Immuno 2 Flashcards
major vs minor histocompatibility complex
strong immune response, major determinant for rapid TRANSPLANT/GRAFT REJECTION, differentiate self from foreign cells –> respond to foreign ag vs less immunogenic and don’t elicit ab, involved in self/nonself recognition but lesser extent than major HC
MHC locus vs MHC I locus vs MHC II locus vs codominant expression
located in region of chrm 6 vs classical: HLA/B/C, nonclassical: HLE/F/G vs HLA-DP/DQ/DR vs all MHC genes from each chrm = expressed –> each person expresses 6 class I and 6 class II
classical MHC I vs nonclassical MHC II
on all nucleated cells and PLTs, presents ag to CD8+ T cells vs on more limited cellular expression; HLA-G = immunosuppressive
MHC structure
heterodimer of 2 proteins w/ at least 1 = transmembrane, has a cavity where self and nonself peptide binds to => peptide-binding groove (PEPTIDE MUST BE IN GROOVE for MHC proteins to fold) (mult peptides can bind to single MHC); can display 1 type of peptide at a time
2 lvls of MHC restriction: self restriction vs ag restriction
TCR only recognizes peptide presented on self HLA vs TCR recognizes specific ag on self HLA
MHC I vs MHC II
MHC-encoded alpha chain and beta2-microglobulin NOT encoded in MHC locus, on all nucleated cells and PLTs, presents ag to CD8+ T cells vs both MHC-encoded alpha and beta chain, on APCs, presents ag to CD4+ T cells
ag processing: endogenous vs exogenous
class I, processing intracellular proteins on MHC I for CD8+; proteins are in cyto –> proteasome digest proteins into peptide in cyto –> peptide diffuse to ER nd bind to TAP –> TAP loads peptide on HLA-A/B/C –> MHC-peptide complex transported to cell membrane vs class II, processing extracellular proteins on MHC II for CD4+; ag phagocytosed –> invariant chain transported to MHCII Compartment (MIIC) w/ CLiP in binding groove –> MIIC and endosome fuse –> peptide loaded onto HLA-DP/DQ/DR –> MHC-peptide complex transported to cell membrane
cross presentation
exogenous ag end up on MHC I: DC phagocytoses ag –> processed peptide or protein escape phagolysosome –> can bind to TAP –> loaded on MHC I –> presented to CD8+; CRITICAL in responding to cytosolic infxn (viruses and tumors)
CD1
MHCs can only present proteins –> CD1 = MHC-like molec that presents lipid ags –> presents to NKT cells
pres of carb ags
endocytosed glycoproteins go thru MHC II: peptide part = inserted in MHC II, carb part = presented to CD4+
immunodominant epitope
peptide ag that has the highest affinity to MHCs
MHC and B cells vs T cells
B cell phagocytoses and present ag to MHC II => exogenous pathway –> activate CD4+ T cells –> CD4+ T cells bind to peptide-MHC complex on B cells –> release cytokines to activate B cell fxns –> clonal expansion and differentiation vs anchor residue of peptide binds to pocket of MHC peptide groove –> side chain of aa out of groove and binds to TCR –> loops of TCR bind to invariant ridge of MHC peptide binding groove –> conformational change (lock and key, ag restriction)
superantigen
bind external surface of TCR beta chain on T cell and MHC II on APC (not peptide groove) –> activate CD4+ cells –> massive cytokine prod –> systemic inflam response; ex: bacterial exotoxins
characteristics of B/T ag receptors (4)
multimeric (BCR have light/heavy chains, TCR have alpha/beta or gamma/delta chains), have variable regions that bind ag w/ high specificity, have constant regions for signaling, have no intrinsic signaling abilities –> need additional receptors
each locus has a complete set of what genes?
variable genes, joining genes, constant genes (VJC)
somatic recombination
irreversible. BCR have heavy chains/TCR have beta chains w/ VJCD genes; BCR have light chains/TCR have alpha chains w/ VJC genes; VDJ recombinase/RAG1&2 recognize recombination signal sequence (RSS) –> randomly cleaves and bind DNA segments
allelic exclusion
when somatic recombo starts on 1 chrm, it inhibits recombo on other chrm –> ensures 1 BCR/TCR is expressed on each B/T cell
variable region vs constant region
for specificity –> binds to single specific ag; it’s specific via combo of 3 CDRs at ag binding site vs for functionality –> conserved regions bind to accessory molec
pos selection vs neg selection
Allow maturation of cells that respond to ag and self MHC correctly vs not allowing maturation of cells that don’t respond to ag and self correctly –> apoptosis
seq of events of T cell maturation (7)
- Expression of CD25
- T cell progenitors express CD3 but not CD4 or 8 => double neg
- TCR VDJ genes rearrange
- Expression of CD3,4, AND 8 => double pos
- if they react to self MHC-ag –> pos selection OR if they don’t react to self MHC-ag –> neg selection –> apop
- Expression of either CD4 OR CD8 chosen at corticomedullary jxn => single pos
- mature naive T cells go to circ
alternative/nonconventional T cells: gamma/delta T cells vs NK T cells
both still mature in thymus, have TCR, and respond more rapidly than conventional alpha/beta T cells. express CD3 and CD8, conc in skin and mucosa, recognize phosphor-ag and stress proteins (dmged cells, heat shock protein) vs express CD3, CD4, and killing receptors of NK cells, recognize glycolipid ag
seq of events of B cell maturation (4)
- BCR VDJ rearrangement until surface igM receptor expressed
- if fxnal heavy chain expressed –> go make light chain; if not –> apop
- if fxnal light chain expressed –> leave bone marrow; if not –> try again –> if still not –> apop
- transitional B cell expresses surface igD –> mature naive B cell –> goes to secondary lymph organ
steps of T cell immune response (8)
- ag recognition
- T cell activation
- T cell proliferation
- T cell differentiation - become right effector for ag
- T cell migration
- T cell effector fxn - kill/control pathogen
- T cell contraction - dec response
- T cell memory
how to fully activate T cell? (3 signals)
Binding of TCR (by MHC-peptide complex)
Binding of costimulatory molecules (CD80/CD86 on APC to CD28 on T cell) (CD40 on APC to CD40L on T cell)
Binding of cytokine receptor