Adaptive Immunity

• heavy chain: 14
• kappa light chain: 2
• lambda light chain: 22
• alpha chain: 14
• beta chain: 7
• HLA complex: 6

the part of an antigen to which an antibody binds

• two types
• nonamer, heptamer, 12 bp spacer
• nonamer, heptamer, 23 bp spacer

In order to join V, D, or J gene segments, you need a 12 spacer and a 23 spacer

• set of enzymes used to recombine V, D, and J gene segments.
• consists of RAG1 and RAG2

adds nucleotides to opened hairpin DNA strands

coreceptors for immunoglobulins that function to interact with intracellular signaling proteins.

random introduction of single nucleotide substitutions throughout the variable regions of heavy and light chains

converts cytosine --> uracil, so CG pairs become AT pairs

B cells that have mutant high-affinity immunoglobulin receptors compete more effectively for binding of antigen, thus they are preferentially selected to mature into antibody secreting plasma cells.

brings in a new constant region to interact with the variable region sequence

The TAP transporter dimer is critical for transfer of peptides from the cytosol into the endoplasmic reticulum

in the ER, if the MHC class I molecule is loaded with a peptide that is too long, ERAP removes N-terminal amino acids until the peptide is abou 8-10 residues

prevents peptides from binding to a MHC class II molecule until it reaches endocytic vesicles

when the invariant chain is cleaved, CLIP is left behind and is bound to the MHC class II molecule

catalyzes the release of CLIP from the MHC class II molecule, thus allowing for peptides to bind

each individual is likely to express 2 different allelic HLA molecules from each locus

refers to the duplication of HLA genes

• c-kit (on B cell) binds to stem cell factor (of stromal cells in bone marrow).
• kit causes the B cell to proliferate

• consists of VpreB and lambda 5
• the binding of the surrogate light chain with the heavy chain on Pre-B cell receptors is the first checkpoint

required for the differentiation of the pre-B cells to immature B cells

• secrete chemokines in the lymph node that attract immature B cells to enter via the high endothelial venule.
• they also secrete another chemokine that attracts the B cell to the primary follicle
• interactions with the follicular dendritic cell and cytokines drives maturation of the B cell. This is indicated with the expression of more IgD compared to IgM.

T cell production decreases with age

• T cell receptors that bind to MHC with a moderate affinity move to the next stage (which is negative selection)
• double positive thymocyte becomes a CD4 T cell or CD8 T cell

T cells that bind too tightly to MHC on dendritic cells, macrophages, etc are signaled to die

A T lymphocyte can only respond to a peptide antigen in the conext of the same MHC type encountered during the selection process in the thymus.

LFA-1 is a cell surface adhesion molecule on the T cell that binds with ICAM-1 of the dendritic cell

LFA-1 is a cell surface adhesion molecule on the T cell that binds with ICAM-1 of the dendritic cell

• T cell response to foreign MHC
• two modes of cross-reactive T cell recognition that may explain alloreactivity - peptide dominant and MHC dominant binding

• CD3 is a co-receptor that is always expressed with the T cell receptor.
• CD3 is critical for transmitting the signal from the APC to the T cell

• ITAMs are the cytoplasmic tails fo the CD3 proteins.
• phosphorylation of the ITAM by Lck allows for ZAP-70 to bind to it
• ZAP-70 initiates the intracellular signaling pathway  leading to T cell activation

ZAP-70 binds to phosphorylated ITAMs, which then initiates the intracellular signaling pathway leading to T cell activation

• phosphorylate ITAMs
• get phosphorylated (activated) when the TCR/MHC/co-receptor complex binds together

same function as lck

protein tyrosine phosphatase that activates lck and fyn by removing the phosphate from the inhibitory site.

• TCR/co receptor binding of MHC/peptide complex
• CD28-B7 co-stimulation

• co-stimulatory molecule found on T cells
• binds to B7

• co-stimulatory molecule found on APC
• binds to CD28

T cell becomes permanently disabled when there is no co-stimulation

• an inhbitory receptor expressed on T cells
• CTLA-4 binds B7 more avidly than does CD28 and delivers inhibitory signals to activated T cells

• function: promotes T cell proliferation
• T cell activation causes the secretion of IL-2 and expression of IL-2 receptors
• IL-2 binds to the IL-2 receptors to cause T cell growth in an autocrine fashion

released from granules of cytotoxic T cells and inserts into the target cell membrane to form pores

serine proteases, which activate apoptosis once in the cytoplasm of the target cell

has antimicrobial actions and can induce apoptosis

activate macrophages to destroy engulfed bacteria

kills chronically infected macrophages

induces macrp[hage differentiation in the bone marrow

activates endothelium to induce macrophage adhesion and exit from blood vessel at site of infection

causes macropphages to accumulate at site of infection

• IFN-gamma and CD40 ligand
• Fas ligand or LT
• IL-2
• IL-3 + GM-CSF
• TNF-alpha + LT
• CXCL2

• IL-4
• IL-5
• IL-10
• IL-13
• TGF-beta

• IFN-gamma
• LT
• perforin
• granzymes
• granulysin

limit the activities of effector and autoreactive CD4 and CD8 T cells