Innate Immunity I know pornography when I see

  • Slides: 33
Download presentation
Innate Immunity I know pornography when I see it. I know a pathogen when

Innate Immunity I know pornography when I see it. I know a pathogen when I see it.

Definition • Natural ability to fight pathogens. • Acts rapidly. • Does not depend

Definition • Natural ability to fight pathogens. • Acts rapidly. • Does not depend upon previous contact with the pathogen.

Don’t let your competition define you • Textbook definition of innate immunity: non -clonal

Don’t let your competition define you • Textbook definition of innate immunity: non -clonal immune defenses. • It is the adaptive immune response that needs a special definition as it is the most recent addition to our repertoire.

Adaptive immunity is a recent arrival from an evolutionary point of view

Adaptive immunity is a recent arrival from an evolutionary point of view

Organisms do well without an adaptive immune response Oldest Largest Diverse http: //Bee. Lab.

Organisms do well without an adaptive immune response Oldest Largest Diverse http: //Bee. Lab. cas. psu. edu

Genetic resistance to disease • Malaria: sickle cell anemia, thalesemia, duffy coat, G 6

Genetic resistance to disease • Malaria: sickle cell anemia, thalesemia, duffy coat, G 6 PDH • Cholera: cystic fibrosis • AIDS: CCR 5

Glucose 6 -phosphate dehydrogenase (G 6 PDH) • Most polymorphic human gene. • Principal

Glucose 6 -phosphate dehydrogenase (G 6 PDH) • Most polymorphic human gene. • Principal source of reducing power. Glucose-6 -phosphate NADP 6 -phosphogluconate NADPH

Malaria and polymorphisms coincide

Malaria and polymorphisms coincide

G 6 PDH protects against severe malaria infections • Severe malaria sufferers are less

G 6 PDH protects against severe malaria infections • Severe malaria sufferers are less likely than control groups to be heterozygous or hemizygous for G 6 PDH. • Female heterozygotes odds ratio: 0. 54 • Male hemizygous odds ratio: 0. 42

The deficiency has some costs • Severe jaundice at birth • Hemolytic anemia •

The deficiency has some costs • Severe jaundice at birth • Hemolytic anemia • Severe sensitivity to free radical production

Pythagoras: “avoid the bean”

Pythagoras: “avoid the bean”

Fava beans and favism • Fava beans can cause hemolytic anemia in G 6

Fava beans and favism • Fava beans can cause hemolytic anemia in G 6 PDH deficient patients • Meals, mothers milk, pollen • Staple food in areas where • G 6 PDH is prevelant

Fava bean active ingredients • Two pro-oxidants: vicine and convicine • Glycosidase releases active

Fava bean active ingredients • Two pro-oxidants: vicine and convicine • Glycosidase releases active compounds which can react to produce H 2 O 2. • Normally these are reduced by glutathione which is reduced by NADPH • All of this happens at a slower rate in G 6 PDH deficiency patients

Results • Normal RBC + vicine: • Hemizygous G 6 PDH • Homozyogous G

Results • Normal RBC + vicine: • Hemizygous G 6 PDH • Homozyogous G 6 PDH 1 +/- 0. 053 0. 76 +/- 0. 043 0. 33 +/- 0. 103

Equilibrium is shifted reduction oxidation G 6 PDH Fava beans Plasmodium does poorly under

Equilibrium is shifted reduction oxidation G 6 PDH Fava beans Plasmodium does poorly under oxidizing conditions

Main points • Genetics of host is critical in defining the disease. • Behavior

Main points • Genetics of host is critical in defining the disease. • Behavior can modify natural susceptibility.

Flora and Disease • Body ecology can prevent disease • Microorganisms occupy and defend

Flora and Disease • Body ecology can prevent disease • Microorganisms occupy and defend their niche. • This can be use in an applied manner.

Chagas Disease: Trypanosoma cruzi

Chagas Disease: Trypanosoma cruzi

How do you know it is a symbiont? • Grow the bugs axenically -

How do you know it is a symbiont? • Grow the bugs axenically - fail to thrive • Add back bacteria to their food.

What antimicrobial do you use • • Antimicrobial peptide Ecoli 23 u. M Rodococcus

What antimicrobial do you use • • Antimicrobial peptide Ecoli 23 u. M Rodococcus rhodnii 500 u. M Trypanosoma cruzi 150 u. M

Transform gut bacteria with cecropin • • • Create a shuttle vector Clone in

Transform gut bacteria with cecropin • • • Create a shuttle vector Clone in cecropin Transform bacteria Introduce to insect Stability is an expected problem.

Paratransgenic triatomines cannot vector T. cruzi In hindgut

Paratransgenic triatomines cannot vector T. cruzi In hindgut

Triatomines are caprophagic Cruzigard; seeded mock bug frass

Triatomines are caprophagic Cruzigard; seeded mock bug frass

Other applications of this model • BT corn: proteinaceous toxin cloned into corn to

Other applications of this model • BT corn: proteinaceous toxin cloned into corn to kill insect pests. • Mosquito expressingle chain antibody against Plasmodium. • Mosquito expressing peptide blocking Plasmodium binding.

Main points • Flora is an important part of an immune system. • Flora

Main points • Flora is an important part of an immune system. • Flora can be manipulated.

Parasite defense

Parasite defense

Parsitoid wasps lay eggs in insect hosts

Parsitoid wasps lay eggs in insect hosts

Process reconstructed in vitro • Cells purified based upon size and adhesive properties •

Process reconstructed in vitro • Cells purified based upon size and adhesive properties • Plastic bead used as surrogate egg • Monoclonal antibodies raised against different cell types • Factors affecting cell behavior purified

Bead encapsulation

Bead encapsulation

Wasp carries a provirus • • • Polydna virus Poly disperse DNA virus Made

Wasp carries a provirus • • • Polydna virus Poly disperse DNA virus Made only in calyx Injected into larva with egg and toxin Induces apoptosis of granular cells only

How don you demonstrate viral activity • Apoptosis seen in blood cells in natural

How don you demonstrate viral activity • Apoptosis seen in blood cells in natural infection • Add calyx extracts to purified cells and perform tunel assays

Main points • Complex cellular interactions are used to destroy parasites • Apoptosis can

Main points • Complex cellular interactions are used to destroy parasites • Apoptosis can be used by the host to prevent the spread of infection. • Apoptosis can also be used by the parasite to destroy the immune system.