Cellular barriers to the innate immune system Flashcards
where did cells of the inante immunity arise from?
- differentiation from myeloid stem cells
- however also include natural killer cells whcih arose from Lymphoid stem cells lineage (associated with adaptive immunity)
*get ris of cells that have damage - cross talk between innate and adaptive
*think of immune has having two arms - ones that arose frmo myeloid and those from lymphoid
immune cells in blood
- RBC (erythroctes) and WBC (leukocytes)
- platelets
*leukocytes include cells of the innate and adaptive immune systems
how are leukocytes formed
- by differentiation of myeloid stem cells produced in bone marrow
what are granulocytes
- mast cells, basophils, eosinophils and neutrophils/PMNs (polymorphonuclear leukocytes)
*have antimicrobial things stores in granules
what are agranulocytes
- monocytes, macrophages and dendritic cells
- NK cells (lymphoid lineage)
what do basophils and eosinophils do?
- release toxins to poison microbes and parasties
*granulocytes
what do neutrophils and monocytes do
- engluf and destroy microbes by phagocytosis
neutrophil = graulocyte
monocyte = agraulocyte
what do monocytes differentite into
macrophages and dendritic cells - they are phagocytes
*they are a link between the innate and adaptive immune systems
how do enutrophils trap pathogens
- with NET (neutrophil extracellular traps)
- after interacting with or sensing nearby pathogens, neutrophils can undergo an unusual form of cell death called NETosis
- ejects a lattice of chromatin impregnated with antimicrobial (NETs) into vicinity
- ensnares and kills the pathogens
- prevent speading of microbe
*Pus at site of infection contains these heroic cells
diagnostic value of white blood cell ratios
Netrophils > lymphocutes > monocytes > eosinophils > basophils
**most neutrophils by far 54% -62%
lymphocytes 25%-33%
monocytes 3-7
eosinophils 1-3
basophils 0-0.75
*dont memroize percetnages just know relative
whena re neutrophil levels elevated
- during bacterial infections (often increase in immature forms
when are eosinophil levels elevated
parasitic infections
whena re basophil levels elevated
allergies
when are lymphocyte levels elevated
during viral ifnections
when are monocyte levels elevated
during chronic infections
how do NK cells destroy infected and canerous host cells
- kill target by contract dependent mechanisms
- healthy host cells have surface MHC Class 1 antigens -recognized by receptor on NK cells to not kill
- infected host cells signals an ‘altered self’ response
*exact mech unknown but thought to involve reduction of cell surface MHC Class I and expression of a ligand recognized by NK activating mol
- when an NK cell meets a host cell lacking NHC1 it attaches to cell and secretes perforins (punch holes into membrane) and granzyme toxin (enter the infected cells to induce death via apoptosis)
what is most liekly to make first contact with indvading pathogens
- macrophages
- present in most body tissues
- adhere to surfaces - develop pseudopods (projections/processes)
- secrete cytokine proteins which attract and activate other cells
**macrophages and dendritic cells serve as antigen presenting cells to cells of the adaptive immunity
what serves as antigen presenting cells to adaptive immunity
macrophages and dendritic cells
what are phagocytes
- cells that eat (just like an amoeba does)
- include macrophages, dendritic cells, monocytes and enutrophils
what are the steps to phagocytosis
- recognition of the microbs via receptors on phagocyte membrane
- pseudopods extend and engluf the target - want to capture and keep in one place
- invagination adn trapping withing a phagosome vesicle - acidification starts
- phagosome fuses with lysosome (low pH vesicle) to form phagolysosome - acidication ramps up to activate digestive enzymes (toxic oxygen species and secretion of antimicrobial peptides)
- Pieces of the destroyed bacterium are expelled fomr phagocyte
*note: small pieces of the mrocessed microbe components are used to present to adaptive immunity
what are teh two pathways used by phagocytes to kill pathogen within the phagolysosome
oxygen dependent and oxygen independent
describe the oxygen independent pathway used by a phagocyte to kill a pathogen
- uses defensins/antimicrobial peptides
- iron sequestering proteins (lactoferrin)
- enzymes (lysozyme, lipases, proteases and DNAses)
describe the oxygen dependent pathway for phagocytes to kill a pathogen
- possess enzymes for generative a toxic reactive oxygen species (superoxide ions, hydrozyl radical, hydrogen perioxide_
- toxic reactive nitrogen species (nitric oxide, nitrite)
- together ROS create a measurable oxidative burst (ramp up o2 but not sued for respiration) to damage the pathogen
- short lived and contained within phagosome so that cell si not affected
how do phagocytes recognize invaders
- phagocytes must recofnize surface particle as foreign
- host cell must have glycoprotein CD47 that prevents attack
^ if doesnt have this then phagocytosis will occur
- phagocytosis is enhanced by helper molecules - opsonins liek complement C3b, antibodies
- cells of the innate system have specialized receptors called pattern recognition receptors (PRRs) that recognize PAMPs (pathogen associated molecular patters)
*pamps are on surface, somehting thats not suppsed to be in there
*PAMPS are invariant and essential mircobial components that are unique to microbes
what are TLRs
troll like receptors - are PRRs
- transmembrane receptor that recognize microbial and viral PAMPs
- TLRs are lcoated mostly on the surface memrbane - few are cytoplasmic
- TLRs are evolutionarly conserved - first identified in drosphila
- are expressed by cells of the inante immune response
- *TLRs recognize PAMPS
what occurs upon binding fo TLR to specific ligand/PAMP
- causes host cell to relase cytokines
- induce rpoduction of antimicrobial peptides
- induce cells to engage the invader (phagocytosis)
example of TLR that targets PAMP
TLR4
- PAMP recognized = LPS, heat shock protin
- source of PAMP = bacteria
*means that if have TLR4 receptor it will be activated by LPS whicht henc ause production of cytokines, antimicrobial epptides and maybe phagocytosis of pathogen
LRP3, NLRP4
- RAMP recognized = peptidoglycan ; CpG, dsRNA
- source of PAMP = bacteria and viruses
- cytoplasmic located TLR
NOTE: 9 tlr receptrs have been identified TLR1-TLR8
*know these exmaples
what enhances phagocytosis
- opsonization
ex: microbial cells are coated with C3b (innate immune response) or antibodies (in adaptive immune response) - phagocytes ahve membrane receptors for C3b and antibodies
what defnses have bacteria envolved against innate immunity attack
- intracellular pathoens inhibit phagosome-lysozome fusion to escape killing
- biofilms and capsuls prevent phagocytosis - some are toxic to phagocytes
- mask RAMPS (LPS, teichoic acids, memrbane proteins)
- protect against killing by alternate complement pathways
- casules are continually sloughed off and replaced
describe inflammation
*critical defense of innate immunity
- damges tissue secreted bradykinin - signalling ‘danger’
- this stimulates MAST cells to degranulate and release histamine
- histamine INC permeabiltiy of capillary walls and blood flow -> protaglandin is released which stimulated nerve endings, induces pain and signals itching
- monocytes and leukocytes extravasate into tissues
- complement is activated generating opsonins and anaphylatoxins
- Resident macrophages phagocytose bacteria, release cytokines - other cells are activated (neutrophils and monocytes)
what are the 5 cardinal signs of inflammation?
- redness, warmth/heat, pain swelling and altered function at affected site
describe acute vs chronic inflammation
- acute = response to infection that is quickly resolved
chronic = results from persistent presence of a foreign object, which causes permanent tissue damage
ex: pathogens that resist host defenses, non living irritant material, autoimmune disease
- the body walls off the site of inflammation forming a granuloma
describe fever, what causes it
- hypothalmus acts as bodys thermostat
- fever is elevated body temp, natural reaction to ifnection
- pyrogens are substances that cause fever
- exogneous pathogens induce release of endogenous pyrogens (ex: IFN, TNF, IL-6 cytokines)
- stimultes production of prostaglandins - cross the BBB, changes the responsiveness of the thermosenestive enruonst hat make up the thermoregualtroy center
ie: turns up the thermostat
