Diebel Test 4 Flashcards
Anergy
Naive T cells always present CD28. APC’s must also present CD80/86 (only macrophages that don’t constituitively present 80/86).
If APC’s don’t also present 80/86 = anergy and T cells die.
Failsafe mechanism to ensure T cells are only appropriately active.
CTLA-4
Even stronger binder to 80/86 that is produced after a burst of IL-2 to prevent runaway T cell response.
When CTLA-4 binds 80/86 = activation inhibition
TAP 1 and 2
Transporter associated w/ Antigen Processing
Complex that extends across the RER membrane and facilitates the passage of cytosolic pathway peptides to the lumen of the RER where loading of the peptides to Class I molecules can take place.
Found at same locus as HLA.
Calnexin
Protein that holds the alpha chain and waits for beta piece to join.
ERAAP
Trims excess protein. Then MHC I is mature and can move through golgi to cell membrane.
DRiPs
Defective Ribosomal Products
Proteins synthesized incorrectly that are rapidly degraded and presented on the cell surface via MHC I molecules.
Allows the recognition and killing of cells that have aberrant DNA and thus produce aberrant proteins.
Fas
The death receptor that when bound by CTL or NK cells results in apoptosis.
Granulysin
Protein released by CTL or NK cells that activates apoptosis by cleavage of capsases.
Perforin
Released by CTLs or NKs when Fas ligand is bound triggering apoptosis.
Form a pore on target cell membranes.
Invariant chain
=CD74
Assists in the folding of class II alpha and beta chains, binds to the peptide-presenting site of the class II molecules, and assists in the transport of the MHC II molecules from golgi to cytoplasmic vesicles.
CLIP
CLass-II associated Invariant chain Peptide.
Proteolytic cleavage gradually digest the invariant chain leaving the short CLIP fragment bound to the antigen presenting site on the MHC II.
CD45R
Receptor for cell growth and differentiation that remains expressed on the surface as intermediate pro-B cells and remains expressed throughout the remainder of B-cell ontogeny.
c-Kit
Binds to stem-cell factor expressed on bone marrow stromal cells. This induces the pro-B cells to proliferate and differentiate into pre-B cells
IL-7
Promotes B-cell lineage development.
Blys
B-lymphocyte stimulator
Signaling through its receptor BR3 is important for the survival of pre-immune B-cell stages from transition stage onwards.
IL-4, IL-3, and low-molecular-weight B cell growth factor (L-BCGF)
Important signaling molecules for initiatiing the process of B-cell differentiation.
BTK
Gene encoding the enzyme Bruton’s Tyrosine Kinase.
Key enzyme involved in signal transduction downstream of the pre-BCD and BCr.
Mutated in immunodeficiency XLA. –> very few circulating B cells and negligible serum Ig.
85% of agammaglobulinemia (AKA Bruton’s Agammaglobulinemia)
T-Independent Antigens (TI)
Antigens that can activate B cells without MHC class II restricted T cell help.
Can be divided into two groups (TI-1 and TI-2) based on the manner in which they activate B cells.
Activate B1 B cells (IgM only)
Poor memory
TI-1
Predominately bacterial cell wall components. Prototype = LPS.
TI-2
TI-2 antigens are predominately large polysaccharide molecules w/ repeating antigenic determinants.
Superantigen
Complexes bind TCR and MHC regardless of costimulatory molecules causing extreme levels of T cell activation which is toxic.
CD25
High affinity receptor for IL-2 found on the surface of mature CTL’s.
IL-12 (produced by APC after TH1 production of IFN-y) causes switch to CD25 active receptor form naive CD8.
L-selectin and CCR7
Cause homing and retiention in lymph nodes.
Expressed high levels in Naive CTL-P
Low levels in Effector CTL
LFA-1
On CTL and binds to ICAMS on target cell.
Antigen activation converts LFA-1 from low affinity state to high affinity state for better binding.
Returns to low affinity state after 5-10 minutes resulting in CTL disassociation from target cell.
CD56low NK cells
90% of NK cells.
Effective killers of target cells.
CD56high NK cells
Release cytokines (IFN-y). Tilts immune response towards TH1’s and M1’s. Don’t have granules
10% of NK cells.
CD16
Expressed by NK cells. (also NKRs).
Recognized IgG bound to cells.
NKG2
Lectin like receptors
Bind to HLA-E and MHC I.
Most are activating
All are heterodimers except NKG2B
NKG2A is inhibitory and trumps all others.
NKG2E is main activating signal.
KIR
=killer cell immunoglobulin-like receptors
Bind to most MHC class I molecules (HLA-A, HLA-B, and HLA-C)
Most receptors are inhibitory.
Antibody Dependent Cell-mediated Cytotoxicity (ADCC)
Effector cells: NK cells, mphages, monocytes, nphils, ephils
Effector cells bind the antigent via Fc receptor
Killing is mediated by:
- cytolytic enzyme release by mphages, nphils, and ephils
- TNF release by NK cells, monocytes, mphages
- perforin release by NK and ephils
- granzyme release by NK
