Innate & Adaptive immunity

Question 1

What are the components of innate immunity?

Answer 1

Neutrophils

Monocytes/ Macrophages

Dendritic cells

Natural killer NK cells (lymphoid)

Complement

Physical epithelial barriers

Secreted enzymes

Question 2

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

Answer 2

Adaptive immunity

Question 3

What are the components of adaptive immunity?

Answer 3

T cells

B cells

circulating antibodies

Question 4

Which type of immunity is germline encoded?

Answer 4

Innate immunity

Question 5

What is the mechanism of adaptive immunity?

Answer 5

Variation through V(D)J recombination during lymphocyte development

Question 6

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

Answer 6

Adaptive immunity

Question 7

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

Answer 7

Adaptive immunity

Question 8

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

Answer 8

Innate immunity

Question 9

Which type of immunity develops over long periods of time?

Answer 9

Adaptive immunity

Question 10

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

Answer 10

Adaptive immunity

Question 11

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

Answer 11

Innate immunity

Question 12

What are the proteins secreted during innate immunity?

Answer 12

Lysozymes

complement

C-reactive proteins (CRP)

defensins

Question 13

Immunoglobulins are secreted in which type of immunity?

Answer 13

Adaptive immunity

Question 14

Adaptive immunity secretes which type of proteins?

Answer 14

Immunoglobulins

Cytokines

Question 15

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

Answer 15

Innate immunity

Question 16

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

Answer 16

Toll-like receptors TLRs

Pathogen-associated molecular patterns PAMPs

Activation of NF-κB

Question 17

What are examples of pathogen-associated molecular patterns PAMPs?

Answer 17

LPS (lipopolysaccharides) of gram (−) bacteria

LTA (lipoteichoic acids) of gram (+) bacteria

Nucleic acids

Peptidoglycans

Lipoproteins

Glycoproteins

Flagellin (bacteria)

Nucleic acids (viruses)

Question 18

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?

Answer 18

Adaptive immunity

Question 19

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

Answer 19

Memory response:

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

Question 20

Immunoglobulins are secreted in which type of immunity?

Answer 20

Adaptive immunity

Question 21

What is respiratory burst?

Answer 21

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

Question 22

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

Answer 22

Myeloperoxidase

Question 23

Myeloperoxidase is contained in which part of the phagocyte?

Answer 23

Lysosome

Question 24

What is NADPH oxidase function in O2 dependent killing?

Answer 24

Reduces o2 → superoxide anion (O2-)

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

• Peroxidation of lipids
• Oxidation of proteins
• DNA damage

Question 25

NADPH oxidase deficiency causes which disease?

Answer 25

Chronic granulomatous disease (CGD) genetic

Question 26

Mechanisms of intracellular killing?

Answer 26

``` 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)

Question 27

What is O2 dependent killing? Where does it take place?

Answer 27

- 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]

Question 28

What is O2 independent killing? Where does it take place?

Answer 28

-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]

Question 29

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

Answer 29

NADPH oxidase [free radicals] -Superoxide O2- -hydroxyl OH- [non-radicals] - singlet oxygen 1O2 - hydrogen peroxide H2O2 Myeloperoxidase - Hypochlorous acid HOCl - hypochlorite ClO- (bleach)

Question 30

In a patient with chronic granulomatous disease (CGD) which killing mechanisms are affected? Which are spared? Protection against & susceptibility to which kind of organisms?

Answer 30

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)

Question 31

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

Answer 31

Lipids -Peroxidation of lipids Proteins -Oxidation of proteins -DNA damage

Question 32

Why are CGD patients susceptible to Catalase +ive bacteria?

Answer 32

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)

Question 33

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

Answer 33

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

Question 34

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

Answer 34

Staphyloccocus -Aureus Enterobacter - E.Coli - Salmonella - Shigella - Klebsiella - Serratia Pseudomonas Aspergillus Candida H pylori

Question 35

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

Answer 35

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

Question 36

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

Answer 36

NADPH oxidase

Question 37

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

Answer 37

Myeloperoxidase

Question 38

Hallmark test for CGD chronic granulomatous disease?

Answer 38

NBT | Nitroblue tetrazolium reduction test

Question 39

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

Answer 39

Catalase

Question 40

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

Answer 40

Young & male X-linked genetic

Question 41

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?

Answer 41

Inducible nitric oxide synthase iNOS IFN-γ

Question 42

The macrophage-based immunity to M. tuberculosis is mediated by which cells? by which cytokine? leading to which pathological microscopic lesion?

Answer 42

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

Question 43

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

Answer 43

IFN-γ TNF

Question 44

What is pyocyanin? Role?

Answer 44

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)

Question 45

How can ROS reactive O2 species be generated?

Answer 45

Phagocyte oxidative/ respiratory burst Pyocyanin (Gram -ive bacterium Pseudomonas aeruginosa)

Question 46

What is lactoferrin?

Answer 46

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

Question 47

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

Answer 47

Lysosome - Lysozymes - Defensin

Question 48

What are PAMPs?

Answer 48

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))