Immunology Course 2023

12 Dec 2023

Day 2 · Innate Immunity: PRRs and Cytokines

December 12, 2023

Session 2: Prof. Carla Rothlin, Yale School of Medicine

Innate Immunity:

Structure Based Recognition

• Case: DNA - Pattern-Based Recognition:
  • DNA is generally in the nucleus.
  • Foreign DNA in the cytoplasm activates CGAS (Cyclic GMP AMP Synthase), which recognizes foreign DNA, produces c-GAMP (messenger), activates STING, and eliminates the foreign DNA.
• Case: RNA:
  • Strategies:
    • Phagolysome (receptors activated at acidic pH):
      • TLR-3 (dsRNA), TLR-7 (ssRNA), TLR-9 (DNA).
    • RNA from virus into cytoplasm:
      • Sensors like RIR-I and MDA-5.
      • Human messenger RNA (mRNA) has a cap, distinguishing it from foreign RNA.
      • MDA-5 can recognize double-stranded RNA.
• Sensors: NOD I/II:
  • Recognize peptidoglycan.

  Pattern Recognition Receptors of various cells source: https://doi.org/10.1093/annonc/mdx179

Recognition of Damage

• Inflammasomes:
  • NLRP3 sensor detects damage, leading to assembly with ASC (an adaptor) and CASPASE-1 (enzyme).
  • CASPASE-1 cleaves pro-IL-1, inducing inflammation.
  • Mechanism of pro-IL-1 release needs clarification.
• Signaling Cascades:
  • TLR-4 uses MyD88 adaptor → TAKI enzyme → IKK → NF(kappa)(beta) induction of inflammatory mediators.
  • Dendritic Cells (Mature) → T-cells (activation).
  • Inflammatory Response → Cytokines and chemokines.

  Damage associated molecular patterns source: https://doi.org/10.3389/fpls.2019.00646

Cytokines

• Type I Interferons:
  • Discovered 70 years ago for interfering with viral infections.
  • Induce antiviral genes via JAK-STAT pathways.
  • Prevent viral replication machinery but not recommended for neurons, heart cells, or germ cells.

Group Discussion: mRNA Vaccine & Nobel Prize in Medicine 2023

• Exploring mRNA functionality, vaccine mechanisms, and addressing challenges.

Session 3: Dr. Dipyaman Ganguly, IISER

Me or not Me: Towards a Standard Model for Cellular Immunology

• Standard model evolution: Self vs. non-self, central tolerance, exceptions.
• Evolutionary necessity of an immune system: Understanding self and not self.
• Various models’ limitations: self-nonself, immune system reactions to infectious entities, exceptions in graft rejections, and pregnancy.

Danger Model: Poly Matzoinger

• Focuses on harm-causing entities regardless of origin but lacks explanation for NK cell behavior.

History of Immune Models source: Matzinger’s “danger model” vs. the classical theory of self vs. self-nonself

Antigenic Discontinuity Theory by Thosma Pradeu and Eruc Viver (2013)

• Suggests NK cell reaction to cellular changes.

Evolution

• Evolution’s role in the emergence of multicellular organisms and the necessity of an immune system to counter defectors.
• Multicellular organismality and ethical aspects.

Cancer Immunity Cycle

• Highlights the deviation in cancer cells from standard cellular functionalities.

Metaflammation & Alzheimer’s

• Links between cellular dysfunctions and related health issues.

Autoimmunity

• Conflicts and cues leading to autoimmunity.

Talk-4: Dr. Vinitha

How to Read Research Papers

What is Science?

• A system of acquiring knowledge and its accumulation.
• Everyday science: mundane tasks to complex research.

What is Technology?

• Systematic treatment of art and its practical application.

Paper: Vaccine Treatment of Splenomegaly in Chronic Malaria by BE Ingram Johnson LRCP Ed (15th Aug 1925)

• First report on malaria vaccine.

• Critique on methodological apparatus: lack of control, missing references, and interpretations.

• Consideration of premunition (balanced immunity) and the Hayflick limit in analyzing the results.
• WHO approval of the malaria vaccine in 2021.

Research, report findings, and publish!

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