Micro Exam #3 11.1-12.1

Microbiome

collection of genomes from all the microorganisms in the environment

Microbiota

microorganisms found within a specific environment

How many microbiomes can be cultured?

less than 1% of microbes in our bodies can be cultured

Norman Pace

first to isolate, sequence, and analyze DNA from complex environmental samples

sequenced the 165 rRNA because it is highly conserved in microbes

Their 165 rRNA sequence data were used in phylogenetic studies to determine identities (if known) of microbiome inhabitants

Human Microbiome Project (HMP)

approx. 100 trillion microbes live in the human body, HMP goal was to characterize our gut, skin, and oral microbiomes, as the composition can impact IBS, susceptibility to diabetes, obesity.

Metagenomes

sequenced community DNA

Metatranscriptomes

sequences community RNA

Proteomes

mass spectroscopy of protein fragements

Metabolomes

mass spectroscopy of small molecules

How to analyze a metagenome

1) define a target community

2) break open cells and isolate DNA (reagent-based, physical methods)

3) create library

4) Read DNA sequence

5) Assemble and analyze DNA

Benefits of microbes in the body

food digestion, nutrition, metabolic regulation, development: terminal differentiation of mucosa, “education”, colonization resistance to pathogens

What can be associated with shifts in the microbiota

IBS, obesity, autoimmune diseases, atherosclerosis, diabetes, eczema, etc

Human colon microbiomes

humans conduct microbial fermentation in colon (favors bacteria capable of digesting fiber that pass through the small intestine)

Dysbiosis

imbalance in the microbiome

Probiotics

living microbes that are ingested to restore the natural microbial balance

Prebiotics

molecules that help restore balance or facilitate growth of beneficial microbes (fiber)

Characterizing microbial diversity

richness: number of different kinds of organism’s present

evenness: similarity in the population size of each organism

diversity: richness and evenness

Effect of diet on microbiome

low fat, high fiber = microbiome towards fiber degraders, decreased inflammation, decreased markers of cancer risk

high fat, low fiber = microbiomes towards fat degraders, increased inflammation, increased markers of cancer risk

Hygiene hypothesis

microbiota shaped by intimate contact with natural environments. Today, segregated from nature, our microbiota appear less diverse. Microbiome trains our immune system, narrowing the diversity of our microbiomes contributing to inflammatory and autoimmune diseases

Hypersensitivity

exaggerated response of the immune system against pathogens triggered by the interaction of the immune system with an antigen (allergen)

Type I hypersensitivity

overproduction of immunoglobulin E (IgE)

Immunoglobulin E (IgE)

antibody that is involved in defense against allergic reactions

Mast cell degranulation

release of histamine from mast cells (special WBC for allergic reaction), promotes an inflammatory response

What happens after allergen enters host

1) APC processes antigen and presents to T_H2 cell

2) T_H2 cell releases IL-4 and IL-12 which activate B cell

3) B cells proliferate and differentiate into plasma cells that make IgE antibody

4) IgE binds mast cell by Fc region, sensitizing it

5) mast cell with IgE bind to antigen and release inflammatory molecules resulting in allergy symptoms

Where can histamine bind

H1 receptor (brain, lung, vessel, heart), H2 receptor (heart, brain, stomach, fat), H3 receptor (digestive, lungs, heart, nerve), H4 receptor (digestive, fat)

Role of histamine

itchiness, gastric and secretion, blood vessels dilate, contraction of respiratory ways

Antihistamine (Claritin, benadryl)

block H1 receptors

Type II (cytotoxic) hypersensitivity

ADCC, autoimmune system disease

Antibody dependent cell mediated cytotoxicity (ADCC)

mechanism by which large pathogens are marked fro destruction by specific antibodies

killed by secretion of cytotoxins by NK cells, macrophages, or eosinophils

Autoimmune system disease

antigen may be a self-antigen, reaction would also be describes as autoimmune disease

Hemolytic transfusion reaction (HTR)

condition resulting after an incompatible blood transfusion: caused by type II hypersensitivity reaction and destruction of RBC

Rh classification system

based on Rh antigen

if present on RBC: + type and doesn’t have anti-Rh antibodies

if absent from RBC: - type and doesn’t have anti-Rh antibodies until exposed to Rh+ blood

Rh- person exposed to Rh+ blood

sensitized to Rh antigen (start producing anti-Rh antibodies

immune system of Rh- person will then mount a response with subsequent exposures to Rh+ blood)

Three main categories of parasitic infection

Soli-transmitted: hookworm and round worms

Vector-borne: protozoans (plasmodium falciparum = malaria)

Food/Water-borne: toxoplasma, giardia, cryptosporidium(protozoa)

Which category of infectious parasite affects the most globally? In the US?

soil-transmitted infection, food/water-borne infection

Helminths (parasitic worms)

parasitic worms living inside a host to gain nourishment and protection

roundworms, tapeworms, flukes

Neglected tropical diseases

infectious diseases that affect people in impoverished communities

largely ignored by major research

STHs infect millions

Common transmission features

fecal-oral contamination of soil

poor sanitation and hygiene

open defecation

Ascaris lumbricoides (giant roundworm) symptoms

cough and fever, digestive issues, abdominal pain, malnutrition, stunted children

roundworm lifecycle

ingested, enter blood system to infect lungs, eggs survive in soil for months, adult worms live 1-2 years

hookworm symptoms

skin penetration causes itching, attach to intestine and feed on blood, iron deficiency anemia

hookworm life cycle

enter skin (foot), can migrate to lungs

STH diagnosis and treatment

stool examination, PCR, antigen tests

anti-parasitic drugs, WASH (water, sanitation, hygiene) interventions

protozoans def

eukaryotic and unicellular

found in almost all moist environment, including freshwater, saltwater, damp soil, inside bodies of larger organisms

life stages of protozoans

trophozoite: feeding, growing stage: analogous to bacterial vegetative cell

cyst: resistant, survival stage: analogous to bacterial spore

Plasmodium falciparum (malaria)

cardiovascular and nervous system complication

vector: female mosquito

multistage life cycle in the mosquito and human host

affects RBC and liver

How does plasmodium harm the host?

lyses RBC — anemia

uninfected RBC also massively lysed via host immune response

intense fever, chills, weakness, vomitting

modifies RBC surface to avoid clearance by the spleen

Treatment against malaria

antimalaria medications: ACTs (first line), Chemoprophylaxis (supress blood stage)

Sickle cell and malaria

one allele of sickle cell makes it an inhospitable environment for malaria

toxoplasma gondii (food borne): the master manipulator

symptoms: asymptomatic in adults, severe if immunocompromised, birth defects

life cycle: main host cats, intermediate host all warm blooded animals, cyst form persists for life (can’t die)

Giardia: the flagellated menace

symptoms: asymptomatic carriers, acute infection, chronic malnutrition

life cycle: cyst enters through contaminated food or water, trophozoite attaches to small intestine then blocks food absorption

cryptosporidium: chlorine reistant parasite

limited effect in immunocompetent hosts, life threatening to AIDS patients

outbreak: swimming pools, water parks, contaminated food, agriculture