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MD4001 Physiology > Autoimmunity > Flashcards

Autoimmunity Flashcards

1
Q

How common are autoimmune diseases?

A

5 - 8% in most western populations

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2
Q

What percentage of autoimmune diseases affect females?

A

75% (4th largest class of disease in females)

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3
Q

What are autoimmune diseases caused by?

A

Usually complex, interplay between multiple genes, and external factors (genetic predisposition and environmental modulators/triggers)

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4
Q

What autoimmune diseases are caused by a single gene?

A
  • Autoimmune polyglandular syndrome type 1 (APS-1), AIRE

- Autoimmune lymphoproliferative syndrome (ALPS) FAS, FASL

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5
Q

What organ does autoimmune uveitis affect?

A

Eyes

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6
Q

What organ does sjogrens syndrome affect?

A

Mouth

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7
Q

What organ does pemphigus affect?

A

Skin and mucosa

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8
Q

What organ does Goodpasture’s affect?

A

Lung

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9
Q

What is tolerance?

A

The process that keeps the immune system from attacking ‘self’

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10
Q

What cels are deleted in the thymus?

A

T cells which bind to your own MHC and self peptides with too much high affinity - some may escape

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11
Q

What is peripheral tolerance?

A

Works on the ability of T cells which can react with self peptides and self MHC not becoming active and releasing pro inflammatory cytokines - but becoming a T regulatory cell - release cytokines that stop other autoreactive T cells from becoming activatied through suppresive cytokines (IL-10 TGFB) dapmen down immune responses

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12
Q

What are the mechanisms involved in the breakdown of tolerance?

A
  • Failure to delete autoreactive lymphocytes (APS-1, ALPS)
  • Central or peripheral tolerance failure
  • Molecular mimicry
  • Abnormal presentation of self antigens
  • Aberrant expression of HLA class II molecules
  • Release of sequestered self antigens
  • Overproduction of self anitigens
  • Cyptic T cell epitopes
  • Epitope spreading
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13
Q

What is a classic example of molecular mimicry?

A

Rheumatic fever

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14
Q

WHat is Rheumatic fever?

A
  • Group A Streptococcus infection, typically in throat
  • Antibodies generated against Strep carbohydrate GlcNAc
  • These antibodies cross react on cardiac myosin
  • T cells also produced
  • Heart valves damage, but also brain/neuronal damage possible
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15
Q

What are the signs/symptoms of Systemic Lupus Erythematous (SLE)?

A
  • Butterfly rash
  • Raised red patches on skin
  • Light sensitivity
  • Mouth ulcers
  • Heart / Lung lining inflammation
  • Seizures / nerves problems
  • Proteinuria (lupus nephritis)
  • Raynaud’s phenomenon (cold pale fingers)
  • Arthritis
  • ANA - antinuclear antibodies
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16
Q

What are the treatments for Systemic Lupus Erythmatous (SLE)?

A
  • Systemic corticosteroids
  • Steroid creams
  • Antimalarials (hydroxychloroquine)
  • Monoclonal antibodies (rituximab)
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17
Q

What are the signs/symptoms of Sjorgen’s syndrome?

A
  • Typically presents with dry salivary glands
  • Articular problems (38%)
  • Glandular (palpable glands e.g parotid) (22%)
  • Pulmonary (11%)
  • Cutaneous (10%)
  • Lymph nodes enlarged (9%)
  • Constitutional symptoms (9%)
  • Peripheral neuropathy (6%)
  • Renal (5%)
  • Muscular (2%)
  • CNS (2%)
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18
Q

What is the treatment of Sjogren’s syndrome?

A
  • Eye drops
  • Antifungals
  • NSAIDs
  • Hydroxychloroquine
  • Methotrexate
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19
Q

What cancer is at a 5x increased risk in Sjorgen’s syndrome?

A

Non-Hodgkin lymphoma (swollen glands, night sweats, unexplained weight loss)

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20
Q

What is a classic Autoimmune disease of the thyroid?

A

Grave’s disease

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21
Q

What happens in Grave’s disease?

A
  • Overstimulation of thyroid
  • Antibodies generated against TSH receptor which mimics TSH
  • Causes typically buldging eyes
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22
Q

What is the treatment of Grave’s disease?

A
  • Methimazole
  • Thyroidectomy
  • Radioactive iodine
23
Q

What is hashimoto’s thyroiditis?

A
  • Autoimmune hypothyroidism
  • Antibodies to thyroglobulin and thyroid peroxidase
  • Fatigue, feeling cold, TSH increase, weight gain, enlarged thyroid
24
Q

What is an example of a condition which causes an underactive thyroid?

A

Hashimoto’s thyroiditis

25
Q

What is the treatment for Hashimoto’s thyroiditis?

A

Replacement therapy - levothyroxine

26
Q

What do antibodies attack in myasthenia gravis?

A

Ach receptors

27
Q

What are the signs symptoms of myasthenia gravis?

A
  • Long-term neuromucular problems
  • Double vision (diplopia)
  • Ptosis
  • Affects other facial muscles
  • Skeletal muscle weakness esp after exercise
28
Q

What is the treatment for myasthenia gravis?

A
  • Thymectomy
  • Immunosuppressive drugs
  • Plasmapherisis to remove circulating antibodies
29
Q

What is autoimmune pernicious anemia?

A
  • Autoimmune condition of the stomach
  • Antibodies generated to parietal cells and intrinsic factor
  • Deficiency in vitamin B12 results as no binding to intrinsic factor and absorption
30
Q

What is the treatment of Autoimmune pernicious anemia?

A

B12 injections

31
Q

What is autoimmune haemolytic anemia?

A
  • Antibodies binding to RBC
  • Lysis, clumping, clearence by spleen
  • Induced by drug or agent modifying RBC surface, neo antigen created
32
Q

What are the symptoms of autoimmune haemolytic anemia?

A
  • Chills
  • Jaundice
  • Tachycardia
  • Pale
  • Fatigue
  • Dark urine
33
Q

What is the treatment for autoimmune hemolytic anemia?

A
  • Avoid activating drug
  • Plasmapherisis
  • Splenectomy
34
Q

What cells attack the myelin sheath in MS?

A

CD4 and CD8 T cells

35
Q

What are possible treatments for MS?

A
  • Steroids, muscle relaxant for spasm

- Stem cell transplant

36
Q

How many people does rheumatoid arthritis affect in the UK?

A

350,000 people

37
Q

What is rheumatoid arthritis characterised by?

A

Inflammation of the lining or synovium of the joints - maylead to long term joint damage, chronic pain, and disability

38
Q

When does rheumatoid arthritis usually diagnosed occur?

A

Between ages of 30 and 50 but can also affect young children

39
Q

What gender does rheumatoid arthritis affect

A

3 times more common in women than men

40
Q

WHat are the typical joints affected by Rheumatoid arthritis?

A
  • Foot ankle and knee
  • Hip (usually later onset)
  • Hands and wrists
  • Elbow
  • Shoulders
41
Q

What other organs are affected by Rheumatoid arhtritis?

A
  • Blood (hypochromatic-microcytic anemia with low serum ferritin and low or normal iron-binding capacity)
  • Nerves (cervical spine instability)
  • Heart (pericardial effusion)
  • Lungs (interstitial lung disease)
  • Eyes (keratoconjunctivitis sicca, episcleritis, scleritis)
  • Skin (rheuamatoid nodules in 50% of patients, dermal vasculitic lesions)
42
Q

What genes are associated with rheumatoid arthritis?

A
  • Specific human leukocyte antigen (HLA)-DR genes
  • HLA-DR4 (2/3s of whites with RA)
  • Reside in the MHC and participate in antigen presentation
  • Higher risk of severity of disease; increased by homozygosity
43
Q

What are the potential roles of HLA-DR genes?

A
  • Binds to arthritogenic peptides
  • Serves as a target for autoreactive T cells
  • Closely linked to other genes in the MHC
44
Q

What lab test can be done to diagnose rheumatoid arthritis?

A
  • Imaging studies - Erythrocyte Sedimation Rate
  • Blood tests - C-reactive protein
  • Rheumatoid factor - Antinuclear antibodies (ANA)
45
Q

What are the focuses of rheumatoid arthritis treatment?

A
  • Relieving pain
  • Reducing inflammation
  • Stopping or slowing joint damage
  • Improving fnctioning and sense of well-being
46
Q

What are the medications used for rheumatoid arthritis?

A 
Symptomatic medications 
- NSAIDs
- Analgesics 
- Corticosteroids
Disease Modifying Drugs 
- Methotrexate 
- Sulfasalazine- Azathioprine 
- Cyclosporine - Hydroxychloroquine 
- Minocycline 
Biologic modifiers 
- Inflixamab (anti-TNF) - Rituximab (anti-CD20)
- Combination DMARD therapy
47
Q

What organ is attacked in Coeliac disease?

A

Small intestines (autoimmune reaction to gluten)

48
Q

How common is coeliac disease?

A

1 in 100 (2 - 3 x higher in females)

49
Q

What are the symptoms/signs of coeliac disease?

A
  • Diarrhoea
  • Abdo pain
  • Bloating
  • Complications (osteoperosis, iron, B12 deficiency, folate-deficiency anaemia, bowel cancer)
50
Q

What genes can cause coealiac disease?

A
  • HLA class II link - DQ 2.5 (most common)

- DQ8 and DQ2.2 (less common)

51
Q

What is gluten?

A

Overall term for a series of proteins called gliadins

52
Q

What protein attacks glutamine in coeliac disease?

A

Transglutamidase 2 (TG2) (changes into glutamic acid)

53
Q

What does glutamic acid bind to a higher affinity for in coeliac disease - how does this affect the disease?

A

Class II molecules - stimulates autoreactive T cells - inflammatory response dmage gut lining (Th1 and Th17) - pro inflammatory cytokines can then damage gut wall

MD4001 Physiology (22 decks)

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