(04) Innate Immunity Flashcards

1
Q

what is the first line of defence against pathogens? give examples

A

anatomical and physiological barriers

eg. intact skin, cilliary clearance, low stomach pH, lysozymes in tears / saliva

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2
Q

what are the two types of innate immunity?

A

Cellular
Humoral (or soluble)

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3
Q

types of cells involved in cellular innate immunity

A

Macrophages
Neutrophil

Also:
Eosinophils
Natural killer cells
Dendritic cells
Mast cells

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4
Q

elements involved in humoral immunity

A

complement
LPS Binding Protein
Antimicrobial Peptides
C Reactive protein
Mannose binding lectin

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5
Q

describe innate immunity

A

discrimination between self and non-self
immediate response to pathogen invasion
has no memory

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6
Q

name three processes that provide the body with innate immunity

A

Complement
Myeloid cells and phagocytosis (macrophages + neutrophils)
Pattern Recognition Receptors

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7
Q

three types of pathogens

A

virus
bacteria
protozoa and parasites

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8
Q

describe viruses, give examples

A

intracellular pathogens
the simplest form of life

eg. influenza, polio, smallpox, varicella, HIV

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9
Q

describe bacteria and give examples

A

mostly extracellular pathogens (exists outside cells)
engulfed and destroyed by phagocytic cells

eg. staph, tuberculosis (intracellular), strep, cholera

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10
Q

describe protozoa and parasites, give examples

A

complex multicellular organisms
require direct killing by chemical mediators released by specialist myeloid cells

eg. filarial worm

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11
Q

what testing process is used to distinguish types of bacteria?

A

a Gram stain

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12
Q

describe gram positive bacteria

A

thick peptidoglycan cell wall as defence
requires phagocytosis
resistant to complement MAC lysis

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13
Q

describe gram negative bacteria

A

thin peptidoglycan layer surrounded by outer membrane
can often by lysed directly by complement MAC

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14
Q

how do antibiotics work?

A

stops the ability of the organism to make peptidoglycan (defensive wall in bacteria)

beta-lactam antibiotics eg. penicillin

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15
Q

how do antibiotics work?

A

stops the ability of the organism to make peptidoglycan (defensive wall in bacteria

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16
Q

describe the appearance of a neutrophil

A

three-lobed nuclei and granules

17
Q

what is neutrophil extravasation?

A

the process by which white blood cells leave the bloodstream and enter tissue to fight infection or injury

18
Q

name the five steps of neutrophil extravasation

A

Activation
Tethering
Adhesion
Diapadesis
Chemotaxis

19
Q

describe the first step of neutrophil extravasation

A

activation: chemokines (secreted proteins) from injury / inflammation activated local endothelial cells lining adjacent capillary wall

20
Q

describe the second stage of neutrophil extravasation

A

tethering: neutrophils slow and tether to the inside capillary wall

21
Q

what is tethering mediated by?

A

selectins (cell surface lectins mediating adhesion)
sialyl Lewis X (carbohydrate antigen on neutrophils)

22
Q

describe the third step in neutrophil extravasation

A

adhesion: strong binding between neutrophil integrins and ICAM-1 on the endothelium
neutrophils flatten

23
Q

what is diapadesis

A

the neutrophil squeezes between endothelial cells into the interstitial space

24
Q

describe the last step in neutrophil extravasation

A

chemotaxis: neutrophil migrates along CHEMICAL GRADIENT (chemokine gradient) to the site of infection

25
Q

what receptor do neutrophils have on their surfaces to respond to chemoattractants?

A

Complement receptors (from the complement cascade)
neutrophils migrate up the chemoattractant gradient

26
Q

what happens as neutrophils migrate up the chemoattractant gradient?

A

polymerises actin filaments at their leading edge
depolymerising filaments at trailing edge
allows neutrophil to migrate

27
Q

define myeloid

A

having to do with bone marrow

28
Q

what receptors do all myeloid cells have?

A

complement receptors CR1, 2, 3, 4

CR1 is the main neutrophil receptor, binds to C3b (main component of complement cascade)

29
Q

how do receptors allow neutrophils to destroy organisms?

A

complement receptors crosslink to initiate phagocytosis
causes the neutrophil to engulf the organism

30
Q

define FcR mediated phagocytosis

A

a specific type of phagocytosis that requires the involvement of antibodies and Fc receptors

(antibody mediated phagocytosis)
FcR = Fcgamma Receptors

31
Q

describe how phagocytosis is activated via FcR

A

Antibody (IgM and IgG) bind to bacterial antigens
exposes antibody Fc region
neutrophil FcR binds multivalent Fc
activates phagocytosis

32
Q

name the main phases in phagocytosis

A

chemotaxis
adherence
ingestion / fusion –> phagolysosome
acidification
digestion / killing
exocytosis

33
Q

what are virulence factors

A

factors that enhance the ability of an organism to defend itself against innate immunity

generally virulence factors are good at inhibiting one of the steps of phagocytosis

34
Q

further expand on the ingestion / digestion stages of phagocytosis

A

bacterium captured by receptors, membrane INVAGINATES into a phagosome
FUSION of phagosome + lysosome –> phagolysosome
ACIDIFICATION as H+ is pumped in
activates proteases + production of superoxides (eg. peroxide H2O2 or hyperchlorous acid HOCl), kills bacteria
EXOCYTOSIS - digested microbe is expelled

35
Q

what is molecular pattern recognition?

A

Pattern Recognition Receptors (PRR) bind complex molecules unique to microbes

important innate mechanism

36
Q

what is one type of PRR?

A

Toll-like receptors (TLR) are a type of Pattern Recognition Receptor

TLR are Leucine Rich Repeat (LRR) receptor

37
Q

What are PAMPs?

A

Pathogen Associated Molecular Patterns

these are unique to microbes and are recognised by PRRs
structurally complex, evolutionarily stable (doesn’t change too much)

38
Q

what is TLR4 the receptor for

A

lipoplysaccharide (LPS)
which is a membrane component of all gram negative bacteria

39
Q

what is lipopolysaccharide?

A

LPS is a membrane component of all gram negative bacteria, induces powerful response
a pyrogen (causes fever)

can cause septic shock