Brainscape's Knowledge GenomeTM

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


See full index

CSIM2 > MAID 2.9-2.14 > Flashcards

MAID 2.9-2.14 Flashcards

1
Q

Causes of ‘misfire’ in AI disease?

A

Change to own protein, molecular mimicry, attacking cells in wrong place, exposure of normally hidden self proteins.

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

Two stages of T cell central tolerance?

A
  1. Positive selection (choosing T cells that can bind to own MHC)
  2. Negative selection (deleting T cells that bind strongly to self Ag in assocation with MHC)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Peripheral tolerance: anergy?

A

TCR engaged without co-stimulation

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

Immune privileged sites?

A

A mechanism of peripheral tolerance in that it prevents mature T cells from reacting to self Ag; includes eye/brain/tests

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

Summary of tolerance?

A

State of unresponsiveness to Ag, either foreign or self. Key to immune system so have central and peripheral mechanisms to prevent autoimmunity. Failure gives AI disease.

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

Why is AI disease often chronic?

A

Failure of T/B cell tolerance gives activated T and B cells, which damage self Ag, releasing more self Ag. By definition cannot clear autoantigens.

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

Which Gell and Coombs classes are B/T cell mediated?

A

I-III = Ab; IV = CMI. However, once one cell goes awry, others pile in!

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

Type II HS?

A

IgG/M binds to Ag on cell surface; opsonisation then phagocytosis or complement-mediated lysis. Goodpasture’s, MG, Graves.

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

Type III HS?

A

Ig binds to circulating Ag; forms IC and lodges in body, then get inflammatory cells and complement recruitment e.g. SLE, RA, farmers lung (inhaled Ag)

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

Type IV HS?

A

Delayed, cell-mediated. CD4 cells direct CD8 cells. Temporal arteritis, MS, GVHD

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

Antigen in Goodpasture’s?

A

Type IV collagen (BM of alveoli and glomeruli)

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

Some ways that allergy can present?

A

Rhinoconjunctivits, oral allergy syndrome, asthma, eczema, urticaria, contact dermatitis, anaphylaxis, perennial allergic rhinits.

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

Gell and Coombs for allergy?

A

Type 1 (IgE mediated) for allergy and anaphylaxis. Allergic contact dermatitis is Type IV (CMI) which is what is tested for in patch test

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

Three phases of IgE mediated hypersensitivity?

A

Sensitisation, immediate phase, late phase

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

Sensitisation phase of allergy?

A

APC presents Ag to T cells, get B cell clonal expansion and class switching to IgE; new specific IgE attaches to mast cells

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

Immediate phase of allergy?

A

Type I reaction; Ag binds to IgE (facing ‘out’) on mast cell, they cross-link and get degranulation (histamine, cytokines etc.)

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

Effects of histamine in immediate phase of allergy?

A
  1. Lungs: bronchoconstriction and mucous secretion
  2. Vasodilation and increased vascular permeability (get oedema, hypotension)
  3. Gut; increased peristalsis (abdominal pain, n & v, diarroea)
  4. Nerve stimulation (dread, headache, confusion and drowsiness)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Late phase of allergy?

A

Begins within 12 hours. Th cells recruit many other inflammatory cells (leukocytes, eosinophils into area), prompted by earlier release of cytokines. Also get IgE release to prime the mast cells for future.

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

Investigations for allergy?

A
  1. Skin prick. Need positive control (histamine) and negative (saline). Get wheals; T1 HS.
  2. Intradermal testing (done for Abx etc.)
  3. Patch testing. Done for delayed (type IV) cell-mediated allergy so takes longer.
  4. RAST. Add allergen to serum sample, patients IgE binds to allergen, then add labelled anti-IgE to sample and measure signal strength. Allergen is attached to solid phase so unbound IgE washed away.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Diagnosing anaphylaxis (not anaphylactic shock!)?

A

Highly likely if three of:
1. Rapid (onset and progression) AND
2. Life-threatening (changes to A (swelling of tongue/mouth), B or C) AND
3. Skin/mucosal changes (urticaria, angioedema, flushing) OR
4. Other signs e.g. abdo pain, vomiting.
Skin changes alone not enough.

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

AABCDE of anaphylaxis?

A

A = 0.5ml of 1:1000 adnrenaline (500mcg).

Also, give fluid bolus, chlorphenamine IV, hydrocortisone IV.

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

Thing to measure post-anaphylaxis?

A

Serum tryptase! Peaks at 0.5-1.5 hours then stays elevated for 12 hours or so. Confirms that was indeed anaphylaxis. Give EpiPen!
IgE not helpful acutely because will be disordered from reaction
Keep in to observe for 12 hours or so (second phase WILL have started by then).

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

Most likely organism to cause SBP?

A

E. coli!

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

Summary of common histopathological techniques?

A

Staining, IHC, flow cytometry, electron microscopy, molecular pathology, cytogenetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

IHC in pathology?

A

Far more specific than simple stains. Can find origins of cancers etc. Can allow for computer analysis!

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

Electronmicroscopy in pathology?

A

Can be used in kidney disease e.g. minimal change disease, or undifferentiated cancers where IHC not helpful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Flow cytometry in pathology?

A

Used in diagnosis of haem cancers; cells are passed through laser and scattering interpreted as proportions and abnormal cells identified

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Molecular pathology and cytogenetics in pathology?

A

Molecular pathology relates to analysis of genetic materials; cytogenetics is of chromosomes specifically (using FISH and direct sequencing). Can be used to find mutations (Bcr-abl, BRCA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Three types of pathology specimens?

A
  1. Whole organs
  2. Biopsies
  3. FNA (liquid rather than solid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When is cytology used in pathology?

A
  1. Gynae (cervical smears)

2. Non-gynae (FNA, fluid [ascites, pleura, joint], CSF, urine, washings [peritoneal, BAL, bladder])

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Coroner’s autopsy?

A

Done to find cause of death; no consent from NOK needed. Done for violent/suspicious/sudden death, death without medical assistance or during surgical procedures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Hospital autopsy?

A

Done for clinical interest (research or confirm disease). Can also confirm standard of care at hospital and help prevent future deaths. Need consent from NOK. Can be partial. Rarely done except neonatal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Anatomical/academic autopsies?

A

Done by students of anatomy for study purposes only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Virtual or imaging autopsies?

A

Done using CT/MR only.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Peri/neonatal autopsy?

A

Important because unexpected findings are much more likely, and is relevant for family planning. May help parents psychologically.

36
Q

Significance of autopsy generally?

A
  1. Can correct/clarify/confirm diagnosis; helps improve medical knowledge. Unique position to correlate anatomy and clinical picture.
  2. Aim to reach minimal acceptable diagnostic errors
  3. Can be compared with imaging to help future diagnostic patterns
  4. Evaluate new drugs/techniques
  5. Reveal impact of ingestion of chemicals etc.
  6. Important for accuracy of death certificates as this is key epidemiology
  7. Reveal and prevent malpractice
37
Q

PTP in Alzheimers?

A
  1. APP (ubiquitous transmembrane protein) is cleaved to amyloid- B, which is small and very hydrophobic so aggregates. Point mutations in APP gene, or in Down’s (trisomy 21 = 3 copies of APP) get increased deposition and early Alz. Plaques.
  2. Also Tau is hyperphosphorylated (PTP) and aggregates (tau tangles) INTRANEURONALLY. Means unable to bind to microtubules like normal.
38
Q

Therapeutic PTP targets in Alzheimers?

A

APP cleaved to AB by y/b-secretin. Could inhibit these., or could promote a-secretin which cleaves A-B! Or inhibit aggregation, or vaccinate (passively).
For Tau, could use Tau aggregation/phosphorylation inhibitors.
Not likely to be effective once disease has manifested

39
Q

PTP in FTLD?

A

Tau tangles (no AB, unlike Alzheimers).

40
Q

PTP in PD/DLB?

A

Familial PD has amplified a-synuclein gene so accumulates and aggregates, or mutated. Phosphorylation also drives aggregation in SN. A-synuclein is hydrophobic (as with AB). Therapeutic targets = prevent phosphorylation, or passive immunisation.

41
Q

Felty’s syndrome?

A

Combination of RA, hypersplenism and neutropenia

42
Q

Basis of lysosomal storage disease?

A

Defect in lysosomal enzyme required to break down molecule; instead accumulates in cells. Rare, usually AR. Usually classified by nature of stored material e.g. lipid storage disorders (sphingolipidoses), glycoprotein storage disorders

43
Q

Targets for treatment in lysosomal storage disease?

A

Replace enzyme, or USE CHAPERONES TO ENCOURAGE CORRECT FOLDING, remove substrate, or even enzyme inhibitors e.g. in Gaucher disease. Or just symptomatic.

44
Q

Lysosome storage disorders: Gaucher’s?

A

Sphingolipidosis. Ashkenazi Jews. Deficiency of glucocerebrosidase enzyme; means glucocerebroside accumulates in macrophages. Get hepatosplenomegaly, prog neuro disease, SOB. Pancytopenia (hypersplenism). Severe bone pain.

45
Q

What character of AB makes it so problematic?

A

Extremely hydrophobic. Usually lies within membrane of APP; when exposed precipitates.

46
Q

AB in CSF of Alzheimers?

A

Actually decreases, probably because dragged into the aggregates

47
Q

Testing for protein levels in Alzheimer’s?

A

Raised phosphorylated Tau and LOW AB in CSF has very high spec/sens for AD

48
Q

How would Tau aggregation inhibitors work?

A

Use flat planar compounds to prevent strands binding

49
Q

Where do lysosomal storage disorders tend to manifest?

A

Macrophage-reticulo-endothelial system (high metabolic turnover) so get hepatosplenomegaly. Aka mononuclear phagocyte system. Can get CNS/PNS involvement.

50
Q

False substrates in lysosome storage disorders?

A

Aka pharmalogical chaperones; aim to stabilise protein (enzyme) when folding in ER. Occurs because problem seems to be folding rather than coding mutation. Example is ivacaftor in CF.

51
Q

Pathophysiology of hereditary haemochromatosis?

A

Defect in HFE (gene & protein); Normall iron binds to TfR2; causes HFE to activate hepcidin to decrease ferroportin levels (enzyme of blood side of enterocytes) Means get uncontrolled absorption from gut then deposition in tissues. Can get mutations in hepcidin/ferroportin.

52
Q

Why does haemochromatosis present later in females?

A

Menstruation

53
Q

Where in the brain does iron deposit in haemochromatosis?

A

Pituitary; hence hypotrophic hypogonadism.

54
Q

Treatments for haemochromatosis?

A

Firstline treatment is venesection (usually every two weeks). Desferrioxamine (chellates iron) is second line.

55
Q

Inborn errors of copper metabolism?

A

None exist because would not be compatible with life (copper is essential enzyme cofactor)

56
Q

Pathophysiology of Wilson’s?

A

AR!!! Defects in ATP7B. Cannot package copper into holocupoproteins like caeruloplasmin, so cannot secrete cae into blood hence low levels of careuloplasmin (with high serum/urinary copper, as copper leaks out free instead).

57
Q

Rx for Wilson’s?

A

Chellating agents e.g. BAL (British antilewisite), penicillamine (bind copper so can be excreted). Giving high levels of zinc can stop copper being absorbed.

58
Q

Tay-Sachs?

A

Deficiency in hexosaminidase A (a lysosomal enzyme); get ganglioside accumulation in neurons (sphingolipidosis). AR. Common in Ashkenazi Jews.

59
Q

Hunter syndrome?

A

I2S def. X-linked. An MPS disease. GAG accumulates. have large head, developmental delay, hepatosplenomegaly, lung, joints.

60
Q

MPS-1?

A

Three types: Hurler (most severe), Scheie, and Hurler Scheie

61
Q

Difference between Hurler and Hunter syndrome?

A

Both lysosomal storage disorders relating to mucopolysaccharies, but Hunter is X-linked recessive and Hurler is AR recessive.

62
Q

Hurler syndrome?

A

Hepatosplenomegaly, dwarfism, mental retardation. Cloudy cornea, enlarged tongue. Get hernias. Similar symptoms to Hunter (so probably don’t learn).

63
Q

Three places discontinuous endothelium is found?

A

Liver, spleen, BM

64
Q

Three places fenestrated endothelium is found?

A

Glomeruli, exocrine glands, intestinal mucosa

65
Q

What is special about BBB endothelium?

A

Tight junctions are much “tighter”; protects from toxins/infections etc. Highly selective (need active transport) though small/lipid soluble molecules cross easily.

66
Q

Endothelial cells and angiogenesis?

A

Mature endothelial cells can divide in situ (clonal expansion), migrate locally or be helped by circulating progenitors; grow towards chemotactic gradient (VEGF/PDGF) for wound repair; exploited by tumours.

67
Q

Malignancy and angiogenesis?

A

Promotes growth of primary tumour and facilitates metastasis; good target for intervention.

68
Q

Why do primary CNS tumours rarely metastasise?

A

Endothelium is too tight

69
Q

How is vascular tone rapidly adjusted?

A

Endothelium-derived NO (dilate), neuronally-derived NE (constrict)

70
Q

What do basal endothelial function favour?

A

Anti-platelet aggregation, fibrinoylsis, anticoagulation. Chronic endothelial damage reduces this.

71
Q

How does endothelial damage promote coagulation?

A

Reveals tissue factor, which complexes with factor VII to activate X to Xa.
Also exposes collagen, which binds to VWF (and then links platelets)

72
Q

Role of endothelium regarding immune cells?

A

Inflammation causes endothelial cells to upregulate adherins (ICAM-1) and selectins; allows for extravasation/diapedesis of immune cells. Inflammation (IL-1/6/TNFa) also increases permeability of vessels to allow this.

73
Q

Endothelium in sepsis?

A

IL-1/6, TNFa activate endothelium and vascular SM. Get necrosis, weakened junctions, increased NO/prostacyclin, more adhesion molecules, release of VWF/other prothrombotic factors. = immune stimulation, oedema, extravasation, reduced perfusion therefore acidosis, DIC.

74
Q

Endothelium: vasoactive substances?

A 
Dilate = NO, prostanoids, hyperpolarising factors
Constrict = endothelin, ATII.
75
Q

DIC pathophysiology?

A

TF exposed, extrinsic pathway activated by FVII (key). Also more VWF. Thrombin generated SYSTEMICALLY. Antithrombin consumed, leaks and liver underperfused so can’t make more = anticoagulation overwhelmed. Also less protein C and TFPI and fibrinolysis (supppressed by PAI-1)

76
Q

What is PAI-1?

A

Plasminogen activator inhibitor 1 (prothrombotic)

77
Q

Endothelial dysfunction in atherosclerosis?

A

Damaged by hyperglycaemia/smoking/HTN; more permeable to lipoprotein AND retains it, cholesterol is inflammatory and upregulates receptors increasing immune diapedesis, exposing TF/collagen, promoting coagulation and vasoconstriction (reduced NO availbility) so get plaque!

78
Q

Significance of reduced NO availability in atherosclerosis?

A

Explains mechanism for angina and why GTN helps; reduced endogenous NO so can’t respond to exercise.

79
Q

HCO3- and K+?

A

Usually go in opposite directions. Hypokalaemia = alkalosis. Relates to their antiporter.

80
Q

Situations that give disproportionately high urea?

A

GI bleed, liver failure (can’t metabolise urate and low creatinine production because no muscle), dehydration

81
Q

Things that are important to tell when ordering investigations?

A

Bleeding risk, radiation appropriate, renal function, diabetes.

82
Q

Age of lymphocytes and tolerance?

A

Increased sensitivity to tolerance when immature i.e. will be negatively selected; if encounter same Ag when mature can cause immune respone.

83
Q

Are Tregs central or peripheral tolerance?

A

Both - main action is to to suppress self-(or foreign) reactive T cells peripherally but can be generated from self-(or foreign) reactive T cells in the thymus during differentiation

84
Q

Key cytokine for Treg differentiation?

A

TGF-B

85
Q

Treg selection process?

A

Very finely tuned; excess reactivity to self Ag = killed, little = become effector T cell. Have much larger TCR diversity than effector T cells, and are biased towards self Ag.

86
Q

IPEX?

A

Mutation in FOXP3 transcription factor; defective Treg function/differentiation so can’t repress self-reactivity so get plethora of AI disease

CSIM2 (21 decks)

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