33. Antigen processing and presentation Flashcards
ANTIGEN PRESENTATION is used in which immune response
ADAPTIVE
Antigen presentation is the key to ACTIVATING the
adaptive immune response
4 key features of ADAPTIVE IMMUNE RESPONSE
- SPECIFICITY
- DIVERSITY (can recognise huge RANGE of antigens)
- MEMORY
- can DISCRIMINATE between SELF/NON-SELF
when we are born are cells are…
Naïve (not yet been exposed to antigen)
are present in very low numbers
and need to be primed/expanded (so that our immune system can respond to the specific challenge)
ANTIGENS need to be PRESENTED to which cells
T-CELLS
what happens when an ANTIGEN is PRESENTED to CD4+ T CELL
recognises and
- sends HELP SIGNAL to B CELL (responds by producing antibodies)
- sends HELP SIGNAL to CD8+ T CELL (recognise and kill virus infected cells)
what do both CD4+ and CD8+ T CELLS RECOGNISE on the surface of cells
MAJOR HISTOCOMPATIBILITY COMPLEXES (MHC)
MHC CLASS I interaction is with which T cell
CD8+
MHC CLASS iI interaction is with which T cell
CD4+
CD8+ T Cells recognise which type of cells
VIRALLY INFECTED
what is the role of CD4+ T cells
provide HELP to the immune system
eg. activate B cells
HELP = production of CYTOKINES/CHEMOKINES (cellular messengers)
what is the name of the GENE that encodes for the different protein chains that make up the MHC COMPLEXES (class I class II)
HLA - HUMAN LEUKOCYTE ANTIGEN
what is the difference between MHC CLASS I and CLASS I STRUCTURE in terms of HEAVY CHAINS
CLASS I :
SINGLE heavy chain with 3 DOMAINS (alpja 1,2,3)
CLASS II:
2 heavy chains- ALPHA CHAIN & BETA CHAIN
2 domains each - BETA 1, BETA 2, ALPHA 1, ALPHA 2
what is CLASS I MHC associated with that class II isnt
BETA-2 MICROGLOBULIN
what bonds are found in MHC MOLECULES (class I & II)
DISULPHIDE BONDS
where are MHC CLASS I molecules EXPRESSED (which cells)
on ALL NUCLEATED CELLS
(CD8+ cells are looking for cells expressing MHC class I to check if they are normal/abnormal)
what are the 3 different MHC CLASS I molecules
A, B, C
coded for by 3 different genes: HLAA,HLAB,HLAC
MHC CLASS II (more restricted) is EXPRESSED on which types of CELLS
- B CELLS
- ANTIGEN PRESENTING CELLS (eg dendritic cells)
- MACROGPHAGES
MHC CLASS II molecules are coded for by 3 different GENES:
DP (HLADP)
DQ (HLADQ)
DR (HLADR)
MHC GENE LOCUS is on which human CHROMOSOME
6
(p/short arm)
HLA ALLELES are…
POLYGENIIC
-multiple genes for HLA alleles
HLA class I alleles: A,B,C
HLA class II alleles: DP,DQ,DR
& highly POLYMORPHIC
HLA genes are highly…
POLYMORPHIC
- each HLA gene locus has many different potential alleles
e.g. 2041 possible A alleles
(more possibilities for class I)
Result of Polygenic and Polymorphic nature of MHC (HLA) GENES
HLA TYPE
: each allele can present a
different peptide
: allows for a vast array of
different peptides to be
presented to T cells
(can inherit a different HLA allele from each parent so can have 2 of each allele eg A1, A2
resulting in 6 different HLA alleles on cell surface, 2 As, 2 Bs, 2 Cs)
why is POLYMORPHIC NATURE of MHC important for PROTECTION
PATHOGENS try to EVADE (AVOID) the immune defence system - eg MUTATE
if only had 1 MHC type, pathogen could evade/mutate, no protection, resulting in death
why are VARIANTS (alleles) of each MHC GENE important
encode proteins that increase the
RESISTANCE of the population from rapidly MUTATING or NEWLY encountered PATHOGENS
without increasing the number of types of MHC molecule
what are the 2 main ANTIGEN PROCESSING PATHWAYS
ENDOGENOUS pathway
EXOGENOUS pathway
what is the ENDOGENOUS pathway in ANTIGEN PROCESSING
- processes proteins expressed INSIDE CELL
to CD8+ T-LYPHOCYTES
presenting MHC CLASS I
what is the EXOGENOUS pathway in ANTIGEN PROCESSING
- processes proteins CAPTURED from OUTSIDE the cell
to CD4+ T-LYMPHOCYTES
presenting MHC CLASS II
ANTIGEN PROCESSING PATHWAY for MHC CLASS I - ENDOGENOUS
- virally infected cell
- Endogenous Protein eg. virus protein (INSIDE cell) contains antigenic peptide (9 amino acids) in CYTOPLASM
- Endogenous Protein fed through PROTEASOME which DEGRADES protein to form shorter peptipe - EPITOPE
- EPITOPE pumped into ENDOPLASMIC RETICULUM through TAP1 & TAP2 transporters
- inside ER proteins: CALRETICULIN, ERp57, CALNEXIN ensure MHC CLASS I FOLDS correctly and brings it to the top of the PEPTIDE LOADING COMPLEX
TAPASIN bridges MHC CLASS I to TAP
- PEPTIDE LOADING onto MHC CLASS I
- once peptide loads onto MHCL class I, it moves to cell surface and PRESENTS to T-cell (CD8+)
ANTIGEN PROCESSING PATHWAY for MHC CLASS I - ENDOGENOUS:
what is used to DEGRADE the virus protein in the Cytoplasm to form EPITOPE
PROTEASOME
ANTIGEN PROCESSING PATHWAY for MHC CLASS I - ENDOGENOUS:
how does the EPITOPE move into the ER
through transporters made up of 2 TAPS: TAP1 & TAP2
ANTIGEN PROCESSING PATHWAY for MHC CLASS I - ENDOGENOUS:
name the proteins used in the ER (4)
CALRETICULIN
ERp57
CALNEXIN
- ensure correct folding of MHC class I and bring to peptide-loading complex
TAPESIN
- bridge MHC class I with TAP
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS
- antigen is CAPTURED outside the cell
- ends up in a endosome/lysosome by endocytosis
- DEGRADATION of antigen in lysosome due to ACIDIC environment and lysosomal PROTEASES: CATHEPSINS, ASPARAGINYL ENDOPEPTIDASE (AEP)
- in ENDOPLASMIC RETICULUM, we have MHC CLASS II (and class I) with an INVARIANT CHAIN that
PREVENTS PEPTIDE BINDING (occupies binding region) - also DIRECTS MHC CLASS II to a CIIV VESICLE
- CIIV VESICLE FUSES with ENDOSOME/LYSOSOME to form MIIV VESICLE
- in MIIV VESICLE the MHC CLASS II INVARIENT CHAIN has mostly degraded, and left with smaller peptide, CLIP
- in MIIV VESICLE, HLA DM acts as a CATALYST FOR PEPTIDE EXCHANGE, REMOVES CLIP so PEPTIDE can BIND
- once bind, moves to cell surface to PRESENT to T-cells (CD4+)
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
what are the names of the PROTEASES in lysosome that DEGRADE the ANTIGEN
CATHEPSINS (Cat) - B, D, E, H, L, S
(many more)
ASPARAGINYL ENDOPEPTIDASE (AEP)
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
what causes DEGRADATION of ANTIGEN in LYSOSOME
proteases: Cathepsins, Asparaginyl endopeptidase (AEP)
ACIDIC environment (low pH)
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
where is the MHC CLASS II found
ER
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
difference between MHC CLASS I and MHC CLASS II
- directed in different directions/pathways
CLASS II directed to CIIV VESICLE - PEPTIDE CANNOT BIND to CLASS II due to INVARIANT CHAIN
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
what happens after MHC CLASS II enters CIIV VESICLE
FUSES with ENDOSOME/LYSOSOME to form MIIV VESICLE
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
in MIIV VESICLE, the INVARIANT CHAIN has DEGRADED. a small peptide is left called…
CLIP
ANTIGEN PROCESSING PATHWAY for MHC CLASS II - EXOGENOUS:
how is CLIP removed from MHC CLASS II so PEPTIDE can BIND in the MIIV VESICLE
using HLA DM (catalyst for peptide exchange)
what is the difference between the PEPTIDE BINDING POCKETS in MHC CLASS I & CLASS II
MHC CLASS II is more OPEN at the ENDS And slightly BIGGER
PEPTIDES BOUND by MHC CLASS I are generally how many amino acids in length
9 AMINO-ACIDS
PEPTIDES BOUND by MHC CLASS II are generally how many amino acids in length
13-25 AMINO-ACIDS
(so more variable)
MOST of the POLYMORPHISM in the HLA ALLELE is found in which area
around the PEPTIDE-BINDING POCKET
- so lots of different peptides can
be bound
what is AUTOIMMUNITY
immune response to self-antigen
auto-reactive antibodies
or T cells (CD4+ or CD8+)
some MHC GENES are linked with DISEASE :
AUTOIMMUNE DISEASES
eg. Ankylosing spondylitis
Graves disease
Systemic lupus erythematosus
Multiple sclerosis
Goodpasture’s syndrome
Rheumatoid arthritis
people with B27 HLA ALLELE have very high risk of developing which autoimmune disease
Ankylosing Spondylitis
MOST AUTOIMMUNE diseases are associated with which HLA CLASS ALLELES
HLA CLASS II
(but some with HLA Class I)
certain HLA ALLELES lead to higher RISK of developing…
AUTOIMMUNE DISEASE
