Innate Immunity and Inflammation Flashcards
immune response
coordinated reaction to an antigen or pathogen
pathogen
a microorganism that can cause disease;
virus, fungus, bacteria, protozoa, helminths
antigen
any substance that elicits an immune response (exogenous or endogenous); proteins, carbohydrates, nucleic acids
antigen examples
- surface proteins on a pathogen
- noninfectious environmental agents (pollens, foods, bee venom)
- clinical products (drugs, vaccines, transplanted tissues)
immune system functions
- prevents infection and cell injury
- distinguish self from non-self
- destroy infected and malignant cells
- initiates repair
normal immune responses
- pruritus (itching)
- malaise (general feeling of unwellness)
- anorexia (loss of apetite)
- limited collateral damage of normal tissue
abnormal immune responses
- immune deficiencies, acquired or congenital; (not enough of a response)
- hypersensitivities (allergies), autoimmune diseases; (exaggerated or over-active immune response)
first line of defense
prevent injury/infection; barriers
second line of defense
inflammation
third line of defense
adaptive immune response
innate immunity
- present at birth
- immediate
- non-specific
- activates inflammation and the adaptive immune response
innate immunity: physical barriers
- prevent entry
- tight junctions- epithelial tissue throughout the body
- temperature- cool skin limits bacteria growth
- epithelial turnover- cornea turns over every 7 days
innate immunity: mechanical barriers
- blinking
- coughing/sneezing
- mucociliary escalator
- swallowing
- GI tract peristalsis
- vomiting
- defecation
- urination
- ejaculation
innate immunity: biochemical barriers
secretions and synthesized materials:
- tears (antibacterial)
- gastric juices (pH)
- mucus (antibacterial)
- sweat (pH, antibacterial)
- sebum (antibacterial)
- earwax (antibacterial)
- saliva (digestive enzymes)
normal bacterial flora:
- commensal
- 1-3% of human body mass
inflammation
- part of the innate immune system
- responds rapidly, non-specifically, repeatably
- vascular and cellular responses
inflammation causes the following to occur
- activation of immune system components
- mast cell degranulation
- cellular injury
inflammation goals
- limit infection and further damage
- control bleeding
- interact with adaptive immune system
- prepare the area of injury for healing
- limit and control the inflammatory process
tissue name + “-itis”
inflammation of that tissue
systemic manifestations of inflammation
- fever
- increased pulse
- increased blood pressure
- leukocytosis
- increased plasma synthesis
- cytokine effects
fever
pyrogens (endogenous or exogenous) act on hypothalamus to increase body temp
leukocytosis
increasing the number of circulating WBCs
increased plasma protein synthesis
complement, coagulation, and kinin cascades; helps w/ scabbing
cytokine effects
malaise and lethargy
cardinal signals of inflammation
- calor/heat
- rubor/redness
- tumor/swelling
- dolor/pain
- functio idesa/loss of function (secondary)
calor/heat
blood at body core temp enters site
rubor/redness
influx of RBCs to the area
tumor/swelling
fluid entering tissues
dolor/pain
inflammatory mediators sensitize nerve endings
vascular response
deliver fluid to area of injury:
- contains WBCs and other immune components
- dilutes bacteria, etc., at injury site
- provides nutrients and oxygen for immune cells and wound repair
vascular response- how?
1) brief vasoconstriction
2) mast cells release histamine
3) vasodilation
4) increased capillary permeability
5) exudation (leakage/build up) of fluid and cells (cellular emigration)
serous exudate
water exudate; indicates early inflammation; common w/ friction like a blister;
ex: central serous chorioretinopathy
fibrinous exudate
thick, clotted exudate; indicates more advanced inflammation; can lead to dysfunctional wound healing and scarring;
ex: pseudomembrane
purulent exudate
pus; indicates a bacterial infection;
ex: bacterial conjunctivitis
hemorrhagic exudate
exudate contains blood; indicates vascular disease;
ex: diabetic retinopathy
cellular mediators of inflammation
- mast cells
- natural killer cells
- platelets
- granulocytes (“phils”)
- monocytes
- dendritic cells
- lymphocytes
*all originate in the bone marrow
cellular mediators activated by:
- plasma protein system products
- inflammatory cell secretions
- microbial molecules
- debris from cellular destruction
pattern recognition receptors (PRRs)
- found on surface of resident and circulating immune cells
- recognize pathogen-associated molecular patterns (PAMPs)
- also recognize cellular debris
mannose
large carbohydrate molecule not found on human cells; found on all bacteria cells - tells us that it is non-self
neutrophils, eosinophils, and macrophages emigrate toward source
1) margination
2) adherence
3) diapedesis
4) chemotaxis
phagocytosis
- opsonization, recognition, and adherence
- engulfment
- phagosome formation
- fusion with lysosomal granules (reactive oxygen species, lactoferrin, defensins, lactic acid)
- destruction of the target
mast cells are the key initiator of ___
inflammatory and immune response
mast cells are located ____
in loose connective tissue in high-risk areas of the body- GI tract, lungs, skin, other mucosal tissues
mast cells are sensitive and stimulated by ____
multiple stimuli:
- pathogens
- allergens
- physical injury
- chemical agents
mast cell degranulation
immediate
mast cell degranulation products
- histamine
- chemotactic factors
histamine
- vasodilator
- increased glandular production
- CNS effects (histamine makes you more alert)
chemotactic factors
- chemicals that induce movement
- neutrophil chemotactic factor
- eosinophil chemotactic factor of anaphylaxis (ECF-A)
mast cell synthesis
delayed
mast cell synthesis products
- leukotrienes
- prostaglandins
leukotrienes
- product of the arachidonic acid cascade
- similar effects to histamine in later stages
prostaglandins
- induce pain
- pro- and anti- inflammatory properties
mast cells in atopic individuals
- more numerous
- have a higher number of antigen receptors
- more easily activated
natural killer (NK) cells
- recognize and eliminate virus infected cells and cancer cells
- release perforin (puts holes in cell membrane) and granzyme (induces apoptosis in damaged/defective cells)
platelets
- contribute to clot formation
- multiple triggers
- degranulate upon activation
- contribute to wound healing
- pro- and anti- inflammatory
neutrophils
- aka polymorphonuclear neutrophils (PMNs)
- early responder in inflammation (within hours)
- ingest bacteria, dead cells, and cellular debris
- dysfunction increases risk of bacterial infection
eosinophils
- mildly phagocytic
- defend against parasites
- implicated in allergies and asthma
- regulate vascular mediators (vasodilation)
monocytes/macrophages
- monocytes produced in the bone marrow and are in the blood; once they leave the blood they mature and replicate which turns them into macrophages
- mature and replicate at inflammatory site (3-7 days)
- ingest bacteria and cellular debris
- contribute to activation of adaptive immune system
- initiate wound healing
termination of inflammation
- removal of an offending agent usually ends response
- checks exist to control course of inflammation
checks exist to control course of inflammation:
- neutrophil life span is short
- inflammatory mediators degrade rapidly
- anti-inflammatory cytokines
outcomes of acute inflammation
1) complete resolution
2) scarring
3) abscess formation
4) progression to chronic inflammation
complete resolution
structure and function recoverable; back to normal
scarring
substantial damage to connective tissue
abscess formation
pus confined in a closed space; active proteases produce fluid increasing osmotic pressure; usually have to drain
progression to chronic inflammation
body cannot remove offending agent; persistent bacteria/toxins or autoimmune diseases
chronic inflammation
- inflammation lasting 2 weeks or longer
- often related to an unsuccessful acute inflammatory response
causes of chronic inflammation
- high lipid and wax content of microorganism
- ability to survive inside the macrophage
- toxins
- chemicals
- particulate matter
- physical irritants
with chronic inflammation, there is dense infiltration of ___
lymphocytes and macrophages
with chronic inflammation, there is fibrosis, which is ___
thickening and scarring of connective tissue
with chronic inflammation, there is angiogenesis, which is ____
production of new blood vessels (VEGF)
with chronic inflammation, there is granuloma formation, which is ____
walling off of offending agent
