dont know (8) Flashcards
L3- Complement in disease?
aquired or inherited. complement malfunction=
C1, C2, C3, C4: removal of Ag/Ab complexes:
Lupus-like illness
Chronic renal disease
Repeated infections
* C5, C6, C7, C8:
Repeated Neisseria infection (gonorrhoea, meningitis)
* C9: normal (as it is only in the final step of mac)AUTOIMMUNE DISEASE (adaptive immunity)
- Systemic Lupus Erythematosus (SLE): C1, C4, C2
- Rheumatoid Arthritis: C1q, C2
- Systemic Sclerosis: C3
- Inflammatory bowel disease: CD55/DAF
Diagnosis:
1. Test overall complement activity: Ch50 or Ch100 test
2. Quantification of specific complement protein levels
Treatment:
1. Overreactive: immunosuppressants
2. Deficiency: supplementation, antibiotics (prophylactic)
L3- Complosomes?
not circulating complement. is immune cell derived (can be produced by immune cells like T cells) so function inside cells.
Complement links innate and
adaptive immunity
* Is activated intracellularly
(autocrine) in T cells
* Is not only pro-inflammatory –
resolution in T cells
* Interacts with T cell metabolism
L6- antigen processing in mhc class 1?
partly folded mhc class one chains bind to calnexin until B2m /?binds.
mhc class 1 alpha: ( β2-microglobulin) B2m complex is released from calnexin, binds a complex of chaperone proteins (calreticulin and ERP5) binds to TAP via tapasin.
cytosilic proteins and defective ribosomal proteins (DRPs) are degraded to peptides by the proteosome. TAP delivers peptides to the ER.
A peptide binds the mhc class 1 and completes its folding. the mhc class 1 molecule is released from tap complex and exported to cell membrane.
TAP (Transporter Associated with Antigen Processing)
mhc class 1 alpha= mhc class 1’s alpha chain
L6- peptide loading complex?
-tap, calreticulin (general chaperone), Erp57: protein disulphide isomerase. assists disulphide bridge formation in peptide loading.
tapasin: encoded in mhc class 2 genome region. induced by ifn-y. reduced mhc class 1 expression in mutant cells. tapasin stabilises mhc class 1 binding to tap. forms a disulphide-linked dimer with Erp57. facilitates peptide binding _ edits? peptide binding for max affinity.
L6- mhc class 2 invariant chain?
MHC Class II Protein Association with Invariant Chain
Invariant Chain: A specialized protein that assists MHC Class II molecule assembly Also called CD74
Key functions:
Prevents premature peptide binding in ER
Guides MHC Class II to correct cellular compartments
Structural Details
Type 2 Transmembrane Protein
Forms homotrimers (three identical protein units)
Not polymorphic (doesn’t vary genetically)
Encoded outside the MHC genome region
Molecular Mechanism
In Endoplasmic Reticulum (ER)
Binds to MHC Class II α and β dimers
Blocks peptide binding groove
Prevents premature peptide loading
Trafficking Mechanism
Targets MHC Class II molecules to lysosomal compartments
Lysosome contains degraded proteins
Allows proper peptide loading later in the process
Key Concepts
Prevents inappropriate peptide binding in ER
Guides MHC Class II to correct cellular processing sites
Ensures proper antigen presentation mechanism
L6- mIIc + HLA-DM?
MIIC (MHC Class II Compartment) is specifically the compartment where MHC Class II molecules load peptides. It contains the class 2 chaperone HLA-DM. class 2 reside here 2-4h before going to cell surface. similar to endosomes and lysosomes (low ph +proteases present)
cathepsins S+L are proteolytic enzymes.
Invariant chain processing occurs here, where the chain is cleaved in mIIc, so the only peptide fragment is left in the groove. this fragment is CLIP (class 2 associated invariant chain peptide).
this invariant chain processing:
Prevents premature peptide binding
Guides MHC Class II trafficking
Prepares groove for actual antigen peptides
Occurs in MIIC compartment
antigen and mhc class 2 meet in mIIc. antigen taken up from extracellular space into intracellular vesicles. in early endosome (neutral ph) endosomal proteins inactive. acidification of vesicles activates proteases to degrade antigen into peptide formation. vesicles containing peptides fuse with vesicles containing mhc class 2.
HLA-DM: Encoded in class 2 region of the genome. expression induced by ifn-y. detection of hla-dm: class 2 unable to bind peptides from internalised proteins. have clip proteins bound. localised to MIIC compartment where it releases CLIP from class 2, stabilises empty class 2 proteins and catalyses binding of peptides to class 2.
L6- cross presentation?
Cross-Presentation Mechanism
Definition: Process where exogenous antigens are presented on MHC Class I molecules. Unique to dendritic cells. Bridges innate and adaptive immunity
Specific Scenario
Example: B virus infection
Normally, viral antigens would be presented on MHC Class II
Dendritic cells can present these viral antigens on MHC Class I
This allows CD8+ T cells to recognize and respond to the infection
Significance
Enables immune response to:
Extracellular pathogens
Viruses
Tumors
Allows CD8+ T cells to recognize antigens not from intracellular sources
Key Characteristics
Specialized function of dendritic cells
Breaks typical antigen presentation rules
Critical for comprehensive immune surveillance
L5- characteristics/motifs of class 1 and 2?
class 1: 8-10 aa long
hydrophobic or basic residues at c terminus
every mhc class 1 allele has its own peptide binding motif with specific anchor residues that interact with polymorphic mhc residues
interaction with mhc is stabilised by: nh+ and cooh- terminus
13-24 aa
protrude from the groove.
NH+ COO- do not contribute
interaction with mhc is stabilised by: peptide backbone with conversved mhc residues, anchor residues with polymorphic mhc residues.
mhc binds to 10^5-10^6 different peptides. mhc polymorphism localised to peptide binding cleft. s unique pattern of pockets in pbc + peptides presented by each allele are different. so particular combination of mhc alleles inherited determines peptides displayed to t cells (responsiveness)
what are anchor residues?
anchor residues are specific amino acids within the peptide that fit into corresponding pockets within the peptide binding groove, allowing a peptide to bind. they are similar for peptides that bind to the same mhc molecule. ?
larger amino acids can cause the peptide to bulge- check if for mhc class 1
L1- cells of adaptive?
cellular: y8 T cells, NK, ILC, Th, B cells soluble: cytokines, chemokines, AB
(INNATE- LIKE T CELLS) MAIT: mucosal associated invariant T cells. Cytokine secretion (pro inflammatory), mucosal patrolling (gut, airways) (ILT) NKT: recognise lipids in microbes, cytokine production. (ILT) y8 T cells: tissue specific immunity. cytoxicity, cytokine production. (ab T cells) CD4/Th: activate macrophages (ab) Tc/CD8+: recognise infected+ tumour cells. cytotoxicity, Cytokines *alpha beta T cells recognise specific ag to TCR Naive B cells + plasma cells *recognise ag via BCR
