Innate & Adaptive immunity Flashcards

1
Q

What are the components of innate immunity?

A

Neutrophils

Monocytes/ Macrophages

Dendritic cells

Natural killer NK cells (lymphoid)

Complement

Physical epithelial barriers

Secreted enzymes

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2
Q

T cells, B cells and circulating antibodies are components of which type of immunity?

A

Adaptive immunity

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3
Q

What are the components of adaptive immunity?

A

T cells

B cells

circulating antibodies

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4
Q

Which type of immunity is germline encoded?

A

Innate immunity

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5
Q

What is the mechanism of adaptive immunity?

A

Variation through V(D)J recombination during lymphocyte development

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6
Q

Variation through V(D)J recombination during lymphocyte development is the mechanism of which type of immunity?

A

Adaptive immunity

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7
Q

Which immunity has a highly specific and refined response to pathogens?

A

Adaptive immunity

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8
Q

Which type of immunity occurs rapidly (minutes to hours) ?

A

Innate immunity

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9
Q

Which type of immunity develops over long periods of time?

A

Adaptive immunity

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10
Q

Which type of immunity has a faster and more robust memory response?

A

Adaptive immunity

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11
Q

Which type of immunity is limited by epithelial tight junctions and mucus?

A

Innate immunity

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12
Q

What are the proteins secreted during innate immunity?

A

Lysozymes

complement

C-reactive proteins (CRP)

defensins

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13
Q

Immunoglobulins are secreted in which type of immunity?

A

Adaptive immunity

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14
Q

Adaptive immunity secretes which type of proteins?

A

Immunoglobulins

Cytokines

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15
Q

Toll-like receptors TLRs & pattern recognition receptors that recognize pathogen-associated molecular patterns PAMPs are key features in which type of immunity?

A

Innate immunity

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16
Q

What are the key features of pathogen recognition in innate immunity?

A

Toll-like receptors TLRs

Pathogen-associated molecular patterns PAMPs

Activation of NF-κB

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17
Q

What are examples of pathogen-associated molecular patterns PAMPs?

A

LPS (lipopolysaccharides) of gram (−) bacteria

LTA (lipoteichoic acids) of gram (+) bacteria

Nucleic acids

Peptidoglycans

Lipoproteins

Glycoproteins

Flagellin (bacteria)

Nucleic acids (viruses)

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18
Q

A stronger, quicker immune response by activated B & T cells to subsequent exposure to a previously encountered antigen is a key feature of which type of immunity?

A

Adaptive immunity

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19
Q

What are the key features of pathogen recognition in adaptive immunity?

A

Memory response:

activated B & T cells to subsequent exposure to a previously encountered antigen → stronger, quicker immune response

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20
Q

Immunoglobulins are secreted in which type of immunity?

A

Adaptive immunity

21
Q

What is respiratory burst?

A

Oxidative burst

Metabolic process occurs during phagocytosis → activates NADPH oxidase → rapid release of reactive oxygen species (ROS)/ O2 metabolites: which are toxic to ingested microorganisms → O2 dependent intracellular digestion

(1) NADPH oxidase reduces O2 to free radicals [microbicidal]
→ superoxide anion (O2-)
→ hydroxyl radicals (OH-)
→ hydrogen peroxide (H2o2)

(2) Myeloperoxidase in lysosomes acts on hydrogen peroxide (H2o2) & chloride ions (Cl-)
→ Hypochlorous acid (HOCL-)
→ hypochlorite (ClO-)/ bleach [microbicidal]

(3) K+ influx → release lysosomal enzymes

22
Q

The blue-green, heme-containing pigment that gives sputum its color is called?

A

Myeloperoxidase

23
Q

Myeloperoxidase is contained in which part of the phagocyte?

A

Lysosome

24
Q

What is NADPH oxidase function in O2 dependent killing?

A

Reduces o2 → superoxide anion (O2-)

→ hydroxyl radicals (OH-) & hydrogen peroxide (H2o2) [microbicidal]

  • Peroxidation of lipids
  • Oxidation of proteins
  • DNA damage
25
Q

NADPH oxidase deficiency causes which disease?

A

Chronic granulomatous disease (CGD)

genetic

26
Q

Mechanisms of intracellular killing?

A
O2 independent killing
[Lysosome]
-Lysozyme
-Defensin
-Lactoferrin
-Hydrolytic enzyme

O2 dependent killing
[Phagosome membrane/ phagolysosome]
-NADPH oxidase (O2-, OH-, H2O2)
-Myeloperoxidase (+ H2O2 → HOCl → ClO-)

Reactive nitrogen
[phagosome & cytoplasm]
-Inducible nitric oxide synthase iNOS converts arginine → nitric oxide NO & free radicals (antimicrobial esp M.TB)

27
Q

What is O2 dependent killing?

Where does it take place?

A
  • NADPH oxidase → ROS (superoxide O2-, hydroxyl OH-, hydrogen peroxide H2O2)
  • Myeloperoxidase + hydrogen peroxide H2O2 (from previous) → Hypochlorous acid HOCl → hypochlorite ClO- (bleach)

[takes place in phagosome membrane/ phagolysosome]

28
Q

What is O2 independent killing?

Where does it take place?

A

-Lysozyme
(digest bacterial wall by cleaving peptidoglycan)

-Defensin
(proteins forms channels in bacterial cell membranes → H20 influx → ↑osmotic pressure ruptures bacterial membranes)

-Lactoferrin
(protein in secretory fluids and neutrophils; chelates iron making it unavailable for bacteria)

-Hydrolytic enzymes

[takes place in Lysosome]

29
Q

What are the ROS reactive oxygen species formed in phagocyte killing?

A

NADPH oxidase
[free radicals]
-Superoxide O2-
-hydroxyl OH-

[non-radicals]

  • singlet oxygen 1O2
  • hydrogen peroxide H2O2

Myeloperoxidase

  • Hypochlorous acid HOCl
  • hypochlorite ClO- (bleach)
30
Q

In a patient with chronic granulomatous disease (CGD) which killing mechanisms are affected?

Which are spared?

Protection against & susceptibility to which kind of organisms?

A

NADPH oxidase deficiency (O2-, OH-, 1O2, H2O2 pathway)

Intact:
Myeloperoxidase + H2O2 → HOCl
Lysosomal contents
-Lysozyme
-Defensin
-Lactoferrin
-Hydrolytic enzymes

Catalase -ive bacteria
H2O2 (hydrogen peroxide) waste product produced by Catalase -ive bacteria can be used as substrate for myeloperoxidase pathway

Catalase +ive bacteria (Staph aureus, E.Coli, Klebsiella, Salmonella, Shigella, Pseudomonas, Aspergillus, Candida, Serratia)
Catalase +ive bacteria destroy H2O2 so both NADPH oxidase & myeloperoxidase pathway gone (no ROS). Only lysosomal contents pathway left which is inadequate.

(catalase is an enzymatic antioxidant)

31
Q

What are the various targets of ROS reactive oxygen species (what do they affect) ?

A

Lipids
-Peroxidation of lipids

Proteins
-Oxidation of proteins

-DNA damage

32
Q

Why are CGD patients susceptible to Catalase +ive bacteria?

A

Catalase +ive bacteria destroy H2O2 (hydrogen peroxide) so both NADPH oxidase & myeloperoxidase pathway gone. Only lysosomal contents pathway left which is inadequate to control rampant infection.

(catalase is an enzymatic antioxidant - catalyzes decomposition of hydrogen peroxide to water and oxygen)

33
Q

Why does catalase -ive bacteria not affect patients with CGD chronic granulomatous disease?

A

H2O2 (hydrogen peroxide) waste product produced by Catalase -ive bacteria can be used as substrate for myeloperoxidase pathway & converted to ROS

(although NADPH oxidase is not producing H2O2, cells use the H2O2 which the bacteria is producing)

Catalase -ive bacteria cannot neutralize their own H2O2 but catalase +ive bacteria can which makes CGD pts more susceptible to +ive

34
Q

What are some of the catalase +ive bacteria which cause chronic, recurrent infections in CGD patients?

A

Staphyloccocus
-Aureus

Enterobacter

  • E.Coli
  • Salmonella
  • Shigella
  • Klebsiella
  • Serratia

Pseudomonas

Aspergillus

Candida

H pylori

35
Q

Failure of phagocytic cells to generate O2 radicals are detected by which test?

A

Nitroblue tetrazolium reduction test NBT test
-measures ROS generated by both leukocytes (CGD) & spermatozoa (male infertility)

  • NBT > reduced > formazan → turns BLUE → positive/ normal
  • NBT x not reduced x formazan → remains colorless/ yellow → negative/ abnormal

[Normal neutrophils produce ROS, which reduce NBT (type of oxidant salt) to formazan (artificial blue dye by-product of the reduction of tetrazolium salts).
CGD pts have genetic NADPH oxidase deficiency → do not produce ROS → NBT is not reduced → cells fail to turn blue]

Flow cytometry

  • Neutrophil oxidative index NOI
  • Dihydrorhodamine test
36
Q

A toddler has recurrent infections. Neutrophils failing to turn blue upon nitroblue tetrazolium chloride exposure is due to the lack of which enzyme?

A

NADPH oxidase

37
Q

Name the neutrophil enzyme which aids in killing phagocytosed organisms by catalyzing the production of hypochlorite from hydrogen peroxide & chlorine?

A

Myeloperoxidase

38
Q

Hallmark test for CGD chronic granulomatous disease?

A

NBT

Nitroblue tetrazolium reduction test

39
Q

An infant has recurrent skin infections. Neutrophils fail to turn blue upon nitroblue tetrazolium chloride exposure. Bacteria isolated from skin lesions produce which substance?

A

Catalase

40
Q

CGD chronic granulomatous disease is seen commonly in which age & gender?

A

Young & male

X-linked genetic

41
Q

Various components of the mycobacterial cell are destroyed by a series of reactions initiated by an enzyme which produces reactive nitrogen intermediates & free radicals. What is the enzyme?

Which cytokine stimulates the release of this enzyme?

A

Inducible nitric oxide synthase iNOS

IFN-γ

42
Q

The macrophage-based immunity to M. tuberculosis is mediated by which cells?

by which cytokine?

leading to which pathological microscopic lesion?

A

T helper cells
mature T helper cells produce IFN-γ
→ macrophage maturation → phagolysosome formation (which contain harsh bactericidal acids) + iNOS destroy M.TB components.

IFN-γ → activated macros → produce TNF → recruit monocytes → differentiate into epithelioid histiocytes → circular cluster around M.TB closing it in → caseating granuloma (limit bacteria spread)

Caseating granuloma

43
Q

Which cytokines contributes to the caseating granuloma in lung of TB patient?

A

IFN-γ

TNF

44
Q

What is pyocyanin?

Role?

A

PYO pyocyanin is a redox active pigment produced by Gram -ive bacterium Pseudomonas aeruginosa.

  • secondary metabolite with the ability to generate ROS (oxidise and reduce other molecules) and therefore kill microbes competing against P. aeruginosa
    +
  • important role during biofilm development in lung cells in cystic fibrosis

(PYO auto-poisoning for survival: double-edged sword. Under nutrient-available conditions, PYO is produced and can help cells achieve redox homeostasis. However, when bacteria depletes available carbon & nutrients, PYO becomes toxic and poisons the majority of its own population so that a small, PYO-insensitive population persists and multiplies when nutrients again become available)

45
Q

How can ROS reactive O2 species be generated?

A

Phagocyte oxidative/ respiratory burst

Pyocyanin (Gram -ive bacterium Pseudomonas aeruginosa)

46
Q

What is lactoferrin?

A

Iron-binding protein found in lysosome in

secretory fluids
(milk, saliva, tears, nasal secretions & human colostrum)

neutrophils
(PMNs)

innate immunity (antibacterial) chelates iron making it unavailable for bacteria

47
Q

Lactoferrins & hydrolytic enzymes are contents of which phagocytic structure along with which other components?

A

Lysosome

  • Lysozymes
  • Defensin
48
Q

What are PAMPs?

A

Pathogen-associated molecular patterns

LPS (lipopolysaccharides) of gram (−) bacteria
LTA (lipoteichoic acids) of gram (+) bacteria
Nucleic acids
Peptidoglycans
Lipoproteins
Glycoproteins 
Flagellin (bacteria)
Nucleic acids (viruses)

recognized by Toll-like receptors TLRs & pattern recognition receptors; CD14 (receptor for PAMPs → binds lipopolysaccharide (LPS))