includes physical, mechanical, and biochemical barriers. It also includes inflammation
First line of defense
innate resistance (surface barriers) at birth
second line of defense
inflammatory response- prevent inflammation of injured tissue and promote healing. It is rapid and nonspecific (biochemical and cellular mechanisms)
third line of defense
adaptive (acquired) immunity- slower and more specific pathogen and involves memory for rapid future response to the same organism
prevent inflammation of injured tissue and promote healing. It is rapid and nonspecific (biochemical and cellular mechanisms)
defined as relatively impenetrable "cellular roadblock" to microorganisms
physical and mechanical barriers
skin- tightly associated epithelial cells, and the linings of the GI, genitourinary, and respiratory tracts (mechanical clearance)
physical and mechanical barriers
when pathogens try to get through the physical barriers, they may be prevented from doing so simply by means of mechanical clearance
a consequence of being sloughed off with dead skin cells as they are routinely replaced, being expelled by coughing or sneezing, flushing by urine, vomiting, mucus (epithelial cells of upper respiratory tract) and cilia help expel mucus), low surface body temperature inhibits microorganisms
epithelial surfaces provide biochemical as well as physical barriers to trap and destroy pathogens
mucus, sweat, saliva, tears, cerumen, sweat, and sebum. These all contain substances that will kill microbes. Skin pH 3-5 acidic.
the small molecular weight proteins secreted by the epithelial cells, generally positively charged strings of approximately 15-95 amino acids.
antimicrobial peptide that is toxic to certain bacteria, fungi, viruses. Disrupt cell membranes
antimicrobial peptide that contains three intrachain disulfide bonds and can be separated into alpha and beta types and also disrupt cell membranes of bacteria
normal bacterial flora
bacteria-derived chemical, nonpathogenic bacteria protecting us against pathogenic bacteria. Prolonged use of antibiotics could alter intestinal flora (yeast Candida albicans or bacteria Clostridium difficile). Lactobacillus in normal vaginal flora produces hydrogen peroxide, lactic acid, bateriocins, and other molecules to prevent vaginal and urologic infections
produced by the lung, known as surfactant proteins A thru D, which are hydrophobic. Only surfactant A thru D appear to participate in innate resistance by promoting phagocytosis and interacting with the acquired immune system
occurs at the site of injury, caused by a variety of materials: infection, mechanical damage, ischemia, nutrient deprivation, genetic or immune defects, chemical agents, temperature extremes, radiation, etc.
similar to barriers in two different ways, depends on activity of both cellular and chemical components (inflammation is usually initiated by cell injury) 2. it is nonspecific. it takes places the same way regardless of the stimulus
inflammation occurs in vascularized tissue and results in a group of classic and superficially observable characteristics: redness, heat, swelling, and pain. The three characteristic changes occur at the vascular level. (arterioles, capillaries and venules)
blood vessel dilation, 2. increased vascular permeability and leakage of fluid out of the vessel, 3. WBC adherence to inner vessel walls and their migration through vessel walls to the site of injury
effects of this on vasculature are visible in seconds
first: arterioles near the site of injury constrict briefly, then vasodilation causes slower blood velocity and increases local blood flow to injured site, the increased flow and cap permeability result in leakage of plasma from vessels, causing edema at the site. As plasma moves outward, the remaining blood thickens with RBC's and slows movement causing redness and warmth.
these adhere to the vessel walls and biochemical mediators stimulate endothelial cells of capillaries and venules to retract, creating spaces at junctions between cells. E.g. Histamin, bradykinin, leukotrienes, substance P, and prostoglandins
cells and chemicals associated with inflammation will do the following: limit and control the inflammatory process, prevent and limit infection and further damage, interact with components of the adaptive immune system, and prepare the area of injury for healing
begins immediately after cell injury or infection. It may result in resolution and healing of the injured site or progress into chronic inflammation. It continues until the treat is eliminated. Usually 8-10 days from onset to healing.
may result in healing or progress to development of a granuloma
healing and reconstruction
the damaged tissue heals and reconstructs
plasma protein systems
the inflammatory response includes activation of three key systems, the complement system, the clotting system and the kinin system
inactive enzymes whose activation is required for action
plasma protein systems
sequentially activated, first proenzyme is converted to an active enzyme, substrate of the activated enzyme becomes the next component in the series which then initiates the cascade. Therefore, activation of the entire cascade is initiated simply by activation of the first component
contains several plasma proteins (10% of total plasma protein). THis is a very important system. Can destroy pathogens directly and are among the body's most potent defenders against bacteria infection. Activates or collaborates with every other component of the inflammatory response
activated by proteins of the acquired immune system (antibodies) bound to their specific targets (antigens)
activated by certain bacterial carbohydrates
activated by gram-bacterial and fungal cell wall polysaccharides
the most important aspect of this is the activites of the small fragments generated during activation of C2, C3, C4, and C5.
adheres to the surface of a pathogenic microorganism and serves as an efficient opsonin.
molecules that "tag" pathogenic microorganisms for destruction by cells of inflammation (neutrophils and macrophages)
a major chemotactic factor for neutrophils.
is a biochemical substance that attracts leukocytes to the site of inflammation
C3a and C5a are these and they induce rapid degranulation (release of granular contents) and release histamine from mast cells causing vasodilation and increase capillary permeablility
have four different means and its products have four different functions: opsonization, anaphylatoxic activity resulting in mast cell degranulation, leukocyte chemotaxis, cell lysis (their goal is to destroy the cell)
forms a fibrous meshwork at an injured or inflamed site, prevents the spread of infection, keeps microorganisms and foreign bodies at the site of greatest inflammatory cell activity, forms a clot that stops bleeding, provides a framework for repair and healing
the main substance (or final product of the coagulation cascade) is an insoluble protein called fibrin
like the complement cascade, it can be activated through different pathways that converge at the point where each pathway produces the same substance
in this cascade, the extrinsic pathway and the intrinsic pathway converge at factor X. From that point the cascade proceeds on a common pathway until fibrin is formed
this system can be activated by many substances that are release during tissue destruction and infection. As with the complement cascade, activation of this cascade produces fragments that enhance the inflammatory response. Some fragments are chemotaxic for neutrophils and increase vascular permeability for enhancing the effects of bradykinin (kinin system)
the third plasma protein system, interacts closely with the coagulation system and therefore also functions to compartmentalize and trap invading pathogens
primary role is to activate and assist inflammatory cells, primary kinin is bradykinin,
causes dilation of blood vessels, acts with prostaglandins to induce pain, induces smooth muscle contraction, affects vascular permeability and leukocyte chemotaxis
mostly found in blood but also in tissues
primary circulating WBC's with many enzyme-containing granules in the cytoplasm which include:neutrophils, basophils, eosinophils). Other blood components include: platelets, agranular monocytes (precursors to tissue macrophages), and lymphocytes
continually contact endothelial cells lining the blood vessels. Changes in the interactions of endothelium with circulating leukocytes and platelets occur during inflammation
cells of inflammation
both secrete and respond to biochemical mediators. They are recruited and activated by products of activation of the plasma protein systems and by biochemicals released during cell destruction.
cell surface receptors
both innate and acquired immunity must recognize and respond to abnormal components of their environment
pattern recognition receptors, recognize molecular patterns on infectious agents
the products of cellular damage (necrosis and apoptosis) that the PRRs recognize during inflammation
expressed on the surface of many cells (e.g. neutrophils, monocytes, macrophages) that have direct and early contact with potential pathogenic microorganisms
recognize a variety of fragments produced through activation of the complement system (e.g. granulocytes, monocytes/macrophages, lymphocytes, mast cells, erythrocytes, platelets)
primarily on macrophages and facilitate recognition and phagocytosis of bacterial pathogens, as well as damaged cells and altered soluble lipoproteins associated with vascular damage (e.g. HDL, LDL (cholesterol))
a central cell of inflammation