5663044
T cells +MHC
- Antigen
recognition by T
cells
- The adaptive immune system recognises two kinds of antigens : B cell
antigens and T cell antigens (see S3 for difference between the two)
- Two types of TCRs (S5-8 )
- The adaptive immune system recognises two kinds of antigens : B cell
antigens and T cell antigens (see S3 for difference between the two)
- Structure, function and
expression of TCR
- The T cell receptor: TCRϒδ T cells= unusual – DO NOT
recognise MHC- peptide complexes + don’t usually express
CD4 or CD8. They recognise lipid + carbohydrate Ag. The
dominant human type recognise a phospholipid expressed by
Mycobacterium tuberculosis. The αβ T cell receptor (TCR)
recognises antigen ONLY if it is shown to it (presented) by an
MHC molecule on the surface of a cell (S7). TCR binding 2
peptide antigen presented on MHC results in activation of cell
signalling pathways + gene expression resulting in: T cell
activation, T cell proliferation, cytokine production
- The T cell receptor: TCRϒδ T cells= unusual – DO NOT
recognise MHC- peptide complexes + don’t usually express
CD4 or CD8. They recognise lipid + carbohydrate Ag. The
dominant human type recognise a phospholipid expressed by
Mycobacterium tuberculosis. The αβ T cell receptor (TCR)
recognises antigen ONLY if it is shown to it (presented) by an
MHC molecule on the surface of a cell (S7). TCR binding 2
peptide antigen presented on MHC results in activation of cell
signalling pathways + gene expression resulting in: T cell
activation, T cell proliferation, cytokine production
- Structure, function +
expression of MHC Class
1 and 2
- Class 1 MHC: found on all body cells (except RBCs), presents INTRACELLULAR Ag, Interacts with CD8
on T-cells MHC class 1 expressed by ALL cells (except erythrocytes + neurones), MHC class 1 presents
host’s own phenotype of protein molecules- which are continually synthesise + degraded in host cell.
Each MHC 1 molecule displays a molecular fraction of host cells protein- like a meter indicating
balance of proteins within the cell. If cell is infected with virus..Viral peptides will b presented on cell
surface, MHC class 1 presents Ag to CD8+ T cells, Three MHC class 1 gene loci in human HLA –A, -B, -C,
Also MHC class Ib HLA-E Class 2 MHC: Found only on antigen presenting cells (APCs), presents
EXTRACELLULAR/ MEMBRANE Ag, Interacts with CD4 on T-cells, MHC class 2 expressed only by APCs
(e.g. dendritic cells, macrophages+ B cells), presents Ag taken up from outside the cell, presents Ag
to CD4+ T cells, 3 MHC class 2 gene loci in human HLA, -DP, -DQ, -DR
- Class 1 MHC: found on all body cells (except RBCs), presents INTRACELLULAR Ag, Interacts with CD8
on T-cells MHC class 1 expressed by ALL cells (except erythrocytes + neurones), MHC class 1 presents
host’s own phenotype of protein molecules- which are continually synthesise + degraded in host cell.
Each MHC 1 molecule displays a molecular fraction of host cells protein- like a meter indicating
balance of proteins within the cell. If cell is infected with virus..Viral peptides will b presented on cell
surface, MHC class 1 presents Ag to CD8+ T cells, Three MHC class 1 gene loci in human HLA –A, -B, -C,
Also MHC class Ib HLA-E Class 2 MHC: Found only on antigen presenting cells (APCs), presents
EXTRACELLULAR/ MEMBRANE Ag, Interacts with CD4 on T-cells, MHC class 2 expressed only by APCs
(e.g. dendritic cells, macrophages+ B cells), presents Ag taken up from outside the cell, presents Ag
to CD4+ T cells, 3 MHC class 2 gene loci in human HLA, -DP, -DQ, -DR
- MHC-peptide- TCR
binding
- MHC or HLA in humans MHC= receptors which
interact with Ag + CD4/CD8 on T cells, 3
subgroups: class1, class2 & class 3, MHC= most
polymorphic locus in mammals- many, many
different alleles, Each MHC molecules can bind
many dif peptides fragments via ANCHOR
RESIDUES. Thus each MHC molecule has peptide
binding motif. Contrast this to the Ab/BCR/TCR
specificity to Ag.
- MHC or HLA in humans MHC= receptors which interact with Ag + CD4/CD8 on T cells, 3 subgroups:
class1, class2 & class 3, MHC= most polymorphic locus in mammals- many, many different alleles,
Each MHC molecules can bind many dif peptides fragments via ANCHOR RESIDUES. Thus each MHC
molecule has peptide binding motif. Contrast this to the Ab/BCR/TCR specificity to Ag. CD4 is
expressed on T helper cells + CD8 is expressed on T cytotoxic cells. It’s the relationship between MHC
+ CD4 or 8 which defines the type of immunological reaction which will take place (S20)
- Antigen processing is carried out by: Any
nucleated cell via Endogenous pathway (of
intracellular antigen) for presentation on
MHC Class 1 Professional antigen
presenting cells (APCs) via the Exogenous
pathway (of extracellular antigen) for
presentation on MHC Class 2) e..g
macrophages, dendritic cells
- Antigen processing is carried out by: Any
nucleated cell via Endogenous pathway (of
intracellular antigen) for presentation on
MHC Class 1 Professional antigen
presenting cells (APCs) via the Exogenous
pathway (of extracellular antigen) for
presentation on MHC Class 2) e..g
macrophages, dendritic cells
- MHC or HLA in humans MHC= receptors which
interact with Ag + CD4/CD8 on T cells, 3
subgroups: class1, class2 & class 3, MHC= most
polymorphic locus in mammals- many, many
different alleles, Each MHC molecules can bind
many dif peptides fragments via ANCHOR
RESIDUES. Thus each MHC molecule has peptide
binding motif. Contrast this to the Ab/BCR/TCR
specificity to Ag.
- Superantigens
- Some pathogens can produce
superantigens e.g. lectin mitogens,
polysaccharides (e.g. LPS), which can
activate T cells non-specifically- w/o a
specific antigen binding 2 TCR.
Results in POLYCLONAL Tcell
activation + massive cytokine release
e.g. IFNϒ, TNFα producing
uncontrolled inflammation +
widespread damage/ death from
shock + multiple organ failure. These
SAg-activated T cells ill eventually
undergo deletion/ anergy- resulting in
a severely compromised immune
system
- Some pathogens can produce
superantigens e.g. lectin mitogens,
polysaccharides (e.g. LPS), which can
activate T cells non-specifically- w/o a
specific antigen binding 2 TCR.
Results in POLYCLONAL Tcell
activation + massive cytokine release
e.g. IFNϒ, TNFα producing
uncontrolled inflammation +
widespread damage/ death from
shock + multiple organ failure. These
SAg-activated T cells ill eventually
undergo deletion/ anergy- resulting in
a severely compromised immune
system
- MHC polymorphism
- S26-31
- S26-31
- Focus on cells of innate
immune system-
neutrophils
- FIRST LINE OF DEFENCE, neutrophils=
type of granulocyte (along wiv
basophils, mast cells + eosinophils).
they can cause direct harm 2
pathogen by: phagocytosis + release
of contents of their granules (also
pro-inflammatory + tissue
remodelling effects), spitting out
neutrophil extracellular traps (NETs)
onto extracellular pathogens (S33-
end)
- FIRST LINE OF DEFENCE, neutrophils=
type of granulocyte (along wiv
basophils, mast cells + eosinophils).
they can cause direct harm 2
pathogen by: phagocytosis + release
of contents of their granules (also
pro-inflammatory + tissue
remodelling effects), spitting out
neutrophil extracellular traps (NETs)
onto extracellular pathogens (S33-
end)
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