Brainscape's Knowledge GenomeTM

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


See full index

Liv Path > Immuno - Autoinflammation/Autoimmunity, Hypersensitivity Disorders and Transplantation > Flashcards

Immuno - Autoinflammation/Autoimmunity, Hypersensitivity Disorders and Transplantation Flashcards

1
Q

Familial Mediterranean Fever

A
  • MEFV mutation (monogenic auto inflammatory condition)
  • Periodic fevers and serositis
  • Abnormal TNFa/IL1 signalling
  • Affects pyrin-mamrenostrin complex which controls activation of neutrophils

Rx:
oColchicine - disrupts tubules in neurophils
oAnakinra- IL1-R antagonist
oEntanercept- TNFa inhibitor

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

Crohn’s

A
  • NOD2/CARD15 mutations (polygenic auto inflammatory disease)
  • Affects ability of innate immune system to recognise bacteria = abnormal inflammatory response to microbes
  • Risk also affected by: other genes, environment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

HLA-B27 Mutations

A

Ank spon, psoriatic arthritis, behcets. HLA-B27 affects CD8 T cells, Th17 cells, NK cells etc.

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

RA, Myasthenia Gravis, pernicious anaemia, SLE

A

Polygenic autoimmune diseases

Risk affected by:
HLA associations
Mutations in: 
- PTPN22 -ve T cell regulator
- CTLA4 -ve T cell regulator
- Dysregulation of T cells → autoimmunity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Goodpastures HLA

A

DR15

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

Graves HLA

A

DR3

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

SLE HLA

A

DR3

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

T1DM HLA

A

DR3/DR4

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

Rheumatoid arthritis HLA

A

DR4

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

APECED

A

Central tolerance breakdown - mutation of TF AIRE – usually causes expression of self-antigens in thymus to enable -ve selection of autoreactive T cells

  • Autoimmune
  • PolyEndocrinopathy - hypoparathyroidism
  • Candidiasis
  • Ectodermal - skin/nails
  • Dystrophy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

IPEX

A

Mutation in FoxP3 – required for T reg cell development

CD25+ FoxP3+ = T reg cell

  • Immune dysregulation
  • Polyendocrinopathy
  • Enteropathy
  • X-linked
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

ALPS

A

Mutation of Fas pathway (apoptosis)
T cells not killed in thymus → enter periphery untolerised

  • Autoimmune
  • Lymphoproliferative
  • Syndrome

Splenomegaly, lymphadenopathy, autoimmune cytopenia, lymphoma

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

T1 Hypersensitivity Reactions

A

IgE and mast cell mediated –> vasodilation, increased permeability and smooth muscle spasm

Sx: angioedema, urticaria, rhino conjunctivitis, wheeze, D&V

Conditions: atopic dermatitis, food allergy, oral allergy syndrome, latex food syndrome (certain foods associated with latex allergy), allergic rhinitis, acute urticaria (50% idiopathic, 50% food/drugs/febile illnesses etc - wheals completely resolve within 6 weeks), anaphylaxis

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

Anaphylaxis

A

IgE-mediated mast cell degranulation - peanut, penicillin, stings, latex
Non-IgE-mediated mast cell degranulation: NSAIDs, IV contrast, opioids, exercise.

Rx: elevate legs, adrenaline, chlorphenamine, hydrocortisone

Ix:
Skin prick testing
RAST –> measure levels of IgE in serum against specific antigen. Less sensitive than skin prick.
Component-resolved diagnostics - tests for specific allergen proteins
Challenge test - do in hosp

During an acute ep -mast cell tryptase

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

Type 2 Hypersensitivity Disorders

A

Ab mediated

  • Haemolytic disease of the newborn
  • Autoimmune haemolytic anaemia (+ITP = Evan’s syndrome)
  • ITP - abs to glycoprotein IIb/IIIa on platelets
  • Goodpastures
  • Pemphigus vulgaris
  • Graves
  • Myasthenia gravis (ACh receptor)
  • Acute thematic fever
  • Pernicious anaemia
  • Wegner’s
  • Churg Strauss
  • Microscopic polyangitis
  • Chronic urticaria (wheals lasting >6 weeks, associated with angioedema in most cases. IgG against FceR1 or IgE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Type 3 Hypersensitivity Disorders

A

Immune complex mediated

SLE
Serum sickness
Polyarteritis nodosa - assoc with Hep B
Mixed essential cryoglobulinaemia

17
Q

SLE - Presentation and Rx

A

Main intercellular components (e.g. dsDNA).

4 of these 11: serositis, seizures, apthous ulcers, arthritis, photosensitivity, discoid rash, malar rash, haematology, kidney findings, Antinuclear antibody (ANA +ve),
immunological findings (anti- dsDNA, anti-sm).

SOAP BRAIN MD: serositis, oral ulcers, arthritis, photosensitivity, blood disorders, renal involvement, ANA+, immunologic (anti-SM, anti-dsDNA), neurologic, molar rash, discoid rash

↓C4 (↓C3 only in SEVERE
disease) Ab’s to dsDNA, Histones (Drug Induced), Ro, La, Sm, U1RNP
↑ESR, normal CRP
(N.B.
Hydralyzine, Procainamide and Isoniazid can cause
Drug induced SLE).

Rx:
Analgesia Steroids and cyclophosphamide

18
Q

Serum Sickness - Presentation and Rx

A

Reaction to protein in penicillin. Rashes, Itching, arthralgia, lymphadenopathy, fever and malaise. Symptoms take 7-12 days to develop.

↓C3
Blood shows immune complexes or signs of blood vessel
inflammation.

Rx: Discontinue pen and give steroids, antihistamines and analgesia.

19
Q

Polyarteritis nodosa

A

Hep B, Hep C virus Antigens

Fever, fatigue, weakness, arthralgia, skin, nerve and kidney involvement, pericarditis and MI. Associated with Hep
B

Diagnosed by clinical criteria and Biopsy (↑ESR, ↑WCC,
↑CRP)
‘Rosary sign’

Rx: Prednisolone and Cyclophosphamide

20
Q

Mixed Essential Cryoglobulinaemia

A

IgM against IgG +/- hepatitis C antigens

Joint pain, splenomegaly, skin, nerve and kidney involvement.
Associated with Hep C.

A mixture of clinical and biopsies

Rx: NSAIDs,
Corticosteroids and plasmaphoresis

21
Q

Type 4 Hypersensitivity Reactions

A

Delayed hypersensitivity - T cell mediated

T1DM

MS - demyelinating. CSF shows oligoclonal bands of IgG on electrophoresis

RA (can also be type 3), Rheumatoid factor (85% sensitive), Anti-CCP (95% specific)

Contact dermatitis

Mantoux test

Crohn’s- TH1 mediated NOD2 gene mutation in 30%

22
Q

Stages of transplant rejection

A

Recognition
Activation
Effector function

23
Q

Transplant - HLA Matching

A

Matching DR, A and B is most important (as they are highly polymorphic) –> 2 of each so there is the potential for up to 6 mismatches

Parent to child - >=3 matches
Sibling to sibling:
25% 6 mismatches e.g. 2:2:2MM
50% 3 mismatches
25% 0 mismatches --> 0:0:0MM
24
Q

Immune reaction to transplant - Recognition stage

A

HLA
ABO blood antigens

Can be DIRECT: 
DONOR APC (expresses high levels of MHC and costimulatory molecules) presenting antigen and/or MHC to recipient T cells (Tc and Th response). --> acute rejection mainly by this mechanism.

or INDIRECT:
RECIPIENT APC presenting DONOR antigen to recipient T cells –> i.e. immune system working as it would normally. Mainly chronic rejection (CD8 cells can’t kill the graft cells as they recognise it as self, CD4 mediated - principal mechanism = cytokine production and inflammation).

25
Q

Immune reaction to transplant - Activation Stage

A

Activation of antigen-specific lymphocytes; proliferation and maturation of B cells with Ab production

26
Q

Immune reaction to transplant - Effector Stage

A

1) Graft infiltration by alloreactive CD4+ cells
2) Cytotoxic T cells – release of toxins to kill target (granzyme), punch holes in target cells (perforin), apoptotic cell death (fas-ligand)
3) Macrophages – phagocytosis, release of proteolytic enzymes, production of cytokines, production of oxygen radicals and nitrogen radicals

4) Abs bind to graft endothelium (HLA peptides)
–> complement activation –> MAC –> cell lysis
OR
Endothelial cell activation –> increase in procoagulant factors –> increased risk of thrombus formation.

27
Q

Hyperacute Graft Rejection

A

Mins-hours

Preformed ab –> activates complement

Thrombosis and necrosis

Rx: main prevention - HLA and ABO matching

28
Q

Acute - Cellular Graft Rejection

A

Weeks-months

CD4 activating a T4 hypersensitivity reaction

Cellular infiltrate

Rx: T-cell immunosuppression

29
Q

Acute - Antibody Mediated Graft Rejection

A

Weeks-months

B-cell activation –> ab attacks vessels/graft endothelium (happens within the capillary space not the interstitium)

Vasculitis and CD4 deficiency

Rx: ab removal (plasmapheresis) and B cell immunosuppression (rituximab)

30
Q

Chronic Graft Rejection

A

Months-years

Immune and non-immune mechanism

RFs: multiple acute rejections, HTN, hyperlipidaemia

“Chronic allograft vasculopathy” - Fibrosis, glomerulopathy, vasculopathy (ischaemia), bronchiolitis obliterates (lung)

Rx: minimise organ damage

31
Q

Graft vs Host Disease

A

Days-weeks

Donor T cells attacking recipient MHC.

RFs: BM/liver transplant, T cell immunodeficiency, newborns.

FTT, skin rash, GI problems (D&V, bloody stool), liver involvement (jaundice) –> need to biopsy

Prophylaxis: methotrexate/cyclosporine/tacrolimus

Rx: steroids

32
Q

Check matching of ABO and HLA by

A

CDC = Complement Dependent Cytotoxicity

FACS = Flow Cytometry

Luminex = like solid phase FACS – can pick up Abs to individual HLAs

Recheck these post transplant to check for the formation of new antibodies.

Liv Path (24 decks)

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