Continuum of wound healing
- Injury
- Acute inflammation
- Chronic inflammation
- Granulation tissue
- Foreign body reaction
- Fibrous encapsulation
Inflammation def and steps
Inflammation is a complex reaction of the innate immune system involving vascularized tissue
What actually happens:
1.Increased vascular permeability
2.Infiltration of blood plasma proteins and leukocytes 3.Opsonization and phagocytosis of foreign material
Inflammation symptoms
Symptoms:
1.Swelling, edema
2.Heat
3.Pain
4. Redness
Acute vs chronic inflammation
Acute inflammation: occurs immediately after injury in the first few hours post assault
* Process designed to exit the body from hemostasis
Chronic inflammation: changes that occur in the weeks to months following injury
* Involves components of the coagulation cascade, complement, and lymphocytes
Innate vs aquired immunity
- Innate (non specific) immunity: first line of defense against foreign pathogens - born with these defenses
- Acquired (specific) immune response: targets specific diseases and pathogens - this ability is acquired through vaccinations and/or exposure to pathogens, the body then remembers these targets
Innate versus adaptive immune system
Innate immune system: non-specific, no memory, first line of defense against foreign pathogens
* Hypothesized that this part of the immune system evolved first, found in plants and animals
Adaptive immune system: specific, involves highly specialized, systemic cells and processes that prevent pathogenic growth
* provides the ability to recognize and remember specific pathogen (found in vertebrates)
Sources of innate immunity
- Anatomic barriers (skin and mucous membranes)
- Physiologic barriers (body temperature, pH)
- Phagocytic cells (granulocytes)
- Inflammation
- These occur in combination
Antibody
- Antibody: a large Y-shaped protein produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses.
- Also called immunoglobulins (Ig)
Opsonin
- An opsonin is any molecule that targets an antigen for an immune response. However, the term is usually used in reference to molecules that act as a binding enhancer for the process of phagocytosis (cellular uptake of solid particles)
- Antibodies: IgG and IgM (Adaptive)
- Components of the complement system: C3b, C4b, and iC3b (Innate) * Mannose-binding lectin (initiates the formation of C3b) (Innate)
Complement system
- The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism.
- It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual’s lifetime.
General features of the complement system
AMPLIFICATION: multi-component system involving sequential proteolysis of protein to generate a protease (zymogen cascade)
SOLID-STATE: multiprotein complex remains bound to target, increases local protein concentration
SOLUBLE SIGNALS: cleaved fragments act as signaling molecules to enhance and regulate inflammation
MULTIPLE INHIBITORS: host cells contain numerous complement inhibitors, inhibitors also present in circulating serum
Complement disorders
complement deficiencies -> recurring bacterial infection.
improper resolution, over-activation, loss of complement regulators -> inflammatory disorders
Result after severe burns
- Skin is damaged – easier for pathogens to enter the body
- Often develop sepsis – infection of the body which can progress to severe
sepsis followed by septic shock (can be lethal) - Overactivation of the immune system and coagulation cascade leads to lack of blood flow and clots
- Often develop sepsis – infection of the body which can progress to severe
- The components of the immune system can be overwhelmed – infection spreads
What is the central element of both complement pathways
Proteolysis of C3, most abundant complement protein
Alternative complement pathway
Components of the alterative pathway are abundant in serum
At a wound site, abundant complement proteins are available rapidly
Lectin pathway
Lectin Pathway (newest pathway to be discovered):
* homologous to the classical pathway, but with the opsonin, mannose- binding lectin (MBL), and ficolins
* lectins are proteins that bind sugars
Complement regulation
- Complement regulatory proteins – soluble and membrane bound
- Importance of rapid regulation of complement – soluble inhibitors abundant in serum
- Cleaved products are normally only reactive for brief periods – ensures
limited diffusion and local concentration
