Week 7: Autoimmune Diseases

• Immune System

  • Made up of different leukocytes
  • Neutrophils
  • Monocytes/macrophages
  • Lymphocytes
  • Eosinophils
  • Basophils
• Neutrophils

  • Makes up ~60-70% of total WBC count normally
  • Granulocytic segmented cells
• Neutrophils

  • Mostly white cytoplasm with small amount of granules
  • Primary granules are called azurophilic granules
  • Lysosomes that supply enzymes to digest ingested bacteria, viruses, and cell debris
• Neutrophil's Job

  • Usually 1st to respond of WBCs to an immune response
  • Responds heavily to bacterial infections
  • Will respond to inflammatory processes as well
• Neutrophil's Job

  • 3 functions
  • Phagocytosis
  • Release of neutrophil extracellular traps (NETs)
  • Degranulation of either extracellular or intracellular granules
• Neutrophil's Job

  • Also very important in recruiting other leukocytes
• Monocytes/Macrophages

  • Monocytes are in blood and macrophages are in tissues
  • boosts immune responses by showing antigens on its surface to other cells of the immune system
• Monocytes/Macrophages

  • 3-8% of WBC count but generally largest leukocyte
• Monocytes/Macrophages

  • Agranulocytic non-segmented leukocyte
  • have a blue-grey cytoplasm, lobulated nucleus, and a lacy chromatin pattern
  • Usually seen with vacuoles in cytoplasm
• Macrophage's Job

  • Phagocytosis process
  • Use their acidic pH to kill phagocytized microbes
  • Bacteriostatic proteins- proteins that inhibit bacterial protein synthesis pathways
  • Use degradative enzymes
• Macrophage's Job

  • Uses hydrogen peroxide much more than neutrophils
  • Eventually become the most common at inflammatory site
  • “Clean up crew”
• Lymphocytes

  • Starts out in bone marrow and then moves to lymphoid tissue
  • Has large (immature) and small (mature) cells
• Lymphocytes

  • Agranulocytic non-segmented cells (20-40% of circulating WBC)
  • Dog and cat are classic small cells with smudged or smooth chromatin (heterochromatin) and scant amounts of light blue cytoplasm
  • Nuclei are round to slightly indented or irregular
• Lymphocytes

  • Develops into T and B cells
• Lymphocyte’s Jobs

  • Cell-mediated immunity (T cells)
  • Involves the formation of a lot of lymphocytes to destroy foreign substances like antigens
  • T cells destroy cells that have already been infected
• Lymphocyte’s Jobs

  • Humoral immunity (B cells)
  • B cells make the antibodies to signal other cells to attack
• Lymphocyte’s Jobs

  • 3 types of T cells○ Cytotoxic (killer)○ Memory○ Helper
• Lymphocyte’s Jobs

  • 2 types of B cells○ Plasma○ Memory
• T Cells

  • Cytotoxic
  • Receptors bind to specific receptors that activate cell to release toxic substances into foreign cell
  • Big culprit of transplant rejection syndrome
  • Spurred on by antigens causing activatio
• T Cells

  • Helper
  • Most numerous
  • Assists in activation of cytotoxic T cells and B cells
  • Makes response more intense
• T Cells

  • Memory
  • Long-lived that are capable of responding to the same antigen a long time later
• Humoral Immunity

  • Antibodies can inactivate antigens 4 ways
  • Agglutination and Precipitation
  • Antigens are clumped together by bivalent antibodies
  • Precipitation is soluble antigens and antibodies combining to be insoluble complex
  • Agglutination is combo of specific antigens and antibodies that form a clump
• Humoral Immunity

  • Neutralization
  • Uses antibodies to block entry of a pathogen into a cell so unable to infect healthy cells, and it is unable to replicate and cause severe infection
• Humoral Immunity

  • Lysis
  • Antibodies activate complement system
  • A system that has many enzyme precursors used to destroy foreign material
  • Do opsonization and chemotaxis
• B cells

  • Plasma (or effector)
  • Produce large quantities of antibodies that will attach to antigens to signal other cells to destroy it
  • Will only do this once activated
• B cells

  • Memory
  • Act very similar to memory T cells
  • long-lived and quiescent cells that are poised to quickly respond to antigen upon recall
  • Will turn into effector cells if encounter same antigen at a later date
• Autoimmune Diseases

  • Immune-mediated Hemolytic Anemia (IMHA)
  • Immune-mediated Thrombocytopenia (IMTP)
  • Immune-mediated Polyarthritis (IMPA)
• What is IMHA?

  • Condition where immune system attacks its own RBCs and signals for their destruction
  • Normally will either be removed by spleen or liver or will rupture once at end-of-life
• What is IMHA?

  • Disease due to too many RBCs being “tagged” with antibodies for destruction
  • Causes intravascular and extravascular destruction and removal of RBCs
• What is IMHA?

  • Generally idiopathic immune-mediate, but can be caused by trauma, infections, toxins, and neoplasia
• Pathophysiology

  • Extravascular
  • Antibody-coated RBCs are recognized and phagocytosed by macrophages in organs like spleen
  • Hemoglobin is released inside macrophages and metabolized to bilirubin
• Pathophysiology

  • Intravascular
  • Antibody and complement on RBC surface leads to direct cell lysis in circulation
  • Hemoglobin released directly into bloodstream
• IMHA- Clinical signs

  • Pale/icteric gums
  • Lethargy
  • Collapse
  • Exercise intolerance
  • Anorexia
• IMHA- Clinical signs

  • +/- dark orange/brown urine
  • Tachypnea
  • +/- vomiting
  • +/- fever
  • Necrosis of distal extremities
• IMHA- Risk Factors

  • Predisposed breeds secondary to Pyruvate kinase deficiencies:
  • Basenjis, Beagles, West Highland White Terriers, Cairn Terriers; Abyssinian and Somali cats
• IMHA- Risk Factors

  • Others predisposed: Cocker and Springer Spaniels, Poodles
  • Usually happens in dogs 2-8yrs of age
  • 4x more likely in females
• IMHA- Physical exam

  • Depressed-obtunded
  • Severe weakness
  • Tachycardia
  • Tachypnea
  • Bounding pulses
• IMHA- Physical exam

  • Those with severe anemia often have a grade I-II systolic left-sided murmur
  • Mild to marked systemic jaundice
  • Hemoglobinemia
  • Hemoglobinuria
• IMHA- diagnostics *Start w/ CBC/chem*

  • Severe regenerative anemia (<15% HCT/PCV often found), elevated reticulocyte count (⅓ of cases will see a decrease instead), leukocytosis with profound neutrophilia, mild to moderate thrombocytopenia (~55% of cases)
• IMHA- diagnostics *Start w/ CBC/chem*

  • Hyperbilirubinemia (if extravascular), elevated ALT, and hemoglobinemia