Innate

• The innate immune system is the first line of defense against pathogens.
• Innate immunity


  Defenses against infection that are ready for immediate action when a host is attacked by a pathogen
• Two parts of innate immunity

  • External defense system
  • Internal defense system
• External defense system

  • Composed of physical, chemical, and biological barriers that function together to prevent most infectious agents from entering the body
• Internal defense system

  • Includes cellular responses that recognize specific molecular components of pathogens
• External defense system

  1. Cough and sneeze reflexes expel microbes

  2. Lacrimal glands

  3. Salivary glands

  4. Lysozyme

  5. Mucus traps microbes, cilia expel mucus
• Skin

  • Epidermis - outer layer of skin, contains tightly packed epithelial cells coated with keratin
  • Dermis - thicker layer with blood vessels, hair follicles, sebaceous glands, sweat glands, and white blood cells
  • Lactic acid in sweat and fatty acids from sebaceous glands maintain skin pH around 5.6
  • Psoriasin - antibacterial protein produced by skin cells
• Respiratory tract

  1. Mucous secretions block bacterial adherence

  2. Surfactants bind to microorganisms to help move pathogens out

  3. Cilia motion clears away deposited material

  4. Coughing and sneezing help move pathogens out
• Urinary tract

  1. Flushing action of urine and slight acidity helps remove potential pathogens

  2. Lactic acid production keeps vagina at pH around 5.7
• Digestive tract


  Stomach's hydrochloric acid keeps pH as low as 1
• Lysozyme


  Enzyme found in many bodily secretions that attacks cell walls of microorganisms, especially gram-positive
• Colicins


  Proteins produced by resident microorganisms that bind to and kill certain bacteria
• Internal defense system

  • Composed of both cells and soluble factors with specific and essential functions
  • Phagocytic cells engulf and destroy foreign cells or particles
• Phagocytosis


  Enhanced by specific receptors on cells that capture invaders through identification of unique microbial substances
• Acute-phase reactants


  Soluble factors that act to facilitate contact between microbes and phagocytic cells or recycle important proteins after phagocytosis
• Pathogen recognition receptors (PRRs)

  • Toll-like receptors (TLRs)
  • C-type lectin receptors (CLRs)
  • Retinoic acid-inducible gene-I-like receptors (RLRs)
  • Nucleotide-binding oligomerization domain receptors (NOD)
• Toll-like receptors (TLRs)


  Membrane-spanning glycoproteins that share a common structural element called leucine-rich repeats (LRRs) and bind to specific pathogenic substances to activate immune responses
• TLR receptors

  • TLR1, TLR2, TLR4, TLR5, TLR6 - found on cell surfaces
  • TLR3, TLR7, TLR8, TLR9 - found in endosomal compartments
• 1. type lectin receptors (CLRs)


  Plasma membrane receptors that bind to mannan and β-glucans found in fungal cell walls and produce cytokines and chemokines to eliminate microbes
• Retinoic acid-inducible gene-I-like receptors (RLRs)


  Recognize RNA from RNA viruses in the cytoplasm of infected cells and induce inflammatory cytokines and type I interferons
• Nucleotide-binding oligomerization domain receptors (NOD)

  Bind peptidoglycans found in bacterial cell walls and help protect against intracellular protozoan parasites
• 1. Reactive Protein (CRP)


  Member of the pentraxin family that acts like an antibody, capable of opsonization, agglutination, precipitation, and activation of complement<|>Main substrate is phosphocholine, a common constituent of microbial membranes<|>Widely used indicator of acute inflammation and risk marker for cardiovascular disease
• 1. Reactive Protein (CRP)


  • Increases rapidly within 4-6 hours of infection/injury, peaks within 48 hours, and returns to normal rapidly once condition subsides
  • Elevated levels found in bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis, and after a heart attack
• Serum Amyloid A (SAA)


  Major protein secreted during acute inflammation<|>Apolipoprotein synthesized in the liver that removes cholesterol from macrophages, recruits immune cells, and plays a role in cholesterol metabolism
• Complement


  Series of serum proteins involved in mediation of inflammation, opsonization, chemotaxis, and cell lysis
• Alpha1-Antitrypsin (AAT)


  Plasma inhibitor of proteases released from leukocytes, especially elastase<|>Deficiency can result in premature emphysema, especially in smokers or those exposed to noxious chemicals
• Haptoglobin


  Alpha-globulin that binds irreversibly to free hemoglobin to protect kidneys and prevent iron loss<|>Used to monitor hemolysis
• Fibrinogen


  Coagulation factor integral to clot formation that serves as a barrier to prevent spread of microorganisms
• Ceruloplasmin

  Copper transporting protein that converts toxic ferrous ion to nontoxic ferric form, stimulates immune system, and regulates histamine<|>Deficiency causes Wilson's disease with copper deposits damaging organs
• Sedimentation factor


  Makes blood more viscous and serves to promote aggregation of red blood cells (RBCs) and platelets
• Sedimentation factor levels

  • Increase with tissue inflammation or tissue destruction
• Normal sedimentation factor levels

  200 to 400 mg/dL
• Ceruloplasmin


  Converts the toxic ferrous ion (Fe²*) to the nontoxic ferric form (Fe3+)<|>Principal copper transporting protein in plasma, plays a role in iron metabolism and histamine regulation<|>Stimulates the immune system to fight infections, repair injured tissues and promote healing
• Ceruloplasmin


  • Copper deposits in the liver, brain, kidneys, and the eyes
  • Deposits of copper cause tissue damage, necrosis (death of the tissues), and scarring, which causes decreased functioning of the organs affected
  • Liver failure and damage to the central nervous system (brain, spinal cord) are the most predominant, and the most dangerous, effects of the disorder
• Normal ceruloplasmin levels

  20 to 40 mg/dL
• Mannose Binding Protein (MPB)


  Main function: cell lysis<|>Also called mannose-binding lectin<|>Trimer that acts as an opsonin, which is calcium-dependent<|>Able to recognize foreign carbohydrates such as mannose and several other sugars found primarily on bacteria, some yeasts, viruses, and several parasites
• Characteristics of Acute-Phase Reactants

  • C-reactive protein
  • Serum amyloid A
  • Alpha1-antitrypsin
  • Fibrinogen
  • Haptoglobin
  • Ceruloplasmin
  • Complement C3
  • Mannose-binding protein
• Inflammation


  Body's overall reaction to injury or invasion by an infectious agent<|>Plays a role in initiating, amplifying, or sustaining the reaction and a delicate balance must be maintained for the process to be speedily resolved
• Four cardinal signs or clinical symptoms of inflammation

  • Redness (erythema)
  • Swelling (edema)
  • Heat
  • Pain
• Major events that occur rapidly after tissue injury

  1. Increased blood supply to the affected area

  2. Increased capillary permeability caused by contraction of the endothelial cells lining the vessels

  3. Migration of WBCs, mainly neutrophils, from the capillaries to the surrounding tissue in a process called diapedesis

  4. Migration of macrophages to the injured area

  5. Acute-phase reactants stimulate phagocytosis of microorganisms