coevolution, evolution, and medicines - part 1

what is a pathogen?

• something that causes disease

• a foreign entity that reproduces and disrupts your normal body systems

ex: bacteria, fungi, prions, viruses, protozoans, worms

what occurs in a mutualistic coevolution?

both species benefit

what occurs in an antagonist coevolution?

changes in one species will decrease the fitness of the other

why hasn’t natural selection provided humans with impenetrable defenses?

• most pathogens have a far shorten generation time then their hosts → selection acts much faster on pathogens

• pathogens have a much larger population size than their hosts

• certain pathogens have very high mutation rates → makes it difficult for immune system to recognize 

• certain environments can increase transmission rate of pathogens

whats a disease?

disrupts the normal function of the body

how do pathogens affect human evolution?

pathogens act as a major selective pressure (natural selection) causing the genes that confer immunity or resistance to be more common in the human population over time

how do pathogens contribute to genetic variation?

• human populations that have migrated have encountered different local pathogens, leading to the evolution of distinct local immune adaptations

• the constant threat from pathogens has driven the evolution of complex defense mechanisms, including the immune system’s ability to remember past infection

ex: sickle cell anemia and malaria

what is disease susceptibility?

genetic variation that helps people survive one infection can make them more susceptible to others

ex: blood types

what disease caused Napolean to sell the Louisiana purchase?

yellow fever

what mechanisms evolved to combat pathogens?

nonspecific innate immune system, specific adaptive immune response, vaccination

what are examples of nonspecific innate immune response?

skin, inflammation, phagocytes (macrophages, neutrophiles), natural killer cells, interferons, fever

what is nonspecific innate immune response?

• oldest part of the immune system

• first evolved in unicellular eukaryotes

• seen in invertebrates and vertebrates

• first and second line of defense

• acts as a precursor for adaptive immunity

what are pathogen-associated molecular patterns (PAMPs)?

structures and molecules that are found on the pathogens but not on the host cells

ex: peptidoglycan layers, lipoproteins

what are pattern recognition receptors (PRP)?

leukocytes have membrane bound or soluble proteins that recognize PAMPs

what are some immune strageties?

• detecting characteristic components of pathogens that stay constant over long periods of time

• creating variation through sexual selection

  • prevents pathogens from specializing on any host genotype

what is the red queen hypothesis?

sexual reproduction is an adaptation allowing hosts to generate sufficient genetic variation to keep up with their pathogens and parasites in the coevolutionary arms race

what is a fever?

a nonspecific mechanism to fight infections

includes endotherms (regulates its own body temp) and ectotherms (cannot regulate their body temp)

what is an example of an ectotherm?

when a lizards’s body senses it has an infection, so it’ll move itself for a higher temp (sun)

why is a fever beneficial?

• cause hypothalamus to reset body temp

• higher temp → increases phagocytosis and antibody production

  • slows down bacterial growth

what is the downside of having a fever?

• Very high temperature (>40.6 degrees Celsius) can damage host tissues and macromolecules (proteins)

• detrimental to brain cells because of finite # of cells

given their cost, why are fevers so common?

b/c of the body responding the infection as a false positive

what is a false positive?

when a defensive response is initiated in the absence of a threat, typically imposes only a modest energetic cost

what is a false negative?

when no defensive reaction is imposed even in the presence of a threat

is it better to have a false positive or a false negative?

it is better to have a false positive (a minor nuisance) than a false negative (catastrophe) especially when it comes to responding to infectious disease

what is a specific adaptive immune response

• the third line of defense

• recognizing and remembering the pathogen

• most complicating and most time to initiate

what is an example of specific adaptive immune response?

T and B cells

what does penicillin do?

attacks the peptidoglycan layer of the bacterial cell walls

what does rifampin do?

attacks the bacterial RNA polymerase 

what does streptomycin do?

attacks the bacterial ribosome

what does nystatin do?

attacks the fungal cell membrane

what does tamiflu do?

prevents spreading of the influenza virus

what are some examples of antimicrobial drugs/amtibiotics?

penicillin, rifampin, streptomycin, nystatin, tamiflu

what is vaccination?

a weakened or inactive form (antigen) of pathogen (virus or bacterium) is introduced into the body

what does vaccination do?

triggers the immune system to produce antibodies against the antigen and keeps a memory of the pathogen

what is the result of vaccination?

exposure to the real pathogen will allow a faster immune response (adaptive response)

what is evolutionary maladaptive explanations for why humans are vulnerable to disease?

one of the factors of a pathogen, virulence, cause disease in humans

what is virulence?

the ability of a pathogen to cause disease (this can vary significantly from one pathogen to another)

ex: common cold may slow a person down for a day or two, whereas the flu can keep a person in bed for weeks

what is the trade-off hpothesis?

• a pathogen’s virulence (harm to the host) is balanced against its ability to transmit to new hosts

• as a pathogen becomes more virulent, the host gets sicker and is less likely to transmit to new hosts

what is virulence dependent on?

dependent on virulence factors of the pathogen

anything made by the pathogen to help it cause disease → more dangerous to human host

ex: capsule, toxins

what was the deadliest pathogen in human history?

the influenza virus

• 1918 influenza pandemic: largest single -year loss of life in recorded history

what is the influenza virus?

a single-stranded negative sense RNA virus that is the causative agent of the flu

transmitted mainly through the airborne route

what are the major virulence factors of the influenza virus?

hemagglutinin, non-structural protein 1 (NS1), M2 (matrix-2) protein, neuraminidase

what major proteins are significant to the influenza virus?

hemagglutinin, M2, and neuraminidase because it faces constant attack from immune system leading to evolutionary changes

what is hemagglutinin?

glycoprotein that is used for attachment and fusion with the host’s cell (sialic acid→must be present to attach) in the respiratory tract

what is non-structural protein 1 (NS1)?

disable the host’s immune response and promote viral replication

what is M2 (matrix-2) protein?

needed for efficient release of the viral genome during virus entry

what is neuramindase?

needed for liberation of the virus from the host’s cell

what is the pathogenesis of the influenza virus?

1. viruses bind ciliated cells of respiratory mucosa

2. viruses multiply in epithelial cells lining the lungs → rapid shredding of these cells releasing loads of viruses

3. death of infected epithelial cells weaken the lungs’ epithelial lining (severe inflammation and irritation in the lung)

what are the symptoms of the influenza virus?

high fever, fatigues, cough, body aches, damage to the lung, others

if a patient has the influenza virus, what are the susceptible to?

pneumonia and other secondary bacterial infections

how do humans counter the influenza virus?

early treatment of drugs (Tamiflu → blocks activity of neuraminidase & xofluza → blocks activity of the viral RNA polymerase) to inhibit viral replication

what are escape variants?

variants form of a pathogen not recognized by the immunological memory of previously infected hosts

how does the influenza virus subvert the immune system?

by undergoing antigenetic drift and antigenetic shift

what is antigenetic drift?

natural selection on seasonal influenza viruses that alters the structure of surface proteins, allowing them to evade the antibody-mediated immunity induced during previous infections or vaccinations

what is antigenetic shift?

a dramatic change in the surface protein of influenza virus brought about by the reassortment between viral strains, leading to a severe drop in immunity to the resulting strain and the potential for a new flu pandemic

what occurs for there to be different influenza strains?

reassortment occurs when genetics segments from different influenza strains become mixed into new combinations within a single individual

what is HIV?

a positive-sense RNA retrovirus that causes AIDS (acquired immunodeficiency syndrome)

what does HIV destroy?

destroys the immune system by infecting macrophages and certain T cells

what type of pathogen is HIV?

an opportunistic pathogen that can kill the immunocompromised host

how does one catch HIV?

through sexual intercourse, blood transfusions and breast feeding

what are the major virulence factors of HIV?

reverse transcriptase, protease, integrase, gp141, and nef/vif proteins

what is reverse transcriptase?

converts viral RNA into DNA

what is protease?

cleaves viral proteins into functional components (assembles virus into active form)

what is integrase?

inserts viral DNA into the host cell’s genome

what are nef/vif proteins?

proteins that weaken the immune system

what is gp141?

promotes viral entry into host cells

what is SIV?

simian immunodeficiency virus

a virus that infects non-human primates

what gave rise to the two strains of HIV?

the continued evolution of SIV gave HIV-1 and HIV-2

what are the stages of HIV-1 infection?

1. acute infection

2. clinical latency

3. acquired immunodeficiency syndrome (AIDS)

what happens in acute infection?

asymptomatic or flu-like illness (fever, headache, rash)

what happens during clinical latency?

• viral load will gradually increase and certain T cell count will decrease (inverse relationship)

  • can last for many years

what happens during acquired immunodeficiency syndrome (AIDS)?

• most severe phase

• destruction of the immune system

• very susceptible to opportunistic infections

what is Karposi’s?

sarcoma

a subgroup pf patients who were diagnosed with a condition where their T cell counts were low and their immune systems deficient

a virus identified as the cause of AIDS

how can humans counter from sarcoma?

using protection

abstinence

PrEP (pre-exposure prophylaxis)

antiretroviral therapy (ART)

what are some examples of antiretroviral therapy?

reverse transcriptase inhibitor

integrase inhibitor

protease inhibitor

fusion inhibitor

what is a reverse transcriptase inhibitor?

prevents virus from replicating its genetic information

what is a integrase inhibitor?

prevents virus from integrating its viral DNA into the host cell’s genome (needed for permanent infection)

what is a protease inhibitor?

prevents virus from assembling inside the host’s cell

what is a fusion inhibitor?

prevents virus from entering the host’s cell

how did AIDs evolved to subvert the immune system?

high rate of mutations through reverse transcriptase which allows the virus to change its surface proteins

mutations in the reverse transcriptase and integrase genes also make the virus more resistant to the antiretroviral drugs

has a latent phase

desctruction of immune system

what’s a latent phase?

asymptomatic phase lasting 2-15 years

continues to replicate at low but deadly rates

increase the chance to spread of others