Garantie de satisfaction à 100% Disponible immédiatement après paiement En ligne et en PDF Tu n'es attaché à rien
logo-home
Samenvatting Applied Medical Biotechnology (I0I27A) €10,49   Ajouter au panier

Resume

Samenvatting Applied Medical Biotechnology (I0I27A)

1 vérifier
 92 vues  6 fois vendu

Bio-Ingenieurwetenschappen, Master Cellular and Genetic Engineering. De powerpoint, samen met goede en zeer volledige lesnotities (!) worden samengevat tot een soort van cursus/samenvatting. Het volgt dus de structuur van de powerpoints! Behaald: 1ste zittijd , 19/20 Prof: Van den Steen Phil...

[Montrer plus]

Aperçu 4 sur 119  pages

  • 3 octobre 2023
  • 119
  • 2022/2023
  • Resume
Tous les documents sur ce sujet (1)

1  vérifier

review-writer-avatar

Par: nezqba • 5 mois de cela

avatar-seller
feline2
APPLIED MEDICAL BIOTECHNOLOGY: Course part 1

Chapter 1: malaria as an infectious human disease (world-wide)

1. Introduction: the disease Malaria

• Malaria worldwide
o = caused by protozoan parasites of the Plasmodium genus (~120 species)
o = most important infectious disease worldwide (number of malaria cases & deaths are huge (S2))
o 5 species infect humans
▪ * P. falciparum: most prevalent, causes most severe disease
▪ * P. vivax: prevalent outside Africa
▪ * P. malariae: less frequent
▪ * P. ovale: less frequent
▪ * P. knowlesi: parasite infecting monkeys and then jumps over to humans = zoonotic disease
o Who? → Mainly children, also pregnant women (and travelers) are at high risk
o Where? → Sub-Saharan Africa (= a tropical region):
▪ ~92% of all malaria cases
▪ ~20-35% of the “under-five” mortality
• → every 2 minutes, a child dies from malaria
▪ ~1,3% of gross domestic product of whole Africa
• Malaria symptoms
o 1) Severe fever peaks (systemic) every
▪ 36-48 hours (P. falciparum)
▪ 48 hours (P. vivax, P. ovale)
▪ 72 hours (P. malariae)
▪ = symptoms of uncomplicated malaria (no death)
o 2) Flu-like symptoms
▪ Central: headache
▪ Muscular: fatigue & pain
▪ Back: pain
▪ Skin: chills & sweating
▪ Respiratory: dry cough
▪ Spleen: enlargement
▪ Stomach: nausea, vomiting
▪ = symptoms of uncomplicated malaria (no death)
o 3) immunopathologies and complications: see further
▪ = symptoms of complicated malaria (risk of death)
• Malaria symptoms: cause of fever
o Parasite infects RBC → Multiplies in RBC → RBC bursts → parasitic molecules flow into the
bloodstream that can cause fever (fever peak = burst)
o → All parasites of P. vivax, P. malariae burst simultaneously → regular pattern of fever
o → Parasites of P. Falciparum burst not simultaneously → irregular pattern of fever
• Diagnosis:
o 1) By microscope of a thin blood smear or thick blood smear + staining
▪ Thin smear: visualize individual RBC infected with malaria
▪ Thick smear: can’t visualize individual RBC
▪ → morphology of the parasite can be used to discriminate between species (P. falciparum,
P. vivax, P. ovale, P. malariae)
o 2) PCR (expensive)
o 3) Rapid diagnostic test or antibodies

1

, ▪
= based on the detection of malaria antigen with antibodies

1) Buffer (flushing agent) + parasitized blood + labelled Ab that catches parasite antigens →
run along the nitrocellulose strip
▪ 2) Formation of labelled Ab-Ag complex captured by bound AB of test band (if parasite is
present)
▪ 3) Formation of labelled Ab captured by bound AB of control band
• Diagnosis: Notes
o RDTs
▪ Lower sensitivity than thick smear microscopy
▪ But faster & more easy
o qPCR methods
▪ More sensitive
▪ But less practical
o Histidine-rich protein-2 (HRP-2) often used as malaria antigen for RDT
▪ but: increasing prevalence of HRP-2-deficient parasites
▪ → escape from diagnosis (and thus treatment)!
▪ → solution: use of other antigens
• Plasmodium parasites
o = protozoan parasites: unicellular, eukaryotic, no cell wall  yeast: unicellular, eukaryotic, cellwall
o = part of Apicomplexa group: protozoan parasites with an apical complex
▪ = a complex of organelles for cell invasion (of hepatocytes, RBC,..)
o P. falciparum and P. vivax
▪ Genome has more than 5300 – 5400 genes
▪ P. falciparum: A+T content is very high (80% - 90 %)

2. Malaria lifecycle

• Malaria lifecycle: Involves 2 hosts: human & mosquito (zie verder)
• Preerythrocytic stage (hepatic / liver stage)
o Lifecycle: Human liver Stages: Exo-erythrocytic (hepatic) cycle (initial multiplication in liver)
▪ During blood meal, a malaria infected mosquito injects sporozoites into a human →
sporozoites migrate through blood to liver → infection of hepatocytes → multiplication into
schizonts containing merozoites → rupture of schizont & release of merozoites into blood
o Mosquito bite and invasion of the blood vessels
▪ 1) Mosquito bites through the skin until it bleeds (bloodvessel found) & sucks up blood
▪ 2) Mosquito injects saliva containing anti-coagulants to avoid blood clothing (& sporozoites)
o Mosquito: Anopheles species, including A. gambiae and A. funestus, can only transfer malaria
o The Sporozoite: Elongated cells with
▪ 1) Apical complex for cell invasion of hepatocytes
▪ 2) Circumsporozoite protein (CSP)
• Location: in micronemes and on surface coat
• Function: essential for motility vb migration to blood after injection in skin
• Skin -> blood
o 1) CSP produced at the tip & migrate along the sporozoite → movement of S
o 2) Then cleavage by cysteine protease posteriorly → which leaves a trail
• Blood -> liver
o CSP binds to glycosaminoglycans (“GAGs”) and LRP-1 (lipoprotein receptor-
related protein-1) in the liver (°)
• Main target for vaccination
o The Sporozoite: Invasion of hepatocytes (°)

2

, ▪ 1) Sporozoite arrives via blood in the liver & recognizes a Kupffer cell → enters Kupffer cell &
leaves at the basolateral side → to contact hepatocytes
▪ 2) The sporozoite migrates through nr of different hepatocytes until it finds a suitable
hepatocyte for multiplication into a schizont
▪ Opm: Kupffer cell = macrophage of the liver, in between endothelial cells
• Preerythrocytic stage (hepatic / liver stage)
o P. vivax and P. ovale form hypnozoites in the liver:
▪ 1) may remain dormant for many years
▪ 2) cause relapse infections by invading the bloodstreams, weeks or even years later
o Relapse ≠ recrudescence
▪ 1) Relapse (P. vivax & P. ovale): originates from hypnozoites (in the liver)
▪ 2) Recrudescence (P. falsiparum): originates from erythrocytic stage (in the RBC)
• Vb: antimalaria drugs or immune system eliminate the parasite → but a few
parasites remain in RBC circulating → continue to proliferate → 2 weeks later you
can have recrudescence & you are ill again
• Erythrocytic stage
o Lifecycle: Human blood Stages: Erythrocytic cycle (asexual multiplication in erythrocytes/RBC) (*)
▪ Merozoites infect RBC
• 1) Immature trophozoites (ring stage) → mature to mature trophozoites → mature
then into schizonts → rupture of schizont & release of merozoites → new
merozoites reinfect other RBC etc (*)
o → The blood stage parasites cause the symptoms of malaria
• 2) Some immature trophozoites (ring stage) → differentiate into gametocytes →
male and female gametocytes are ingested by a mosquito during blood meal
▪ Opm: no reinfection of other hepatocysts
• Gevolg: the exo-erythocytic cycle /hepatic cycle stays silent
o The Merozoite: resemble Sporozoite
▪ 1) Apical complex for cell invasion of RBC
▪ 2) But different shape (shorter, lemon shaped)
▪ 3) But not motile
o The Merozoite: Invasion of red blood cells
▪ 1) recognition through surface proteins
• MSP-1 (merozoite surface protein-1) → bind EB-3 (erythrocyte band 3 protein)
▪ 2) re-orientation of merzoite such that apical complex contacts RBC
• EBA-175 (erythrocyte binding antigen-175) → glycophorin A (determines ABO
bloodgroup)
▪ 3) Tight junction formation (initially 1 point, then a ring) + “motor”-driven invasion
• shedding of surface coat by a protease named SUB2
• parasites EBA-175 is connected to actin myosin system via linker proteins → like this
parasite moves inside the RBC, providing itself EN for invasion
▪ 4) Formation of a parasitophorous vacuole (= vacuole formed by RBC membrane)
▪ 5) proteolytic removal of adhesins by rhomboid
▪ 6) resealing of RBC membrane
▪ Opm: RBC cannot do endocytosis, thus the parasite does endocytosis itself in an active way
o The Merozoite: after invasion of red blood cells
▪ 1) The merozoite feeds itself on the content of the RBC vb cytosol (full of hemoglobine)
▪ 2) Hemoglobin ingestion into the food vacuole and degradation by proteases:
• Hemoglobin → large peptides + heme → small peptides → amino acids for protein
synthesis or efflux out of the parasite

3

, • Heme (containing Fe2+) is toxic for the parasite because it binds O2 → oxidative
reactions → kills parasite
• Heme (containing Fe2+) accumulation in neutral lipid nanospheres in the food
vacuole → crystallization into hemozoin crystals
o Reden: heme = toxic for the parasite because it binds O2 → oxidative
reactions → kills parasite
▪ 3) Transport of other nutrients from outside the RBC
• Vb: glucose, Ile, purine, panthotenate, phosphate
• → through native and new permeability pathways
• Erythrocytic stage
o 1) Invasion of red blood cells
o 2) Merozoite with a food vacuole with hemoglobine = Ring stage
o 3) When hemozoin is made = Trophozoite
o 4) When nucleus divide into multiple nuclei = Schizont
o 5) When nuclei segregate = Merozoite in the Schizont
o 6) When vacuole membrane degrades, schizont swells & bursts & releases merozoites and hemozoin
crystal in the circulation → pathogenesis
• Erythrocytic stage
o Outcome
▪ Parasitic clearance after infection → not ill
▪ Asymptomatic presence of parasite in blood → not ill
▪ Uncomplicated malaria → ill, but can be cured
▪ Severe complicated malaria (cerebral malaria, severe malarial anemia, placental malaria,
acidosis, ALI/ARDS, blackwater fever) → ill, often death
o The outcome is influenced by a lot of different factors:
▪ Immune evasion, immune stimulation, anti-parasite immunity, inflammation
▪ Metabolism, erythropoiesis, RBC destruction, blood flow/tissue oxygenation, vascular
integrity, (anti- coagulation,..
• Gametocytogenesis and mosquito stages
o Lifecycle: Mosquito stages: Sporogonous cycle (multiplication in the mosquito)
▪ In the mosquito’s stomach the male & female gametocytes leave RBC & mate generating a
zygote → zygote becomes motile & elongated (ookinete) → ookinete invades the midgut
wall of the mosquito where they develop into oocysts → oocyst proliferate/myosis into
haploid sporozoites → oocyst rupture & release sporozoites → sporozoites move to the
mosquito’s salivary glands → stap 1)
o Mosquito immune reaction
▪ Complement like proteins, e.g. TEP-1
▪ Function: they induce a melanisation (PO/polymerization reaction) to block parasite when its
migrating through epithelium
• Semi immunity
o People have no full immunity: always low parasite numbers remain present due to evasion of IS
o Acquired through continuous exposure (up to 5years) to the parasite
▪ Gevolg: mostly in adults of endemic region
•  children (below 5y) (and tourists) are the most susceptible: first 6months
antibodies of mother after birth → then they disappear and don’t have semi-
immunity yet → children below 5y become ill → once 5y, semi-immunity rises
o Rapidly lost (e.g. in African students travelling to Europe)
• High transmission areas: central Africa → semi-immunity
• Lower transmission area: south Africa → no semi-immunity → adults also get severe malaria

4

Les avantages d'acheter des résumés chez Stuvia:

Qualité garantie par les avis des clients

Qualité garantie par les avis des clients

Les clients de Stuvia ont évalués plus de 700 000 résumés. C'est comme ça que vous savez que vous achetez les meilleurs documents.

L’achat facile et rapide

L’achat facile et rapide

Vous pouvez payer rapidement avec iDeal, carte de crédit ou Stuvia-crédit pour les résumés. Il n'y a pas d'adhésion nécessaire.

Focus sur l’essentiel

Focus sur l’essentiel

Vos camarades écrivent eux-mêmes les notes d’étude, c’est pourquoi les documents sont toujours fiables et à jour. Cela garantit que vous arrivez rapidement au coeur du matériel.

Foire aux questions

Qu'est-ce que j'obtiens en achetant ce document ?

Vous obtenez un PDF, disponible immédiatement après votre achat. Le document acheté est accessible à tout moment, n'importe où et indéfiniment via votre profil.

Garantie de remboursement : comment ça marche ?

Notre garantie de satisfaction garantit que vous trouverez toujours un document d'étude qui vous convient. Vous remplissez un formulaire et notre équipe du service client s'occupe du reste.

Auprès de qui est-ce que j'achète ce résumé ?

Stuvia est une place de marché. Alors, vous n'achetez donc pas ce document chez nous, mais auprès du vendeur feline2. Stuvia facilite les paiements au vendeur.

Est-ce que j'aurai un abonnement?

Non, vous n'achetez ce résumé que pour €10,49. Vous n'êtes lié à rien après votre achat.

Peut-on faire confiance à Stuvia ?

4.6 étoiles sur Google & Trustpilot (+1000 avis)

80364 résumés ont été vendus ces 30 derniers jours

Fondée en 2010, la référence pour acheter des résumés depuis déjà 14 ans

Commencez à vendre!
€10,49  6x  vendu
  • (1)
  Ajouter