1How is adaptive immunity characterized?
1. specificity for each individual pathogen / microbe
2. ability to remember prior exposure
3. increased response to pathogen upon repeated exposure
2When do progenitors for T and B cell appear?
in fetal liver at 8 weeks of pregnancy, shifting to bone marrow
3What is the primary producer of hematopoietic cells?
bone marrow
4What drives the migration to cell precursors to the outer cortex of thymus?
chemokines
5What is the job of cytokines?
recruit specific cells to particular site
6What are T cell precursors called?
thymocytes
7Where do early precursors enter thymus?
corticomedullary junction (and migrate to outer cortex)
8What happens as thymocytes travel through thymus?
rearrangement of the genes coding for the antigen receptor
9What are thymic stromal cells?
epithelial cells, mq, fibroblasts, dc
10What is critical for thymocyte growth and differentiation?
interaction with stromal cells under the influence of cytokines (especially IL-7)
11What is the selection process for thymocyte maturation?
positive and negative selection
12What are double-negative (DN) thymocytes?
thymocytes that lack CD4 CD8 markers
13Where do DN thymocytes proliferate?
outer cortex (under influence of IL-7)
14When does rearrangement of genes for TCR begin?
double-negative stage
15What is the importance of TCR?
builds diversity; allows T cell to respond to different antigens that body can encounter
16What are the chains of TCR?
α and β
17What is the function of the 6 chains of nonspecific CD3 do?
assist in signaling when an antigen binds to T cells
18How are the α and β chains of TCR coded?
selection of certain gene segments and deletion of others in a random fashion
19Where is the rearrangement of β chain coded?
chromosome 7
20Where is the rearrangement of α chain coded?
chromosome 14
21What does α chain on cell surface do?
sends signal to suppress any further B chain gene rearrangements
22What is allelic exclusion?
selection of an allele on one chromosome
23What does the appearance of β chain trigger?
triggers thymocyte to become CD4+ and CD8+
24What happens when there is not productive rearrangement for a β chain?
rearrange and express γ or delta chains (10% of the time)
25What do γ and delta chains on T cells lack?
CD4 and CD8
26What are the jobs of γ and delta T cells?
healing and protection of epithelium; recognize antigens without being presented by MHC
27What are double-positive (DP) thymocytes?
express both CD4 and CD8 antigens
28What do young DP thymocytes rearrange?
genes coding for α chain
29What happens when CD3-αβ complex (TCR) is expressed?
positive selection process
30What happens during positive selection?
allows only DP cells with functional TCR receptors to survive
31What is the criteria for T cell survival?
T cells must recognize foreign antigen in association with MHC molecules
32What activates kinases (enzymes)?
When thymocytes bind to self-MHC antigens in the cortex with newly formed TCR
33What happens after kinases are activated?
causes a change in cell shape and motility (for increased cell survival)
34What is MHC restriction?
the selection of thymocytes that will only interact with the MHC antigens on host cells
35What happens to thymocytes that have either a low or high affinity for self-MHC antigens?
die by apoptosis
36What is the importance of killing thymocytes that have high / low affinity for self-MHC?
because functioning T cells must be able to recognize foreign antigen along MHC molecules
37What cells reach negative selection?
surviving DP T cells
38Where does second selection (negative selection) take place?
corticomedullary region and the medulla of the thymus (because medullary epithelial cells express wide variety of self-antigens)
39What happens to thymocytes that have strong reactions with self-peptides other than MHC?
triggers apoptosis
40What is clonal deletion?
process of elimination of clones of T cells that would be capable of autoimmune response
41What happens after thymocytes survive selection?
only have one type of marker (CD4 or CD8)
42What MHC do CD4+ T cells recognize?
class II
43What MHC do CD8+ T cells recognize?
class I
44What are T cells with CD4 receptors?
T helper (Th) cells
45What are T cells with CD8 receptors?
cytotoxic T cells
46What do Th1 cells produce?
IFN-γ, IL-2, TNF-β
47What is the purpose of Th1 cells?
protect cells against intracellular pathogens by activating cytotoxic lymphocytes and mq
48What do Th2 produces?
interleukins (-4.-5.-6.-9.-10.-13)
49What are the job of interleukins produced by Th2 cells?
help B cells produce antibodies against extracellular pathogens and generally regulate B cell activity
50What antigens do T regulatory cells (Tregs) possess?
CD4 and CD25
51What is the role of Tregs?
suppressing immune response to self antigens; inhibit proliferation of other T cell populations by secreting inhibitory cytokines
52What kind of response is Tregs?
antigen-specific
53What is the purpose of Th9?
warding off fungi and extracellular bacteria on epithelial surfaces
54What do Th9 stimulate while warding off extracellular bacteria?
growth of hematopoietic cells (especially mast); promote autoimmune inflammation
55What do Th17 produce?
IL-17 and IL-22
56What is the purpose of IL-17 and IL-22 (produced by Th17)?
increase inflammation and join destruction
57What are IL-17 and IL-22 associated with?
rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease
58Where do single-positive T cells go after selection?
released from thymus to seed peripheral lymphoid organs and recirculate through blood spleen
59Why are T cells constantly recirculating?
ensures that T cells make contact with antigen
60What happens when there is antigen recognition in secondary lymphoid tissue?
T cells activated and differentiate into functionally active small lymphocytes and produce cytokines
61What Th plays a role in cell-mediated immunity?
Th1 and Th17
62What cytokines play a role in cell-mediated immunity?
IFN-γ, TGF-β, IL-17, IL-22
63What is cell-mediated immunity?
antibody production, eliminating tumor and other target cells, rejecting grafts, stimulating hematopoiesis, and initiating delayed hypersensitivity reactions
64Where are B cells derived from?
hematopoietic stem cell that develops into early lymphocyte progenitor in the bone marrow
65How are B cells different from T cells for differentiation?
T cells leave bone marrow and travel to thymus to mature whereas B cells remain and mature in bone marrow
66What is the purpose of niches for B cell precursors?
keep B cell precursors localized to receive signals for differentiation
67What is the purpose of B cell differentiation?
prepares them for role in antibody production and (at the same time) restricts types of antigens to which one cell can respond
68What are the 3 phases of B cell differentiation?
1. development of mature immunocompetent B cells
2. activation of B cells by antigen
3. differentiation of activated B cells into plasma cells (which produce antibodies)
69What is the result of the first phase of B cell development?
(in bone marrow) results in antigen independent B cell
70What is antigen-independent phase?
mature B cells that have not yet been exposed to antigen, in distinct subpopulations
71What are the subpopulations of the antigen-independent phase?
pro-B cells (progenitor cells)
pre-B cells (precursor B cells)
immature B cells
mature B cells
72What do B cell progenitors require to differentiated into pro-B?
requires direct contact with bone marrow stromal cells; transcription or growth factors necessary
73What are the factors that can stimulate B cell progenitors to pro-B?
E2A
early B-cell factor (EBF)
interferon reg factor (IFR8)
paired box protein 5 (PAX5)
IL-7
74Where are the factors that lead to a pro-B cell produced?
microenvironment of bone marrow
75What is the first step in pro-B phase?
rearrangement of genes that code for heavy and light chains of an antibody molecule
76What are the variable regions of the B cell?
make each antibody molecule specific for a certain antigen or group of antigens
77How are the rearrangement of B and T cells similar?
antigen specificity built into α and β chains of TCR
78What chromosome codes for heavy chain of B cells?
chromosome 14
79What chromosome codes for light chain of B cells?
chromosomes 2 and 22
80Where does the rearrangement of genes for B cell happen first?
chromosome 14 (heavy chain of antibody)
81What triggers the activation of rearrangement of chromosome 14?
C-kin, a receptor on pro-B, that interacts with stem cell factor (cell surface molecule)
82When do pro-B cells differentiate into pre-B cells?
upon successful rearrangement of H chain genes on chr 14.
83What happens if rearrangement of genes on chr 14 is not successful?
rearrangement of genes on second chromosome 14. if both unsuccessful --> development of cell is halted
84What pro-B cells become pre-B cells?
successful rearrangement of one set of heavy-chain genes
85When does the pre-B stage begin?
after synthesis of heavy-chain part of antibody molecule
86What are the first heavy chains synthesized? (pre-B)
IgM (μ)
87What happens during pre-B cell stage?
μ heavy chain accumulates in cytoplasm and surface with surrogate light chains, stimulating burst of clonal expansion
88which pre-B cell survive to further differentiation?
pre-B cells expressing μ heaving chains in association with surrogate light chains
89What does signaling through the pre-B receptors formed do?
stimulates burst of clonal expansion
90What happens if gene rearrangement does not work during pre-B cells?
B-cell development is halted and cells are apoptosized
91How are immature B cells distinguished?
by appearance of complete IgM molecules on cell surface
92What does IgM on cell surface indicate?
rearrangement of genetic sequence coding for light chains on either chromosome 2 or 22
93What does completion of light chain rearrangement indicate?
committed cell to produce an antibody molecule with specificity for a particular antigen or group of related antigens
94What determines specificity for antigen?
variable region (of both light and heavy chains)
95How is diversity of receptors for antigen a hallmark of adaptive?
means that the capability to respond to a specific antigen is built in before a B cell ever encounters an antigen
96What happens when surface immunoglobulins appear on B cell?
μ chains are no longer detectable in cytoplasm
97What are other surface proteins that appear in immature B cell?
CD21, CD40, class II MHC
98What is the job of CD21?
enhances likelihood of contact between B cells and antigens because antigens become frequently coated with complement fragments during immune response
99What does CD40 and class II MHC do?
interaction of B cells with T cells
100What happens at the immature B cells stage?
self-antigens give negative signal to immature B cells; B cells tightly bind self-antigens receive signal to halt development
results in arrested maturation and cell death
101What is central tolerance?
elimination of B cells that bear self-reactive receptors
102Where do immature B cells become mature?
in spleen
103What are the 2 kinds of mature B cells?
marginal zone B or follicular B cells
104What is the purpose of marginal B cells?
remain in spleen to respond quickly to any blood-borne pathogens that may come into contact
105What do follicular B cells do?
constantly recirculate through secondary lymphoid organs
106What do all mature B cells exhibit (in addition to IgM)?
IgD
107What is the purpose of IgM and IgD on B cell?
provide primary activating signal to B cells when contact with antigen takes place
108What is the purpose of IgD (if not cell function)?
prolong the life span of mature B cells in periphery
109What happens if a B cell is stimulated by antigen (when mature stage)?
undergoes transformation to a blast stage that eventually forms memory cells and antibody-secreting plasma cells
110What is antigen-dependent phase (B cell)?
B cell stimulated by antigen, forming memory and antibody-secreting plasma cells
111What is humoral immunity?
production of antibodies by plasma cells
112How can you identify plasma cells?
presence of abundant cytoplasmic immunoglobulin and little to no surface immunoglobulin
113What is the main function of plasma cells?
antibody production
114Where are plasma cells generally located?
germinal centers in the peripheral lymphoid organs or in bone marrow
115How do plasma cells survive in bone marrow?
in niches surrounded by stromal cells
116What is the importance of stromal cells around a plasma cell?
stromal cell provide chemical stimulation by cytokines, allowing plasma to be long-lived and continually produce antibodies