lesson 9 Flashcards
Rise of Autoimmune and Inflammatory Diseases
Autoimmune diseases occur when the immune system attacks the body’s own tissues.
Examples: type 1 diabetes, Crohn’s disease, multiple sclerosis, rheumatoid arthritis, celiac disease.
These diseases are increasingly common in industrialized societies.
Hypothesized to result from evolutionary mismatch due to reduced microbial exposure.
Type 1 diabetes
underproduction of
insulin – body attacks insulin producing
cells in pancreas
Multiple sclerosis
Multiple sclerosis – disease of the CNS,
immune system attacks myelin which
coats nerve cells
Crohn’s disease
Crohn’s disease – IBD (inflammatory
bowel disease) – immune system
attacks harmless gut bacteria – cause
chronic inflammation
Asthma –
Asthma – inflammation and narrowing of
airways, caused by immune response to
pollution, allergens – Autoimmune status
controversial but it is coincident with other
diseases.
Rheumatoid arthritis
chronic inflammation
(commonly of joints) when immune system
attacks connective tissues
Celiac disease
Celiac disease – immune reaction to eating
gluten, triggered in small intestine – causes
destruction of gut lining, leads to nutrient
malabsorption
major histocoompatibility complex
The MHC is a group of 20 genes on chromosome six
that are highly polymorphic – with 50 variants each
MHC encode proteins that exist on the plasma
membranes of all body cells - also called Human
Leukocyte Anigens (HLAs) – differentiate your own
and foreign tissues
MHC - part of the adaptive immune system
producing Class 1 (virus detecting) and Class 2
(bacteria detecting) receptor proteins
Variation in MHC provide strong risk factors to many
autoimmune diseases – but exact mechanisms
poorly understood
immune rresponse
B-Cells attack invaders outside of cells,
T-Cells attack infected cells
Tregs – are t cells that regulate /
suppress other cells in immune
system (Nobel Prize, 2018)
Schistosomiasis
Schistosomiasis – affects poor and rural
communities with poor sanitation
People become infected by a parasite that
develops in freshwater snails, penetrate
skin when exposed to infested water
Become blood borne ‘flukes’ - cause
anemia, stunting and a reduced ability to
learn, inflammation, chronic conditions
including liver and kidney failure, bladder
cancer
we have co evolved with parasites….
Humans co-evolved with parasites (e.g., whipworms, tapeworms).
Parasites regulate immune responses (e.g., increase Treg cells, reduce inflammation).
Trade-off: helminths can cause harm, but their absence may increase autoimmune risk.
Bedbugs
Bedbugs originate from bat hosts and likely started to feed on humans when we first lived in caves
Lice
Lice human species diverged from
chimpanzee lice, genetically, about 6 million years ago – differentiated
head/body lice with origins of clothing
Tapeworms
Tapeworms human species are similar to hyena tapeworms, likely date to
earliest meat consumption
T. trichiurainate (human whipworm)-
T. trichiurainate (human whipworm)- Infects 460 million people
worldwide
Trichuris suis (pig whipworm)
Trichuris suis (pig whipworm)
- found in pigs worldwide
Schistosoma japonicum
Schistosoma japonicum – genetic distances of
fluke mtDNA show parasite originated and
spread with early rice farmers in
The Hygiene (or ‘Old Friends’) Hypothesis
Also called the “Old Friends” hypothesis.
Suggests that improved hygiene, antibiotics, and reduced parasite load have dysregulated immune systems.
Evidence:
Farm children have lower allergy and asthma rates.
Schistosoma infections reduce autoimmune disease risk in animal models.
parasites-helminths
Humans
have had parasites, such as
intestinal worms, for the vast
majority of our evolution
Currently affect 1.5 Billion people in
the world today
Transmission cycles involve soil and
water contaminated with human
feces
Infected are nutritionally, physically,
and in extreme cases cognitively
impaired
- The human microbiome includes trillions of microorganisms, primarily in the gut.
- Influences:
Digestion
Immune response
Inflammatory diseases - Highly variable by diet, geography, delivery method (vaginal vs. C-section), antibiotic exposure.
- Hadza microbiome is more diverse than urban populations and better suited for plant degradation.
- Western diets decrease microbial diversity and increase metabolic/inflammatory diseases.
FMT
Fecal Microbiota Transplants (FMT)
* The last 5 years have seen a
massive increase in research
demonstrating that fecal
transplants between
pathogenic microbiomes and
‘health’ microbiomes can treat
disease in mice
* This has led to development and clinical
trials of new treatments – sample
treatment and microbiome isolation
* 80-90% effective in treating some
forms of antibiotic resistant diarrhea
* Has seen limited success in clinical
trials relating to IBD – Crohn’s disease
why question the hygiene hypoothesis
- Microorganisms in the modern home are
typically not those required for immunity - Vaccines protect from infection, but also
strengthen immune systems, reduce risks of
exposure - Micro-organisms of natural environments
important, but domestic cleaning have no
impact on ‘natural’ environment - Associations between cleaning home and
health problems exist, but linked to chemical
exposure that can cause damage, allergy
immune functioon and life histoy trade offs
Immune responses are energetically expensive:
Increase metabolism, fat mobilization, and oxygen consumption
Compete with growth, reproduction.
Examples:
Amazonian children with higher immune activity show stunted growth
Gambia: CRP increases during fasting (Ramadan), showing energy–immune trade-offs.
leptin
Hormone from fat stores that regulates immunity and appetite.
High body fat enhances immune function, but obesity dysregulates it.
