Autoimmune Disorders: Animal Models

Autoimmune Disorders: Animal Models

• Immunodeficient mice have defects in one or more immune components (like T, B, or NK cells).
• Triple immunodeficient mice can host xenografts (tissue from other species), human immune cells, and enable studies of tumor biology, immunology, infectious disease, graft-versus-host disease (GvHD), hematopoiesis, and tissue transplantation.

Nude Mice

• Nude mice were the first immunocompromised strain used in cancer research.
• They lack a thymus and have a suppressed immune system due to fewer T cells.
• Nude mice don't reject tumors, making them ideal for tumor and tissue studies.
• They are hairless, aiding in tumor identification.

SCID Mouse Model

• SCID stands for severe combined immunodeficiency disease.
• SCID mice exhibit a severe deficiency that affects both B and T lymphocytes (white blood cells involved in the immune response).
• SCID mice have been invaluable for research on a wide range of topics, including human stem cell development, human diseases, their interactions with the human immune system, vaccinations, and cancer.
• The mutation in SCID mice was discovered from the CB/17 mouse line and is due to a mutation in the gene for a protein kinase.
• The protein plays a crucial role in repairing double-stranded DNA breaks. This process is essential for B and T cell development, specifically V, D, or J segment rearrangements within DNA.
• SCID mice have lymphocyte precursors but are unable to mature into fully functional B and T lymphocytes.
• As a result, they lack these cells in their thymus and secondary lymphoid organs.
• Some SCID mice can produce monocytes, granulocytes, and erythrocytes from their bone marrow, but they commonly die young unless kept under sterile conditions.

SCID Mice in Research

• SCID mice can be used in research related to human physiology and diseases, as they can accept human hematopoietic stem cells.
• This enables the development of human adaptive immune cells in the mouse, allowing study in in vivo conditions.

Hypersensitivity

• Hypersensitivity describes exaggerated or inappropriate immune responses to antigens or allergens.
• Immediate hypersensitivity reactions occur within 24 hours and affect type I, II, and III reactions.
• Four types of hypersensitivity:
  • Type I: Mediated by IgE antibodies, causing allergies and anaphylaxis.
  • Type II: Cytotoxic reactions through IgG or IgM antibodies.
  • Type III: Immune complex-mediated reactions.
  • Type IV: Delayed reactions mediated by T cells.

Type I Hypersensitivity

• This occurs within minutes after exposure to an allergen.
• Antibodies (IgE) bind to mast cells and basophils.
• Subsequent exposure to the allergen leads to cross-linking of IgE antibodies.
• Release of potent chemical mediators (histamine, etc.) causes the allergic reaction.
• A severe reaction can lead to anaphylaxis.

Type II Hypersensitivity

• Characterized by IgG / IgM antibodies attacking target cells.
• Examples:
  • Haemolytic disease of the newborn
  • Autoimmune haemolytic anemia
  • Goodpasture's syndrome.

Type III Hypersensitivity

• Immune complexes (antigen-antibody) deposit in tissues.
• This activates the complement system leading to inflammation and tissue damage.
• Examples:
  • Serum sickness
  • Post-streptococcal glomerulonephritis
  • Systemic lupus erythematosus

Type IV Hypersensitivity

• Delayed-type hypersensitivity reactions (24-72 hrs).
• T cell-mediated, and not antibody-mediated.
• Examples:
  • Contact dermatitis
  • Mantoux test for tuberculosis

Specific Impaired Functions in Lymphoid and Myeloid Lineages

• Lymphoid lineage includes T, B, and NK cells.
• Myeloid lineage includes megakaryocytes, erythrocytes, granulocytes, and macrophages.