L3.3 Rheumatoid Arthritis & psoriasis Flashcards Preview

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Flashcards in L3.3 Rheumatoid Arthritis & psoriasis Deck (22)
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1

What is central and peripheral tolerance?

Self-reacting usually prevented by central & peripheral tolerance

  • Central =  regulating the type of T cell produced via CD8+ immune surveillance
  • Peripheral = involves a series of suppressions on T and B cells

2

What is autoimmunity and how does it occur?

immune system unable to discriminate b/w non-self & self

  • Occurs via:
  • Breakdown of tolerance
  • Post-translational modifications (env + epigenetics + susceptible genes)

Hard to remove AI disease if memory T & B cells are involved

 

3

Into what cytokines do CD4 cells differentiate into?

  • Th17 produces th17 cytokines
    • Brings neutrophils to injury sites

4

What can th17 cells be induced into?

Could be induced into:

  • Th17 - from TGF-B & IL6
    • Produces IL17
  • Th1 - from T-bet
    • Produces IF-γ

5

Features of R.A

  • Unknown etiology (origins)
  • Females > males (3:1)
  • Diagnosis:
    • Morning stiffness > one hour
    • Arthritis in 3 or more joints
    • Disease symmetrical
    • Radiological changes
  • Smoking is the main risk factor

6

Mechanism of RA

  1. Synovial membrane (synovitis)
  2. Inflammation not resolved
  3. Tissue hyperplasia, inflammatory cells invade & pannus formation
    • Pannus = benign tumour
  4. Pannus self-irritates → grows → recruits more inflammatory cells
  5. Neoangiogenesis → to sustain inflammatory cells to site
    • Generalise vasculitis → ↑risks of heart attack
  6. Pro-inflammatory cytokines permeate bones → cartilage/bone degeneration
    • GM-CSF irritate macrophage → promotes further breakdown of joint tissues
    • May also affect brain functions (depression)

7

Drugs targeting RA

  • CCR1 Antagonists
  • p38 inhibitors
  • ICE inhibitors
  • NSAIDs

8

CCR1 antagonists

  • Block chemokine receptors that assist leukocyte infiltration into tissue 
  • But fairly non-specific - problems with infection 

9

p38 inhibitors

  • P38 is one of the main signalling molecules in inflammation cascades 
  • Ass with lots of problems e.g. lung infections 

10

ICE inhibitors

  • ICE is a converting enzyme that converts many molecules  

11

NSAIDs

  • Classically target PGE2

12

Limitations of GC

  • Systemic SE with long term admin
  • Represses cartilage and bone formation
    • Accelerates joint degeneration

 

13

Limitations of DMARDs

  • "Disease modifying anti-rheumatic agents
  • Immunosuppressant of T-cells
  • ↑side effects & ↓effectiveness
  • Delayed onset on action

 

14

Changes in treatment

  • Earlier use of aggressive treatment
  • Biological + combination therapy → allows earlier/permanent remission

15

2 examples of Anti-TNF biologicals

  • Etanercept & Infliximab

16

Why are TNFs targeted?

 

  • TNF abundant in joint fluid (pro-inflam)
    • Further activates macrophages 
  • Anti-TNF antibodies → mops up excessive secreted TNF
    • Binds via CDR regions → blocks TNF from bidning to receptor
    • Macrophage not activated → TNF removed via immune system

 

17

Features of Psoriasis

 

  • Auto-immune skin disease
  • Irritation to skin repair system
    • Attacks connective tissues under skin → chronic inflam → hyperprolif
  • Skin becomes thick & scaly → keration stacks
  • Bacteria lodged in fissures/lesions → infections

 

18

Pathogenesis of psoriasis

MHC link → shows immune reaction to skin self antigen

19

What are langerhan cells

  • (type of dendritic cell)
  • where APC is localised to skin

20

Treatments for psoriasis: topical

 

  • Steroids → effective but large S.E
    • Dermal atrophy
    • Betamethosone, anthraline
  • Coal tar derivatives
    • Local suppression for macrophages and T cells
    • Promotes skin cacer
  • Vit D analogues
    • Calcipotriene
    • Teratogenic (causes birth defects)

 

21

Treatments of psoriasis: Phototherapy

  • UV light to suppress growth of hyper replicating dermis
  • Cancer risk

22

Treatment of psoriasis: Systemic

 

  • Vit A analogues
    • Forces cells to mature, go into quiet state
    • Also teratogenic
  • Cyclosporin
    • Immune suppressant
  • Methotrexate - anti-prolif
  • Biologicals
    • Anti-TNF & Anti-IL17 (IL17 found in plague form of disease)
      • Effective in around 40% of people
      • Ustekinumab (blocks IL12)
      • Brodalumab & ixekizumab (blocks IL17)