Non-Specific (Innate) Immunity

Innate or Non-Specific Defenses

• physical & mechanical

• chemical

• cellular

Innate / Non-Specific Immunity

• need no induction in adults

• not well established in neonates

• not specific for specific pathogens

• influenced by nutritional and physiological state of host

Physical & Mechanical Defenses

• Hair

• Skin

• Blinking

• Cilia in throat and lungs

• Peristaltic action

• Flow of urine

Mucous Membranes

• Thick sticky substances composed of proteins & polysaccharides

• Contains antimicrobial enzymes

  • Lysozyme

  • Lactoferrin

  • Lactoperoxidase

• Protects, respiratory tract, gastrointestinal tract, & urogenital tract

Lysozyme

breaks down peptidoglycan → cell wall

Lactoferrin

iron binding proteins found in milk & tears → prevents bacteria from using it for growth

Lactoperoxidase

produces superoxide → will damage bacteria if no way to detoxify

Mucus-Associated Lymphoid Tissues (MALT)

• Immune barrier

• Underlies skin & mucous membranes

• Involved in early antigen detection

Resident Microflora

• Normal populations of microbes associated w/ particular body tissues

  • 90% of cells in human body are microbes

• Human fetus - sterile; acquire microbial residents over time

• Normal residents are tissue specific

• Some tissues are protected from colonization by any microbes - brain, kidneys, bloodstream

Benefits of Resident Microflora

• Provide nutrients

• Protect from harmful organisms

  • take up space

  • compete for nutrients

  • may produce toxic products - colicins

Detriments of Resident Microflora

• may get in wrong location - opportunistic

• may work synergistically w/ pathogen - tetanus

• may inactive antibiotics

• If G-, could release endotoxin when they lyse (lipid A)

Myeloid stem cell

A stem cell in bone marrow that develops into many blood cells like red blood cells, platelets, and certain white blood cells (where innate immunity comes from)

• Megakaryocyte

• Erythrocyte

• Mast Cell

• Myeloblast

Mast cell

An immune cell that releases granules (like Histamine & Leporine) which stimulate immune response

Myeloblast

An immature bone marrow cell that develops into granulocytes such as neutrophils, eosinophils, and basophils

• Basophil

• Neutrophil

• Eosinophil

• Monocyte

Neutrophil

A white blood cell that quickly responds to infections by engulfing and destroying bacteria (first responders to get infection)

Monocyte

A white blood cell that circulates in the blood and can develop into macrophages or dendritic cells (when it moves from blood to tissues)

• Macrophage

• Dendritic Cell

Macrophage

A large immune cell that engulfs pathogens, dead cells, and debris through phagocytosis

Dendritic cell

An immune cell that captures antigens and presents them to T cells to activate the adaptive immune response

Hematoposesis

The process of producing all blood cells in the bone marrow

Phagolysosomal killing

1. Hydrolytic enzymes

   • Lysosome, proteases, nuclease

2. Cationic Peptides (defensins)

   • Insert into bacterial membranes & increase permeability

3. Toxic biochemicals

   • Toxic oxygen intermediates

     • Superoxide, hydroxyl radical, hydrogen peroxide

   • Toxic nitrogen intermediates

     • Nitric oxide → inhibits respiration of bacteria in the vacuole

Complement Cascade

Collection of glycoproteins in blood that play a role in removal of bacterial pathogens

1. Activation – The complement system is triggered by pathogens or antibodies

2. Protein Cascade – Complement proteins activate one another in sequence

3. Opsonization – Pathogens get coated so phagocytes can recognize and eat them easier

4. Inflammation – Signals attract immune cells and increase inflammation

5. Cell Lysis – A membrane attack complex (MAC) forms holes in the pathogen, causing it to burst and die

Mechanisms to Activate Complement Cascade

• Classical - antibody bound to pathogen

• Lectin - mannose → binding protein bound to mannose on pathogen (marker)

• Alternate - repeating cell surface structures → LPS, LTA

Major Roles of Complement Cascade

1. Direct killing of G^- pathogens, innactivates enveloped viruses

2. Production of anaphylatoxins (causes degranulation of mast cells & chemotaxins (attract phagocytes to damage)

3. Production of opsonin (bridging molecule like antibody) → helps phagocyte recognize pathogen

Membrane Attack Complex (MAC)

forms a pore in outer membrane of Gram -

Inflammatory Response

• Localized response to tissue damage

• Four cardinal characteristics

  1. Redness

  2. Edema (swelling)

  3. Pain

  4. Heat

Acute Inflammation

Overall affects of inflammation

• ↑ blood flow to area (redness & heat)

• ↑ permeability - capillaries become leaky (edema)

• migration of neutrophils (& macrophages) into tissue

• nerves are stimulated (pain)

Diapedis

phagocytes binds to endothelial cells & squeeze through spaces from capillary to tissue

Pathogen Recognition by Phagocytes

• Opsonin-dependent (bridging)

• Opsonin-independent (direct binding)

• PAMPs (pathogen associated molecular patterns)

Opsonin-dependent

bridging

• C3B

• Antibodies

Opsonin-independent

direct binding

• Lectin - carbohydrate

• Protein - protein (RGD sequence on bacterial protein)

• Hydrophobic interactions

Pathogen-Associated Molecular Patterns (PAMPs)

• specific to microbes - LPS, PG, unmethylated CpG DNA

• Recognized by pattern recognition receptors (PRR)

• Important in signaling host cells of invader presence

• triggers reaction between innate & adaptive immunity

Phagocytosis

• Pathogen is recognized and consumed by phagocyte into a Phagosome

• Lysosome combines w/ phagosome to form a Phagolysosome

• Lysosome releases toxins and degrades pathogen into the Digestive Vacuole

• Degraded pathogen is used for nutrients in the Residual Body and then eliminated by Exocytosis

Natural Killer Cell (NK Cell)

a type of lymphocyte in the innate immune system that destroys virus-infected cells and cancer cells without needing prior exposure to the pathogen