Innate Immunity Patho Flashcards
Describe Physical Barriers of Defense
tightly associated epithelial cells to prohibit passage of microorganisms into underlying tissue (skin)
Describe Mechanical Barries of Defense
normal cell turnover/”washing” of surfaces (skin sloughing off, mucous being excreted)
Describe some biochemical barriers of defense
epithelial-derived chemicals - substances secreted to trap or destroy microorgansisms (mucus, earwax, sweat, saliva, tears, sebaceous glands)
what is a normal microbiome
colonization of surface where there is a mutualistic relationship and does not normally cause disease (can be disrupted by antibiotics)
How does normal microbiome contribute to defense against pathogens
the microbiome offers innate protection through outcompeting pathogens for nutrients
What are first lines of defense?
Physical, Mechanical, Biochemical, and Microbiome
What are second lines of defenes?
non-specific innate immunity - ie inflammation, fever
What is a mast cell?
most important cellular activator of the inflammatory response - contains granules that are released or synthesized when activated
What is mast cell degranulation
release of mast cell granules (histamine, chemotactic factors, cytokines)
What is mast cell synthesis
new production and release of of mediators (leukotrienes, prostaglandins, platelet-activating factors) slower acting
What is the function of histamine
1.causes temporary constriction of smooth muscle lading to vasodilation & increased blood flow to area
2. causes increased vascular permeability through retraction fo endothelial cells & increased adherence of leukocytes to endothelium
3.H1 = proinflammatory, augments neutrophil chemotaxis and activates mast cells and neutrophils
4. H2 = antiinflammatory, opposite of H1
What are the functions of Platelet Activating factor
1.endothelial retration –> increased permeability
2.leukocyte adhesion to endothelial cells
3. platelet activation
What are the functions of prostaglandins
- increase vascular permeability
- smooth muscle contraction
- Works with bradykinin on nociceptors to induce pain
- can suppress release of histamine from mast cells and lysosomal enzymes from neutrophils to inhibit inflammation
What are the functions of leukotrienes
*similar to histamine but slower acting and has prolonged effect
1.smooth muscle contraction
2.increased vascular permeability
3.neutrophil/eosinophil chemotaxis
What are the function of Chemotactants
directs movement of cells along a chemical gradient
1. Neutrophil CF
2. Eosinophil CF of anaphylaxis
3. Leukocyte chemotaxis
What are the functions of growth factors
help with tissue regeneration and angiogenesis
ex) VEGF (endothelial cell proliferation) and PDGF (connective tissue and smooth muscle proliferation)
What are the three plasma protein systems essential to inflammatory response?
Complement, Clotting, and Kinen
Describe the Complement System
- bacteria activate complement cascade
- Proteins form a membrane attack complex (MAC) that break off and form a pore in bacterial membranes, leading to cell lysis and death
What three pathways lie within the Complement System?
Classical, Alternative, and Lectin
Describe the Classical Complement pathway
antibodies activate the first complement component
Describe the Alternative Complement pathway
bacterial products activate cascade, antibodies not required
Describe the Lectin Complement pathway
mannose-binding lectin bind to bacterial polysaccharides containing mannose, activating the cascade
Describe the Clotting System
activated by both intrinsic (within the vessel) or extrinsic (TF, damaged endothelium) pathways, the clotting cascade results in clot formed by fibrin mesh adn platelets to plug damaged vessels, stop bleeding, and trap microorganisms. Leads to leukocyte migration, chemotaxis, and increased vascular permeability
Describe the Kinin system
initiated by clotting system, factor 12 –>factor 12a -> prekallikrein and results in production of bradykinin, which increases vascular permeability and leukocyte - augments inflammation and leads to pain
Describe macrophage activation
monocytes –> macrophages; PRRs (including TLRs) expressed on surface recognize pathogens, when bind to PAMP or DAMPs this activates the macrophage, which causes it to release cytocines and chemokines
What is a PRR
pattern recognition receptor
What is a TLR
toll-like receptor
Define PAMPs and DAMPs
pathogen-associated and damage associated molecular patterns
what is the function of a chemokine?
induce leukocyte chemotaxis
what is the function of a cytokine?
intercellular signalling to regulate innate and adaptive immunity, can be pro on anti inflammatory
what is the function of a TLR
recognize fungal, viral and bacterial patterns –> initiates intracellular signlaing to activate macrophages release chemokines and cytokines
what are the most important proinflammatory cytokines?
TNF, IL, and IFN
What is the function of TNF
promotes innate immune response to injury or infection, including chemotaxis, adherance of neutrophils, phagocytosis, and cell proliferation
What is the function of ILs
regulate cell adhesion molecules, attract leukocytes (chemotaxis), proliferation of leukocytes in bone marrow, and enhance or suppress inflamation
What is the function of IL-1
growth factor, pyrogen (fever inducing) that reacts with hypothalamus
what is the function of IL-6
induces hepatocytes to produce proteins needed for inflammation and stimulates growth and differentiation of blood cells in bone marrow and growth of fibroblasts required for wound healing
What is the function of IFN
produced and released by virally infected cells, induce antiviral proteins in neighboring healthy cells, can activate Macrophages
define anti-inflammatory cytokines
diminish and control inflammatory response, IL-10 and TGF-b
define the role of dendritic cells
APC, recognized invaders by PRRs adn phagocytose them. Unlike macrophages they migrate through lymphatic vessels
What is the vascular response to injury or infection
vasodilation, increased vascular permeability, diapedesis (leukocyte adherence to inner vessel walls)
What is the cellular response to injury or infection
neutrophils & macrophages perform phagocytosis, eosinophils defend against parasites and regulate mediators released by mast cells
phagocytosis: recognition and adherence of phagocyte to target through PRRs, engulfment, fusion with lysosomal granuels, adn destruction of target
What are four cardinal signs of inflammation
redness, heat, swelling, and pain
What events lead to swelling/edema
increased vasodilation and capillary permeability lead to plasma leaking into interstitial space, caused by mast cell degranulation
what causes redness/heat?
histamines, leukotrienes, and prostaglandins cause smooth muscle to relax leading to vasodilation –> increased blood flow
what causes fever?
IL-1 and TNF through hypothalamus stimulation
what causes function loss due to inflammation?
injury, edema, swelling close to joint
What causes pain during inflammation
edema and badykinins activate nociceptors
define acute inflammation
resolves in 8-10 days, self-limiting
What are three systemic manifestations of inflammation?
- Fever
- Leukocytosis (>leukocytes in blood)
- Increase in circulating plasma proteins (increased fibrinogen leads to increased ESR)
What are the four stages of a successful inflammatory response
- initiation
- cell recruitment
- debris removal
- repair and regeneration
What is a granuloma?
dense infiltration of lymphocytes and macrophages that the body tries to isolate
cause by chronic macrophage-t cell interations
what are examples of dysfunctional inflammatory responses
1.adhesions (excessive bleeding & fibrin)
2. keloids (raised scar outside boundaries)
3. hypertrophic scar (raised scar within boundaries)
4. contractures
What 2 characteristics of the neonatal immune system make them more susceptible to infection?
-depressed inflammatory function (neutrophils and monocytes incapable of efficient chemotaxis)
-deficient in collectins
what are considerations that must be taken in regards to the aging population and inflammation?
-may be on steroids due to chronic illness
-more susceptible to bacterial infections of lungs, urinary tract, and skin
-cellular components of innate response deficient (macrophage) or have diminished activity (chemotaxis, phagocytosis)
