Microbiology

Differences btn Eukaryote and Prokaryote :

Need to Know Bcoz:
It is the basis of antibiotic therapy
To understand Selective toxicity

Main differences:
Neuclear Membrane
Cell Wall (specific for prokaryotes ; pro=before, karyote= nucleus
Ribosomal Structure (prokaryote = 70s, Sub-units 50s &30s)

#Each ribosome is made up of two small sub-units ; as for eukaryote 80s(60s &40s)
s= Svendberg (pronounciation vad- berg;
The unit is named after the Swedish chemist Theodor Svedberg (1884-1971), winner of the Nobel prize in chemistry in 1926 for his work in the chemistry of colloids and his invention of the ultracentrifuge.)

's' is determind by the rate of sedimantation in a centrifuge machine.

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Plasmodium:

Life Cycle of Plasmodium
The sexual cycle occurs in the mosquito and the sporozoites in mosquito saliva
are injected into the host while feeding on human blood. Asexual reproduction
happens in the human host, and it consists of the exoerythrocitic cycle followed by
the erythrocytic cycle.

1) Exoeryrocytic cycle
 Injected sporozoites travel to liver (takes 1 hour), penetrate and
infect liver parenchymal cells 
 Sporozoites divide inside cell over a period of 1.5 weeks
(asymptomatic). 
 Infected cell ruptures and releases merozoites into blood
circulation

2) Erythrocytic cycle
 Merozoites infect RBCs.
 Merozites form into “signet ring” - trophozoite
 RBC develops into a schizont, which ruptures releasing merozoites
 The merozoites infect other RBC’s (amplification)
 Some merozoites will develop into the sexual haploid form:
macrogametocyte (female) or a microgametocyte (male). The
mosquito picks this up and the sexual cycle occurs
 Bursting RBC = symptoms (1.5 – 2 weeks of replication inside
RBC’s)

o Fever every 3-4 days, paroxysms of shaking chills
o Symptoms when other organs involved
o Hemolysis: icterus, jaundice, enlarged spleen
o Make sure to ask about travel!
 Non-immunologic mechanisms for controlling malaria:
o Spleen – traps RBC
 Outcome: death or chronic illness

3) Sexual Cycle in mosquito: the definitive host

 Gametocytes picked up in blood meal
 Male gametocyte pairs up with female and develop into oocyst in gut
 Thousands of sporozoites develop inside oocyst, escape from oocyst,
and move to salivary gland ready to be injected into humans.
 Mosquito cycle (sexual) gives the malaria diversity so that there is
drug resistance. The gametocytes are taken up and in the stomach the
sporozoites are released and go to the saliva. (slide 40) It would be
great to prevent oocysts formation in the stomach or sporozoitic life in
the saliva. There are many targets (e.g. exflagellation of
microgametocyte).
P. Falciparum

Pathogenesis

 Destruction of erythrocytes
 Liberation of parasite and erythrocyte material into the circulation.
 Host rxn to these events – TNF alpha and other inflammatory mediators; Release
of cytokines after glycolipid release on merozoite rupture
 A moving junction moves the parasite into the RBC. Once inside of the RBC
attachment factors are expressed on RBC – histadine-rich proteins that cause
attachment of RBC’s to the capillaries and postcapillary venules leading to
sequestration. In the early stages of P. falciparum you may not find RBC that are
infected because they are all lodged in the postcapillary venules. Ultimately once
there are enough parasites in the circulation you will pick them up when a thin
prep blood smear is performed.
 It is thought that this type of instability in blood flow leads to poor oxygenation
that leads to cerebral malaria, which is the primary cause of death. Cytokine
release has an impact on this process. P. falciparum’s unique sequestration in
micro-circulation of vital organs interfering with flow and metabolism
preferentially involves the white brain matter, heart, kidney, liver (hence cerebral
malaria). 
 The classic fever pattern for P. falciparum is every 3 days once it synchronizes.
This tertian pattern of fevers was recorded as long ago as Hippocrates time.

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• The characteristic fever spike has been correlated with incremental rises in serum levels of TNF-a associated with the release of parasite proteins during erythrocytic rupture.
• IMMUNE RESPONSE 
  
  The immune response to malaria is not well understood. The presence of serum antibodies in individuals living in regions where malaria is endemic indicates that the immune system mounts a humoral response against the parasite. This immunity is strain-specific and can be lost if the individual migrates to a region where malaria is not endemic. Furthermore, the efficacy of the humoral response is limited by the intracellular tendencies of the parasite as well as its ability to alter its surface molecules through various maturational stages. The humoral response is bolstered by a variety of non-specific effector mechanisms. The presence of excess type-1 cytokines, including IFN-g , IL-2, IL-12, and TNF-a , has been confirmed in infected individuals. However, the ability of the infected to generate CTL activity is severely limited; the infected hepatocytes are the only cellular targets expressing the requisite class I MHC molecule.