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Immunology
Questions
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What is each TLR specific for?
What are the 4 ways viruses may invade the T cell response?
What is one of the ways host cells are protected from complement? Which pathway does
this protect them from??
Give an example of a microbial surface protein that can subvert complement
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Name 4 Cytotoxic T cell effector molecules
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g
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pneumoniae
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pneumoniae capsule subvert the immune system?
Do we have an effective vaccine against s
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(ignore signalling)
When can cells become γδ T cells?
What signals cause progression to each stage? Where does each signal come from and what
does it do?
What are CD25 and CD44?
What happens when T cells are double positive?
What mediates positive selection?
What is negative selection and where does it occur?
In a few words, what has negative and positive selection ensured?
Multiple sclerosis is what type of hypersensitivity?
What is auto-reactive in multiple sclerosis? What does this cause?
Describe the structure of MHC class I molecules
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What is rheumatoid factor?

Answers
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All converge on a few molecules related
to transcription factors
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TLR 1,2 and 6 = lipoprotein (gram +ve), TLR3 = ds RNA, TLR4 – LPS (gram –ve), TLR 5 =
flagellin, TLR 7 = ss RNA, TLR 9 = cpG DNA
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(MIMI) mimicry (large DNA viruses), interference (Herpesvirus saimiri), mutation (HCV),
invisible proteins (EBNA – Epstein bar virus nuclear antigen)
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Factor H – alternative pathway
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PspC/A - s
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(UP To Class ET) Ubiquitin – regulatory protein signals for degradation via, Proteasome –
contain proteases which cut into fragments 15/22 AA long, TAP 1 and 2 – transport
fragments into the ER lumen, Calnexin – chaperone protein to bring B2M subunit to MHC
class I, ERAP – ER aminopeptidases which cleave to 8/9AA long, Tapasin – transmembrane
glycoprotein which helps optimal peptide loading onto MHC
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Mycobacterium Tuberculosis initially invades alveolar macrophages
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Chr 6… HLA-DP, -DQ, -DR
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Contain a semi-specific groove which recognises classes of peptides to present to immune
cells
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APCs… exogenous pathway… 50 AAs due to open groove… CD4 T cells (helper)
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Antigenic drift is a small change, often a single gene mutation which results in a subtly
different virus, e
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1 point mutation in 1 of the 8 influenza gene segments
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Recombination events produce a whole new virus, e
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the replacement of a whole flu segment
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IFNg – inhibits viral replication, counteracts immunosuppressive IL-10 and
activated macrophages
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TNFa - induces inflammation and apoptosis
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Tolerance is induced via the absence of co-stimulatory signals
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Tolerance is also induced by the presence of coinhibitory signals
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g
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The cons of tolerance induction are via induction from both cancer and
pathogens
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The liver dampens
the immune system response to these antigens by inducing tolerance, inhibiting CD8 T cells
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T cells enter the paracortex of the LN via high endothelial venules (HEVs)
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Leukocyte homing occurs through the T cell
receptor L-selectin, which binds GlyCAM-1 and CD34 on the HEVs, causing a rolling
interaction
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LFA-1 binds to ICAM-1 causing adhesion and migration of the T cell
across the HEV via diapedesis
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The T cell scans 1000s of mature DCs in the paracortex of the LN, looking for its matching Ag
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However, if a
suitable match is found, the T cells is retained in the LN where it is activated, proliferates
and after roughly 6 days can leave the LN and migrate to target tissues
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In order to leave the LN, the leukocyte homing receptor on the T cells, L-selectin, is down
regulated allowing exit from the LN
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Up-regulation of VLA-4 on T cells binds to up-regulated VCAM on inflamed tissues
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C3 convertase
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C3b opsonises pathogens via the exposure of a thioester moiety which covalently attaches
to bacteria
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(IECHE) Invariant chain – in the ER when it helps the assembly of the a and B chain of the
MHC class II molecule
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Has a targeting signal that guides the MHC to
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HLA-DM – is a protein
promoting the dissociation of the CLIP, freeing the groove
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HLA-DO downregulates
HLA-DM)
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Then
loaded
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When exogenous peptides leak out of endosomes and into the cytoplasm, where they can
be presented on MHC class I molecules
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Autophagy or ‘self-eating’ occurs especially during times of stress like starvation
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This can merge
with the endosomal loading compartment, allowing endogenous peptides to be presented
on MHC class II molecules
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C2 helps form the C3 convertase
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pneumoniae
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There are
IgG/M antibodies against certain cell wall proteins of s
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g
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These antibodies again help neutrophil mediated killing
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The capsule prevents IgG/M and complement recognition, and also blocks the physical
accessibility of these components to the cell wall
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We have an effective vaccine against 13 of them
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The classical pathway - Ab binding to Ag
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The alternative pathway – recognition of bacterial wall components (not sugars)
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C3a, C5a – pro inflammatory via the degranulation of mast cells
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C3b - clearance of immune complexes
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C3d – B cell activation
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Lineage commitment, Education (+ve selection), Self-tolerant (-ve selection)
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Germline arrangement
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DN1 – both a and b chain loci are in germline configuration
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The b chain genes begin to
rearrange DB-JB
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CD44 reduced
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These T cells can progress onto
the next stage (B selection)
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If not a successful rearrangement then
that T cell dies
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This
complex demonstrates to the thymus that this early T cell can make a competent receptor,
and any further b gene rearrangement is stopped (B allelic exclusion, so only one chain is
formed)
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massive expansion
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IL-7 drives b chain gene rearrangement, and is
produced from the thymic stroma (thymic cortical epithelial cells)
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Notch: signalling is required throughout DN stage from the
thymus (as lack forms B cells instead)
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And a chain is expressed on the surface forming TCR
with an a and b chain
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Move deeper into thymic cortex so selection of useful and beneficial TCRs
can occur
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Recognition of self:MHC, self:Peptide with an appropriate affinity, causes the T cell to
survive, as it needs to recognise specific MHC for each individual, which is positive selection
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TCRs which bound with too low affinity die by neglect
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Cortical epithelial cells have long branching processes that express both MHC class I and II
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Occurs in the thymic medulla, and it is the selection of a functional repertoire of T cells
which will be able to bind self:MHC and forgein:peptides
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If TCR
binds with too high affinity to self:MHC then cells die by apoptosis
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Diverse repertoire of functional, self-restricted, self-tolerant T cells
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Type 4 autoimmune disease
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Autoreactive T cells that target myelin basic protein and myelin oligodendrocytes
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This causes demyelination of
neurones leading to muscle weakness and other neurological symptoms
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MHC class I is made up if an alpha chain with three subunits and a B-microglobulin (B2M)
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All nucleated cells to CD8 T cells
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Complement receptors… Fc receptors
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Failure to process and present certain self-peptides… T cell anergy through a lack of
costimulation…
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T cells specific for self, activate B cells specific for various components of a complex antigen,
which can then present many diff antigens and produce a different secreted antibody for
another antigen of self
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When autoreactive B cells bind self-antigen and a cross-reactive antigen
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Antigen Segregation – physical
barrier of auto antigens to lymphoid system, peripheral organs
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Regulatory cells
– suppression by cytokines and intracellular signals, SLO + inflam sites
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Clonal deletion –
apoptosis post-activation, SLO+IS
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Weakly self-reactive lymphocytes can often also make an immune response to foreign Ags,
therefore deleting them would impaired the immune system
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AIRE is the autoimmune regulator gene which promotes the expression of tissue specific
antigens on medullary thymic epithelial cells which are presented to single positive
thymocytes
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Viral infn causes damage to the target cell
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This stimulates the adaptive immune response
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Induced in the
periphery when recognise self in the presence of TGF-b
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Early activation phase involving a few autoantigens
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This is enhanced by epitope spreading
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Damage of tissue sin inflammation leads to sequestration which is the release of previously
hidden autoantigens which can activate other autoreactive immune cells
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Antibody against the Fc part of IgG

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