Chapter 17: Innate Nonspecific Host Defenses

First line of defense

Surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartments.

• Innate, nonspecific

• Physical, Chemical, and Genetic barriers.

Second Line of defense

Cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses.

• Inflammatory response, Interferons, Phagocytosis, Complement.

Third line of defense

Specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells. This form of immunity is marked by its activity toward specific pathogens and development of memory.

• Acquired, specific

• B and T lymphocytes, antibodies, cytotoxicity.

Cellular Barriers

Deny entry to pathogens.

• Ex: Skin, mucous membranes, endothelial cells.

Mechanical Defenses

Remove pathogens from potential sites of infection

• Ex: Shedding of skin cells, mucociliary sweeping, peristalsis, flushing action of urine and tears.

Microbiome

Compete with pathogens for cellular binding sites and nutrients.

• Ex: Resident bacteria of the skin, upper respiratory tract, gastrointestinal tract, and genitourinary tract.

Chemical Defenses

• Sebum (skin Ph acidic)

• Lysozyme

  • Tears/Saliva

  • Kills Gram+ org.

• Sweat

  • Lactic acid and electrolytes

• Gastric juice in stomach (HCI acid)

• Digestive enzymes and bile

• Semen (antimicrobial chemicals)

• Vaginal secretions (acidic ph)

• Antimicrobial peptides (AMPs)

• Plasma protein mediators

  • Complement proteins, cytokines

Hemopoiesis/Hematopoiesis

Production of blood cells.

Leukocytes

White blood cells

Granulocytes

Lobed nucleus, granules present

• Polymorphonuclear leukocytes

Agranulocytes

Unlobed-round nucleus, no distinct granules.

Neutrophiles

Phagocytic; particularly effective against bacteria; release cytotoxic chemicals from granules.

• Appearance: Nucleus lobes inc. w/age; pale lilac granules

• Most common leukocytes

• Granulocytes

Eosinophils

Phagocytic cells: effective w/antigen-antibody complexes. Release antihistamines. Increase allergies and parasitic infections.

• Nucleus generally two-lobed: bright red-orange granules.

• Granulocytes

Basophils

Promotes inflammation.

• Nucleus generally two-lobed but difficult to see due to presence of heavy, dense, dark purple granules.

• Granulocytes

• Least common

Lymphocytes

Primarily specific (adaptive) immunity: T cells directly attack other cells (cellular immunity); B cells release antibodies (humoral immunity): natural killer cells are similar to T cells but nonspecific.

• Nucleus occupying much of the cell’s volume; stains purple; seen in large (NK cells) and small (B/T cells) variants.

• Agranulocytes

Monocytes

Very effective phagocytic cells engulfing pathogens or worn out cells; also serve as antigen-presenting cells (APCs) for other components of the immune system.

• Largest leukocyte with an indented or horseshoe-shaped nucleus

• Agranulocytes

• Become macrophages with tissue-specific properties

Mast Cells

Function similarly to basophils by inducing and promoting inflammatory responses

• Migrate from the blood to various tissue

Perforins

NK cells release ____, which polymerize and form a hole in the enemy cell membranes.

Granzymes

____ enters perforin hole and degrade enemy cell enzymes.

Pathogen-Associated Molecular Patterns (PAMPs)

• Expressed by microorganisms (not by host)

• Recognized by PRRs

• Signal innate immune cells to activate

• Shared by entire class of pathogens (not specific)

Pattern Recognition Receptors (PRRs)

Receptors on/in phagocytic cells

• Not specific to single cell type

• Toll-like receptors (TLRs)

Pathogenic Recognition

Detect foreign molecules and signal the macrophages to produce chemicals to stimulate an immune responses.

• Pathogen-associated molecular patterns (PAMPs)

• Pattern-recognition receptors (PRRs)

Diapedesis

Migration of cells out of blood vessels into the tissue.

Chemotaxis

Migration in response to specific chemicals at the site of injury or infection.

Inflammatory Response

Classic signs and symptoms characterized by:

• Redness, warmth, swelling, pain, and loss of function

Fever

Initiated by circulating pyrogens.

• Exogenous pyrogens

• Endogenous pyrogens

Exogenous Pyrogens

Products of infectious agents

Endogenous pyrogens

Released by leukocytes; e.g. interleukin-1 (IL-1), tumor necrosis factor (TNF)

Macrophages

Chief phagocytic cells, derived from monocytes

Phagocytosis

Include the engulfment of a pathogen, the formation of a phagosome, the digestion of the pathogenic particles.

1. Chemotaxis

2. Adherence

3. Ingestion

4. Digestion

5. Killing

Interferons

• Small proteins produced by certain WBCs and tissue cells

• Produced in response to viruses, RNA, immune products, and various antigens

Complement System

• Consists of 26 blood proteins that work in concert to destroy bacteria and viruses

• _______ ______ are activated by cleavage (cascade reaction)

• Pathways

  • Classical

  • Lectin pathway

  • Alternative

Classical

Activated by the presence of antibody bound to microorganism

Lectin pathway

Nonspecific reaction of a host serum protein that binds mannan

Alternative

Begins when complement proteins bind to normal cell wall and surface components of microorganisms.