Immunology L6: Autoimmunity

Question 1

T Cell Activation

Answer 1

• Requires 2 signals:
  
  • Signal 1 via TCR
  • Signal 2 via co-stimulatory molecules
• Signal 1 in absence of signal 2 leads to anergy.

Question 2

Anergy

Answer 2

• functional inactivation of lymphocytes following encounter with Ag (Ag presention w/o co-stimulation)
• peripheral tolerance
• Suppression by T regulatory cells
• Activation-induced cell death

Question 3

Immune Ignorance

Answer 3

• Failure to elicit immune response due to sequestering of Ag away from immune cells
• Immune-privileged sites: Testis, eye, brain
• ? Gut mucosal barrier: Enteric bacteria

Question 4

Autoimmune Susceptibility Genes

Answer 4

• Certain HLA alleles
• PTPN-22 (protein tyrosine phosphatase): RA, Type I DM, others
• Genes for bacterial sensing
• Cytokine genes

Question 5

Immune-Mediated Inflammatory Diseases

Answer 5

Mediated by Abs and immune complexes

– Organ-specific (MG, Graves disease)

– Systemic (SLE, PAN)

Mediated by T cells
– Organ-specific (Type I DM, MS)
– Systemic (RA, SS, Sjogren’s, IBD)

Question 6

SLE

Answer 6

• Malar rash
• Discoid rash: red, raised, disk-shaped patches
• Photosensitivity
• Oral ulcers
• Arthritis
• Serositis
• Kidney disorder
• Neurologic disorder
• Blood disorder
• anti-ds DNA, anti-phospholipid, anti-nuclear Antibodies

Question 7

Environmental Factors in SLE

Answer 7

• UV exposure triggers apoptosis and may render DNA immunogenic
• Sex hormones
• Viral infections (EBV)
• Drugs
  
  • – Hydralazine
  • – Procainamide
  • – D-penicillamine

Question 8

IBD Pathogenesis

Answer 8

• Genetics
  
  • – Variants in >160 genes increase risk
  • – NOD2, ATG16L1,
  • **IL10: **leads to defective negative feedback regulation of immune activation, with decreased/absent Treg activity and severe inflammation.
• Mucosal immune responses: Activation of Th1 and Th17 cells
• Defective epithelial barrier
• Microbiota (biofilms vs. planktonic)

Question 9

Crohn Disease

Answer 9

• Can affect mouth to anus, but more commonly affects ileum and/or colon
• Skip lesions
• Inflammation is typically discontinuous and transmural -> may lead to fistula

Histopath:

• deep fissuring
• Granuloma formation in 1/3 of Pt

Question 10

Ulcerative Colitis

Answer 10

• Always involves the rectum and extends proximally in a continuous fashion to involve part or all of the colon.
• Continuous colonic involvement, beginning in rectum
• Proctitis, colitis

Colonoscopy findings

• Hyperemia
• Exudates
• Bleeding at touch

Histopath

• LP infiltrated with lymphocytes
• Crypt abscesses common