Adaptive Immunity Flashcards
Expression of MHC molecules
Major histocompatibility complex molecules
Class I on all cell types
Class II on specialised antigen presenting cells
MCH structure
Class I
3 IG domains that build up heavy chain, associate with small soluble molecule (beta2microglobulin)
=> stimulate cytotoxic T-cells (CD8+)
Class II
2 chains, alpha and beta, that form peptide binding cleft
=> stimulate helper T-cells (CD4+)
Discovery of MHC molecules
Rolf Zinkernagel, Peter Doherty
TCR
T cell receptor => alpha and beta chain => recognizes antigen presented on MHC molecules
MHC class I antigen processing
Ubiquitination => proteasome
=> immune system uses octameric-monomeric peptides, first degradation product => import into ER by TAP (transporter associated with antigen presentation), MHC has already been inserted co-translationally into ER => if peptide is good fit for MCH => peptide binding groove closes => vesicle moves to surface => display, where T-cells scan
MCH class II antigen processing
Lysosomes: vesicular compartment for hydrolase activity
MHC classII is loaded in lysosomal compartments, first co-translationally inserted into ER membrane => chaperone (invariant chain Ii) binds to prevent loading with peptides
=> cytosolic chain leads to trafficking of complex into lysosomal compartment => hydrolases in lysosome degrade chaperone but final peptide is left in binding groove => foreign material is taken up into cell => endosomal compartment fuses with lysosome => chopped up by hydrolases => chopped peptide replaces remaining peptide of invariant chain => display on cell surface
important diff btw MHC classes
Where presented material comes from
I: inside
II: outside
Cross presentation pathway
Dendritic cells can utilize MHC I for presentation of exogenous/extracellular antigens
And MHC II for intracellular?
MHC I variation
3 Loci, each occupied by 2 alleles:
Each one of us can express 6 MHC class I molecules
each locus thousand+ sequences (allele composed of diff sequences)
HLA
Human leukocyte antigen = MHC in humans
different aminoacids in binding groove bind different peptides => for presenting
Semiallograft during pregnancy
=> father and mother: “donor” of MCH molecules => placenta-mediated tolerance against foreign (father) MHC molecules
T cell system clonal selection
T cells originate from bone marrow => educated in thymus => removal of self-antigen recognizing T-cells => swim around in blood => if contact with foreign antigen in secondary lymphoid tissue => proliferation and differentiation to form clones = effector cells => effector cells eliminate antigens
Why is acquired immune response slow?
Dendritic cell has to find T-cell for foreign antigen + time for proliferation = ca. 1 week
High diversity in TCRs (T cell receptors)
Somatic T-cell receptor recombination
Puzzling together of segments (variable, joining, constant and (diversity segments in beta chains))
Beta chain of T-cell consists of
constant, joining, variable and diversity segment
Thymic selection of T-cells
From bone marrow into cortical region of thymus => rearrange T-cell receptors (double negative stage) => express both CD8 (MHC I recognition) and CD4 coreceptors (MHC II recognition)
positive selection through interaction with cortical epithelial cell => recognize MHC molecules?
=> weak interaction, specialize on CD8 or CD4 depending on interacting MHC molecule (I or II)
negative selection through interaction woth medullary epithelial cells or dendritic cells or other cell types => deleted if high affinity interaction with MHC that presents self peptides
Redult: T cells that recognize MHC molecules but don’t recognize self peptides
Afferent vs efferent immune response?
Afferent => into lymph node
Efferent => out of lymph node
Tailored efferent immune responses
Shaping of naive T-cells upon contact with dendritic cells
=> CD4: production of diff cytokines depending on pathogen
ILC 1 & NK produce IFN gamma
ILC 2 produces IL-4 &13
ILC 3 produces IL17a & 17f
+ regulatory cells that help or dampen T-cell responses
=> CD8: cytotoxic effector
Immunological synapse
suction ring of adhesion molecules
pSMAC and cSMAC
Information of dendritic cell: MHC presentation, cytokines, co-stimulation is delivered through center of synapse
ILCs
Innate lymphoid cells
Effector functions similar to T cells
=> produce diff cytokines
ILC1 (innate)/TH1 => IFN, antivirals
ILC2 (innate)/TH2 => against extracellular pathogens
ILC3 (innate)/TH17 => fungal infections
Killer cells are adaptive counterpart to NK cells
Humoral immunity
soluble
Antibody
Immunoglobulin family
=> puzzled together from ig domains
Soluble counterpart of B-cell recepror
Per end for recognizing antigen: 2 variable regions (one from light chain, one from heavy chain) + constant region
Discovery of chemical structure of antibodies
Gerald Edelman & Rodney Porter
B-cell receptor
anchored in membrane
slightly lower diversity than in TCR molecules
