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Infection & Immunity > CE Chronic Inflammation & RA [Unfinished] > Flashcards

CE Chronic Inflammation & RA [Unfinished] Flashcards

1
Q

Why is inflammation required?

A

To recruit white blood cells to the site of infection

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2
Q

What do the WBCs do once recruited?

A

Eradicate the infection and repair any damage

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3
Q

What happens if problems occur with inflammation?

A

Localised inflammation can become systemic or spread within an organ

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4
Q

What happens if regulatory processes break down?

A

The acute inflammation progressively worsens and becomes long-term (chronic)

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5
Q

How were many treatments for RA discovered?

A

Existing agents serendipitously discovered to have anti-rheumatic effects

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6
Q

What is Rheumatoid Arthritis?

A

a progressive inflammatory condition of the joints

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7
Q

What are the symptoms of RA?

A

Affected joints will exhibit the cardinal signs of inflammation:

  • Pain
  • Swelling
  • Heat
  • Loss of function
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8
Q

What are the cardinal signs of inflammation?

A
  • Heat
  • Loss of function
  • Pain
  • Redness
  • Swelling
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9
Q

What are the first joints to normally be affected in RA?

A

Small joints in the extremities i.e the hands and feet

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10
Q

What symptoms will RA patients initially notice?

A

Joint pain and stiffness (particularly in the mornings after periods of inactivity)

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11
Q

What joints are affected in RA as the condition progresses?

A

Larger joints, particularly those involved with movement. I.e knee, elbow and neck joints

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12
Q

What happens if RA is left untreated?

A

extensive deformity

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13
Q

What is the main area of destruction in RA?

A

The cartilage of the joint

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14
Q

What is the function of cartilage?

A

Protective covering over the joints

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15
Q

What is the characteristic deformity seen in RA patients?

A

Swan-neck finger joints (in later stages of the disease)

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16
Q

Why does movement become more limited as RA progresses?

A

Increased swelling and deformity

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17
Q

What is the Rheumatoid Factor?

A

an autoantibody against IgG (anti-IgG)

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18
Q

Is Rheumatoid Factor specific for RA?

A

No.

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19
Q

Are Anti-Citrullinated protein antibodies specific for RA?

A

More so than RF, and can be used in the diagnosis of RA.

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20
Q

Describe the structure of a normal joint

A

Two bones, each protected by a cartilage layer. These are held within a capsule called the ‘synovium’ which contains synovial fluid that acts as a lubricant.

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21
Q

In RA what happens to the cartilage?

A

It is attacked and degraded

22
Q

How does the destruction of cartilage occur?

MAKE SEPARATE SHEET FOR THIS

A
  1. Fibroblast cells (synovial fibroblasts) infiltrate and proliferate uncontrollably in the synovium leading to cellular accumulation
  2. Inflammatory cells (particularly macrophages and TH1 cells) accumulate within the joint
  3. The accumulating cells draw fluid into the joint which leads to swelling
  4. The cells restrict the movement of the joint leading to loss of function
  5. When the cartilage is destroyed the bones in the joint begin to rub together (this is the main cause of the pain)
23
Q

What is the main cause of pain in RA?

A
  • Joints rubbing together

- Pressure on the nerve endings

24
Q

What are the main types of inflammatory cell that accumulate within the joint in RA?

A
  • Macrophages

- TH1

25
Q

Is bone regeneration possible?

A

Yes but it is difficult and limited

26
Q

Why is rapid medical intervention required with RA?

A

To prevent permanent damage.

By the time the inflammatory symptoms are seen, the joint will have already been damaged

27
Q

Who is most commonly affected by RA?

A

Older people

28
Q

When does juvenile RA usually develop?

A

Late teens to early 20s

29
Q

What percentage of the UK adult population does RA affect?

A

0.8%

30
Q

Is there a genetic risk of getting RA?

A

Yes

31
Q

If one twin has RA what is the chance that the other twin will develop it?

A

16%

32
Q

Is there a hormone related component to RA?

A

Yes (Females have higher chance of developing RA)

33
Q

Who are more likely to develop RA? Men or Women?

A

Women

34
Q

Why is incidence of RA higher in smokers?

A

Increased genetic mutations

35
Q

Which allele is RA associated with?

A

the MHC allele ‘HLA-DR4’

  • People with HLA-DR4 are more predisposed to developing RA
36
Q

Where are Class II MHC located?

A

Antigen presenting cells

37
Q

What types of cells are antigen presenting?

A
  • B cells
  • Macrophages
  • Dendritic cells
  • Neutrophils
38
Q

What do Class II MHC located on antigen presenting cells do?

A

Presenting antigen fragments to T cells to activate the immune system

39
Q

What are the classes of Class II MHC?

A

DR, DQ and DP

40
Q

What is the suggested mechanism of HLA-DR4 increasing chance of getting RA?

A

May present a certain self-antigen (may be collagen or a component of cartilage) to T cells in such a way that the T cells recognise it as foreign

41
Q

Are there any other HLA alleles associated with the development of RA?

A

Yes, a number of others

42
Q

Is there an environmental link with RA?

A

Yes

43
Q

Exposure to what can increase the risk of developing RA?

A
  • Cigarette smoke
  • Inner city environments
  • Immunosuppressant chemicals
  • Immune reacting chemicals
  • Infection (in many patients RA has been found to follow severe infection)
44
Q

What is Molecular Mimicry?

A

Some pathogenic antigens look similar to self-antigens, it therefore takes the immune system a long time to recognise the pathogen.
The immune system therefore recognises the self-antigen as pathogenic following the infection.

45
Q

Which infections are associated with an increased risk of RA? and Why?

A
  • Mycobacterium infections
  • Streptococcal throat infections
  • They take a long time to eliminate
46
Q

What happens to the pathogens in long term infection?

A

They remind in the body and the immune system cannot eradicate them

47
Q

Long term activate of the immune system is associated with the presence of…

A
  • Pro inflammatory mediator secreting macrophages
  • Cytokine secreting T cells
  • Antibody secreting B cells
48
Q

What do B cells secrete?

A

Antibodies

49
Q

What do T cells secrete?

A

Cytokines

50
Q

What do Macrophages secrete?

A

Pro inflammatory mediators

51
Q

What does prolonged immune activation mean?

A

The body starts to target similar self-antigen.
The immune system then becomes perpetually activated as there is a large amount of collagen in the body which it now recognises this as foreign

Infection & Immunity (14 decks)

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