Ch.14 Innate Immunity Flashcards
What are first line defenses?
prevent entry
- skin and mucus membranes
- antimicrobial substances
What are sensor systems?
detect invaders
- pattern recognition receptors (PRRs)
- complement system
detect damage and microbial invasion
What are innate effector actions?
eliminate threat/ invader
- interferon response
- phagocytosis
- complement activation
- inflammatory response
- fever
What is dermis?
tightly woven fibrous connective tissue
What is epidermis?
many layers of epithelial cells
* outermost are dead and filled with keratin
* repels water
* continually flake off
* epidermal dendritic cells phagocytize pathogens
True or False
Salt inhibits growth of pathogens
True
True or False
Antimicrobial peptides (defensins) form pores in microbial membranes
true
True or False
Lysozyme destroys cell wall of bacteria
True
True or False
Sebum secreted by sebaceous oil glands help keep skin pliable and lowers skin pH
True
Where are mucous membranes in the body?
respiratory, digestice, urinary, and reproductive tracts
True or False
Goblet and ciliated columnar cells help remove invaders
True
True or False
Epithelial cells are living and single layered
True
True or False
Peristalsis of intestines remove microbes
True
where are lysozymes found?
tears, saliva, mucus
Where are antimicrobial peptides present?
mucus
Where are peroxidases present?
- saliva
- breast milk
- tissue fluids
Where is lactoferrin present?
saliva, mucus, breast milk, and some phagocytes. This is an iron binding protein
What is microbial antagonism?
members of the microbiome make it hard for pathogens to compete
* consumption of nutrients
* create unfavorable environments to other microbes
* prevent pathogens from attaching to host cells
* provide vitamins to host
What is the function of first-line defenses?
prevent microbial entry
What is the function of sensor systems?
detect damage and microbial invasion
What is the function of innate effector actions?
eliminate invader
Is the skin easy or difficult for microbes to penetrate?
difficult
what are the outermost epithelial cells of the epidermis characterized by?
dead and filled with keratin with repels water and maintains a dry environment
what part of the epidermis phagocytize pathogens?
epidermal dendritic cells
what role does skin play in innate immunity?
skin has chemicals that defend against pathogens
what chemicals does the skin use to defend against pathogens?
- salt
- antimicrobial peptides
- lysozymes
role of salt as an antimicrobial substance
inhibits growth of pathogens
role of antimicrobial peptides (defensins) as antimicrobial substance
forms pores in microbial membranes
role of lysozyme as antimicrobial substance
destroys cell wall of bacteria
What do mucous membranes line?
body cavities open to the environment
what do goblet cells and ciliated columnar cells in the epidermis do?
help remove invaders
peroxidases
part of systems that form antimicrobial compounds
what methods does microbial antagonism use to make it difficult for pathogens to compete?
- consumption of nutrients
- create environment unfavorable to other microbes
- prevent pathogens from attaching to host cells
- help stimulate the body’s second line of defense
- generate antimicrobial compounds
- promote overall health by providing vitamins to host
disruption of microbiome with antibiotics leads to what?
infections
when does the body’s second line of defense operate?
when pathogens penetrate the skin or mucous membranes
what is the body’s second line of defense composed of?
- cells
- antimicrobial chemicals
- processes
many of the components of the second line of defense are contained in or originate in ________
blood
neutrophils consist of what percentage of circulating WBCs?
50%
types of granulocytes
- neutrophils
- basophils
- eosinophils
what is the first granulocyte recruited?
neutrophils
what do basophils cause?
release of histamine which causes an allergic response
which granulocyte is released to fight ectoparasites?
basophils
what are eosinophils used for?
parasite defense and allergic response
what do eosinophils release? what does this do?
histamines, which breaks down histamine
what do granulocytes contain?
granules with active chemicals
how do neutrophils kill bacteria?
phagocytosis
what do the granules of basophils contain and what do they do?
histamine and other chemicals that increase capillary permeability during inflammation
what are basophils involved in?
allergic reactions and inflammation
what do granules of eosinophils contain?
antimicrobial substances and histaminase
lifespan of a neutrophil
1-2 days
neutrophil extracellular traps
A network of chromatin (DNA) fibers formed from dead neutrophils that binds microbes inhibiting colonization
when do monocytes differentiate into macrophages?
upon migration into tissue
where are monocytes found?
circulating blood
function of macrophages
sentinel; tissue specific phagocytes
specific types of macrophages
- microglia
- kupffer cells
what types of tissues contain macrophages?
almost all tissue types
function of dendritic cells
bring material to adaptive immune system for inspection
dendritic cells
specialized WBCs that act as a bridge between innate and adaptive immunity
function of lymphocytes
produce antibodies
types of lymphocytes
- T cells
- B cells
- innate lymphoid cells (natural killer cells)
how do innate lymphoid cells differ from T and B cells?
ILCs have a similar function to T/B cells but lack specificity of antigen recognition
cell communication allows _________
coordinated response
surface receptors
serve as the eyes and ears of the cell
where are surface receptors found?
span the membrane and connect outside to inside
what induces a response from surface receptors?
binding to specific ligand
cytokines
chemicals that are produced by cells, diffuse to others, and bind to appropriate receptors to induce changes
what changes can cytokines induce?
cytokines induce?
- growth
- differentiation
- movement
- cell death
function of cytokines
voices of the cell
do cytokines act at a low or high concentration?
low
adhesion molecules
allow cells to adhere to other cells
example of adhesion molecules
endothelial cells can adhere to phagocytic cells and allow them to exit the bloodstream
pattern recognition receptors
see signs of microbial invasion and lead to cytokine secretion
what do pattern recognition receptors (PRRs) detect?
microbe-associated molecular patterns (MAMPs)
what do microbe-associated molecular patterns include?
- cell wall components (peptidoglycan, lipoteichoic acid, lipopolysaccharide, lipoproteins)
- flagellin subunits
- microbial nucleic acid
PAMPs are ____________-associated, but not exclusive to ____________
pathogen; pathogens
damage-associated molecular patterns (DAMPs)
indicate cell damage
where are pattern recognition receptors located?
- cell surface
- in endosomes and phagosomes
- free in cytoplasm
what do PRRs on the cell surface detect?
microbial components present in the cell’s surroundings
what do PRRs in phagosomes and endosomes detect?
components of microbes ingested by the cell
what do PRRs in the cytoplasm detect?
cell damage as well as microbial components in the cell’s cytoplasm
T/F: phagocytes always have pattern recognition receptors
T
where are toll-like receptors found?
anchored in membranes of sentinel cells
what do surface TLRs do?
monitor extracellular environment
what do TLRs in phagosomal or endosomal membranes of organelles characterize?
ingested material
TLRs are specific for what?
distinct MAMPs
dendritic cells have both TLRs and _______
CLRs (C-type lectin receptors)
RIG-like receptors (RLRs)
detect viral RNA (often double stranded)
where are RIG-like receptors found?
cytoplasm
NOD-like receptors (NLRs)
detect microbial components of cell damage
where are NOD-like receptors found?
cytoplasm
NLRs in macrophages or dendritic cells combine with other proteins to form _________
inflammasome
interferon response
- PRRs detect viral DNA; cell produces interferon (IFN)
- IFN causes neighboring cells to express inactive antiviral proteins (iAVPs)
- iAVPs activated by viral dsRNA
- mRNA is degraded, protein synthesis stops, and infected cells undergo apoptosis
types of cytokines
- chemokines
- colony-stimulating factors
- interferons
- interleukins
- tumor necrosis factor
chemokine function
chemotaxis of immune cells
colony-stimulating factors function
multiplication and differentiation of leukocytes
interferons function
control of viral infections and regulation of immune responses
interleukins function
important in innate and adaptive immunity
what produces interleukins?
leukocytes
tumor necrosis factor function
causes inflammation and apoptosis of tumor cells
do cytokines act alone or in groups?
in groups or in sequence to generate a response
what are adhesion molecules needed for?
to leave circulation and enter tissue
complement system
proteins in the blood that help antibodies kill their target and complements activities of adaptive immune system
what proteins are involved in the complement system?
C1 through C9
the complement system is activated by how many different pathways?
three
what does the activation of the complement system lead to?
formation of C3 convertase, which splits C3
what are the 3 pathways of activation for the complement system?
- alternative pathway
- lectin pathway
- classical pathway
alternative pathway of complement system
triggered when C3b binds to foreign cell surfaces (C3 is unstable, so some C3b always present)
lectin pathway of complement system
pattern recognition molecules (mannose-binding lectins or MBLs) bind to mannose of microbial cells and interact with complement system components
classical pathway of complement system
activated by antibodies bound to antigen, which interact with complement system
activation of the complement system produces what 3 major outcomes?
- opsonization
- inflammatory response
- lysis of foreign cells
opsonization
coating antigen with antibody enhances phagocytosis
how does activation of the complement system cause opsonization?
C3b binds to bacterial cells and foreign particles, promoting engulfment by phagocytes that attach to opsonins like C3b
how does activation of the complement system cause inflammatory response?
C5a attracts phagocytes to area; C3a and C5a increase permeability of blood vessels, inducing mast cells to release cytokines
how does activation of the complement system cause lysis of feign cells?
membrane attach complexes (MACs) formed by proteins C5b, C6, C7, C8, and C9 molecules assembling in cell membranes of Gram-negatives
what does regulation of the complement system prevent?
prevents host cells from activating the complement system
how does regulation prevent host cells from activating complement system?
molecules in host cell membranes bind regulatory proteins that inactivate C3b, preventing opsonization or triggering of alternative pathway
phagocytosis
phagocytes engulf and digest material and pathogens
What cells go through phagocytosis?
neutrophils, dendritic cells, and macrophages
chemotaxis
phagocytes recruited by chemoattractants
chemoattractants
products of microorganisms, phospholipids from injured host cells, chemokine, C5a
steps of phagocytosis
- chemotaxis
- recognition and attachment
- engulfment
- phagosome maturation and phagolysosome formation
- destruction and digestion
- exocytosis
recognition and attachment step of phagocytosis
direct (receptors bind mannose) and indirect (binding to opsonins)
engulfment in phagocytosis
pseudopods surround and form phagosome
phagosome maturation and phagolysosome formation in phagocytosis
directed by TLRs; fuse with lysosomes containing enzymes
destruction and digestion in phagocytosis
toxic ROS and nitric oxide produced; pH decreases; enzyme degrade; peptides damage membrane of invader; lactoferrin binds iron
exocytosis in phagocytosis
vesicle fuses with cytoplasmic membrane, expels remains
what do macrophages do?
phagocytize dead cells and debris and destroy invaders
how long do macrophages live?
weeks or month
what do macrophages regenerate?
lysosomes
macrophages are always present where?
in tissues
what are macrophages replaced by?
monocytes
activated macrophages are a response to what?
cytokines
M1 macrophages vs M2 macrophages
- M1 macrophages have greater killing power
- M2 macrophages lessen inflammation
if activated macrophages are insufficient, they can fuse to form ___________
giant cells
granulomas
walled-off organisms or material-resistant to destruction which prevent escape but interfere with normal tissue function
granulomas cause what types of disease?
tuberculosis, etc.
what makes up granulomas?
- macrophages
- giant cells
- T cells
why are macrophages important sentinel cells?
they alert other immune cells
what causes inflammation?
infection or tissue damage
purpose of inflammation
contain site of damage, localize response, eliminate invader, and restore tissue function
what does inflammation result in?
- swelling
- redness
- heat
- pain
- sometimes loss of function
what causes PRRs to trigger?
detection of MAMPs and DAMPs
what occurs after PRRs are triggered?
host cells release inflammatory mediators (cytokines and histamine)
inducers of inflammation
microbes, tissue damage
MAMPs causes the release of what? what does this do?
tumor necrosis factor (TNF) which induces the liver to produce acute phase proteins that activate complement
blood vessel damage starts what? what does this lead to?
2 enzymatic cascades, leading to coagulation and increased vessel permeability
inflammatory process steps
- dilation of small vessels
- migration of leukocytes from bloodstream to tissues
- clotting factors wall off site of infection
- dead neutrophils and tissue debris accumulate as pus
why does the inflammatory process cause dilation of small blood vessels?
- greater blood flow (heat and redness); slower flow rate
- leakage of fluids (swelling, pain)
- fluids contain transferrin, complement, and antibodies
what occurs when leukocytes migrate from bloodstream to tissues in inflammatory process?
- endothelial cells “grab” phagocytes and slow them down
- phagocytes squeeze between cells of vessel (diapedesis)
purpose of clotting factors walling off site of infection in inflammatory process
prevents bleeding and stops the spread of microbes
inflammatory response prevents ________ but damages ___________
spread; tissues
which part of the inflammatory response causes damage to tissues?
enzymes and toxic compounds released from phagocytic cells
necrosis
traumatic cell death due to damage
apoptossi
programmed cell death; does not trigger inflammatory response
pyroptosis
PRRs in a macrophage trigger an inflammatory response that sacrifices infected cells
why does fever occur with infection?
- temperature-regulation center in the brain normally holds at 37ºC, but raises during infection in response to pyrogens
- growth rates of bacteria optimized for 37ºC typically drop sharply above optimum, allowing more time for defenses
- moderate temperature rise increases rates of enzymes
what oral temperature is considered a fever?
> 37.8ºC
what are pyrogens made by?
the body or microbes
what does temperature rise do for the body during infection?
- enhances inflammatory response
- phagocytic activity
- multiplication of lymphocytes
- release of attractants for neutrophils
- production of interferons and antibodies
- release of leukocytes from bone marrow
How is Inflammation caused?
dilutes and leaks fluids from vascular system
classical pathway of complement system
activated by antigen-antibody complex
alternative pathway of complement system
is activated on microbial cell surfaces in the absence of antibodies and is a component of innate immunity
lectin pathway of complement system
activitaed by a plasma lectin that binds to mannose on microbes & activates the classical system pathway in the absence of antibody
what are the 3 lines of defense of the immune system?
- skin, mucous membranes, enzymes, natural flora on the skin and in the GI tract
- innate immunity: phagocytes, natural killer T cells, granulocytes, complement proteins, macrophages
- acquired immunity: antibodies, B and T lymphocytes
