Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

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

Autoinflammatory and Autoimmune Disease 1 Flashcards

(87 cards)

Start Studying
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
Features of APS1/APECED
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)
26
Features of IPEX
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
27
Features of ALPS
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
28
Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
Familial Mediterranean Fever
29
Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias
ALPS
30
Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
IPEX
31
Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
Familial Mediterranean Fever
32
Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias
ALPS
33
Single gene mutation involving FOXp3 resulting in abnormality of T reg cells
IPEX
34
Pathogenesis of polygenic auto-inflammatory diseases
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
35
What is the pathogenesis of Crohns disease
IBD1 gene on chromosome 16 identified as NOD2 (CARD15, caspase activating recruitiment domain 15)
36
What is the normal role of NOD2
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
What conditions are mutations in NOD2 associated with
Crohns disease. Blau syndrome Some forms of sarcoidosis.
38
By how much does NOD2 increase the risk in Crohns disease
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
What are the factors that contribute to the development of Crohns disease
Abnormal NOD2/CARD15 Other genetic influences Environmental factors (e.g. microbes)
40
What is the histology in Crohns
Focal inflammation in/around the crypts Formation of granulomata Tissue damage with mucosal ulceration
41
Clinical features of Crohn's disease
Abdominal pain and tenderness Diarrhoea (blood, pus, mucous) Fevers, malaise
42
Treatment of Crohn's disease
Corticosteroid Azathioprine Anti-TNF alpha antibody Anti-IL12/23 antibody
43
Pathogenesis of mixed pattern diseases
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
Presentation of ankylosing spondylitis
Low back pain and stiffness Large joint arthritis Enthesitis Uveitis
45
Treatment of ankylosing spondylitis
NSAIDs | Immunosuppression: Anti-TNFalpha, anti-IL17, anti-IL12/23
46
Treatment of ankylosing spondylitis
NSAIDs | Immunosuppression: Anti-TNFalpha, anti-IL17, anti-IL12/23
47
Pathogenesis of polygenic auto-immune disease
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
What is required for development of T cell and T cell dependent B cell responses
HLA presentation of antigen
49
What allele is involved Goodpasture disease
HLA_DR15
50
What allele is involved in Graves disease
HLA-DR3
51
What allele is involved in SLE
HLA-DR3
52
What allele is involved in T1DM
HLA-DR3/DR4
53
What allele is involved in rheumatoid arthritis
HLA-DR4
54
What allele is involved in rheumatoid arthritis
HLA-DR4
55
What is PTPN22
Protein tyrosine phosphatase non-receptor 22 Lymphocyte specific tyrosine phosphatase which suppresses T cell activation Allelic variants found in: SLE, RA, T1DM
56
What is CTLA4
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
What are the T cell activation alleles involved in polygenic auto-immune disease
PTPN 22 | CTLA 4
58
What factors contribute to the presentation of polygenic auto-immune disease
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
What is the role of loss of self-tolerance in polygenic auto-immune disease
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
What is the mechanism of central tolerance for T cells
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
What is the mechanism of central tolerance for B cells
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
What do naive T cells require for activation
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
How are T cells co-stimulated
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
How is peripheral tolerance achieved with T cells
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
How are T cells co-stimulated
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
What are the populations of regulatory T cells
Tregs: CD25+FoxP3+ CD4 T cells Tr1 CD4 T cells CD8 regulatory T cells
67
What do Tr1 cells secrete
IL10
68
What do CD25+FocP3+ CD4 T regulatory cells secrete
TGF-beta | IL10
69
What Treg population is absent in IPEX
CD25+FoxP3+ CD4 T regulatory cells
70
What sites in the body are not normally exposed to the immune system
Eyes Testes CNS
71
What is Gel and Coombs
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
What are the Gel and Coombs classifications
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
Gel and Coombes Type 1
Immediate hypersensitivity which is IgE mediated
74
Gel and Coombes Type 2
Antibody reacts with cellular antigen
75
Gel and Coombes Type 3
Antibody reacts with soluble antigen to form an immune complex
76
Gel and Coombes Type 4
Delayed type hypersensitivity....T cell mediated response
77
Mechanism of Type 1 hypersensitivity reaction
``` 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
What can trigger a type 1 hypersensitivity reaction
``` Pollens Drugs Food Insect products Animal hair Possible involvement of self-antigen in some cases of eczema ```
79
Mechanism of type 2 hypersensitivity reaction
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
Some type 2 hypersensitivity reactions
``` Auto-immune haemolytic anaemia Goodpasture disease Pemphigus vulgaris Graves disease Myaesthenia gravis ```
81
Mechanism of type 3 hypersensitivty reaction
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
Effects of type 3 hypersensitivity reactions
Cytokine and chemokine expression leads to granule release from neutrophils which leads to an increased vascular permeability and.... Cutaneous vasculitis Glomerulonephritis Arthritis
83
Syndromes that are type 3 hypersensitivity reactions
Cryoglobulinaemia Systemic Lupus Erythematosus Rheumatoid arthritis
84
Mechanism of type 4 hypersensitivity reaction
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
Syndromes which are type 4 hypersensitivity reactions
T1DM RA MS/Experimental autoimmune encephalitis
86
What hypersensitivity reactions are involved in autoimmunity
Type 2 most often Types 3/4 sometimes involved Type 1 rarely involved
87
Type 1 hypersensitivity syndromes
Anaphylaxis | Atopic asthma

Kat's Pathology (105 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions