Innate & Adaptive immunity Flashcards
What are the components of innate immunity?
Neutrophils
Monocytes/ Macrophages
Dendritic cells
Natural killer NK cells (lymphoid)
Complement
Physical epithelial barriers
Secreted enzymes
T cells, B cells and circulating antibodies are components of which type of immunity?
Adaptive immunity
What are the components of adaptive immunity?
T cells
B cells
circulating antibodies
Which type of immunity is germline encoded?
Innate immunity
What is the mechanism of adaptive immunity?
Variation through V(D)J recombination during lymphocyte development
Variation through V(D)J recombination during lymphocyte development is the mechanism of which type of immunity?
Adaptive immunity
Which immunity has a highly specific and refined response to pathogens?
Adaptive immunity
Which type of immunity occurs rapidly (minutes to hours) ?
Innate immunity
Which type of immunity develops over long periods of time?
Adaptive immunity
Which type of immunity has a faster and more robust memory response?
Adaptive immunity
Which type of immunity is limited by epithelial tight junctions and mucus?
Innate immunity
What are the proteins secreted during innate immunity?
Lysozymes
complement
C-reactive proteins (CRP)
defensins
Immunoglobulins are secreted in which type of immunity?
Adaptive immunity
Adaptive immunity secretes which type of proteins?
Immunoglobulins
Cytokines
Toll-like receptors TLRs & pattern recognition receptors that recognize pathogen-associated molecular patterns PAMPs are key features in which type of immunity?
Innate immunity
What are the key features of pathogen recognition in innate immunity?
Toll-like receptors TLRs
Pathogen-associated molecular patterns PAMPs
Activation of NF-κB
What are examples of pathogen-associated molecular patterns PAMPs?
LPS (lipopolysaccharides) of gram (−) bacteria
LTA (lipoteichoic acids) of gram (+) bacteria
Nucleic acids
Peptidoglycans
Lipoproteins
Glycoproteins
Flagellin (bacteria)
Nucleic acids (viruses)
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?
Adaptive immunity
What are the key features of pathogen recognition in adaptive immunity?
Memory response:
activated B & T cells to subsequent exposure to a previously encountered antigen → stronger, quicker immune response
Immunoglobulins are secreted in which type of immunity?
Adaptive immunity
What is respiratory burst?
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
The blue-green, heme-containing pigment that gives sputum its color is called?
Myeloperoxidase
Myeloperoxidase is contained in which part of the phagocyte?
Lysosome
What is NADPH oxidase function in O2 dependent killing?
Reduces o2 → superoxide anion (O2-)
→ hydroxyl radicals (OH-) & hydrogen peroxide (H2o2) [microbicidal]
- Peroxidation of lipids
- Oxidation of proteins
- DNA damage
NADPH oxidase deficiency causes which disease?
Chronic granulomatous disease (CGD)
genetic
Mechanisms of intracellular killing?
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)
What is O2 dependent killing?
Where does it take place?
- 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]
What is O2 independent killing?
Where does it take place?
-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]
What are the ROS reactive oxygen species formed in phagocyte killing?
NADPH oxidase
[free radicals]
-Superoxide O2-
-hydroxyl OH-
[non-radicals]
- singlet oxygen 1O2
- hydrogen peroxide H2O2
Myeloperoxidase
- Hypochlorous acid HOCl
- hypochlorite ClO- (bleach)
In a patient with chronic granulomatous disease (CGD) which killing mechanisms are affected?
Which are spared?
Protection against & susceptibility to which kind of organisms?
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)
What are the various targets of ROS reactive oxygen species (what do they affect) ?
Lipids
-Peroxidation of lipids
Proteins
-Oxidation of proteins
-DNA damage
Why are CGD patients susceptible to Catalase +ive bacteria?
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)
Why does catalase -ive bacteria not affect patients with CGD chronic granulomatous disease?
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
What are some of the catalase +ive bacteria which cause chronic, recurrent infections in CGD patients?
Staphyloccocus
-Aureus
Enterobacter
- E.Coli
- Salmonella
- Shigella
- Klebsiella
- Serratia
Pseudomonas
Aspergillus
Candida
H pylori
Failure of phagocytic cells to generate O2 radicals are detected by which test?
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
A toddler has recurrent infections. Neutrophils failing to turn blue upon nitroblue tetrazolium chloride exposure is due to the lack of which enzyme?
NADPH oxidase
Name the neutrophil enzyme which aids in killing phagocytosed organisms by catalyzing the production of hypochlorite from hydrogen peroxide & chlorine?
Myeloperoxidase
Hallmark test for CGD chronic granulomatous disease?
NBT
Nitroblue tetrazolium reduction test
An infant has recurrent skin infections. Neutrophils fail to turn blue upon nitroblue tetrazolium chloride exposure. Bacteria isolated from skin lesions produce which substance?
Catalase
CGD chronic granulomatous disease is seen commonly in which age & gender?
Young & male
X-linked genetic
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?
Inducible nitric oxide synthase iNOS
IFN-γ
The macrophage-based immunity to M. tuberculosis is mediated by which cells?
by which cytokine?
leading to which pathological microscopic lesion?
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
Which cytokines contributes to the caseating granuloma in lung of TB patient?
IFN-γ
TNF
What is pyocyanin?
Role?
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)
How can ROS reactive O2 species be generated?
Phagocyte oxidative/ respiratory burst
Pyocyanin (Gram -ive bacterium Pseudomonas aeruginosa)
What is lactoferrin?
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
Lactoferrins & hydrolytic enzymes are contents of which phagocytic structure along with which other components?
Lysosome
- Lysozymes
- Defensin
What are PAMPs?
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))
