Innate nonspecific host defenses Flashcards
what are the categories of nonspecific innate immune defenses
physical defenses
chemical defenses
cellular defenses
what are examples of physical defenses
physical barriers
mechanical defenses
micorbiome
what are examples of chemical defenses
chemicals and enzymes in body fluids
antimicrobial peptides
plasma protein mediators
cytokines
inflammation-eliciting mediators
what are examples of cellular defenses
granulocytes
agranulocytes
what are barriers at the cellular level
cells that are tightly joined to prevent invaders from crossing through deeper tissue
what is an example of cells acting as a physical barrier
endothelial cells lining blood vessels have to cell junctions preventing microbes from entering the blood stream
what are cell junctions composed of
cell membrane proteins that may connect with the extracellular matrix or with complementary proteins from neighboring cells
what are the types of cell junctions
tight
desmosomes
gap
how do microbes attempt to break down junctions
using enzymes such as proteases
what does proteases do to cells
cause structural damage to create a point of entry for pathogens
what kind of barrier is the skin
physical
what are the layers of skin
epidermis
dermis
hypodermis
what does the 2nd layer of skin contain
hair follicles
sweat glands
nerves
blood vessels
what is in the hypodermis
blood and lymph vessesl
what does the epidermis consist of
cells packed with keratin that are tightly connected
what does keratin do for the skins surface
makes it mechanically tough and resistant to degradation by bacterial enzymes
what can a wound serve as
a point of entry for opportunistic pathogens that can infect skin surrounding wound and deeper tissue
what do mucous membranes consist of
epithelial cells that with tight junctions, and antimicrobial peptides
what does mucus do
protects the more fragile cells and traps debris and particulate including microbes,
what type of defense is ciliated epithelial cells
mechanical
what type of defense is the digestive tract
physical
what is the mucociliary escalator
when respiratory epithelial cells propel mucus with debris up and out of the lungs
what is the intestinal tract lined with
epithelial cell with mucus secreting goblet cells
what does the mucus in the intestinal tract do
mixes with material, traps it and peristalsis pushes it out
what are endothelia
epithelial cells in the urogenital tract, blood vessels, lymphatic vessels and other tissue
what does endothelia of blood brain barrier protect
the brain and spinal cord
what do mechanical defenses do
physically remove pathogens from the body
what are examples of mechanical defenses
shedding of skin, expulsion of mucus, excretion of feces, urine and tears, blinking,
how does the microbiome protect against pathogens
through occupation of cellular binding sites and competition for available nutrients
what is an example of microbiome preventing infection
bacteria in the vagina protect against candida by limiting nutrients
what happens when macrobiotic is disrupted
more susceptible to infection
what do antibiotics do to intestinal tract
kill microbiome
what happens when intestinal microbiome is killed
c. diff takes over
what are cellular barriers
skin, mucous membranes, endothelial cells
function of cellular barriers
deny entry of pathogens
examples of mechanical defenses
shedding of skin cells, mucociliary sweeping, peristalsis, flushing action of urine and tears
function mechanical defenses
remove pathogens from potential sites of infections
examples of microbiome defenses
resident bacteria of skin, upper respiratory tract, gi tract, genitourinary tract
function of microbiome
computer with pathogens for cellular binding sites and nutrients
what do chemical mediators do
inhibit microbial invaders
what does endogenously produced mean
proceeded by human body cells
what does exogenously produced mean
produced by microbes that are part of the microbiome
what kind of mediators are produced by fluid of the skin
endogenous and exogenous
what kind of mediator is sebum
endogenous
what does sebum do
seals off the pore of the hair follicle preventing bacteria from invading what glands and surrounding tissue
how do propionibacterium acnes and malassezia degrade subum
using lipase enzymes to degrade it using it as a food source
what is produced when sebum is degraded
oleic acid that makes the skin inhospitable to phathogens
what type of mediator is oleic acid
exogenously
how does low humidity affect microbiota of the skin
decreases sebum production making skin less habitat for microbes that produce oleic acid and more susceptible to pathogens normally inhibited by skins low ph
what mediators does saliva contain
lactoperoxidase enzymes
what mediator is excreted by mucus in the esophagus
antibacterial enzyme lysozyme
what is a mediator in the stomach
acidic gastric fluid
what mediator is in the lower digestive tract
intestinal and pancreatic enzymes, antibacterial peptides, bile produced by liver and pantheon cells that produce lysozyme
what do lower digestive tract mediators kill
pathogens that survive the acidic ph of the stomach
how does the urinary tract act as a mediator
by being slightly acidic
what is lactate in the vagina
an exogenously produced mediator
what produces lactate
the vagina produces glycogen and lactobacilli ferment it to produce the lactate
what does lactate do for the vagina
lowers the ph to inhibit transient microbiota, candida and sti
what chemicals mediators are in tears
lysozyme and lactoferrin
what does lysozyme do
cleaves the bond between nag and nam in peptidoglycan
what are lysozyme and lactoferrin most effective against
gram-positive bacteria
what does lactoferrin do
inhibits microbial growth by chemically binding and sequestering iron starving microbes that need iron for growth
how does cerumen have
antimicrobial properties due to fatty acids lowering the ph
what does mucus in the nasal passage contain
lysozyme, lactoferrin, lactoperoxidase
what do secretions in the trachea and lungs have
lysozyme and lactoferrin and others such as surfactant
what is surfactant
a lipoprotein complex with antibacterial properties
what are antimicrobial peptides
a class of nonspecific cell-derived mediators with broad spectrum antimicrobial properties
when are amp’s produced
some routinely and some in response to a pathogen
what do AMP’s induce cell damage
by damaging membranes, destoying dna or rna or interfering with cell-wall synthesis
what do AMP’s inhibit
some only certain croups and some more broadly
what are defensins
AMPS produced by epithelial cells throughout the body
characteristics of defensins
may be secreted or act inside a host cell
combat microorganisms by damaging plasma memranes
what are bacteriocins
AMP’s produced exogenously by certain members of macrobiotic in gi tract
how are the genes for bacteriocins carried
on plasmids and can be passed between different species through lateral or horizontal gene transfer
bacteriocin is secreted by..
resident microbiotia
bacteriocins body site
GI tract
bacteriocins inhibit?
bacteria
mode of action of bacteriocins
disrupt membrane
cathelicidin is secreted by…
epithelial cells, macrophages and other cell types
cathelicidin body site
skin
cathelicidin pathogens inhibited
bacteria and fungi
cathelicidin mode of action
disrupts membrane
defensins are secreted by
epithelial cells, macrophages, neutrophils
defensins body site
throughout the body
defensins inhibit
fungi, bacteria, many viruses
defensins mode of action
disrupt membrane
dermcidin is secreted by
sweat glands
dermcidin body site
skin
dermcidin pathogens inhibited
bacteria and fungi
dermcidin mode of action
disrupts membrane integrity and ion channels
histamines secreted by
salivary glands
histatins body site
oral cavity
histatins pathogens inhibited
fungi
histamines mode of action
disrupt intracellular function
what does plasma contain
electrolytes, sugars, lipids, proteins to maintain homeostasis and proteins involved in blood clotting
what proteins in plasma are involved in nonspecific innate immune response
acute-phase proteins
complement proteins
cytokines
describe acute phase proteins
antimicrobial mediators produced by the liver and secreted into the blood in response to inflammation molecules from the immune system
examples of acute phase proteins
c reactive protein
serum amyloid a
ferritin
transferrin
fibrinogen
mannose binding lectin
function of c reactive protein and serum amyloid a
coats bacteria, preparing them for ingestion by phagocytes
function of ferritin and transferrin
bind and sequester iron inhibiting growth of pathogens
function of fibrinogen
involved in formation of blood clots that trap bacterial pathogens
function of mannose-binding lectin
activates complement cascade
what is the complement system
a group of plasma protein mediators that act as nonspecific defense while also serving to connect innate and adaptive immunity
what is the complement system composed of
more than 30 proteins that circulate as precursor proteins in blood
when do precursor proteins become activated
when stimulated or triggered by factors including the presence of microorganisms
why are complement proteins considered part of innate nonspecific immunity
they are always present in blood and tissue fluids allowing them to be activated quickly
what is the process by which circulating complement precursors become functional
complement activation
how is complement activation triggered
by one of 3 defense mechanisms
alternative
classical
lectin pathway
how is the alternative pathway initiated
by spontaneous activation of the complement protein C3
what does hydrolysis of C3 produce
C#a and C3b
what happens to c3b if no invaders are present
it is degraded in a hydrolysis reaction using water in the blood
what happens to c3b if invaders are present
it attaches to the surface of the microbe and recruits other complement proteins
what does the classical pathway depend on
production of antibodies by the specific adaptive immune defenses
how is the classical pathway initiated
a specific antibody must bind to the pathogen to for form an antibody-antigen complex activating the c1 complex
what is the c1 complex
a multipart protein complex where each component participates in the full activation of the overall complex
what happens after activation of the c1 complex
the remaining classical pathway complement proteins are recruited and activated in a cascading sequence
what triggers the lectin activation pathway
the binding of manes-binding lectin to the carbohydrates on the microbial surface
how are lectins produced
by liver cells
when are lecitins upregulated
in response to inflammatory signals received by the body during infection
what do complement activation pathways provide
opsonization, inflammation, chemotaxis, and cytolysis
what is opsonization
the coating of a pathogen by a chemical substance that allows phagocytic cells to recognize engulf and destroy it more easily
what are opsonins from the complement cascade
c1q, c3b, c4b, mannose binding proteins and antibodies
what are c3a and c5a
complement fragments with anaphylatoxins wit potent pro inflammatory functions
what do anaphylatoxins do
activate mast cells causing degranulation and the release of inflammatory chemical signals, including meditators that cause vasodilation and increased vascular permeability
what is an additional role of c5a
chemoattractant for neutrophils and other white blood cells
what is a membrane attack complex composed of
c7, c7, c7 and c9
what does the membrane attach complex allow
c9 to polymerize into pores in the membranes of gram-negative bacteria
what do the pros from c9 do
allow water, ions and other molecules to move freely in and out of targeted cell leading to cell lysis and death of the pathogeb
what is Mac effective against
only gram-negative it cannot penetrate wall of gram-positive bacteria
what is more important for gram-positive bacteria
mediated opsonization
what are cytokines
soluble proteins that act as communication signals between cells
what is the role of cytokines in nonspecific innate immune respones
stimulate production of chemical mediators or other funcitions such as cell proliferation, cell differentiation, inhibition of cell division, apoptosis and chemotaxis
how can the function of a cytokine be described
autocrine, paracrine, or endocrine
what happens in autocrine function
the same cell that releases the cytokine is the recipient of the signal ( self stimulation)
what does paracrine function involve
the release of cytokines from one cell to other nearby cells stimulating some response from recipient cells
what is endocrine function
when cells release cytokines into the bloodstream to be carried to target cells further away
what are the most important classes of cytokines
interleukins, chemokine, interferons
what do interleukins modulate
almost every function in the immune system
what are chemokines
chemotactic factors that recruit leukocytes to sites of infection, tissue damage and inflammation
how are chemokine different from chemotactic factors
chemokine are very specific in the subsets of leukocytes they recruit
what are interferons
group of immune signaling molecules that defend against viruses
what are type 1 interferons
interferon a and b produced band released by cells infected with virus
what do type 1 interferons do
stimulate nearby cell to stop production of mRNA, destroy rna already produced and reduce protein synthesis.
stimulate various immune cells involved in viral clearance to more aggressively attack virus infected cells
what are the effects of type 1 interferons
inhibit biral replication and production of mature virus slowing the spread,
what do type 2 interferon (Y) do
activator of immune cells
what happens to cytokine that bind mass cells and basophils
they release histamine
what is histamine
a pro inflammatory compound
where are histamine receptors found
a variety of cells
what pro inflammatory events does histamine activate
bronchoconstriction and smooth muscle contractions
what releases leukotrienes
mast cells
what are leukotrienes
lipid based pro inflammatory mediators produced from the metabolism of arachidonic acid in the cell membrane of leukocytes and tissue cells
how does the pro inflammatory effects of histamine compare to leukotrienes
leukotrienes are more potent and longer lasting
what do histamine and leukotrienes do together
induce cough, vomiting, diarrhea to expel pathogens
what are prostaglandins
chemical mediators the promote the inflammatory effects of kinins and histamines
what do prostaglandins help to do
set the body temperature high to promote activities of white blood cells and inhibit growth of pathogens
what is bradykinin
an inflammatory mediator that contributes to edema
how does bradykinin work
it binds to receptors on cells in capillary walls, causing capillaries to dilate and become more permeable to fluids
what are the three categories of formed elements
erythrocytes
platelets (thrombocytes)
leukocytes
what are platelets
cellular fragments that participate in blood clot formation and tissue repair
where do formed elements of blood come from
pluripotent hematopoietic stem cells in the bone marrow
what is hematopoiesis
differentiation of HSC into different types of blood cells
what dooms HSCs become
erythrocytes
how can leukocytes be divided
granulocytes and agranulocutes
where are granules in granulocytes
in the cytoplasm
how can granulocytes be distinguished from one another
by the appearance of their nuclei and the contents of their granules, that have different traits functions and staining properties
describe the nucleus of a granulocyte
has a nucleus with three to five lobes and small numerous lilac colored granules
how are the lobes of the nucleus in neutrophils connected
by a thin strand of material
describe the nucleus of eosinophils
fewer lobes in the nucleus (2-3) and larger granules that stain reddish-orange
describe nucleus of basophils
two lobed nucleus and large granules that stain dark or purple
what are the granulocytes
neutrophils
eosinophils
basophils
what are neutrophils involved in
the elimination and destruction of extracellular bacteria
what are neutrophils capable of
migrating through the walls of blood vessels to areas of bacterial infection and tissue damage where they seek out and kill infectious bacteria
what do PMN granules contain
defensins and hydrolytic enzymes that help them destroy bacteria through phagocytosis
what happens when neutrophils are brought into an infected area
they can be stimulated to release toxic molecules into the surrounding tissue to better clear infectious agents (degranulation)
What are neutrophil extracellular traps
extruded meshes of chromatin that are closely associated with antimicrobial granule proteins and components
what is chromatin
dna with associated proteins
what does creating and releasing a mesh or lattice like structure of chromatin, coupled with antimicrobial proteins, allow neutrophils to do
mount a highly concentrated and efficient attack against nearby pathogens
what proteins re associated with NET
lactoferrin
gelatinase
cathepsin g
nyeloperoxidase
what is pus
visible accumulation of leukocytes, cellular debris and bacteria at the site of infection
what does the presence of pus indicate
immune defenses have been activated against an infection
what are eosinophils
granulocytes that protect against protozoa and helminths and play a role in allergic reactions
what do eosinophils contain
histamine
degradative enzymes
major basic protein
what does major basic protein do
binds to the surface of carbohydrates of parasites and the binding is associated with disruption of the cell membrane and membrane permeability
what do activated complement fragments c3a and c5a act as
anaphylatoxins
when are c3a and c5a fragments produced
in the activation cascades of complement proteins
how do c3a and c5a act as anaphylatoxins
by inducing degranulation of basophils and inflammatory responses
what are basophils important in
allergic reactions and other responses that involve inflammation
what is the most abundant components of basophil granules
histamine
what makes mast cells and basophils similar
they have the same components and play an important role in allergic reactions and inflammatory response
how are mast cells different from basophils
mast cells leave circulation blood and are found in tissue
what are art cells associated with
blood vessels and nerves or found close to surfaces that interface with the external environment
how can agranulocytes be categorized as
as lymphocytes or monocytes
what do lymphocytes include
B cells
t cells
natural killer cells
how do monocytes differentiate
into macrophages and dendritic cells
what makes natural killer cells different from other lymphocytes
they use nonspecific mechanisms to recognizes and destroy cells
what types of cells do natural killer cells target
cancer cells and cells with viruses
what are mhc markers
marks that say a cell is part of self
how does a natural killer cell know to attack another cell
it lacks the mhc marker
how do natural killer cells make another cell suicide
by expressing cytotoxic membrane proteins and cytokines that stimulate the target cell to undergo apoptosis
what two toxins are used in perform mediated cytotoxicity
perforin and granxymes
what is perforin
a protein that creates pores in the target cell
what are granzymes
proteases that enter through pores in to the target cells cytoplasm and triggers a cascade of protein activation leading to apoptosis
why aren’t natural killer cells considered granulocytes
because their granules a re less numerous than those in true granulocytes
describe monocytes
largest of white blood cells and has a nucleus that lacks lobes, also lacks granules
where do dendritic cells live
in skin and mucous membranes
what macrophage lives in bran and CNS
microglial cells
what macrophage lives in liver
kupffer cells
what macrophage lives in lungs
alveolar macrophages
what macrophage lives in peritoneal cavity
peritoneal macrophages
what is the main function of phagocytes
to seek ingest and kill pathogens
what is extravasation/diapedesis
when leukocytes pass through walls of capillaries to reach infected tissue
what initiates extravasation
complement faster c5a and cytokines released into area by resident macrophages and tissue cells responding to infectious agent
what is transendothelial migration
when cytokines reach the cellular junction, bind to adhesion molecules, flatten out and squeeze through their cellular junction
what allows leukocytes to exit the blood stream and enter infected areas where they can begin phagocytosis invading pathogens
rolling adhesion
does extravasation occur in arteries or veins
no because they have thicker multilayer walls and arterial blood flow is too turbulent for rolling adhesion
how long does it take neutrophils to respond?
hours
how long does it take monocytes to respond
several days
what are pathogen associated molecular pathways
molecular structures common to groups of pathogens
what are some pamps
peptidoglycan
flagellin
lipopolysaccharides
lipopeptides
nucleic acids
what are pattern recognition receptors
structures that allow phagocytic cells to detect pamps
what do toll like receptors do
bind to pamps and communicate with the nucleus of the phagocyte, some embed in the membranes of interior compartments and organelles
what are toll like receptors useful for
binding and recognition of intracellular pathogens that may have gained access to inside the cell before phagocytosis could take place
what is phagocytosis
when a pathogen is engulfed in a vesicle and Brough into the internal compartment of a phagocyte
how do prr’s aid in phagocytosis
by binding to the pathogens surface
how does a phagocyte engulf a pathogen
by forming a pseudopod that wraps around the pathogen and pinches it offf into a membrane vesicle called a phagosome
what happens when the phagosome has the pathogen
it fuses with one or more lysosome to form a phagolysosome
what does formation of the phagolysosome do
enhance the acidification which is essential for activation of ph dependent digestive lysosomal enzymes and production of hydrogen peroxide and toxic reactive oxygen species
what digests pathogens
enzymes such as lysozyme
phospholipase and protease
what happens during a respiratory burst
phagocytes increase their uptake and consumption of oxygen
why do phagocytes increase oxygen if not for energy
to produce superoxide anion, hydrogen peroxide, hydroxyl radicals and other reactive oxygen species that are antibacterial
what triggers inflammation
a cascade of chemical mediators and cellular responses that may occur when cells are damaged and stressed or when pathogens successfully breach the physical barriers of innate immune system
what does inflammation allow for
recruitment of cellular defenses needed to eliminate pathogens, remove damaged cells and initiate repair mechanisms
what can excessive inflammation lead to
local tissue damage and death
what happens immediately following an injury
vasoconstriction of blood vessels to minimize blood loss
what happens after vasoconstriction
vasodilation and increased vascular permeability
what causes vasodilation
the release of histamine from mast cells
what does increased blood flow and vascular permeability do
dilute toxins and bacterial products at the site of injury or infection, associated with influx of phagocytes at site
what are the signs of the inflammatory process
erythema, edema, heat, pain, altered function
how does the complement system enhance the inflammatory process
through production of anaphylatoxin ca5
what does the release of bradykinin cause during inflammation
capillaries to remain dilated, flooding tissues with fluids leading to edema
what happens during period of inflammation
bradykinin is released
neutrophils are recruited
pus forms
macrophages clear out pus
tissue repair begins
what causes chronic inflammation
an on going and lower level battle between the host and pathogen, it may appear healed but pathogens are present in deeper tissue
what can chronic inflammation be involved in
alzheimers, parkinsons, heart disease metastatic cancer, granulomas
what are granulomas
pockets of infected tissue walled off and surrounded by WBC
what infection can cause chronic inflammation
TB, it causes granulomas in lung tissue
what is a fever
inflammatory response that affects the entire body
what normally maintains body temperature
hypothalmus
how do bacterial and viral infections create fever
by producing pyrogens
what are pyrogens
chemicals that alter they hypothalamus to elevate body temp
how does fever enhance innate immune defenses
by stimulating leukocytes to kill pathogens, stimulate the release of iron sequestering compounds from liver to starve ones that need iron out
what happens during a fever
skin is pale due to vasoconstriction in skin, shivering muscles are stimulated,
what is the crisis phase
when fever breaks
how do superantigens cause life threatening fevers
by causing excessive activation of T cells and release of cytokines overstimulating the inflammatory response
what can produce superantigens
staphylococcus aureus and Streptococcus pyogenes
