Brainscape's Knowledge GenomeTM

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


See full index

Kat's Pathology > Autoinflammatory and Autoimmune Disease 1 > Flashcards

Autoinflammatory and Autoimmune Disease 1 Flashcards

1
Q

What immune system does an auto-inflammatory response involve

A

Innate immune response

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

What immune system does an auto-immune response involve

A

Adaptive immune response

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

Features of auto-inflammatory diseases

A

Self-directed inflammation
Local factors at sites predispose to disease lead to activation of innate immune cells such as macrophages and neutrophils, with resulting tissue damage

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

Features of auto-immune disease

A

Self-directed inflammation
Aberrant T cell and B cell responses in primary and secondary lymphoid organs lead to breaking of tolerance with development of immune reactivity towards self-antigens
Adaptive immune response plays the predominant role in clinical expression of disease
Organ-specific antibodies may predate clinical disease by yeas

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

Mixed pattern diseases

A

Ankylosing spondylitis
Psoriatic arthritis
Behcet’s syndrome

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

Polygenic auto-immune diseases

A 
Rhaumatoid arthritis
Myaesthenia gravis
pernicious anaemia
Graves disease
SLE
PBC
ANCA associated vasculitis 
Goodpasture disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Polygenic auto-inflammatory diseases

A 
Crohns disease 
UC
Osteoarthritis
Giant cell arteritis
Takayasu's arteritis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Rare monogenic auto-inflammatory diseases

A

Familial Mediterranean fever

TRAPS

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

Rare monogenic auto-immune diseases

A

APS-1, APECED
ALPS
IPEX

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

Pathogenesis of monogenic auto-inflammtory diseases

A

Mutations in a gene encoding a protein involved in a pathway associated with innate immune cell function.
Abnormal signalling via key cytokine pathways involving TNF and/or IL1 is common

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

What are important proteins that are affected in monogenic auto-inflammatory diseases

A

NALP3

Cryopyrin

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

Inheritance pattern of defects in NALP3 and crypyrin

A

Autosomal dominant

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

What conditions are associated with defective NALP3 and cryopyrin

A

Muckle Wells Syndrome
Familial cold auto-inflammatory syndrome
Chronic infantile neurological cutaneous articular syndrome

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

What condition is associated with a defective pyrin-marenostrin

A

Familial mediterranean fever

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

Inheritance pattern of familial mediterranean fever

A

Autosomal recessive

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

Pathway involved in monogenic auto-inflammatory diseases (i.e. the inflammasome complex)

A

Toxins, microbial pathogens, urate activate crypyrin (or pyrin-marenostrin) –> apoptosis associated speck like protein –> procaspase 1 –> IL1, NFkappaB, apoptosis

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

What does NFkappaB regulate

A

TF that regulates expression of genes in immunity such as TNFalpha

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

Pathogenesis of familial mediterranean fever

A

Autosomal recessive condition
Mutation in MEFV gene
Gene encodes pyrin-marenostrin
Pyrin-marenostrin expressed mainly in neutrophils
Failure to regulate cryopyrin driven activation of neutrophils

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

Epidemiology of familial mediterranean fever

A

Sephardic> Ashkenazy Jews

Armenian, Turkish and Arabic people

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

Clinical presentation of familial mediterranean fever

A

Periodic fevers lasting 48-96 hours associated with:
Abdominal pain due to peritonitis
Chest pain due to pleurosity and pericarditis
Arthritis

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

Long-term risks in familial Mediterranean fever

A

Amyloidosis (including nephrotic syndrome and renal failure)

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

Treatment of familial mediterranean fever

A

Colchicine 500ug bd

Anakinra (Interleukin 1 receptor antagonist)
Etanercept (TNF alpha inhibitor)
Type 1 interferon

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

MOA of colchicine

A

Binds to tubulin in neutrophils and disrupts neutrophil functions including migration and chemokine secretion

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

Pathogenesis of mongenic auto-immune diseases

A

Mutation in a gene encoding a protein involved in a pathway associated with adaptive immune cell function:
Abnormality in tolerance
Abnormality of regulatory T cells
Abnormality of lymphocyte apoptosis

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

Features of APS1/APECED

A

Autosomal recessive
Defect in auto-immune regulator - AIRE (TF involved in development of T cell tolerance in the thymus - upregulates expression of self-antigens by thymic cells, promotes T cell apoptosis)
Antibodies versus parathyroid and adrenal glands (hypothyroidism and Addison’s)
Antibodies versus IL17 and IL22 (candidiasis)

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

Features of IPEX

A

Mutations in Foxp3 which is required for development of Treg cells.
Overwhelming disease leads to early death without treatment
Endocrinopathy (usually insulin dependent DM, thyroid disease)
Diarrhoea
Eczematous dermatitis

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

Features of ALPS

A

Mutations iwthin FAS pathway (e.g. mutations in TNFRSF6 which encodes FAS, disease in heterogeneous depending on the mutation)
Defect in apoptosis of lymphocytes (failure of tolerance, failure of lymphocyte homeostasis)
Auto-immune disease (commonly auto-immune cytopenias)
High lymphocyte numbers with large spleen and lymph nodes
May be associated with lymphoma

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

Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis

A

Familial Mediterranean Fever

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

Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias

A

ALPS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Single gene mutation involving FOXp3 resulting in abnormality of T reg cells

A

IPEX

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

Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis

A

Familial Mediterranean Fever

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

Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias

A

ALPS

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

Single gene mutation involving FOXp3 resulting in abnormality of T reg cells

A

IPEX

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

Pathogenesis of polygenic auto-inflammatory diseases

A

Mutations in genes encoding proteins involved in pathways associated with innate immune cell function
Local factors at sites predisposed to disease lead to activation of innate immune cells such as macrophages and neutrophils, with resulting tissue damage
HLA associations are usually less strong
In general these disease are not characterised by presence of auto-antibodies

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

What is the pathogenesis of Crohns disease

A

IBD1 gene on chromosome 16 identified as NOD2 (CARD15, caspase activating recruitiment domain 15)

36
Q

What is the normal role of NOD2

A

NOD2 expressed in cytoplasm of myeloid cells - macrophages, neutrophils, dendritic cells.
Acts as a microbial sensor - recognises muramyl dipeptide - and stimulates NFKbeta and triggers an inflammatory response.
Some mutations associated with Crohns disease result in a shorter protein that fails to recognise bacteria

37
Q

What conditions are mutations in NOD2 associated with

A

Crohns disease.
Blau syndrome
Some forms of sarcoidosis.

38
Q

By how much does NOD2 increase the risk in Crohns disease

A

NOD2 gene mutations are present in 30% of patients (i.e. not necessary)
Abnormal allele of NOD2 increases risk of Crohn’ disease by 1.5-3 x if one copy and 14-44 x if two copies (i.e. not sufficient)

39
Q

What are the factors that contribute to the development of Crohns disease

A

Abnormal NOD2/CARD15
Other genetic influences
Environmental factors (e.g. microbes)

40
Q

What is the histology in Crohns

A

Focal inflammation in/around the crypts
Formation of granulomata
Tissue damage with mucosal ulceration

41
Q

Clinical features of Crohn’s disease

A

Abdominal pain and tenderness
Diarrhoea (blood, pus, mucous)
Fevers, malaise

42
Q

Treatment of Crohn’s disease

A

Corticosteroid
Azathioprine
Anti-TNF alpha antibody
Anti-IL12/23 antibody

43
Q

Pathogenesis of mixed pattern diseases

A

Mutations in genes encoding proteins involved in pathways associated with innate immune cell function
AND
Mutations in genes encoding proteins involved in pathways associated with adaptive immune cell function
HLA associations may be present
Auto-antibodies are not usually a feature

44
Q

Presentation of ankylosing spondylitis

A

Low back pain and stiffness
Large joint arthritis
Enthesitis
Uveitis

45
Q

Treatment of ankylosing spondylitis

A

NSAIDs

Immunosuppression: Anti-TNFalpha, anti-IL17, anti-IL12/23

46
Q

Treatment of ankylosing spondylitis

A

NSAIDs

Immunosuppression: Anti-TNFalpha, anti-IL17, anti-IL12/23

47
Q

Pathogenesis of polygenic auto-immune disease

A

Mutations in genes encoding proteins involved in pathways associated with adaptive immune cell function
HLA associations are common
Aberrant B cell and T cell responses in primary and secondary lymphoid organs lead to breaking of tolerance with development of immune reactivity towards self-antigens
Auto-antibodies are found
There are environmental factors at all stages

48
Q

What is required for development of T cell and T cell dependent B cell responses

A

HLA presentation of antigen

49
Q

What allele is involved Goodpasture disease

A

HLA_DR15

50
Q

What allele is involved in Graves disease

A

HLA-DR3

51
Q

What allele is involved in SLE

A

HLA-DR3

52
Q

What allele is involved in T1DM

A

HLA-DR3/DR4

53
Q

What allele is involved in rheumatoid arthritis

A

HLA-DR4

54
Q

What allele is involved in rheumatoid arthritis

A

HLA-DR4

55
Q

What is PTPN22

A

Protein tyrosine phosphatase non-receptor 22
Lymphocyte specific tyrosine phosphatase which
suppresses T cell activation
Allelic variants found in: SLE, RA, T1DM

56
Q

What is CTLA4

A

Cytotoxic T lymphocyte associated protein 4
Expressed by T cells and transmits inhibitory signal to control T cell activation
Allelic variants found in: Auto-immune thyroid disease, T1DM, SLE (RA to a lesser extent)

57
Q

What are the T cell activation alleles involved in polygenic auto-immune disease

A

PTPN 22

CTLA 4

58
Q

What factors contribute to the presentation of polygenic auto-immune disease

A

Gender
Immune response: T cells, B cells, NK cells, microglia, astrocytes, mast cells, dendritic cells
The environment: infectious agents, chemicals, drug exposure, pesticides, organic solvents, sunlight/vitamin D
Genetics: chromosomes, parental inheritance, epigenetics, genomic imprinting
Hormones: oestrogen, progesterone, androgens, prolactin
Reproductive function: puberty, pregnancy, microchimerism, menopause.

59
Q

What is the role of loss of self-tolerance in polygenic auto-immune disease

A

Autoimmune disease involves a failure of self-tolerance
Central tolerance
Inappropriate survival of auto-reactive B cells and T-cells
Peripheral tolerance
Aberrant expression of co-stimulatory molecules
Decrease number/function of regulatory T-cells
Damage at immunologically privileged sites

60
Q

What is the mechanism of central tolerance for T cells

A

Pre T cell from the bone marrow.
<10% are positively selected for and exported to the periphery (self MHC restricted, self tolerant)
5% negative selection = apoptosis (too strong recognition of self)

61
Q

What is the mechanism of central tolerance for B cells

A

B cell central tolerance takes place in the bone marrow - self reactive B cells are deleted –> Antigen stimulation/CD4 T cell help –> Immunoglobulin secreting plasma cells

62
Q

What do naive T cells require for activation

A

T cells require co-stimulation for full activation

In absence of co-stimulatory molecules T cells become anergised and do not respond to subsequent challenge

63
Q

How are T cells co-stimulated

A

T cells express CD40 ligand and CD28 receptor.
APCs have CD40, and CD80/86 (binds to CD28)
CD40 is responsible for IFN-g
CD28 is responsible for proliferation

64
Q

How is peripheral tolerance achieved with T cells

A

T cells require co-stimulation for full activation

In absence of co-stimulatory molecules T cells become anergised and do not respond to subsequent challenge

65
Q

How are T cells co-stimulated

A

T cells express CD40 ligand and CD28 receptor.
APCs have CD40, and CD80/86 (binds to CD28)
CD40 is responsible for IFN-g
CD28 is responsible for proliferation

66
Q

What are the populations of regulatory T cells

A

Tregs: CD25+FoxP3+ CD4 T cells
Tr1 CD4 T cells
CD8 regulatory T cells

67
Q

What do Tr1 cells secrete

A

IL10

68
Q

What do CD25+FocP3+ CD4 T regulatory cells secrete

A

TGF-beta

IL10

69
Q

What Treg population is absent in IPEX

A

CD25+FoxP3+ CD4 T regulatory cells

70
Q

What sites in the body are not normally exposed to the immune system

A

Eyes
Testes
CNS

71
Q

What is Gel and Coombs

A

Gel and Coombs clasified skin test ‘hypersensitivity’ reactions according to the type of immune response observed
Antibody or T cell mediated
Effector mechanisms for immunopathology

72
Q

What are the Gel and Coombs classifications

A

Type 1: Immediate hypersensitivity which is IgE mediated
Type 2: Antibody reacts with cellular antigen
Type 3: Antibody reacts with soluble antigen to form an immune complex
Type 4: Delayed type hypersensitivity….T cell mediated response

73
Q

Gel and Coombes Type 1

A

Immediate hypersensitivity which is IgE mediated

74
Q

Gel and Coombes Type 2

A

Antibody reacts with cellular antigen

75
Q

Gel and Coombes Type 3

A

Antibody reacts with soluble antigen to form an immune complex

76
Q

Gel and Coombes Type 4

A

Delayed type hypersensitivity….T cell mediated response

77
Q

Mechanism of Type 1 hypersensitivity reaction

A 
Rapid  allergic reaction
Pre-existing Ig E antibodies to allergen
Ig E bound to Fc epsilon receptors
on mast cells and basophils
Cell degranulation
Release of  inflammatory mediators
Pre-formed: Histamine, serotonin, proteases
Synthesised: Leukotrienes, prostaglandins, 
bradykinin, cytokines
Increased vascular permeability
Leukocyte chemotaxis
Smooth muscle contraction
78
Q

What can trigger a type 1 hypersensitivity reaction

A 
Pollens
Drugs
Food
Insect products
Animal hair
Possible involvement of self-antigen in some cases of eczema
79
Q

Mechanism of type 2 hypersensitivity reaction

A

Antibody binds to cell associated antigen
Antibody dependent destruction (NK cells, phagocytes, complement)

Complement activation = cell lysis
Phagocyte = phagocytosis
NK cells = Ig detection and release of cytolytic granules and membrane attack

Receptor activation or blockade also possible

80
Q

Some type 2 hypersensitivity reactions

A 
Auto-immune haemolytic anaemia
Goodpasture disease
Pemphigus vulgaris
Graves disease
Myaesthenia gravis
81
Q

Mechanism of type 3 hypersensitivty reaction

A

Antibody binds to soluble antigen to form a circulating immune complex

Immune complex formation and deposition in blood vessels
Infiltration of macrophages and neutrophils
Complement activation

82
Q

Effects of type 3 hypersensitivity reactions

A

Cytokine and chemokine expression leads to granule release from neutrophils which leads to an increased vascular permeability and….

Cutaneous vasculitis
Glomerulonephritis
Arthritis

83
Q

Syndromes that are type 3 hypersensitivity reactions

A

Cryoglobulinaemia
Systemic Lupus Erythematosus
Rheumatoid arthritis

84
Q

Mechanism of type 4 hypersensitivity reaction

A

HLA class II molecules present antigen to CD4 T cells.
T cell releases IFNg which influences the macrophages.
Macrophages upregulate HLA, TNF and lymphotoxin causing tissue damage and inflammation.

85
Q

Syndromes which are type 4 hypersensitivity reactions

A

T1DM
RA
MS/Experimental autoimmune encephalitis

86
Q

What hypersensitivity reactions are involved in autoimmunity

A

Type 2 most often
Types 3/4 sometimes involved
Type 1 rarely involved

87
Q

Type 1 hypersensitivity syndromes

A

Anaphylaxis

Atopic asthma

Kat's Pathology (105 decks)

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