Innate Immunity (complete) Flashcards
is innate or adaptive immunity similar in all individuals of a species
innate immunity (adaptive immunity varies from individual to individual)
is innate or adaptive immunity generally enhanced by repeated exposure
adaptive immunity
does innate or adaptive immunity have some sort of “memory”
adaptive immunity
does innate or adaptive immunity use nonspecific mechanisms to identify invaders
innate immunity
adaptive immunity is based on the recognition or specific invader
are the mechanisms of innate or adaptive immunity mobilized immediately, and work quickly?
innate immunity
effector products of adaptive immunity take several days to produce
What happens to the adaptive immune response with each additional exposure to an invader
the response becomes quicker, more specific, and is at a higher level.
what are the 6 types of organisms that can grow in vertebrates
- viruses
- bacteria
- fungi
- parasites
- protozoa
- worms
What barriers/mechanisms must be overcome by organisms that want to grow in humans
- Skin
- mucous membranes
- ciliary escalator in the respiratory tract
which immunity works early in the infection process
innate immunity
T/F the adaptive immune response depends on the innate immune response for activation and for most of its effector functions
True
why haven’t our bodies adapted and evolved enough over time to already destroy these pathogens
because microbes and viruses evolve faster than vertebrates
What are PAMPs
pathogen associated molecular patterns.
certain structures that are only found on pathogens
What are some examples of PAMPs
- double stranded RNA
- LPS (lipopolysaccharide)
- Lipoteichoic acid
- peptidoglycan
on what type of pathogen do you see the PAMP double stranded RNA
viruses
on what type of pathogen do you see the PAMP LPS
gram negative bacteria
on what type of pathogen do you see lipoteichoic acid
the cell wall of gram positive bacteria
on what type of pathogen do you see peptidoglycan
the cell wall of gram positive bacteria
what type of immunity focuses on these PAMPs
innate immune mechanisms
why don’t these organsims evolve and change their PAMPs so they can’t be used to recognize the organism by immune systems
they must be crucial to the organisms and therefor hard to change
What are the three possible immune response outcomes
- normal response (attacks non-self, leaves self)
- immune hyperactivity (allergies, and autoimmunity)
- immune hypoactivity (infections, cancer, immunodeficiency)
what are in eyes that are barriers against infection
lysozome in tears
washing of the eyes
what acts as barriers on the skin against infection
- physical barrier
2. antimicrobial secretions
what acts as a barrier in the respiratory system against infection
- mucus
- cilia
- alveolar macrophages
What acts as a barrier in the genitourinary tracts against infection
- low pH of urine
- washing of urine
- lysozyme
- vaginal lactic acid
what acts as a barrier in the digestive tract against infection
- stomach acidity
- normal flora
- bile
what are commensals in our body
bacteria that live in our body, that aren’t pathogenic.
lysozyme does what, and comes from where?
breaks down peptidoglycan
comes from tears, saliva, nasal secretions, body fluids, lysosomal granules
lactoferrin and transferrin do what, and come from where?
they bind iron, and compete with microorganisms for it
they come from granules of PMNs
Lactoperoxidase does what, and comes from where?
it is inhibitory to many microorganisms
it comes from milk and saliva
B-lysin does what, and comes from where?
effective against gram positive bacteria
it comes from thrombocytes and normal serum
Chemotactic factors do what and come from where
they induce direct migration of PMNs, monocytes, and other cells
they come from bacteria, products of cell injury, denatured proteins, complement, and cytokines
properdin does what, and comes from where?
it activates complement in the absence of the antibody-antigen complex
it is found in normal plasma
cationic peptides do what and come from where
they disrupt membranes and block cell-transportation
they come from PMN granules (defensins)
What are the three lines of defense of the immune system. and which are non-specific, and which are specific
- skin, mucus membranes, chemicals
- phagocytosis, complement, interferon, inflammation, fever
- lymphocytes and antibodies
1-2 non-specific, 3 - specific
What are the roles of phagocytes in an immune response
- production of cytokines and chemokines
- Ingulf and destroy the pathogen (with out without antibodies)
- presentation of antigen fragements to T-cells
which types of phagocytes do the presentation of antigen fragments to T-cells
immature dendritic cells, that have been activated by microbial components and cytokines
What happens with the T-cells that have had antigen fragments presented to them by immature dendritic cells
they become effector cells, they create an adaptive immune response (present it to B-cells)
What do the cytokines and chemokines secreted by phagocytes do
- increase vascular dilation
- increase vascular permeability
- induce production of proteins that recruit more immune cells
= cause inflammation
what does increase vascular dilation and permeability do for an immune response
allows more lymphocytes, antibodies, and complement to enter the site of infection
What are antigens
molecules that trigger a specific immune response
what are epitopes
the portion of the antigen recognized by the antibody or lymphoocyte
how do antigens enter the body
- through breaks in the skin and mucus membranes
- direct injection (bite or needle)
- ingestion or inhalation
What is the type of cell from which all cells of the immune system are derived
hematopeotic stem cell (HSC)
what does a HSC give rise to each time it divides
another HSC and a progenitor cell that is commited to a certain lineage
what are the two lineages of immune cells
myeloid (inflammatory cells)
lymphoid (lymphocytes)
which is the only cell that can be formed from both the myeloid and lymphoid lineages
dendritic cells
what controls the specific differentiation of progenitor cells
hematopoeitins
what cells come through the myeloid lineage
RBCs platelets basophils eosinophils neutrophils monocytes (dendritic cells/macrophages)
what cells come through the lymphoid lineage
B-cells
T-cells
NK cells (natural killer)
do all cells of myeloid lineage complete differentiation in the same location
nope,
bone marrow, peripheral tissues, secondary lymphoid tissue
What are the three types of formed elements in blood
- RBCs (erythrocytes)
- Platelets
- WBCs (leukocytes)
What is the function of RBCs
carry O2 and CO2 in the blood
what is the function of platelets
involved in blood clotting and inflammation
what are the two classes of leukocytes
granulocytes
agranulocytes
What are the different types of granulocytes
neutrophils
eosinophils
basophils
what are the different types of agranulocytes
monocytes
lymphocytes
list the leukocytes from most abundent to least
neutrophils lymphocytes monocytes eosinophils basophils
what do neutrophils do
they are major phagocytes and cause accute inflammation
what do eosinophils do
perform parasite defense and regulate inflammation
what do basophils do
secrete histamine, involved in allergies
what can high levels of eosinophils in the blood indicate
allergies or a parasitic worm infection
what change in white blood cell count does a bacterial infection cause
increase in all leukocytes, but mostly neutrophils
what change in white blood cell count does a viral infection cause
increase in lymphocytes
what is diapedesis
the passages of White blood cells through intact capillaries
what do lymphocytes do
they are the main cells in adaptive immune response
what do monocytes do
mature into macrophages
what are the phagocytic cells
neutrophils
macrophages
dendritic cells
what role do neutrophils play as phagocytes
short lived, but quick destructive phagocytosis
release of cytokines = acute inflammation
what roles do macrophages play as phagocytes
they are found in various tissues, important in their maintenance and repair
long lived = cells of chronic inflammation
release cytokines
which phagocytes are activated by T-cells and antibodies
macrophages
what is phagocytosis
a receptor-mediated process whereby large particles are engulfed.
what can the phagocytic receptors bind
they can bind microbes directly
they can bind opsonized particles
do some pathogens use phagocytosis to their advantage
yes
what are two ways that pathogens can use phagocytosis to their advantage
- they can get phagocytosed, then rupture the phagosome and enter the cytoplasm
- they can block the fusion of lysosomes with the phagosome so they can’t be destroyed
what bacteria rupture the phagosome after they have been phagocytosed and enter the cytoplasm
listeria monocytogenes
burkholderia pseudomallei
what bacteria prevent the fusion of the phagosome and lysosome after being phagocytosed
mycobaterium tuberculosis
salmonella
what can overcome the block of fusion of the phagosome and lysosome by salmonella and mycobacterium tuberculosis
IFN-y (T-cell cytokine)
what are the receptors of macrophages involved in
- scavenging tissue debris from apoptotic cells
- tissue repair and maintenance
- production of anti-inflammatory responses
which cells are the phagocytotic cells in the second line of defense
macrophages
where do macrophages come from
when monocytes leave the blood, they become macrophages in the tissues
what are some names for macrophages that stay in a certain area of the body
- microglial cells (CNS)
- mesangial cells (kidney)
- marginal zone (spleen)
- Kupffer cells (liver)
are all macrophages fixed to certain tissues
nope, some are wandering
are alveolar macrophages fixed, or wandering macrophages
wandering
what makes up the MPS (mononuclear phagocytotic system)
monocytes, macrophages attached to endothelial cells
how are microbes killed in a phagocyte
they are absorbed and bathed in free radicals, which destroy them
what are the different types of dendritic cells
- immature
- mature
- follicular
what do immature dendritic cells do
they phagocytize pathogens, then they become mature
what do mature dendritic cells do
they present antigens to T-cells
what do follicular dendritic cells do
present immune complexes to B-cells
where are dendritic cells very numerous
in epithelia and mucosal surfaces
what are langerhans cells
specialized dendritic cells in keratinized epidermis that can remain there for months
what are dermal or interstitial dendritic cells
dendritic cells that reside in the dermal layer
what are the different dendritic cells that function in the epithelium of the small intestines
- some sample gut contents directly
- some wait below the epithelial cells to have samples of lumen transported to them
- some circulate in the blood and wait for viruses
what is the function of the dendritic cells that directly sample the lumen of the small intestine
they prevent inflammatory response against the gut commensial bacteria
what are the cells that transfer small intestine lumen to lymphoid tissues
M-cells
what are the dendritic cells called that circulate with the blood and wait for viruses
plasmacytoid dendritic cells
what do plasmacytoid dendritic cells do when they encounter viruses
produce lots of type 1 interferons
what are the primary lymphoid organs
the locations where lymphocytes mature
Bone marrow
thymus
what are secondary lymphoid organs
the locations where antigens are trapped, where an immune response takes place lymph nodes spleen MALT (tonsils) GALT (peyers patches)
what are tertiary lymphoid tissues
locations where lymphoid tissues is created at sites of chronic infection
what does the spleen do
filters for antigens in the blood
where do you find the lymphatic tissue (white pulp) of the spleen
around arterioles
where do you find the marginal zone of the spleen
around the white pulp
what do you find in the marginal zone of the spleen
metallophilic macrophages
marginal zone macrophages
specialized B cells
how do antigens get to the GALT
they are transported there by M cells
what is the first type of cell that the antigens sees in GALT
dendritic cells
what do sentinal cells do
recognize pathogens and secrete cytokines to initiate an immune response
can all epithelial cells tolerate microbes on their surface
nope, some can, but places like alveoli and small intestines don’t because they would interfere with their function
how do the alveoli and small intestines prevent the build up of microbes on their surfaces
secreting antimicrobial peptides
defensins and cathelicidins
what are defensins
small antimicrobial peptides with a 3 stranded beta-sheet and 3 disulfide bonds
what are cathelicidins
they are small antimicrobial peptides, but differ from defensins in structure (a-helical regions)
what are the types of defensins
alpha and beta
how do alpha and beta defensins differ
both come from neutrophils, but beta can come from epithelia too
both are antimicrobial, but beta are chemotactic, and induce histamine release
what are the paneth cells of the small intestine
cells that produces alpha defensins in response to bacteria
what do the a-defensins of paneth cells destroy
giardia, but only one of them (cryptdin-3) kills E. coli
how do defensins kill microbes
- they bind to the acidic phospholipids in the membranes of microbes
- they enter the membranes and create pores
- this causes the cells to lyse
how do some bacteria combat the pore creation in their membranes by defensins
they modify their membrane lipids with lysine = reduction of negative charge = insensitive
what are collectins and ficolins
soluble proteins at mucosal surfaces or in blood that recognize carb configurations on microbes.
what are the structures of collectins
they are a long chain, with a big carb recognizing head
what do collectins do
the head binds to a sugar on the microbe, this increases phagocytosis, and activates complement
what is the complement system
a series of about 30 proteins that can be activated in 3 ways
what happens in the activation of the 30 proteins in the complement system
proteins are cleaved into two substances
beta - stays
alpha - leaves
what are the three pathways in activation of the complement system
lectin pathway
classical pathway
alternative pathway
what are the four ends of the complement system
- lysis of bacteria
- chemotaxis of phagocytes to the bacteria
- opsonization of bacteria
- all of which increase inflammation
what are the two main players in the lectin pathway of the complement system
MBL
ficolins
what are the three main players in the classical pathway of the complement system
IgG, IgM, pentraxins
what is the main player in the alternative pathway of the complement system
microbial membranes
the early events of all three pathways of the complement system all lead to what
the cleavage of C3 by C3 convertase
which complements lead to inflammation, chemoattraction
C3a
C5a
which complements lead to induction of phagocytosis
C3b
which complements lead to attack on membranes
C5b, C6, C7, C8, C9
which complements lead to promotion of antibody production
C3b
which complements are the late events
C5-C9
how is the classical pathway of the complement system activated
- C1q/r/s complex couples with pentraxins or antibodies
- C1s cleaves C4
- C4b binds to cell surface
- C2 binds to C4b
- C1 cleaves C2
- C4b-C2b = C3 convertase
- C3 convertase cleaves = C3a, C3b
how is the lecthin pathway of the complement system activated
- MBL or ficolin bind to the microbial surface carbs
- MASP’s bind to MBL/Ficolin
- MASP2 cleaves C4
- C4b stays attached
- C2 binds to C4b
- C2 is cleaved by MASP-2
- C4b-C2b = C3 convertase
- C3 convertase cleaves = C3a, C3b
how is the alternative pathway of the complement system activated
- C3a and C3b bind to the cell surface
- B binds to C3b
- D cleaves B
- C3b-Bb = C3 convertase
- C3 convertase cleaves = C3b, C3a
what happens to C3b that can’t find a microbe to bind to
it is bound by factor H, then factor I cleaves the C3b (making it inactive)
what does properdin do in the complement pathways
it stabilizes the C3b/Bb complex
what happens when C3b attaches to either the C3b/Bb or C4b/C2b complexes
this leads to the cleavage of C5
what does C5a do
it is a proinflammatory peptide that acts on endothelial cells and mast cells.
it is a powerful neutrophil chemoattractant
what does C5b do
it nucleates the formation of the (MAC) membrane attack complex (this makes large holes in the cell)
defects in which components of the complement can cause SLE (systemic lupus erythematosis)
defects in C1 and C4
how do defects in C1 and C4 lead to SLE (systemic lupus erythematosis)
they lack the ability to clear apoptotic cell debris and immune complexes
the deficiency of which complement component is the most severs
C3
what do defects in the late part (C5-C9) cause
severe nisseria infections
how do microbes fight against the actions of the complement system
- make surface proteins that bind factor H (so that it will inactivate C3b)
- make proteins that bind to C4bp (an inactivator of C4b)
- take host control proteins with them as they bud
what microbes make surface proteins that bind factor H to fight against the complement system
HIV S. Pyogenes S. Pneumonia Neisseria B. Burgdorferi gonorrhoeae
which microbes make proteins that bind C4bp to fight against the complement system
gonorrhoeae
B. pertussis
which microbes take host control proteins with them as they Bud
HIV-1
vaccina
which fuse first, primary or secondary granulues
secondary (yep these fuse first)
what does NAPDH oxidase create
O2 H2O2 HOCl OH ONOO (with NO from iNOS)
what does iNOS create
NO
ONOO (with O2 from NAPDH oxidase)
which attack first, the toxic O2 intermediates or the toxic nitrogen intermediates
the toxic O2 intermediates are used immediately, the toxic nitrogen intermediates are used later, and last longer
what happens when you have defects in any subunit of the NADPH oxidase
you will get a chronic granulomatus disease (CGD)
patients have a hard time clearing infections and get persisting granulomas
What are the three types of sentinel immune cells in tissues
- macrophages
- Mast cells
- immature dendritic cells
what do sentinel immune cells do
recognize microbial threats and initiate an inflammatory immune response.
what do sentinel cells have to differentiate between
apoptotic bodies and microbial threats
what allows sentinel cells to distinguish between apoptotic bodies and microbial threats
TLRs (toll like receptors)
what are TLRs (toll-like receptors)
a protein with an extracellular portion with lots of leucine (LRRs) a transmembrane domain, and a Toll/IL-1 receptor (TIR) domain
what can TLRs bind
Nucleic acids
Proteins
Lipids
polysaccharides
are accessory proteins sometimes used to help things bind to TLRs
yes
how do sentinel cells recognize LPS
- LPS is taken from the cell wall by LBP
- LBP gives the LPS to CD14
- CD14 give the LPS to TLR/MD-2 complex
- this sends a signal into the cell
what is required for LPS responsiveness of TLR4
MD-2
is CD14 required for LPS response
no, but it helps a lot
where do you find TLRs that recognize microbial cell wall components
in the plasma memebrane
where do you find TLRs that recognize microbial nucleic acids
in the intracellular membranes (phagosomes or endosomes)
What does the Activation of TLRs lead to
production of cytokines
TNF
IFN (alpha and beta)
IL (6 and 12)
what do NOD1, NOD2 and Cryopyrin do
recognize parts of peptidoglycan, and activate NF-kB (inflammatory cytokine)
when TLRS and sentinel cells recognize microbes, what do they do
release cytokines
release chemokines
release lipid mediators
these lead to a coordinated response by vessels and leukocytes = inflammation
what are the 4 main functions of inflammation mediators
- increase vascular permeability
- change adhesive properties of the epithelium (increased amounts of leukocytes)
- activate phagocytes
- activate NK cells
what are the two proteolytic cascades triggered by activation of endothelial cells
kinin cascade
coagulation cascade
how does the kinin cascade affect inflammation
increases vas. permeability
how does the coagulation cascade affect inflammation
clotting reactions decrease microbial spread
Where does TNF come from
macrophages and mast cells
what does TNF do
increases: vascular permeability endothelial cell adhesiveness activation of phagocytes cytoxicity of NKcells
what does IL-1 come from
macrophages, mast cells, KC, EC
What does IL-1 do
increases chemokine production and endothelial cell adhesiveness
Where does IL-6 come from
macrophages, mast cells, FB
what does IL-6 do
recruites monocytes, systemic effects
what does IL-12 come from
macrophages
what does IL-12 do
increases IFN-y production by NK cells
increases NK cytoxicity
what does IFN-y come from
NK cells
what does IFN-y do
enhances phagocytosis and killing by phagocytes
what do chemokines come from
macrophages, mast cells, EC
what do chemokines do
attract neurtophils. monocytes, effector T-cells
what are the antinflammatory cytokines
IL-10 and TGF-Beta
how does arachadonic acid turn into inflammatory mediators
- a stimulus activates PLA2 and COX-2
- PLA2 pulls arachadonic acid from phospholipids
- COX-2 breaks arachadonic acid into PGH2
- PGH2 is broken down into PGI, PGE, PGF, and thromboxane
what are luekotrienes involved in
chronic inflammation
what are the steps in getting neutrophils out of the blood and into the tissues
rolling
activation
adhesion
diapedesis
what cells dominate acute inflammation
neutrophils
what cells dominate chronic inflammation
macrophages and Tcells
What mediates the shift from acute inflammation to chronic inflammation
IL-6
what effects to proinflammatory cytokines systemically
- TNF uses fat and muscle cells to mobilize energy stores
- IL-1 and IL-6 sitmulate the liver to produce proteins to help fight infection
- IL-1 and IL-6 act on the hypothalamus to induce a fever
what is the acute phase response
when IL1 and IL6 stimulate the liver to produce proteins that help fight infection
what are antiinflammtory actions
- glucocorticoids
- IL10 and TGF-b
- acetylcholine receptors
What are the two types of interferons
type 1 (IFN -a and IFN-b) type 2 (IFN-y)
what is type 1 interferon
IFNa and IFNb
they are produced by infected cells, and by cells sensing viruses through TLR.
they work against virus’s
they leave the infected cells and go to nearby cells. they stop the cells from proliferating the virus
what is type 2 interferon
they are antiviral and antibacterial (IFN-y)
what does type 1 interferon do to cells
- through PKR they shut off all translation
- degrade RNA
- inhibit transcription
what does type 2 interferon do to cells
shut off all translation through PKR
what cells produce Interferons
macrophages, immature dendritic cells, plasmacytoid dendritic cells
which cells produce the most interferons
plasmacytoid dendritic cells
what TLR gives rise to IFN-B
TLR 3
what TLD gives rise to IFN-a
TLR 7,8,9
what is the most potent activator of macrophages
IFN-y
