(8) Autoimmune Diseases Flashcards Preview

2. CP - Core Immunology > (8) Autoimmune Diseases > Flashcards

Flashcards in (8) Autoimmune Diseases Deck (68):
1

What are the 3 factors that influence autoimmune disease?

- immune regulation
- genes
- environment

2

What important process happens to the T cells in the thymus?

Central tolerance

3

Where does deletion of auto-reactive B cells occur?

In the bone marrow

4

What are MHC Class I molecules encoded by?

Encoded by genes in HLA-A, HLA-B, HLA-C

5

What cells are MHC Class I molecules present on?

All nucleated cells

6

MHC Class I molecules present antigens to which cells?

CD8+ T cell

7

When a TCR on an immature CD8+ T cell recognises an antigen presented by an MHC 1, what does it become?

A mature cytotoxic T cell (Tc)

8

What are MHC Class II molecules encoded by?

Encoded by genes in HLA-DP, HLA-DQ, HLA-DR

9

What cells are MHC Class II molecules present on?

Dedicated antigen-presenting cells (APCs)

such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, and B cells

10

MHC Class II molecules present antigens to which cells?

CD4+ T cells

11

When a TCR on an immature CD4+ T cells recognised an antigen presented an MHC Class II molecule, what does it become?

A mature helper T cell (Th1 or Th2)

12

Give 3 examples of 'organ-specific' autoimmune disorders

- type 1 diabetes
- graves disease
- multiple sclerosis

13

What is the relative risk to siblings compared to general population in Graves disease?

15%

14

Give 2 examples of 'systemic' autoimmune disorders

- systemic lupus erythematosus
- rheumatoid arthritis

15

Autoimmunity can be related to FoxP3 mutation. Explain this

Mutation of FoxP3 causes failure to develop regulatory T cells - severe autoimmunity from birth

16

Autoimmunity can be related to PTPN22 mutation. Explain this

Mutations in PTPN22 cause T cells to be activated more easily - stronger immune response in general

17

Mutation in PTPN22 is related to which autoimmune disorders?

- type 1 diabetes
- rheumatoid arthritis
- autoimmune thyroid disease

18

How is age linked to autoimmunity?

Autoimmunity is more common in the elderly

19

What are some other causative associations of autoimmunity?

- sex (hormonal influence)
- age
- sequestered antigens
- environmental triggers

20

How might sequestered antigens cause autoimmunity?

May be recognised as foreign by the immune system (eg. cell nucleus, eye, testis)

Sequestered antigens are those that cannot interact with the immune system during development as they are anatomically sequestered and hence the lymphocytes specific for such sequestered antigens are not deleted

21

Give some examples of environmental triggers that may lead to autoimmunity

- infection
- trauma-tissue damage
- smoking

22

In what way may infections cause autoimmunity as well as a normal immune response?

Infections activate the immune system generally

Molecular mimicry - eg. in rheumatic fever, antibodies against M protein of Streptococcus also react against the glycoproteins of the heart

23

Changes in amount or nature of auto antigens may cause autoimmunity. Give an example of this in terms of rheumatoid arthritis

Citrullination of proteins make them more immunogenic, which leads to rheumatoid arthritis

24

Changes in amount or nature of auto antigens may cause autoimmunity. Give example of this in terms of coeliac disease

Tissue transglutamase alters gluten to help it bind to HLA-DQ, leading to coeliac disease

25

Changes in amount or nature of auto antigens may cause autoimmunity. Give an example of this in terms of SLE

Failure to clear apoptotic debris increases availability of sequestered antigens inside the cell, leading to SLE

26

In what ways do T cells cause inflammation?

- by inflammatory cytokines (macrophages etc)
- by helping B cells make autoantibodies (plasma cells)

27

What are the features of auto reactive B cells and autoantibodies?

- directly cytotoxic
- activation of complement
- interfere with normal physiological function

General inflammation and end-organ damage

28

What are the features of auto reactive T cells?

- directly cytotoxic
- inflammatory cytokine production

General inflammation and end-organ damage

29

What are the general clinical features of autoimmune disease?

- more than 100 different disease
- can affect any organ of the body
- onset in middle/old age
- more common in elderly and women
- leads to loss of organ function
- life-long chronic condition
- characteristic exacerbation and remission
- traditionally divided into organ specific or systematic
- common for diseases to overlap

30

What are the 2 traditional divisions of autoimmune disease?

- organ-specific
- systemic

31

What are the characteristic of organ-specific autoimmune disease?

- affects a single organ
- autoimmunity restricted to auto antigens of that organ
- overlap with other organ specific diseases
- autoimmune thyroid disease is typical

32

What are the characteristic of systemic autoimmune disease?

- affects several organs simultaneously
- autoimmunity associated with auto antigens found in most cells of body
- overlap with other non-organ specific diseases
- connective tissue diseases are typical

33

Which type of diseases are a typical organ-specific autoimmune disease?

Autoimmune thyroid disease

34

Which type of diseases are a typical systemic autoimmune disease?

Connective tissue diseases

35

Give 2 examples of autoimmune thyroid disease?

- Hashimotos thyroiditis
- Grave's disease

36

What is Hashimotos thyroiditis?

- destruction of thyroid follicles by autoimmune process
- associated with autoantibodies to thyroglobulin and to thyroid peroxidase
- leads to hypothyroidism

37

What are the signs and symptoms of Hashimotos thyroiditis?

- fatigue
- difficulty concentrating
- constipation
- weight gain
- increased sensitivity to cold
- puffy face
- delayed relaxation reflexes

38

What is Grave's disease?

- inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
- leads to hyperthyroidism

39

What are the signs and symptoms of Grave's disease?

- anxiety
- weight loss
- diarrhoea
- palpitations
- loss of sensitivity to cold
- difficulty sleeping
- abundance of energy
- rapid pulse
- sweaty hands
- rapid reflexes
- exophthalmos (bulging eyes)

40

What is the characteristic eye sign of Grave's disease?

Exophthalmos

Protrusion of eyes

Swollen, red, bulging eyes

41

What is the key difference between Hashimoto's thyroiditis and Grave's disease?

Hashimoto's thyroiditis = antibodies DESTROY the thyroid leading to HYPOthyroidism

Grave's disease = antibodies STIMULATE the thyroid leading to HYPERthyroidism

42

What is myasthenia gravis?

A rare chronic autoimmune disease marked by muscular weakness without atrophy, and caused by a defect in the action of acetylcholine at neuromuscular junctions

43

Myasthenia gravis causes muscle weakness. Which muscles are most affected?

It mainly affects muscles that are controlled voluntarily – often those controlling eye and eyelid movement, facial expression, chewing, swallowing and speaking

44

What is a common presentation of myasthenia gravis?

- difficulty keeping eyes open
- difficulty speaking
- difficulty swallowing
- hardy smiles anymore
- problems worsen as the day progresses

45

What is the cause of myasthenia gravis?

Autoantibodies block the ACh receptor at the neuromuscular junction and therefore block the action of acetylcholine

46

Pernicious anaemia is due to a failure of absorption of which vitamin?

Vitamin B12

47

How might somebody with SLE present?

- fever
- general tiredness
- joint and muscle aches
- headaches
- rash on face
- rash worse when exposed to sun
- Raynaud's syndrome

48

What is the typical rash in SLE?

Butterfly rash

49

What other complications may be present in SLE?

- pleural effusion
- heart problems
- nephritis
- arthritis

50

How are immune complexes formed?

Anitbodies against antigens in the nucleus combine with their targets to form immune complexes in the circulation

51

How do immune complexes cause inflammation?

Immune complexes deposit in any organ – activate complement and cause inflammation

52

Give 4 examples of connective tissue diseases

- systemic lupus erythematosus
- scleroderma
- polymyositis
- sjogrens syndrome

53

When was the term ‘autoinflammation’ introduced?

In 1999 following identification of the genetic basis of periodic fever syndromes (FMF, TRAPS, CAPS, HIDS)

54

What are the main characteristics of autoinflammation?

- seemingly spontaneous attacks of systemic inflammation
- no demonstrable source of infection as precipitating cause
- absence of high-titre autoantibodies and antigen specific autoreactive T cells
- no evidence of auto-antigenic exposure

55

How do T cells cause inflammation?

By inflammatory cytokines (via macrophages etc) or by helping B cells make autoantibodies

56

What is the immunological disruption in autoinflammation compared to autoimmunity?

Autoinflammation = innate immunity

Autoimmunity = adaptive immunity

57

What is the cellular involvement in autoinflammation compared to autoimmunity?

Autoinflammation = neutrophils and macrophages

Autoimmunity = B cells and T cells

58

What are the clinical features of autoinflammation compared to autoimmunity?

Autoinflammation = recurrent, often seemingly unprovoked attacks

Autoimmunity = continuous progression

59

What is the antibody involvement in autoinflammation compared to autoimmunity?

Autoinflammation = few or no antibodies

Autoimmunity = autoantibodies present

60

What is the conceptual understanding of autoinflammation compared to autoimmunity?

Autoinflammation = tissue-specific factors/ danger signals

Autoimmunity = breaking of self-tolerance

61

What is the main genetic susceptibility in autoinflammation compared to autoimmunity?

Autoinflammation = cytokine and bacterial sensing

Autoimmunity = MHC class II associations and adaptive response genes

62

What is the therapy for autoinflammation compared to autoimmunity?

Autoinflammation = Anti-cytokine (IL-1, TNF, IL-6)

Autoimmunity = Anti-B and T cell

63

Give some examples of autoinflammatory disorders

- monogenic hereditary periodic fevers
- polygenic Crohn’s disease
- spondylarthropathies

64

What is the function of MHC Class I molecules?

To display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with via help of MHC class I protein

65

What is MHC Class I presentation also known as?

Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway

66

What is MHC Class II presentation also known as?

The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in class I); hence, the MHC class II-dependent pathway of antigen presentation is called the endocytic or exogenous pathway

67

How are MHC Class II molecules loaded?

Loading of a MHC class II molecule occurs by phagocytosis; extracellular proteins are endocytosed, digested in lysosomes, and the resulting epitopic peptide fragments are loaded onto MHC class II molecules prior to their migration to the cell surface

68

What is the function of MHC Class II molecules?

Presentation of extracellular pathogens - interact T helper cells (TCD4+) - these trigger an appropriate immune response which may include localised inflammation and swelling due to recruitment of phagocytes or may lead to a full-force antibody immune response due to activation of B cells