Cellular barriers to the innate immune system Flashcards

1
Q

where did cells of the inante immunity arise from?

A
  • 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

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2
Q

immune cells in blood

A
  • RBC (erythroctes) and WBC (leukocytes)
  • platelets

*leukocytes include cells of the innate and adaptive immune systems

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3
Q

how are leukocytes formed

A
  • by differentiation of myeloid stem cells produced in bone marrow
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4
Q

what are granulocytes

A
  • mast cells, basophils, eosinophils and neutrophils/PMNs (polymorphonuclear leukocytes)

*have antimicrobial things stores in granules

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5
Q

what are agranulocytes

A
  • monocytes, macrophages and dendritic cells
  • NK cells (lymphoid lineage)
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6
Q

what do basophils and eosinophils do?

A
  • release toxins to poison microbes and parasties

*granulocytes

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7
Q

what do neutrophils and monocytes do

A
  • engluf and destroy microbes by phagocytosis

neutrophil = graulocyte

monocyte = agraulocyte

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8
Q

what do monocytes differentite into

A

macrophages and dendritic cells - they are phagocytes

*they are a link between the innate and adaptive immune systems

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9
Q

how do enutrophils trap pathogens

A
  • 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

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10
Q

diagnostic value of white blood cell ratios

A

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

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11
Q

whena re neutrophil levels elevated

A
  • during bacterial infections (often increase in immature forms
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12
Q

when are eosinophil levels elevated

A

parasitic infections

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13
Q

whena re basophil levels elevated

A

allergies

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14
Q

when are lymphocyte levels elevated

A

during viral ifnections

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15
Q

when are monocyte levels elevated

A

during chronic infections

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16
Q

how do NK cells destroy infected and canerous host cells

A
  • 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)
17
Q

what is most liekly to make first contact with indvading pathogens

A
  • 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

18
Q

what serves as antigen presenting cells to adaptive immunity

A

macrophages and dendritic cells

19
Q

what are phagocytes

A
  • cells that eat (just like an amoeba does)
  • include macrophages, dendritic cells, monocytes and enutrophils
20
Q

what are the steps to phagocytosis

A
  1. recognition of the microbs via receptors on phagocyte membrane
  2. pseudopods extend and engluf the target - want to capture and keep in one place
  3. invagination adn trapping withing a phagosome vesicle - acidification starts
  4. 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)
  5. Pieces of the destroyed bacterium are expelled fomr phagocyte

*note: small pieces of the mrocessed microbe components are used to present to adaptive immunity

21
Q

what are teh two pathways used by phagocytes to kill pathogen within the phagolysosome

A

oxygen dependent and oxygen independent

22
Q

describe the oxygen independent pathway used by a phagocyte to kill a pathogen

A
  • uses defensins/antimicrobial peptides
  • iron sequestering proteins (lactoferrin)
  • enzymes (lysozyme, lipases, proteases and DNAses)
23
Q

describe the oxygen dependent pathway for phagocytes to kill a pathogen

A
  • 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
24
Q

how do phagocytes recognize invaders

A
  • 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

25
Q

what are TLRs

A

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
26
Q

what occurs upon binding fo TLR to specific ligand/PAMP

A
  • causes host cell to relase cytokines
  • induce rpoduction of antimicrobial peptides
  • induce cells to engage the invader (phagocytosis)
27
Q

example of TLR that targets PAMP

A

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

28
Q

what enhances phagocytosis

A
  • 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
29
Q

what defnses have bacteria envolved against innate immunity attack

A
  • 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
30
Q

describe inflammation

A

*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)
31
Q

what are the 5 cardinal signs of inflammation?

A
  • redness, warmth/heat, pain swelling and altered function at affected site
32
Q

describe acute vs chronic inflammation

A
  • 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

33
Q

describe fever, what causes it

A
  • 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