human parasitology almost everything

first multicellular genome

c elegans 1998

first parasitic protozoan

plasmodium falciparum 2002

first parasitic helminth

Brugiamalayi 2007

how many worm genomes

81

how many parasites have found a home in or on the human body

437

what percent of parasites recorded in humans are rare, sporadic, or nowhere in common

74%

what percent of parasites are common or abundant worldwide

10%

distribution of parasites and their phylum

30% trematodes, 26% nematodes, 19%protozoa, 12% cestodes, 11% arthropods

distribution of transmission methods of parasites

50% oral, 34% skin, 13% fecal, last 3% mammary, placental, venereal

what isnt included in the human genome project

No centromere, telomere, repetitive DNA data•Non-coding RNAs, regulatory sequences

how many genomes in HGP

23,000 protein coding genes

cost of covering 92.3% of genome

$3 billion USD

progression of CSM

Amoebae to slug to sorocarp(fruiting body)

Sorocarp-stalked cells and sporesStalked cells are dead -altruistic, for spore dispersal

chemotaxis signal of CSM

cyclic AMP

official name and phylum of CSM

Dictyostelium discoideum - amoebae phylum

how many times have parasites evolved in animal phyla, playthelminthes, nematoda, arthropoda, and insecta

223 within 15 animal phyla, 13 times, 18 times, 143 times, 87 times

what are the gene families

SCP/TAPs, CAP

parasitic helminths have this gene family and are known as this

SCP/TAPs, VAL (venom allergen like proteins)

hookworms have "this" gene family and include these three things

SCP/TAPs, ASPs (activation associated secreted proteins), neutrophil inhibitory factor (NIF), hookworm platelet inhibitor (HPI)

how do nematomorph parasites get their hosts

ability to induce their terrestrial insect host to enter bodies of water

nematomorphs participate in gene transfer and the evolution of nematomorph driven behavioral manipulation through this species

HGT, mantids

how did chordodes nematomorph acquired many genes from their ancesteral hosts

repeated HGT events

what is the nematomorph's extended phenotype

water entry behavior of hosts

what is an extended phenotype

genes in one organism have phenotypic effects on another organism

what are the 5 disease interventions

control

elimination of disease

elimination of infection

eradication

extinction

drug discovery is these three things

expensive, high risk, lenghty

drugs for NTDs are made through blank & blank co-operations; some of them include two orgs

public & private co-operations; wellcome trust, gates foundation

what is selective toxicity

A drug that kills harmful microbes without damaging the host

what are steps of drug development

target id & validation

assay development

screening to id hits

synthesis and assessment of analogs

what do robotics do for drug development

power to screen large compound libraries

what is structure activity relationship

SAR; the relationship between the chemical or 3D structure of a molecule and its biological activity

what is ADMET

Absorption

Distribution

Metabolism

Excretion

Toxicity

how many phases of clinical trials are there

3

what is piggy backing for NTD drugs

repurposing for a different goal of cure; combination of existing drugs or improvement of current drugs

what is the criteria of drugs for NTDs

field-driven, low costs, short duration of treatment, ability to safely use the drug in the absence of close medical supervision

how can drugs be manufactured for NTDs

public private partnership (PPP), product development partnership (PDP)

how can drugs be delivered for NTDs

mass drug administration (MDA)), mass screening and treatment (MSAT)

what is the parasitologist's dilemma

Is the removal of parasites really helping a population that potentially may lead to overpopulation?

what are some theories of ethics

utilitarianism, deontology, virtue ethics, Rawlsian justice, situation ethics, intuitionism

what is premunition

parasite under control as persistent latent infection

what is concomitant immunity

current parasite infection makes host resistant to related species

what do hematopoietic stem cells do

provide origin of immune cells

what are two types of immunity

innate and adaptive

what do innate lymphoid cells do

produce cytokines

what do defensins do

poke holes in the pathogen

what do complement cells do

enhance response to pathogens

what do toll like receptors (TLR) do

-trigger innate immunity and inflammation

-instruct adaptive immunity

what do pathogen associated molecular patterns (PAMPs) do

distinguish between self and not self

what do macrophages do

engulfing and destroying pathogens, dead cells, and debris through a process called phagocytosis

what are the two clusters of differentiation and what do they do

Two commonly used CD molecules are CD4 and CD8, which are, in general, used as markers for helper and cytotoxic T cells

what are classically activated macrophages (CAMs)

M1 macrophages, demonstrate increased cell spreading, enhanced phagocytosis, and antigen presentation capacities and amplified inducible nitric-oxide synthetase expression for the production of nitric oxide

what do B cells do

produce antibodies

what do T cells do

Manage the immune response

Attack and destroy foreign cells

what do t cell receptors do

bind processed antigens together with the MHC molecules on the cells that present antigens to them

What is the hygiene hypothesis?

focus on the diet and diversified gut microbiome to promote higher levels of health

what is the difference between type 1, 2, and 3 immunity

type 1 focused on intracellular bacteria and viruses, type 2 against parasites like helminths, and type 3 against extracellular bacteria and fungi

what do IgE and esosinophils target

worms

what targets metazoan parasite immunogens

IgE

TfH13 has a blank affinity IgE while Tfh2 has a blank affinity

high affinity leading to anaphylaxis

low affinity induced by worms

what is the enteric tuft cell

cell that increases in number during parasite infections and coordinates type 2 immunity in helminth infections

what are the 5 kingdoms

Monera, Protista, Fungi, Plantae, Animalia

what are the 2 superkingdoms

prokaryota, eukaryota

how are protozoa classified

motility

4 major protozoa groups

sarcodina, mastigophora, sporozoa, infusoria

what molecular evolution does archaea and eubacteria have

ribosomal rna gene sequences

what is the origin of eukaryotic cells

endosymbiont theory

what is asgard archae and what is its significance

thor, odin, loki, hemidall

bridge the gap between pro- and eukaryotic cells, because they encode proteins homologous to eukaryotic ones that are involved in intracellular vesicle trafficking and the regulation of actin cytoskeleton dynamics

what does LUCA stand for

last universal common ancestor

what is alpha proteobacterium

Organism that produces complex organic compounds from simple inorganic molecules and an external source of energy, such as light (photoautotroph) or chemical reactions of inorganic compounds (chemoautotroph).

what are characteristics of lokiarchaeum

thrive anaerobically at 20 degrees celcius on organic carbon sources

divides every 7-14 days

contain hundreds of eukaryotic signature proteins (ESPs), including 4 actin

what is aggregative multicellularity

genetically potentially unrelated lineages cooperate to form transient multicellular groups

what is cohesive multicellularity

cells stick together after division: plants, fungi, animals

what is GK-PID

Guanylate kinase protein interaction domain

a protein that helps animal cells divide and organize into tissues.

Without GK-PID, cells can grow disorganized and sometimes cancerous

what are the 6 supergroups of eukaryotes

Please Always Read Every Chapter, As Often as possible

Plantae

A: rchaeplastida: Includes plants and green algae.

R: hizaria: A diverse group of protists including foraminiferans and radiolarians.

E: xcavata: Contains organisms like Giardia and Trichomonas.

C: hromalveolata: Includes diatoms, brown algae, and certain dinoflagellates.

O: pisthokonta: Includes animals and fungi.

what are the 2 domains of eukaryotes

amorphea (without form/shape)

diaphoretickes (diversity in features)

what are the supergroups of amorphea

CRuMs, Amoebozoa, Obazo

what eukaryotic supergroup is classified under obazoa

opisthokonta

what are the supergroups of diaphoretickes

archaeplastida, SAR, crypista, hapista

what is included in SAR supergroup

Strameonpiles, Alveolata, Rhizaria

what 2 major groups are contained in excavates

metamonada, discorba

what are NTDs part of the Kinetoplastid protozoa

HAT: Human African trypanosomiasis(sleeping sickness)

AT: American trypanosomiasis(Chagas' disease)

Leishmaniasis: cutaneous, mucocutaneous, visceral

Vector borne disease

Tsetse fly; assassin or kissing bug; sand fly

what is kinetoplastid protoza classified as

excavates

what are heteroxenous

NTD infectious agents

salivaria is associated with NTD and stercoraria is associated with NTD

anterior station (HAT)

posterior station (AT)

what are the unique features of kinetoplastid protozoa

molecule: trypanothione

organelles: glycosome, kinetoplast

molecular biology: nuclear gene expression (polycistronic transcription and trans-splicing)

molecular biology: mitochondrial gene expression (RNA editing)

history of trypanosoma brucei

originally in europe, spread to africa after colonization

David & Mary Bruce first discovered it as a cattle disease (Nagan) & as a fly disease

life cycle of sleeping sickness (8 steps)

1. tsetse fly take as a blood meal and injects metacylic trypanosomiasis (MT)

2, inject MT transforms into blood stream trypomastigotes (TG) which is carried to other sites

3. TG multiply by binary fission in various bodily fluids

4. circulating TG in blood during acute phase usually undectable

5. repeat step 1, except tsetse fly takes TG

6. blood stream TG transform into procylic TG in the vector midgut and then multiply via BF

7. PC TG leave midgut and transform into epigastigotes

8. epimastigotes multiply in salivary gland and transform into MT

pathology and diagnosis of sleeping sickness

early - hemolyphatic phase

late - meningo0encephalitic phase

diagnosis with presence of protozoa in blood/CSF/adipose tissue

therapy for sleeping sickness

Suamin

Pentamidine

Elfonithine - DFMO

NECT - nifurtimox

DNDi

Melasoprol - PTRE

Fexinidazole

how many pairs of mega chromosome, intermediate chromosome, genese, pseudogenes, VSG for trypanosoma brucei

11, 5, 9068, 900, 806

LGT or HGT for trypanosoma brucei? how many cases

LGT

46 potential cases of LGT for Trypanosoma brucei

49 for T. Cruzi

68 for leishmania major

what is a variant surface glycoprotein

a protein that densely covers the surface of African trypanosome parasites, acting as a protective coat that allows them to evade the host immune system by rapidly switching their surface antigen, essentially "disguising" themselves from the host's antibodies

what does HDL do to HAT in humans

able to kill HAT in humans due to TLF-1 which is made up of HRP, Apo-L1, and Apo-A1

what are forms of vector control

sterile insect technique (SIT): set out males to mate with females and get ride of the protozoa

blue-black color and traps to capture tsetse flies

chagas disease history

carlos chagas found trypanosoma cruzi betrenic strains Be-62 and Be-78

chagas disease life cycle (8 steps)

1. triatomine bug takes a blood meal (passes metacylic trypomastigotes into bite wound)

2. M TG penetrates various cells at bit wound site, inside cells transform into amastigotes

3. AG multiply via binary fission

4. intracellular amastigotes transform into TG, burst out of cell, enter bloodstream. can infect other cells and become cycle with step 3

5. triatomine bug takes blood meal from mammal, takes TG

6. epimastigotes in midgut

7. multiply in midgut

8. M TG in hindgut

pathology of chagas disease

auto-inoculation

romana's sign - swollen eyelid when parasite infects eye

chagoma - skin lesion at infection site

acute and chronic

myocarditis

megasyndrome of colon and esophagus - enlarging of them

CD causes 70% of cardiac deaths in YA

therapy for CD

Nifurtimox

Benznidazole

Fexinidazole

Benzoxaboroles

Proteasome inhibitors

diagnosis of CD

presence of parasites in blood

xenodiagnoses

t. cruzi genome; # of genes, chromosome pairs

~12000, 41