Cell Signaling and Immunology

Immune Response

• The immune system is essential for our survival, defending us against bacteria, viruses, parasites, and more.
• It is a complex network of cells, organs, proteins, and tissues that can distinguish self from non-self.

Types of Leukocytes

• Phagocytes: surround and absorb pathogens, breaking them down.
  • Neutrophils: attack bacteria.
  • Monocytes: largest type, with multiple roles.
  • Macrophages: patrol for pathogens, remove dead and dying cells.
  • Mast cells: help heal wounds, defend against pathogens.
• Lymphocytes: help the body remember previous invaders and recognize them if they come back.
  • B lymphocytes (B cells): produce antibodies, alert T lymphocytes.
  • T lymphocytes (T cells): destroy compromised cells, alert other leukocytes.

Antigen and Antibody Response

• An antigen is any substance that can spark an immune response.
• B cells recognize the antigen, secrete antibodies (antigen is short for “antibody generators”).
• Antibodies are special proteins that lock onto specific antigens.
• Types of antibodies:
  • Immunoglobulin G (IgG): marks microbes for other cells to recognize and deal with.
  • IgM: kills bacteria.
  • IgA: congregates in fluids, protecting gateways into the body.
  • IgE: protects against parasites, responsible for allergies.
  • IgD: stays bound to B cells, helping them to start the immune response.

T Lymphocytes

• Helper T cells (Th cells): coordinate the immune response.
• Killer T cells (cytotoxic T lymphocytes): attack and destroy infected cells.

Types of Immunity

• Innate immunity: born with it, general protection.
• Adaptive immunity: develops throughout life, specific to diseases.
• Passive immunity: borrowed from another source, short-term.

Eicosanoids

• Signaling molecules derived from arachidonic acid.
• Play a role in mediating inflammatory responses.
• Include prostaglandins, leukotrienes, and thromboxanes.

Cyclooxygenase (COX) Pathway

• COX is an enzyme that converts arachidonic acid to prostanoids.
• Two isozymes: COX-1 and COX-2.
• COX-1: constitutively expressed in most cells and tissues.
• COX-2: upregulated during inflammation.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Inhibit COX, reducing prostaglandin synthesis.
• Examples: aspirin, ibuprofen, naproxen.
• Therapeutic effects: reduce inflammation, fever, pain, and platelet aggregation.
• Side effects: affect GI tract, kidney, and cardiovascular system.

COX-2 Selective Inhibitors (Coxibs)

• Selectively inhibit COX-2.
• Examples: celecoxib (Celebrex).
• Lower incidence of GI side effects compared to non-selective NSAIDs.
• Associated with increased risk of thrombosis, myocardial infarction, and stroke.

Glucocorticoids

• Effects result from changes in gene expression.
• Therapeutic responses require several hours to develop.
• Metabolic effects: hyperglycemia, changes in fat deposition.
• Anti-inflammatory effects: mediated by transcriptional inhibition.

Lipoxygenase/Leukotriene Pathway

• Activated in leukocytes, resulting in the conversion of arachidonic acid to leukotrienes.
• Leukotrienes: inflammatory mediators, resulting in bronchoconstriction, increased secretion of mucus, leukocyte chemotaxis, and histamine release.

Epoxyeicosatrienoic Acids (EETs)

• Produced by cytochrome P450 epoxygenase.
• Act as short-range hormones in the cardiovascular system and kidney.
• Produce vasodilation by activating Ca-activated K channels.