Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMOD/PCM- Block 2 > Path: Autoimmunity > Flashcards

Path: Autoimmunity Flashcards

1
Q

___________ is your lack of immunologic responsiveness to your own antigens.

A

Self-tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

___________ is hating yourself for waking up 2 mins before an 8am TBL.

A

Self-loathing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

________ tolerance takes place in the central lymphoid organs (thymus for T cells and bone marrow for B cells).

A

Central

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

A protein called _________ stimulates expression of some peripheral tissue-restricted self-antigens in the thymus for use in negative selection.

A

AIRE (autoimmune regulator)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Mutation in the AIRE gene can cause a broad spectrum of disease called:

A

autoimmune polyglandular syndrome type 1

aka autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APCED)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Do you remember what Treg cells do?

A

regulate other T cells to prevent them from causing autoimmune reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

In the bone marrow, immature B cells that recognize self-antigens undergo __________ editing that defuses them. Without this, they undergo apoptosis.

A

receptor editing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

If some self-reactive lymphocytes escape the thymus or bone marrow, _______ tolerance will act as a backup defense against these auto-reactive lymphocytes.

A

Peripheral tolerance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Peripheral tolerance renders self-reactive lymphocytes functionally unresponsive, a phenomenon called ______.

A

anergy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the mechanism of peripheral tolerance.

A

APCs present self-antigen to T cells without the B7 co-stimulatory molecule. Without co-stimulation, the T cell is rendered anergic.
A second mechanism is mediated by cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which binds to B7 molecules on APCs more strongly than the CD28 on T cells. This serves an anti-stimulatory function, essentially blocking CD28 on T cells from ever binding to the APC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Briefly explain how malignant tumors use CTLA-4 and Programmed death-1 (PD-1) to their advantage in avoiding an immune response that would otherwise fight them.
Then, briefly explain how ipilimumab can be used to counter this effort, in fighting cancer.

A

some malignant tumors can use CTLA-4 and PD-1 as blockers to prevent their presentation to T cells.

Ipilimumab is an immunoglobulin that will bind/block the CTLA-4 from blocking the APCs presentation of the tumor antigens. In the same way, pembrolizumab and nivolumab are used against PD-1. This allows B7 to bind without inhibition from CTLA-4 and PD-1 to CD28 on T cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Big picture, yo:

What is the underlying cause of autoimmune diseases?

A

the failure of self-tolerance. Love yo’ self, son. Love.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Congenital deficiency of C1q, C2, or C4 can impair the clearance of apoptotic cells and nucleic acid fragments from them uncleared cells can lead to anti-nuclear antibody (ANA) formation and the prototypical multi-organ autoimmune disease:

A

systemic lupus erythematosus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Predisposition to ankylosing spondylitis from having the __________ (MHC haplotype) allele is perhaps the strongest known genetic predisposition to an autoimmune disease.

A

HLA B27

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

_________ destroys the articular cartilage of the sacroiliac joints and apophyseal joints between spinal tuberosities and processes, resulting in bony fusion across joints, presenting as lower back pain and spinal stiffness in middle age.

A

ankylosing spondylitis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the gene most commonly involved in autoimmunity and why does it have this association?

A

Polymorphisms in PTPN22 are associated with rheumatoid arthritis and T1DM, among other autoimmune diseases, and is therefore the gene most commonly involved in autoimmunity is PTPN22.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Polymorphisms in PTPN22 cause what to happen that leads to autoimmunity?

A

Excessive activation of lymphocytes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Polymorphisms in the genes for the _____ receptor (CD25) and _____ receptor alpha chains are associated with MS, due to an autoimmune attack on the myelin coating of axons.

A

IL-2; IL-7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Briefly describe 2 ways that infections can lead to autoimmunity.

A

1- pathogen antigens can mimic self antigens (molecular mimicry)
2- infection can lead to up-regulation of B7 and when a self antigen is presented (as is normal function), B7 can accidentally provide co-stimulation to the T cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Turns out autoimmune disease is also PREVENTED by infection. How the hell is that possible?

A

Stimulation of IL-2, normally done by infection, is essential for maintaining Tregs. MIND BLOWN

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is epitope spreading?

A

In autoimmune disease, tissue damage releases new antigens that stimulate added immune reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Do autoimmune diseases increase or decrease in severity during pregnancy? Why?

A

They remit (decrease) in severity during pregnancy when immunity naturally declines.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Anti-cyclic citrullinated peptide (anti-CCP) is an Ab primarily associated with:

A

rheumatoid arthritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Anti-centromere is an Ab primarily associated with:

A 
CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia)
- a multisystem connective tissue disorder; limited systemic sclerosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Anti-Jo-1 is an Ab primarily associated with:

A

Polymyositis/dermatomyositis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Anti-Scl70 (anti-DNA topoisomerase) is an Ab primarily associated with:

A

diffuse systemic sclerosis

27
Q

Anti-RNA polymerase (anti-U3 RNP) is an Ab primarily associated with:

A

Systemic sclerosis

28
Q

Anti-U1 RNP (anti-RNP not otherwise specified) is an Ab primarily associated with:

A

Mixed connective tissue disease

29
Q

Anti-Smith (anti-Sm) is an Ab primarily associated with:

A

Lupus

30
Q

Anti-dsDNA is an Ab primarily associated with:

A

Lupus

31
Q

Anti-nuclear (ANA) is an Ab primarily associated with:

A

Lupus and many other rheumatic diseases

32
Q

Anti-SSA (anti-Ro) is an Ab primarily associated with:

A

Sjogren syndrome, neonatal lupus, subcutaneous lupus

33
Q

Anti-SSB (anti-La) is an Ab primarily associated with:

A

Sjogren syndrome, neonatal lupus, subcutaneous lupus

34
Q

Anti-myeloperoxidase (perinuclear anti-neutrophil cytoplasmic, P-ANCA) is an Ab primarily associated with:

A

Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg Strauss)

35
Q

Anti-protease-3 (diffuse cytoplasmic anti-neutrophil cytoplasmic, C-ANCA) is an Ab primarily associated with:

A

Granulomatosis with polyantiitis (Wegener’s)

36
Q

Are all people with certain antibodies associated with rheumatoid disease diagnosed with that disease just based on the Ab’s presence?

A

No. Many people with no apparent rheumatological disease have Abs associated with rheumatological disease, and should not be falsely Dx’d on the basis of serology alone.

37
Q

_______ and ________, both calcineurin inhibitors, are given to transplant pts to prevent or treat transplant rejection.

A

cyclosporine and tacrolimus

38
Q

How do calcineurin inhibitors work?

A

The inhibitors bind to intracytoplasmic receptor proteins called immunophilins. This complex binds to and inhibits calcineurin which would otherwise dephosphorylate nuclear regulatory proteins in lymphocytes. This inhibition prevents the regulatory proteins’ translocation into the nucleus and action as intranuclear factors, promoting T lymphocyte activation and secretion of TNF, IFN-gamma, IL-2 and IL-4.

39
Q

_________ __________ is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis. It inhibits proliferation of lymphocytes and is this useful in treating autoimmune diseases, particularly lupus, and in preventing and treating transplant rejection.

A

mycophenolate mofetil

40
Q

_________ is a purine analogue that messes up DNA replication. It is used in treating lupus, rheumatoid arthritis and many other autoimmune diseases.

A

Azathioprine

41
Q

This drug, that has a reputation for low toxicity, is used to treat both malaria and lupus.

A

Hydroxychloroquine

42
Q

These targeted therapies are used to block TNF-alpha, specifically.

A

Infliximab, etanercept, adalimumab

43
Q

________ is an ab to B-cell activating factor.

A

Belimumab

44
Q

_________ is an ab to CD20 on B lymphocytes.

A

Rituximab

45
Q

__________ is an ab that blocks IL-6 receptors.

A

Tocilizumab

46
Q

_________ is an ab with especially strong effect that that seems to mimic AIDS. It is therefore very useful in reducing incidence of graft rejection but also increases the risk of opportunistic infection.

A

Alemtuzumab

47
Q

Alemtuzumab is an ab to what?

A

CD25. CD25 is expressed at high levels by both normal and malignant B and T cells, with lower levels found on macrophages, monocytes and eosinophils.

48
Q

Attack and injury of transplanted organs, by an immune response recognizing them as foreign, is usually mediated by ____ lymphocytes and generally involves both cellular and Ab-mediated mechanisms.

A

T lymphocytes

49
Q

Hyperacute rejection occurs within minutes of transplantation due to:

A

large numbers of preformed Abs in the recipient immediately trashing the transplant.

50
Q

Is hyperacute rejection common?

A

No, it is exceedingly rare.

51
Q

What is C4d?

A

C4d is a degradation product of activated complement C4 and is deposited in peri-tubular capillaries in some cases of kidney transplant rejection, but it is also deposited in some cases with no other evidence of rejection, so positive C4d staining has to be combined with histological evidence of rejection and the finding of donor-specific antibodies in the recipient’s blood before antibody-mediated rejection is diagnosed.

52
Q

Describe how calcineurin inhibitors are toxic.

A

Calcineurin inhibitors are nephrotoxins. They can harm the kidney by causing vasoconstriction with no morphologic change (functional toxicity) or they can visibly harm the renal tubules with structural toxicity manifested by (1) isometric (uniformly sized) vacuolization of tubular epithelial cell cytoplasm, (2) tubular calcifications and (3) giant mitochondria.

53
Q

Kidney transplant biopsies must be evaluated for evidence of _____ virus infection, also called polyomavirus nephropathy. How is this manifested?

A

BK virus. Manifested by intranuclear inclusion bodies and epithelial cell injury and lysis. Immunostains are used to confirm the sighting of BK virus inclusions. Urine is also checked for BK virus by “BK virus activation assays” including quantitative PCR assays, urine cytology and / or urine electron microscopy, but positive urine assays must be correlated with plasma assays because clinically significant urine assays are associated with simultaneously positive plasma assays.

54
Q

What do you use to identify fungal infection in transplants?

A

silver stain

55
Q

What do you use to identify mycobacterial infections like TB in transplants?

A

acid-fast stain

56
Q

What do you use to identify protozoal infections like toxoplasmosis in transplants?

A

immunostain

57
Q

What do you use to identify garden variety bacterial infections like Staph and Pseudomonas?

A

Gram Stain

58
Q

All organ transplant biopsies must also be evaluated for post-transplant lymphoproliferative disorder (PTLD). What is this?

A

PTLD is a spectrum ranging from a proliferation of lymphocytes that halts with decreasing immunosuppressive therapy to a full blown malignant lymphoma that can be resistant to chemotherapy and everything in between. The proliferating lymphocytes are infected with Epstein-Barr virus (EBV), at least in most cases, and immunosuppression can awaken latent EBV, which drives lymphoproliferation.

59
Q

What is graft-versus-host disease?

A

When lymphocytes, brought into the host by the transplanted organ, begin to attack the host tissue.

60
Q

If graft-versus-host disease (GVHD), the attacked cells die by apoptosis or necrosis?

A

Apoptosis, remember, it’s CTLs that are carrying out these effects.

61
Q

How does GVHD manifest in the skin?

A

Erythematous rash, which goes on to cause fibrosis similar to systemic sclerosis.

62
Q

How does GVHD manifest in the liver?

A

In the liver, it causes biliary and hepatocytic injury, manifested clinically by jaundice and elevated liver transaminases.

63
Q

How does GVHD manifest in the GI tract?

A

In the gastrointestinal tract, it causes injury of the epithelium, manifested clinically by bloody diarrhea.

CMOD/PCM- Block 2 (41 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions