CHAPTER 4: ADAPTIVE IMMUNITY

 Adaptive immunity – specificity; memory; Double-Negative Stage

increase response upon repeated exposure
 Early thymocytes / DN thymocytes
 Key cells involved:
o ( - ) CD4 and CD8
o T lymphocytes
o Proliferate in the outer cortex under the
 Regulatory role by providing hel
influence of IL-7
to B cells in responding to Ag
 Rearrangement of genes that code for the antigen
 Kill virally infected target cells
receptor called T-cell receptor (TCR)
o B lymphocytes
o Allows T cells to respond to diff Ag
 Differentiate into plasma cells
o Consists of 2 chains which are both
 Memory based on
variable region
 Clonal selection
 Alpha chain – Ch 14
 Differentiation
 Beta chain – Ch 7; first
 Expansion
 Both occur in complex
 Progenitors of T and B cells appear in fetal liver as with six other chain
early as 8 weeks common to all T cells
 CD3/TCR complex
T-Cell Differentiation o Combination of 8 chains
o Occur in three pairs
 60-80%; thymus  Delta-epsilon
 Within the lobules are two main zones  Gamma-epsilon
o Outer cortex  Tau-tau
o Inner medulla o In the cytoplasm of the cell
 Early precursors enter thymus via cortico-  Rearrangement of β-chain on Ch 7 occurs first
medullary junction o Three gene segments
 Migration is driven by chemokines  V, D, J
o Large family of cytokines that can  Rearranged and combined
recruit specific cells to a site with constant region of β
 Thymocytes – precursors in the thymus o Combination with CD3 = pre-TCR
committed to be T cells receptor
 Maturation – 3 weeks o Appearance triggers the thymocytes to be
 Thymic stromal cells include CD4+ and CD8+
o Fibroblasts  Followed by α-chain on Ch14
o Epithelial cells o Appearance on cell surface sends a signal
o Macrophages to suppress β-chain gene rearrangement
o Dendritic cells  Allelic exclusion
 Interxn w/ stromal cells influenced by o Selection of allele on one chromosome
cytokines (IL-7)  10% rearrange and express when there is not a
o Growth and maturation productive DNA coding for β-chain
 97% of cortical cells die inside thymus by o Gamma chain
negative and positive selection o Delta chain
 Represent dominant T-cell population in
o Skin, intestinal eph, pulmonary eph
 Wound healing and protection of eph
 Recognize Ag without MHC proteins
o Bridge between innate and adaptive
Double-Positive Stage
 When thymocytes express both CD4 and CD8
 Young DP thymocytes begin to rearrange genes
coding for α-chain
 Positive selection – first selection
o Occurs when the CD3-αβ receptor
complex (TCR) is complete and
expressed on cell surface
o Allows only DP cells with fxnal TCR
receptors to survive
 T cells must recognize MHC I or II molecules
 Kinases
o Activated and form a cascade when
thymocytes bind to self-MHC antigens in
the cortex by TCR receptors
o Causes change in shape and motility = ↑
surivival
 MHC restriction
o Selection of thymocytes that will interact
with MHC Ag on host cell
 Very high or very low affinity for self-MHC Ag
= apoptosis
 Negative Selection – second selection
o occur in the corticomedullary region and
the medulla
 Clonal deletion
o Elimination of clones of T cells capable
of autoimmune response
 Because of strong reaction to self-
peptides = apoptosis
 Only 1-3% of DP thymocytes survive this stage
Mature T cells
 Exhibit only CD4 or CD8
 CD4+ T cell (T helper cells)
o Ag and class II MHC protein
o Th1 cells
 produce IFN-γ, IL-2, and TNF-β
 intacellular pathogens
o Th2 cells
 produce IL-4, 5, 6, 9, 10, 13
 extracellular pathogens
 CD8+ T cell (T cytotoxic cells)
o Ag and class I MHC protein
o 1/3
 T regulatory cells (Treg cells)
o CD4 and CD25
o 5% of all CD4+ T cells
o suppress immune response to self-Ag
o secretes inhibitory cytokines
o antigen-specific
 Th 9 cells
o produce IL-9
o proinflammatory effect
o ward off fungi and extracellular bacteria
o stimulate growth of mast cells
o promote autoimmune inflammation
 Th17
o produce IL-17 and IL-22
 ↑ inflammation and joint destrxn
o associated with
 rheumatoid arthritis
 multiple sclerosis
 inflammatory bowel dx
 All single (+) T cells spend 12 days in medulla
o additional proliferation occurs
o released from thymus to peripheral
lymphoid organs every 12-24 hours
 Resting T cells have a life span up to several yrs
 Ag recognition in secondary lymphoid organs →
activated T lymphocytes → differentiate into
functionally active small lymphocytes →
cytokines produced
o Ab production
o eliminating tumor and other target cells
o rejects grafts
o stimulate hematopoiesis in BM
o initiate delayed hypersensitivity
o aka cell mediated immune response
 B-CELL DIFFERENTIATION
Pro-B Cells Pre-B Cells
 remain and mature in the BM
 Bone marrow stromal cells
o form niches where stem cells and B-cell
precursors reside
o keep B-cell precursors to receive signal
for differentiation
o preparation for Ab prodxn and restriction
of response to Ag
 development
 activation
 differentiation
 Antigen-Independent Phase
o divided acc to formation of subpopulation
 pro-B clls
 pre-B cells
 immature B cells
 mature B cells
 earliest devt stage requires direct contact with
bone marrow stromal cells
 transcription or growth factors
o E2A, early B-cell factor, interferon
regulatory factor (IFR8), and paired box
protein 5 (PAX5)
o cytokine – IL-7
 first step in pro-B phase
o rearrangement of genes for heavy and
light chain of Ab molecule
o rearrangement of DNA similar to T cell
 Ag specificity built on α and β
chains of TCR
o Heavy chain: Ch14
 first; random
 if successful = pre-B
 if not= second Ch14
 if not pa rin = devt halted
o Light chain: Ch 2 and 22
o C-Kit
 receptor on pro-B
 interacts with cell surface
molecule called stem cell factor
on stromal cells = activation
o DNA is cleaved → TdT joins the pieces
back together by adding nucleotides