Immunology 08. Autoimmune Flashcards
C4! C3b cannot be measured as they are in the cells!!
3-4 weeks!!!
This has a lot of implications.
1) This means that neonatal graves, which is caused by maternal IgG crossing over placenta, is TRANSCIENT and will resolve itself after maternal IgG in baby breaks down
2) This also means that if a baby has primary immunodeficiencies of B cell/AB production, it will manifest only 3-4 months after birth after passive immunity from maternal IgG is lost
3) Meanwhile for SCID, it manifests right after birth because SCID hits both T and B cells. Having maternal IgG does not confer sufficient passive immunity.
Maternal IgG
2 hallmarks of autoimmune disease? (IMPT!!!)
2 hallmarks of autoimmune disease? (IMPT!!!)
1) Loss of immune tolerance to self antigens
2) Tissue damage or physiological dysfunction due to autoimmunity
Basic immunopathogenesis of SLE?
Basic immunopathogenesis of SLE?
Activation of antigens (Via environment, autoantigen, infection etc)
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Loss of immune tolerance by antibody
-> Activation of immune complexes
-> Leads to decrease clearance by complement
-> deposition of complements within tissues
Define autoimmunity
Define autoimmunity
Adaptive immune responses specific for self antigens
Do we know the exact cause of autoimmune diseases?
Do we know the exact cause of autoimmune diseases?
No, we do not. However, it is likely due to:
1) Cumulative effect of many minor genetic variants
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2) Environmental factors
Explain the use of PD-1 in physiological prevention and curbing of autoreactive T cells.
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Then, how does inhibiting this “checkpoint” help us fight cancer?
[…]
How then is this detrimental to autoimmune disease progression? (IMPT!!!)
[…]
Explain the use of PD-1 in physiological prevention and curbing of autoreactive T cells.
Essentially, PD-1 is a molecule receptor that plays an important role in blocking the effects of TCR signalling and CD28 signalling. It is especially upregulated in chronically activated T cells and can help in reducing autoimmune damage.
Then, how does inhibiting this “checkpoint” help us fight cancer?
However, in the case of cancers, we would want there to be less immune suppression so that the T cells can identify the cancer antigen and mount an immune response against it.
How then is this detrimental to autoimmune disease progression? (IMPT!!!)
However, this might cause reverse peripheral tolerance of T cells to self antigens -> increase autoimmune damage to organs.
How can infection bring about autoimmunity?
How can infection bring about autoimmunity?
Activation of self-reactive lymphocytes in susceptible individuals
How does antibody play a role in Myasthenia Gravis?
How does antibody play a role in Myasthenia Gravis?
Pathological anti-Ach Receptor Abs (Anti-AchR Abs) -> Interferes with transmission across NMJ -> Abnormal muscle fatigue
Will learn more about this in neuroscience. Basically its all about amount of Ach in the NMJ. Anti-AchR Abs will persist but Ach in vesicles will be depleted and broken down by AchE. So the Tug of war will favour Anti-AchR Abs and hence repeated movement in patients with Myasthenia Gravis will present as fatiguability.
How does auto-antibodies play a role in Grave’s disease?
How does auto-antibodies play a role in Grave’s disease?
Pathological anti-TSH receptor antibodies -> excessive thyroid hormone production that is no longer regulated by negative feedback
In SLE, what happens to the levels of C3,C4 complement?
In SLE, what happens to the levels of C3,C4 complement?
They decrease due to complement consumption as part of the autoimmune response
The one you test is C4
Key adverse effect of immune checkpoint blockade (e.g block PD-1) is via which mechanism?
Key adverse effect of immune checkpoint blockade (e.g block PD-1) is via which mechanism?
Via the reverse peripheral tolerance of T cells to self antigens-> causes an increased autoimmune damage to organs
Negative effects of Immunosuppressants?
Negative effects of Immunosuppressants?
Suppression of immunity response against actual infection -> opportunistic infections
So the use of immunosuppressants in autoimmune diseases is a double edged sword. Always keep that in mind.
What are some autoimmune diseases where T cells play the dominant role in causing tissue injury?
What are some autoimmune diseases where T cells play the dominant role in causing tissue injury?
MS (multiple sclerosis), RA (Rheuamtoid arthritis), Type 1 DM
What are some factors contributing to the pathogenesis of SLE? (systemic lupus erythematosus)
What are some factors contributing to the pathogenesis of SLE? (systemic lupus erythematosus)
1) Gender: More frequent in Women by 10-20x more (general rule for autoimmune diseases)
2) Genes: 24% chance if twin has it.
MHC, e.g HLA DR2
Genes for debris-clearing proteins, e.g complement
3) Environmental triggers: Oestrogen , UV Light etc
What are the 2 mechanisms in which T cells can cause autoimmune diseases? (Hint: very similar to the way T cells normally work)
What are the 2 mechanisms in which T cells can cause autoimmune diseases? (Hint: very similar to the way T cells normally work)
1) CD4+ Cytokine mediated
2) CD8+ CTL mediated cytotoxicity
What is a prototypical example of immune complex disease we should be aware of?
What is a prototypical example of immune complex disease we should be aware of?
SLE!!
SYSTEMIC LUPUS ERYTHEMATOSUS
