ihs 340 exam 1 content

the problem this course addresses. . .

allergy prevalence has greatly increased over the past century or so

deadliest pandemics in history

measles, black death, HIV/AIDS, smallpox, spanish flu, cholera, typhus, COVID, tuberculosis, etc.

why is tuberculosis the biggest killer?

not only can it cause death, but if infected individuals don’t die, it has a great effect on the immune system after infection

hidden story in list of leading causes of death in the US

diseases like cancer, heart disease, stroke, etc. all have microbial components

what is the relationship between incidence of infectious diseases and the incidence of immune hypersensitivity diseases?

inverse

infection

• the invasion of an organism’s body tissues by a disease-causing agent

• the multiplication or metabolically-active persistence of those agents

• reaction of host tissues to the infectious agents and any toxic compounds they produce

• has always existed

infectious disease

• disease that can result from infection by a transmissible agent (passed from host to host)

• hasn’t always existed

ex. measles is an infectious disease that will die out in small populations, because it needs a sufficient number of hosts

endemic level of disease

baseline, the amount of a particular disease that is usually present in a community over a sustained period of time

ex. the cold, the flu, COVID

endemic

the constant presence and/or usual prevalence of a disease or infectious agent in a population within a geographic area

sporadic

a disease that occurs infrequently and irregularly

hyperendemic

persistent, high levels of disease occurrence

epidemic

often sudden increase in the number of cases of a disease above what is normally expected in that population in that area

outbreak

same definition as epidemic, but often used for a more limited geographic area

cluster

aggregation of cases grouped in place and time that are suspected to be greater than the number expected, even though the expected number may not be known

pandemic

an epidemic that has spread across the globe, usually affecting a large number of people

allergen

an environmental antigen that typically elicits allergic responses (“a hyper-sensitive immune response”) in susceptible individuals, non-infectious

antigen

• a substance that induces an immune response in the body

• is specifically bound by antibodies or T lymphocyte antigen receptors

what largely mediates the allergic response?

mast cells

mast cells location and action

• prominent in mucosal and epithelial tissues, high numbers found in mucosal surfaces of respiratory and GI tract

• also located in subendothelial connective tissue

• can have limited local response or life-threatening systemic response (anaphylaxis)

key structure of mast cells

• they have granules full of mediators released when the cell gets activated

• the activation and effect of mast cells is very quick because they’re pre-formed and loaded with these mediators

atopy

• the propensity for developing allergy diseases (asthma, food allergies, seasonal allergies, etc.)

• defined operationally by elevated serum levels of allergen-binding IgE or by skin test reactivity to allergens

asthma

a heterogenous disease usually characterized by chronic airway inflammation, involving history of wheezing, SOB, chest tightness, etc. varying over time and intensity

is asthma an allergic disease?

about half of the people with asthma have allergic asthma, other half have non-allergic asthma

contributing factors in pathogenesis of asthma

occupation exposures, exposure to microbial organisms, infections, diet, pollution, stress, poverty, etc.

anaphylaxis

immune system releases flood of chemicals that causes the body to go into shock, BP drops suddenly, airways can become blocked, nausea, vomiting, skin rash, fast and weak pulses also common

conditions mistakenly associated with food allergies

ADD/ADHD, celiac disease, food intolerances, etc.

mucosa

• soft tissue that lines the body’s canals and organs in the digestive, respiratory and reproductive systems

• inside the body but exposed to the outside world

environment-gene interactions underlying allergic diseases

• environmental factors like level of development in a country, family size, home location, antibiotic use, sanitation levels are driving factors for developing allergic disorders or not

• genes are modifying factors for developing allergic disorders or not

robert hooke

• built the first compound microscope, observed mold and lice

• published Micrographia

• coined the term cell

antonie van leeuwenhoek

• built single-lens magnifiers

• first to observe single-celled microbes, called them animalcules

• credited with advancing the field of microbiology

microbe

single-celled organism

why are sizes of microorganisms relevant?

it determines how the immune system deals with the microorganism and how it spreads

gram-positive bacteria

• stains purple

• has peptidoglycan cell call

gram-negative bacteria

• stains pink

• has an inner and outer membrane with a thin peptidoglycan wall in between

fungi

• eukaryotic microbes

• more than 100,000 species

• unicellular and multicellular forms exist (yeast, molds)

parasitic disease

• majority occur in the tropic and sub-tropical regions

• parasites include protozoa and helminths

• usually 2 hosts to complete life cycle

florence nightingale

English social reformer, statistician, and founder of modern nursing

john snow

traced the source of the london cholera outbreak of 1854, although his work was mostly ignored because it was before germ theory was accepted

louis pasteur

• started as organic chemist

• discovered the microbial basis of fermentation

• disproved that microbes arise by spontaneous generation

francesco redi

experimented to disprove spontaneous generation of flies on meat

pasteur’s experiments disproving spontaneous generation of microbes

microbes come from dust particles in the air, not coming from the air or from the broth used in the experiment

pasteurization

process of heating a liquid to below the boiling point to destroy microorganisms but retain flavors of the liquid, first developed for wine

mary catherine evans

showed that drinking unpasteurized milk could transmit brucellosis-causing bacterium from domestic farm animals to humans

ignaz semmelweis

discovered infectious nature of puerperal fever and developed antisepsis technique (washing with chlorinated lime water) to prevent the condition

joseph lister

developed carbolic acid to treat wounds and clean surgical instruments

aseptic

environment is microbe-free

puerperal fever

aka childbed fever, infection of some part of the female reproductive organs following childbirth or abortion

phenol usage and history

aka carbolic acid, the oldest surgical antiseptic but no longer used even as disinfectant because of corrosive effect on tissues and instruments and carcinogenic effects

disinfectants

strong chemical agents that inhibit or kill microorganisms, strong enough to cause tissue damage

antiseptics

disinfecting agents with low toxicity to host cells, can be used on skin, wounds, or mucous membranes, subclass of disinfectants

sterilants

kill both vegetative bacterial cells and bacterial spores when applied to materials for appropriate times and temperatures

classifications of antiseptics and disinfectants

1. those that denature proteins

2. those that cause osmotic disruption of the cell

first two kill microorganisms

3. those that interfere with specific metabolic processes

third one affects cell growth and reproduction without killing the cell

phenol, iodine, alcohols, aldehydes and metallic compound mechanism of action

denature proteins and DNA bases

cationic detergents mechanism of action

interfere with plasma membrane’s permeability and cause leaking of enzyme, coenzyme and metabolites

oxidizing compounds mechanism of action

oxidize functional molecules in the microorganisms

history of listerine

• named listerine because dr. lawrence was a fan of joseph lister

• was promoted to dentists as mouthwash but wasn’t very popular until ads started running about halitosis (bad breath)

• essentially the disease was created with the cure at the ready

robert koch

• discovered that using solid media provided simple way to get pure cultures

• observed that masses of cells (colonies) had different morphologies

why was growing a pure culture of microorganisms needed?

to prove a particular bacterium caused a specific disease

angelina and walther hesse

developed solid medium using agar as improvement over gelatin (bacteria ate the gelatin)

julius richard petri

developed double-dish container to culture bacteria

koch’s postulates

criteria used to establish causative link between an infectious agent and disease

1. microbe is found in all cases of the disease but is absent from healthy individuals

2. the microbe is isolated from the diseased host and grown in pure culture

3. when the microbe is introduced into a healthy, susceptible host, the same disease occurs

4. the same strain of microbe is obtained from the newly diseased host

rabies vaccine

created by louis pasteur, he attenuated the disease from rabbit to rabbit, eventually causing mild disease but protecting against the real disease

how did we learn that viruses are different from bacteria?

iwanowski and beijerinck separately proved that virus from diseased tobacco plants wasn’t diluted with filtration even fine enough to retain smallest bacteria, and it was replicating because it wasn’t diluted between newly infected plants

sterilization by filtration

filtration avoids use of heat on sensitive liquids and gases to sterilize

virus

• metabolically inert sub-cellular agent that can infect specific types of living cells and replicate while inside the cell

• does not exhibit “free-living” or “independent” growth

• RNA viruses need RNA replicases

• retroviruses carry reverse transcriptase

virion

• virus particle, consists of nucleocapsid (capsid/protein coat and nucleic acid)

• two categories - naked and enveloped in lipid envelope

capsomeres

repeating protein subunits that make up capsid

virus morphology

typically smaller than bacteria, highly symmetric

enveloped viruses

• have envelop/lipid bilayer surrounding nucleocapsid with embedded proteins

• envelop makes initial contact with host cell

• much of the membrane is picked up from the host cell during exit

• most infect animal cells

phases of virus life cycle

1. attachment of virus to susceptible host cell

2. entry of virion or its nucleic acid

3. synthesis of virus nucleic acid and protein by cell metabolism as redirect by virus

4. assembly of capsids and packaging of viral genomes into new virions (maturation)

5. release of mature virions from host cell

passive barriers to infection

lysozymes, mucus and cilia, blood and lymph proteins, skin, stomach acidity, flushing of urinary tract, epithelial cells

three layers of mucosa

1. epithelium - single cell wide

2. lamina propria - loose connective tissue

3. muscularis mucosa - smooth muscle

layers of the epidermis

stratum corneum, lucidum, granulosum, spinosum, basale

epithelial surfaces. . .

provide first barrier against infection and against dehydration

airway anatomy

• anatomically contiguous surface

• oral and nasal cavities have a significant resident microbiota

• alveoli not mucus-covered, lipid-covered (surfactant) which allows them to open and close

gut microbiome

• architecture largely determined by diet and physiochemical gut conditions

• pH gets higher when going from stomach to colon

• as pH increases, so does load of bacteria

• mucosal layer prevents microorganisms from engaging directly with the epithelial surface in healthy individuals

mucous membrane in GI tract composition

mucus and host effector molecules like IgA

MALT

mucosa-associated lymphoid tissue, part of immune system, ex. peyer’s patch in small intestines

epithelium in gut

composed of epithelial cells and secretory cells, there are invaginations called crypts, few bacteria are in the crypt

lamina propria

composed of

• non-cellular connective tissue elements like collage and elastin

• blood and lymphatic vessels

• fibroblasts and myofibroblasts

• nerve endings

• few leukocytes

intestinal mucus

• small intestine - penetrable but bacteria are kept away from epithelium by antibacterial products, mucus not attached to epithelium

• large intestine - inner mucus layer is impenetrable to bacteria whereas outer layer is expanded and serves as habitat for bacteria

• major building blocks - large glycoproteins called mucins

human microbioime

• indigenous microbial communities of the human body

• significant positive effects of this symbiotic relationship:

  • helps make necessary metabolites and vitamins, helps digest carbs, competes with pathogens for “parking space”, promotes well-regulated immune response

microbiome throughout the body

each body site is colonized predominantly by only certain bacterial species, driven by pH, mucus type, etc.

acquisition of the microbiome in early life from mother-to-child microbial transmission

• passed on via oral, mammary, cutaneous, and vaginal methods

• healthy of babies delivered via C-section vs. vaginal birth showed difference between bottle-fed and breast-fed, but with bifidobacteria added to formula, no difference in microbiome

microorganisms in large intestine

microbes like to live around undigested particles in the lumen, little to none in the inner mucin later in the healthy state

microbiome role in fiber metabolism

microbiome breaks down fiber into SCFAs like acetate and butyrate, increases epithelium health/function, and decreases inflammation systemically

anti-microbial peptides (AMPs)

• AMPs directly destroy microbial cell walls and membranes

• produced by various cells in body, stored in granules, and released when cell activated

• AMPs that are excreted require transcription and translation after cell activation

defensins

small antimicrobial cationic peptides that can form a pore in bacteria membranes

activation of anti-microbial peptides

activated by proteolysis to release an amphipathic anti-microbial peptide

AMP research

AMPs are our own form of antibiotics, and no AMP resistance found in nature! failed in clinical trials though

mechanisms of infection

• gain access to the body and attain a unique niche (colonize)

• acquire necessary nutrients in vivo

• multiply or persist

• avoid, subvert, or circumvent innate host defenses

• cause tissue damage or disease

mechanisms of infectious disease

same as infection AND exit and transmit infection to new hosts

horizontal transmission

individual-to-individual

vertical transmission

maternal-to-neonatal, infectious agent may cross placenta from the mother to fetus

direct contact transmission

person-to-person spread of microorganisms through actual physical contact

ex. handshakes, sneezing

indirect contact transmission

occurs when a susceptible person comes in contact with a contaminated object or material

fomite

an inanimate object or substance, like clothing, bedding, furniture, soap, etc. that is capable of transmitting infectious organisms from one individual to another

transmission via ingestion

fecal-oral transmission, via the gastrointestinal tract

f-diagram:

feces —> fluids, fingers, flies, fields/floors —> food —> future victim

handwashing

one of the most important means of preventing transmission of infectious agents from person to person

giardiasis

• caused by infection with giardia lamblia

• can parasitize intestinal tract of wide range of vertebrates

• transmission of disease is primarily by injection of water/food contaminated with cysts

• disease spreads very easily, can occur in daycares