chapter 6

Chapter 6

Innate Immunity:
Inflammation and Wound Healing

Immunity

Innate Immunity- the body’s surfaces provide protection. Ie. cough reflex, enzymes in the ears, skin oils, cilia, eye lashes, mucous, bile, gastric acid, saliva, tears and sweat.

Inflammation/inflammatory response- If surface barriers are breached for some reason, an inflammatory response is activated to protect the body, fight off infection and promote healing.

Adaptive/Acquired/Specific Immunity refers to exposure to pathogens and memory.

First Line of Defense

Physical barriers:

Skin

Sloughing off with dead cells

Linings of the gastrointestinal, genitourinary, and respiratory tracts

Mucus and cilia trap microorganisms

Expelled through

Coughing and sneezing

Urination

Vomiting and defecation

First Line of Defense

Cell-derived chemical barriers

Epithelial cells secrete saliva, tears, earwax, sweat, and mucus (trap microorganisms)

Lysozymes (found in sweat, tears and saliva) attack bacteria

Antimicrobial peptides kill bacteria, fungi, viruses

Speaking of Immunity… what movie is this?

First Line of Defense

Normal microbiome

Each body surface is colonized by bacteria and fungi unique to location and individual

Commensal or mutualistic relationship

Functions:

Produces enzymes for digestion

Synthesizes metabolites

Releases antibacterial substances

Competes with pathogens for nutrients

Fosters adaptive immunity

Helps with communication between brain and GI tract

Second Line of Defense: Inflammation

Inflammatory response

Occurs in vascularized tissues (tissues with a blood supply)

What if the vascular system is compromised?

Activation is rapid (within seconds after the injury)

Response includes cellular and chemical components

Nonspecific

Second Line of Defense : Inflammation

Vascular response of inflammation

Hemostasis (coagulation)

Vasodilation

Increased vascular permeability and leakage

White blood cell adherence to the inner walls of the vessels and migration through the vessels. There is also an influx of phagocytes to the injured tissue where they target foreign microorganisms.

Lymphatic vessels which drain extravascular fluid to lymph nodes may become secondarily inflamed resulting in lymphangitis and lymphadenitis.

Local manifestations

Redness, heat, swelling, pain, loss of function

Second Line of Defense : Inflammation

Protective functions

Prevent and limit infection and further damage

Limit and control the inflammatory process

Prepare injury for healing and repair

Facilitates development of adaptive immune response

Plasma Protein Systems

Protein systems—essential for effective inflammatory response

Complement system- histamine is released which induces vasodilation and increased capillary membrane permeability. (edema)

Clotting system- blood clot is a meshwork of fibrin strands and platelets

Kinin system- works closely with the clotting system. Bradykinin causes dilation of blood vessels. It also acts in concert with prostaglandins to induce pain, and increase vascular permeability.

Each system has a unique role in inflammation, all systems have similarities. Each system is composed of proteins and enzymes (usually in the blood in inactive forms). Activated by an injury.

This is why replacing plasma is important with massive blood transfusion protocols

Cellular Components of Inflammation

Cellular components

Respond to molecules at site of damage and are recruited there

Cell surface receptors activated cell and intracellular signaling pathways

Functions:

Confine extent of damage

Kill microorganisms

Remove cellular debris

Activate healing

Cytokines

Responsible for activating other cells and regulating inflammatory response

Chemokines

Chemotaxic—attract leukocytes to sites of inflammation

Synthesized by many cells (macrophages, fibroblasts, endothelial cells)

More than 50 chemokines have been described

Mast Cells

Potent activators of inflammatory response

Contain granules with biochemical mediators that are released with tissue injury

Located in connective tissue and close to vessels

Can be found near body’s surfaces

Skin, GI and respiratory tract linings

Synthesis of Mediators

Leukotrienes

Similar effects to histamine but in later stages

Prostaglandins

Similar effects to leukotrienes; they also induce pain

Aspirin and some other nonsteroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins, thereby inhibiting inflammation and pain.

This action on prostaglandins is why ibuprofen is recommended for dysmenorrhea

Platelet-activating factor

Similar effect to leukotrienes and platelet activation

Endothelial Cells

Regulate circulation through micro-vessels

Control movement of water and solutes

Maintain normal blood flow

Damage to endothelial cell lining

Initiates platelet activation

Promotes recruitment of leukocytes

Facilitate wound healing

Platelets

Activated by vascular injury

Activation leads to interaction with coagulation cascade to stop bleeding

Neutrophils

Also referred to as polymorphonuclear neutrophils (PMNs)

Predominate phagocytes in early inflammation

Activated by bacterial proteins and other factors) arrive early 6-12 hours after injury.

Ingest bacteria, dead cells, and cellular debris

Cells are short lived and become a component of the purulent exudate (Pus) which is removed by either the lymphatic system or through the epithelium

Eosinophils

Mildly phagocytic

Defense against parasites

Regulation of vascular mediators

Basophils

Least prevalent granulocyte

Basophilic granules