytes bearing high-affinity receptors for self-MHC/self-peptide complexes, resulting in self-tolerance Negative selection is necessary to ensure self-tolerance Medullary epithelial cells express a transcription factor called **Autoimmune regulator (AIRE)** **cortical DCs** present self-peptides on MHC I or II also contribute to negative selection single positive T cells can browse self-p:MHC on the surface of thymic epithlial cells and cortical DCs * if TCRs don't bind: cell survive * TCRs bind pMHC: 3 results * 1. clonal deletion: self-reactive T cells die and macrophages clear up (most cases) * 2. clonal anergy: autoreactive T cells are inactivated * 3. clonal editing: second or third chances at rearranging a non-self-reactive TCR gene

Answer 103

induces expression of many tissue-specific proteins in thymic epithelial cells these proteins than processed and presented on MHC I and II this allows T cells to be screened against self-antigens safely in thymus

Answer 104

different process than other T cells

Answer 105

can't eliminate all autoreactive lymphocyte, some will pass through and go into the circulation peripheral mechanisms of tolerance also protect against autoreactive thymocytes * Important for self-reactive T cells that escape negative selection in thymus * Strong self-antigen signaling through the TCR in the absence of costimulation may drive the T cells into anergy (they might not find the signal 2 that allow them to get activated (**nonresponsiveness**) * Regulatory T cells can help maintain peripheral tolerance

Answer 106

Proper gene rearrangement of H and L chain genes to give rise an Ig that shows self-tolerance = negative selection (deletion) of autoreactive B cells B-cell development begins and mainly occurs in the bone marrow and is completed in periphery (including spleen) only negative selection required, no need for MHC restriction

Answer 107

in bone marrow BCRs are tested against self-antigens—3 possible outcomes 1. clonal deletion or strongly autoreactive cells (through apoptosis) 2. receptor editing (reactivation of recombination machinery) 3. anergy (induction of nonresponsiveness to further stimuli, even self-antigen stimuli) No known AIRE equivalent: range of self Ag available is lower than T cells, more B cells will in circulation **Self-Ag are soluble proteins in circulation or presented on stromal cells and other cells** Any potentially self-reactive B cell that's been activated requires the activation from a T cell (因为 T cell少，所以可能并不能被实际激活)

Answer 108

B cells **exported from the bone marrow are still functionally immature** They progress through the **spleen for further maturation** **Mature, primary cells migrate to the lymphoid follicles** * Express high levels of IgM/IgD on their surfaces as well as other receptors * Negative selection here too (peripheral tolerance) * Recirculate between blood and lymphoid organs * Half-life of approximately 4.5 months in periphery

Answer 109

similar for T cells **Receptor editing of potentially autoreactive receptors occurs in light and heavy chains ** Recombination machinery can be turned back on This method is a “last-ditch effort” to salvage the rearrangement, but depends on the first rearrangment (if there is no segments left from the first time than it can't go through the second time) combinatorial diversity and junctional diversity both can involve in self-reactive BCRs

Answer 110

Both B- and T-cell developmental pathways share many characteristics – Rearrangement of gene segments – Screening processes to avoid self-reactivity

Answer 111

1.Location of maturation and screening 2.Screening processes used * Positive and negative in T cells * Negative in B cells 3.Eventual outcomes of antigen receptor stimulation * T cells require presentation and differentiate into helper or killer subsets * B cells require T-cell help and secrete antibodies

Answer 112

**central tolerance** induction of immune tolerance in primary lymphoid organs (bone marrow and thymus) * clonal deletion * receptor editing * clonal anergy **peripheral tolerance** induction of tolerance outside primary lymphoid organs * anergy * deletion * immune regulation (Tregs)

Answer 113

autoimmunity **Organ-specific autoimmunity**: predominant injury of an organ or tissue. **Systemic autoimmunity**: injury of many different tissues. Basic Mechanisms of Autoimmunity: * **Cell-mediated autoimmunity**: mostly T cell-mediated -Sensitive to thymectomy (on mice) -Ex. Multiple sclerosis, type 1 diabetes * **Antibody-mediated autoimmunity**: mostly Ab-mediated -Ex. Lupus

B cell Flashcards

(140 cards)