Adaptive Immunity Flashcards
(127 cards)
1
Q
When B and T cells become activated, they divide and mature into _______ that actually do the job of fighting the microbe
A
When B and T cells become activated, they divide and mature into EFFECTOR CELLS that actually do the job of fighting the microbe
2
Q
Humoral immunity:
A
The type of adaptive immunity that is mediated by antibodies produced by plasma cells. Humoral immunity is the main mechanism for defending against extracellular microbes and their toxins.
3
Q
Cell-mediated immunity:
A
The type of adaptive immunity mediated by T lymphocytes; cell-mediated immunity is the main defense mechanism against microbes that survive within phagocytes (i.e., bacteria that causes Tuberculosis) or that infect the cytosol of non-phagocytic cells (i.e., viruses).
4
Q
What is the effect of Helper T cells?
A
-Activate macrophages -Inflammation -Activation (proliferation and differentiation) of T and B lymphocytes -Eliminate phagocytosed microbes
5
Q
What is the effect of Cytotoxic T lymphocytes?
A
Killing of infected cell
6
Q
What is the effect of regulatory T lymphocytes?
A
Suppression of immune response
7
Q
Describe the stages in the life history of T lymphocytes:
A
Naive T cells: migrate preferentially to lymph nodes, have no effector functions, and very low frequency of response to particular antigens. Activated/effector cells: migrate preferentially to inflamed tissues, have high response to antigens, and secrete cytokines; have cytotoxic activity. Memory cell: Some cells in lymph nodes, some in mucosa and inflamed tissue. Low response to antigen. No effector functions.
8
Q
Describe the immunoglobulin serotype of B cells at various stages in life cycle:
A
Naive B cells - IgM and IgD. Activated B cells - IgG, IgA, IgE. Memory B cells - IgG, IgA, IgE
9
Q
Compare/contrast B cell receptors (antibodies) and T cell receptors (TCRs)
A
B cell receptors recognize whole proteins, polysaccharides, lipids, and nucleotides. TCRs only recognize short peptides when they’re bound to the APCs. Antibodies can be expressed as membrane receptors or secreted proteins; TCRs only function as membrane receptors.
10
Q
What is the serum concentration and secreted form of IgA?
A
3.5 mg/ml; mainly dimer (can be monomer or trimer)
11
Q
What is the serum concentration and secreted form of IgD?
A
trace amounts; monomer
12
Q
What is the serum concentration and secreted form of IgE?
A
0.05 mg/ml; monomer
13
Q
What is the serum concentration and secreted form of IgG?
A
13.5 mg/ml; monomer
14
Q
What is the serum concentration and secreted form of IgM?
A
1.5 mg/ml; pentamer
15
Q
What are the main functions of IgA?
A
Mucosal immunity
16
Q
What are the main functions of IgD?
A
Naive B cell antigen receptor
17
Q
What are the main functions of IgE?
A
Defense against helminthic parasites, immediate hypersensitivity
18
Q
What are the main functions of IgG?
A
Opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity, neonatal immunity, feedback inhibition of B cells
19
Q
What are the main functions of IgM?
A
Naive B cells antigen receptor (monomeric form), complement activation
20
Q
What are the effector functions of B lymphocytes?
A
Free antibodies can neutralize microbes. Also involved with opsonization and phagocytosis of microbes and anti-body dependent cellular toxicity. Within complement, involved with microbe lysis, inflammation, and phagocytosis of microbes opsonized with complement fragments (C3b)
21
Q
MHC I:
A
MHC I molecules are found on all healthy nucleated cells in the body. MHC I molecules are designed to display peptide antigens that are found within the cytoplasm of cells. MHC I molecules and the antigens they present are mainly recognized by CD8+ cytotoxic T cells (and not by CD4+ cells)
22
Q
MHC II:
A
MHC II molecules are restricted to specialized antigen presenting cells such as dendritic cells, macrophages and B cells. Unlike MHC I molecules, which display antigens from the cytosol, MHC II molecules display antigens from microbes within the cell’s vesicles. MHC II molecules and the antigens they display are mainly recognized by CD4+ helper T cells (not by CD8+ cells).
23
Q
What are CD8+ T cells?
A
Cytotoxic T cells (these recognize MHC I)
24
Q
What are CD4+ T cells?
A
Helper T cells (these recognize MHC II)
25
Antibody hypervariable regions:
Greatest diversity in the H and L variable regions are 3 hypervariable regions. Also called complementarity-determining regions (CDRs) because they bind antigen (i.e. it’s the surface of the antibody that has a complementary shape to the antigen). Hypervariable regions extend away from the protein so they can contact antigen
26
What are the heavy chain isotypes?
IgG, IgA, IgM, IgD, IgE
27
What are the light chain isotypes?
kappa and lambda
28
All isotypes are ______ in the membrane-associated form
monomeric
29
What is the structure of TCRs?
T cell receptor recognizes antigen in the context of MHC. Like antibodies, has two chains, 𝛼𝛽 OR 𝛾𝛿 (alpha-beta or gamma-delta). Each chain has a V and a C region. Binding area thus has a V-beta and V-alpha section (or V-gamma and V-delta) Has CDRs in variable region that bind antigen.
30
How do we generate antibody diversity (mechanisms)?
–Multiple VH and VL genes
–Combinatorial association of different V, D, and J gene segments
–Junctional diversity by nucleotide addition
–Combinatorial association of VH and VL regions
–Somatic hypermutation – non-genome encoded
31
What are heavy chain gene segments?
V, D, J, (and a constant region)
32
What are light chain gene segments?
V and J (and a constant region)
33
Within the V-heavy, which complimentary-determining regions (CDRs) are derived from which segments (V, G, J)?
CDR1 and CDR2 are derived from VH segment; CDR3 is derived mainly from DH and JH segments.
34
Within the V-light, which complimentary-determining regions (CDRs) are derived from which segments (V, J)?
CDR1 and CDR2 are derived from VL segment; CDR3 mainly from JL.
35
Antibody genes are in pieces and assembled during _____ development
lymphocyte
36
Each V gene segment has an accompanying leader (L) sequence that:
Codes for the N-terminal signal peptide that targets the proteins to the endoplasmic reticulum.
37
Describe the process of VDJ recombination:
* Chromatin is opened around gene segments to allow recombination enzymes access
* Two gene segments are brought together and a double strand break is made
* Nucleotides are added or removed (creates more diversity) and the ends ligated together
* RNA splicing of introns brings exons together → functional mRNA
38
Each B cell has a different combination of V gene segments and diversity due to:
addition of N/P nucleotides
39
Describe Recombination Signal Sequences (RSSs):
* These mediate recombination.
* These are composed of: 7 nt conserved stretch (heptamer - CACAGTG) separated by a 12 or 23 nt spacer, followed by a conserved AT-rich stretch of 9 nt (nonamer).
* These spaces are about 1-2 turns of a helix. A 12 can only join a 23.
40
For an immunoglobulin gene to be expressed, individual gene segments must first be rearranged to assemble a functional gene, a process that occurs only in:
developing B cells
41
Describe V(D)J Recombination by deletion:
•12 bp spacer segment synapses with a 23 bp segment
–In the case of VH, ensures that the DH segment is not skipped
–Also ensures that two VH segments do not join (or 2 DH or 2 JH segments, etc.)
* Cut between gene segment coding sequence and heptamer
* Ligate gene segments together
–Creates a circle of intervening DNA
42
Describe V(D)J Recombination by Inversion:
* In 50% 𝜅 locus, the RSSs are 3’ of the J𝜅 gene segment and recombination occurs by an inversion mechanism
* The intervening DNA is not removed by a circle but remains present
* RNA splicing of the primary transcript will remove these sequences
43
Rearrangement brings ______ close to the promoter, allowing ______ to occur (explain).
Rearrangement brings ENHANCERS close to the promoter, allowing TRANSCRIPTION to occur.
Promoter is 5’ of V segment and enhancers are in introns between J and C segments and 3’ of C region (3’-flanking sequence). Recombined DNA brings the enhancer closer and transcription proceeeds.
44
Non-homologous end joining (NHEJ) repairs WHAT?
Repairs double stranded breaks by joining the two broken ends together and ligating them. Does not require a template (homologous sequence) for repair.
45
Describe non-homologous end joining:
* Ku70/80 binds to break → recruits DNA-dependent protein kinase (DNA-PK) → DNA-PK phosphorylates and activates Artemis endo-exonuclease → trims unpaired DNA → ligase complex (LIG4, XRCC4, XLF) ligates the DNA
* The joining process uses small (1-3 nt) single stranded regions of homology to enhance repair
46
Mechanism of VDJ Joining (Synapsis):
* Chromatin opens in developing lymphocyte to allow recombination enzymes access to DNA
* Gene segments undergoing recombination have nucleosomes with H3K4 hypermethylation
* Chromosome looping brings gene segments together
* Two recombination proteins, RAG1 and RAG2, form a complex and recognize RSS sequences
* RAG2 binds to hypermethylated H3K4 sites in chromatin and recruits and activates RAG1
47
Gene segments undergoing recombination have nucleosomes with \_\_\_\_\_\_\_\_
H3K4 hypermethylation
48
Two recombination proteins, ____ and \_\_\_\_\_, form a complex and recognize RSS sequences
RAG1 and RAG2
49
RAG1 nicks one strand and the single-stranded DNA forms:
forms a hairpin covalently with the other strand
50
Describe the mechanism of VDJ joining:
[Hairpins are opened and nucleotides added and removed at the junctions]
•Ku70/Ku80 bind to the breaks and recruits DNA-dependent protein kinase (DNA-PK) that is a repair enzyme
–DNA-PK also phosphorylates and activates Artemis
* Artemis endonuclease opens the hairpins
* DNA polymerase fills in nucleotides (P nucleotides)
* Terminal transferase (TdT) adds nucleotides onto the broken DNA ends (N nucleotides)
* DNA Ligase IV/XRCC4 join the ends together
51
Why is the greatest antibody diversity at CDR3?
Junctional diversity
52
Allelic Exclusion:
* Two chromosomes/cell (maternal and paternal)
* If one chromosome undergoes rearrangement successfully, it inhibits rearrangement on the other chromosome
* Chromatin on successful chromosome is open (acetylated) and chromatin on excluded locus is heterochromatized (methylated)
* If the first first rearrangement is nonproductive, the second chromosome undergoes rearrangement
* Allelic exclusion: each B cell only makes one antibody
53
Light chain isotype exclusion:
* Need only one light chain for each B cell
* If the 𝜅 locus undergoes a productive rearrangement, it inhibits 𝜆 rearrangement
* 𝜆 rearrangement only occurs if 𝜅 rearrangement is nonproductive on both chromosomes
* Allelic exclusion also occurs for light chains
54
During an immune response, B cells produce antibodies that progressively have a higher affinity for an antigen. The higher affinity arises by \_\_\_\_\_\_\_\_\_\_\_\_.
somatic hypermutation
55
What is somatic hypermutation?
Once a B cell has been activated by antigen, further diversification of the whole of the V-domain coding sequence occurs through a process of somatic hypermutation. This introduces single-nucleotide substitutions (point mutations) randomly and throughout the rearranged V regions of heavy-chain and light-chain genes.
56
Somatic hypermutation is dependent on the enzyme \_\_\_\_\_\_\_, which is made only by \_\_\_\_\_\_\_\_.
activation-induced cytidine deaminase (AICDA);
proliferating B cells
57
Describe the process of somatic hypermutation:
Mutations cluster in CDR regions. This process requires T helper cells and CD40:CD40L signaling. AICDA converts cytosine in single-stranded DNA to uracil (during transcription, when the two DNA strands of the immunoglobulin gene become temporarily separated). 3 possible outcomes:
* During DNA replication the Us are changed to Ts (C → T mutation)
* UNG (uracil N-glycosylase) excises base and repairs with an error-prone repair system (C → A,C,G or T)
* Mismatch repair enzymes (MSH2, MSH6, and ExoI) remove the aberrant U nucleotides and replace the surrounding DNA using an error-prone DNA polymerase to generate mutations
58
Isotype switching produces immunoglobulins with different ________ but identical \_\_\_\_\_\_\_\_\_\_.
Isotype switching produces immunoglobulins with different CONSTANT REGIONS but identical ANTIGEN SPECIFICITIES.
59
\_\_\_\_ is the first class of antibody made in the primary immune response
IgM
60
Isotype switching, like somatic hypermutation, is dependent on ______ and similarly occurs only in B cells proliferating in response to \_\_\_\_\_\_
Isotype switching, like somatic hypermutation, is dependent on AICDA and similarly occurs only in B cells proliferating in response to ANTIGEN
61
Heavy-chain isotype switching is induced by a combination of _____ and \_\_\_\_\_\_. (explain)
CD40L-mediated signals and cytokines. These signals act on antigen-stimulated B cells and induce switching in some of the progeny of these cells.
62
In the absence of CD40 or CD40L, B cells:
secrete only IgM and fail to switch to other isotypes; indicating the essential role of this ligand-receptor pair in class switching
63
How are membrane receptors converted to secreted?
* Differ in C-terminal tails due to alternative splicing
* Membrane form – C𝜇4 is followed by 26 aa hydrophobic tail (TM) and a 3 aa cytoplasmic tail (CY)
* Secreted form – C𝜇4 is followed by a hydrophilic tail piece
* The secreted form utilizes a poly(A) cleavage site before the TM-CY exons so those exons are not included in the primary transcript
64
T Cell receptor diversity:
* 4 gene families – 𝛼, 𝛽, 𝛾, 𝛿
* 𝛽, 𝛿 – VDJ; 𝛼, 𝛾 – VJ
* 𝛽 has 50 V, 2 D, and 12 J segments; 𝛼 has 45 V and 50 J segments; 𝛾, 𝛿 are much smaller - 7 V genes total
* V regions have CDR1-3 with CDR3 the most diverse, similar to antibody genes
* C region genes: 𝛽, 𝛾 have 2 C regions; 𝛼, 𝛿 have a single C region; only a membrane form of these TCRs
* V(D)J joining and P/T diversity are like antibody genes
65
X-linked hyper-IgM syndrome is caused by mutations in ______ (explain).
* Genetic defects in AID or uracil N-glycosylase (UNG) are defective in class switching (affinity maturation) and somatic mutation
* All antibody is IgM since no switching occurs (hence hyper IgM) – results in susceptibility to infection
* AID deficiency is completely defective in somatic mutation whereas it is preserved but reduced in UNG deficiencies
* Hyper IgM syndrome also caused by defects in CD40, which triggers class switching
66
Cytokines produced by _____ determine which heavy-chain isotype is produced by influencing which heavy-chain constant-region ____ participates in switch recombination.
Cytokines produced by HELPER T CELLS determine which heavy-chain isotype is produced by influencing which heavy-chain constant-region GENE participates in switch recombination.
67
•Production of opsonizing antibodies, which bind to phagocyte Fc receptors, is stimulated by \_\_\_\_\_\_, the signature cytokine of TH1 cells. Many bacteria and viruses stimulate TH1 and related follicular TH responses, which activate effector mechanisms for eliminating these microbes.
IFN-gamma
68
Switching to the IgE class is stimulated by \_\_\_\_\_\_, the signature cytokine of TH2 cells
IL-4
69
Severe Combined Immunodeficiency (SCID):
* Severe mutations or deficiencies in recombination enzymes - RAG1, RAG2, Artemis, DNA-dependent protein kinase (DNA-PK), DNA Ligase 4 - result in a complete loss of B cells and T cells, leading to SCID. Can't fight infections.
* Omenn syndrome – less severe than SCID: due to hypomorphic mutations with reduced (not absent) function of RAG and Artemis genes
70
Lymphoid tumors and translocation
* B and T cell tumors commonly have translocations of oncogenes into antibody loci
* Oncogenes, like MYC, can suffer a double strand break by AID at sequences related to switch (S) sites and then join to the AID-induced class switch recombination (CSR) break in the antibody gene locus
* Result is overexpression of oncogene (commonly a transcription factor) in B or T cells due to active antibody or TCR promoters, contributing to uncontrolled growth
* Also can have RAG-RAG and RAG-AID translocations
71
T cell–mediated immune responses may be only against protein antigens that are:
either produced in or taken up by host cells
72
Antigen presentation occurs in several specific places:
Primary and secondary lymphoid tissue
73
Antigens can only be recognized in the proper context:
- Location (anatomic)
- Setting (microanatomic/molecular)
74
MHC Restriction:
An essential and central theme in the functioning of the adaptive immune system is to understand that the majority of T lymphocytes recognize peptide antigens that are bound to and displayed by major histocompatibility complex (MHC) molecules of antigen-presenting cells.
75
Of all the “professional APC”, ______ are the most effective in initiating adaptive T cell dependent immune responses
dendritic cells
76
MHC genes are highly \_\_\_\_\_\_\_\_
polymorphic
77
MHC molecules are important in presenting peptides to \_\_\_\_\_
T cells
78
How many peptides can MHC molecules display?
Only one peptide at a time
79
MHC Class I structural features:
* Composed of an a chain + b2-microgloblin (not coded in MHC)
* Peptide binding cleft a1 and a2 domains
* Can bind peptide 8-11 amino acids in size
* a3 domain binds CD8 on the T cell
* Polymorphisms mostly in a1 and a2
80
MHC Class II structural features:
* Structure consists of a and b chains.
* a1 and b1 domains are polymorphic and contain the binding site for peptides in cleft (10-30 amino acid peptides)
* b2 domain binds CD4
* Polymorphisms mainly in b chain
81
MHC genes are _____ expressed
codominantly
82
CD4 co-expression is required for T cells to be able to:
fully recognize and respond to peptide antigens in the setting of MHC Class II
83
By the same token CD8 co-expression is required for T cells to:
be able to fully recognize and respond to peptide antigens in the setting of NHC Class I
84
MHC genes are highly polymorphic. Their major products are \_\_\_\_\_\_\_\_\_\_\_, which contain \_\_\_\_\_\_\_\_\_\_\_, where the polymorphic residues are concentrated, and invariant regions, which bind the co-receptors CD8 and CD4, respectively.
MHC genes are highly polymorphic. Their major products are CLASS I and CLASS II MHC MOLECULES, which contain PEPTIDE-BINDING CLEFTS, where the polymorphic residues are concentrated, and invariant regions, which bind the co-receptors CD8 and CD4, respectively.
85
MHC presentation of proteins that are from the extracellular environment:
Proteins that are ingested by APCs from the extracellular environment are degraded by proteolysis within the vesicles of the APCs, and the peptides generated bind to the clefts of newly synthesized class II MHC molecules. CD4 binds to an invariant part of class II MHC, because of which CD4+ helper T can only be activated by class II MHC–associated peptides derived mainly from extracellular proteins.
86
MHC presentation of proteins produced in the cytoplasm of infected cells:
Proteins that are produced in the cytoplasm of infected cells, or that enter the cytoplasm from phagosomes, are degraded by proteasomes, transported into the endoplasmic reticulum by TAP, and bind to the clefts of newly synthesized class I MHC molecules. CD8 binds class I MHC molecules, so CD8+ cytotoxic T lymphocytes can be activated only by class I MHC–associated peptides derived from cytosolic proteins.
87
Microbes activate APCs to express ________ and to secrete ________ that provide signals functioning in concert with antigens to stimulate specific T cells. The requirement for these _________ ensures that T cells respond to microbial antigens and not to harmless, nonmicrobial substances.
Microbes activate APCs to express MEMBRANE PROTEINS (co-stimulators) and to secrete CYTOKINES that provide signals functioning in concert with antigens to stimulate specific T cells. The requirement for these SECOND SIGNALS ensures that T cells respond to microbial antigens and not to harmless, nonmicrobial substances.
88
WIthin the thymus, two very important process occur during Thymic Education:
MHC restriction and Self Tolerance
89
MHC Restriction:
Cortical thymic epithelial cells asks the developing T-cell, “Do you recognize the self MHC molecules I’m expressing?” The correct answer is “Yes, I recognize you.” DP CD4-positive, CD8-positive cells bearing antigen receptors that do not react with self MHC proteins are killed. This results in a **positive selection** for T cells that react with self MHC proteins.
90
Positive Selection:
DP thymocytes with TCR that bind MHC class I or class II molecules with “low to moderate affinity”, receive signals for further development. Cells that cannot bind and recognize self-MHC or bind with too low an affinity undergo apoptosis.
91
Self Tolerance:
Medulla thymic epithelial cells then ask the developing T-cell, “Do you recognize the self peptides on the MHC molecules I’m expressing?” The correct answer is “No, I don’t recognize you.” SP CD4-positive and SP CD8-positive cells bearing antigen receptors for “self” proteins are killed. This process called **negative selection**, results in tolerance to our own proteins.
92
Negative Selection:
DP thymocytes that bind self-peptides/MHC class I or class II molecules with “high affinity” are deleted. This process deletes possible auto-reactive T cells.
93
\_\_\_\_\_\_ is the principal co-stimulatory molecule expressed by naive T cells. What does it bind to?
CD28 is the principal co-stimulatory molecule expressed by naive T cells. it binds to B7 on APCs to create the secondary signal.
94
What are CD3 proteins?
These are closely associated with the TCRs, and have cytoplasmic tails that contain sequences called immunoreceptor tyrosine-based action motifs (ITAMs), which are phosphorylated by PTKs that become activated once TCR clustering occurs folliwing peptide-MHC binding.
95
T cell proliferation is dependent on \_\_\_\_\_\_
IL-2
96
The initiation and expression of IL-2 requires signals delivered by:
The TCR:MHC co-receptor complex and CD28:B7. These co-stimulators are first upregulated by IL-12 secretion by the APC that is presenting to the T cell. IL-2 then functions in an autocrine manner (cytokine is secreted and bound by activated T cells)
97
What is CD25?
The high affinity IL-2 receptor that is upregulated in activated T cells (promotes cell division, helps clonal expansion)
98
How do CD4+ T cells help CD8+ T cells?
CD4+ prodces cytokines that stimulate cytotoxic T lymphocyte differentiation.
CD4+ helper T cells enhance the ability of APCs to stimulate CTL differentiation via binding.
99
Th1 cells target what type of infection?
Intracellular bacteria infections
100
What cytokines are needed to activate Th1 cells?
IFN-gamma and IL-12
101
What cytokines do Th1 cells secrete?
IFN-gamma, TNF-a
(IFN-gamma stimulates macrophages to ingest, induces class switching to produce IgG which promotes opsinization, and blocks differentiation of Th2 cells)
102
Th2 cells target what type of infection?
Helminths
103
What cytokines are needed to activate Th2 cells?
IL-4
104
What cytokines are secreted by Th2 cells?
IL-4, IL-5, IL-13
(IL-4 promotes B cell differentation, IgE class switching, and eosinophils)
(IL-5 promotes B cell growth, activates eosinophils, and enhances IgE)
105
Th17 targets what kind of infection?
Extracellular bacteria and fungi
106
What cytokines are needed to activate Th17 cells?
TGF-B, IL-6, IL-23
107
What cytokines are secreted by Th17?
IL-17, IL-22
| (IL-17 especially is pro-inflammatory)
108
With ____ antigens, the full response of B cells requires the assistance from CD4+ helper T cells
protein antigens;
B cells ingest protein antigens, degrade them, and display peptides bound to MHC Class II molecules for recognition by helper T cells. Helper T cells express cytokines and cell surface proteins, which act together to activate the B cells.
109
Polysaccharides and lipids stimulate the synthesis of what kind(s) of immunoglobulin?
IgM
110
Protein antigens stimulate the synthesis of what kind(s) of immunoglobulin?
IgG, IgA, and IgE
111
What is the Fab region of the antibody?
This is the region that the antigen binds to
112
What is the Fc region of an antibody?
This is the region that macrophages, neutrophils, NK cells, mast cells, etc. can bind to. (basically the area recognized by phagocytic cells).
113
IgA:
IgA antibodies are found in areas of the body such as the nose, breathing passages, digestive tract, ears, eyes, and vagina. IgA antibodies protect body surfaces that are exposed to outside foreign substances (e.g. mucosal immunity)
114
IgG antibodies:
Found in all body fluids. The most common antibody. Very important in fighting bacterial and viral infections. Also the only antibody that can cross the placenta to protect fetuses while pregnant.
115
IgM:
Largest antibodies. Found in blood and lymph and are the first type of antibody made in response to an infection.
116
IgE antibodies:
Found in the lungs, skin, and mucous membranes. They cause the body to react against foreign substances like pollen.
117
IgD antibodies:
principally found on the surface of newly matured B cells. Function as cell receptor, but unclear overall purpose.
118
Which immunoglobulin is most important for transport across epithelium?
IgA
119
What immunoglobulins are most important in diffusion into extravascular spaces?
IgG (somewhat IgA)
120
What are the 3 subsets of Mature B cells?
- Follicular B cells
- Marginal-zone B cells
- B-1 lymphocytes
121
Follicular B cells:
Most mature B cells are called follicular B cells because they are found within lymph node and spleen follicles
122
Marginal zone B cells:
Found at the margins of splenic follicles - develop from the same progenitors as follicular B cells
123
B-1 lymphocytes:
A distinct population found in lymphoid organs and the peritoneal cavity. May develop earlier and from different precursors.
124
Describe the relationship between complement activation and B cell activation:
Complement activation generates C3b, which breaks down to C3d. C3d binds B cells through CR2. This engagement enhances antigen-dependent activation responses of B cells.
125
B cells, like dendritic cells and other leukocytes, express numerous:
Toll-like receptors (TLRs)
126
CD4+ helper T cells and B cells are _____ activated by a protein antigen in _____ regions of a lymph node. (explain)
CD4+ helper T cells and B cells are INDEPENDENTLY activated by a protein antigen in DIFFERENT regions of a lymph node.
B cells process and present antigen to T cells via MHC II. Activated helper T cells express CD40L and secrete cytokines, which act on the B cells and initiate proliferation and differentiation to plasma cells.
127
Activated B and T cells migrate to the \_\_\_\_\_\_. Here, B cells begin to proliferate, forming an organized structure called a \_\_\_\_\_\_\_\_\_.
Migrate to the follicle. Form a germinal center.
Here, B cells undergo extensive somatic mutation of antibody gene variable regions and Ig heavy chain isotype switching.
