BMS 503 Exam 4 materials

Possible Outcomes with an encounter of a microorganism

1. transiently colonize the person
2. permanently colonize the person
3. produce disease

* organisms that colonize humans (transient or permanent) do not interfere with normal bodily functions
* disease occurs when human-microbe interaction leads to damage of the host and interruption of normal function
* not all colonzations produce disease

Beneficial Human-microbial interactions

* animals provide favorable environment for growth
* temperature = consistent
* pH in neutral range
* regular supply of nutrients for growth
* Infections frequently begin at sites in animal’s mucous membranes
* most epithelial tissue in the human body (tissue exposed to outside world) coated in mucous

mucous

innate host defense against infection

* prevents microbial adhesion
* microbes must move through the mucous layer to contact cell surface for infection

Microbiome

Population of microorganisms currently colonzing your body

* aka normal flora
* changes in your ---- that lead to disease = dysbiosis

Commensalism

A normal flora relationship where the host (human) provides benefit to bacteria but the bacteria do not provide benefit or harm host

* ex. Staphylococcus epidermidis, micrococcus luteus are skin flora found on most humans

Mutualism

a normal flora relationship where both bacteria and the host benefit from the colonization

* Esherichia coli K12, normal flora of the intestinal tract, produces Vitamin K and B for the host. Prevent colonization by pathogens

Upper respiratory tract

colonized with many bacterial species

* species of bacteria present is dependent on the part of the respiratory tract
* Nasal cavity/sinus -→ Corynebacterium sp, Staphlyococcus aureus
* Nasopharynx -→ Streptococci sp, Neisseria sp, Haemophilus sp
* Oropharynx -→ anaerobic organisms like Actinomyces sp, Fusobacterium sp, Veilonella sp, Actinobacillus sp, and aerobic organisms like Streptocci sp, Neisseria sp, Haemophilus sp
* Most of flora is non-pathogenic, some can be opportunistic pathogens if they grow outside their niche
* flora is affected by the environment of the person

Enterobacteriaceae

family of bacteria normally found to colonize the intestines

Microbita of the GI tract

extensively colonized with a diverse community of bacteria

* mouth contains large populations of bacteria living in biofilms on teeth and pharynx
* esophagus (flow of liquids) and stomach (pH) are sparsely populated
* as one move further away from the stomach, the small intestine becomes more populated
* large intestine = heavily colonized
* accessory organs (liver, gallbladder, pancreas) = sterile

Dental plaque

a biofilm containing salivary proteins, food debris, and bacterial cells and products

biofilm

a complex community of microorganisms that are adhered to a surface and protected by an extracellular polymeric substance (EPS)

* community of microorganisms in which cells are stuck to each other and/or to a surface
* advantages
* allow adhesion of microorganisms that would be cleared otherwise
* prevents interaction of base cells with immune response
* limits diffusion of antimicrobials
* proximity can allow for quorum sensing gene regulation

EPS (extracellular polymeric substance)

typically composed of extracellular polysaccharide, protein and DNA

Dental caries

tooth decary, cavities that cause pain and tooth loss in affected individuals

* bacteria grow in plaque
* carbohydrates not cleaned off teeth can be utilized by bacteria
* fermentation of carbohydrates at the base of biofilm results in production of acids
* acids result in break down of tooth enamel
* major cause = Streptococcus mutans

Gut microbiome

normal flora is beneficial for many reasons

* competition
* takes up space -→ surfaces colonized by normal flora are not available to be colonized by microbial invaders
* compete with microbial invaders for resources, some produce antimicrobial compounds
* nutritional and digestive benefits
* synthesize number of vitamins that can be utilized (Vitamin K, folate, pyridoxine, biotin, riboflavin
* Development of the Caecum and Mucous associated lymphoid tissues (MALT)
* Immune system
* immune surveillance of normal flora creates antibodies to normal flora bacteria that cross react to pathogenic bacteria
* microbiota differentiated into entertypes based on abundance of specific genera and age, immune status and antibiotic exposure play role

Urogenital microbiome

* vagina of adult female is weakly acidic and contains significant amounts of glycogen
* Lactobacillus acidophilus = resident organism in vagina, ferments the glycogen and produces lactic acid
* lactic acid maintains local acidic envrionment, selecting for specific types of microorganisms
* bladder = sterile in males and females
* altered conditions (ex. change in pH) can cause potential pathogens in urethra (ex. E. coli and P. mirabilis) to multiply and become pathogenic
* E. coli and P. mirabilis frequently cause urinary tract infections in women

Skin microbiome

3 sites have indigenous microbiota


1. Sebaeceous -→ forehead and back, Proprionibacterium acnes in hair follicles
2. moist sites -→ navel, groin, foot, skin folds have Corynebacterium and Staphlyococcus
3. Dry sites -→ forearms, hands, buttocks most diverse with Staphlylococcus, Acinetobacter and Micrococcus

organisms compete with pathogens for a niche -→ many produce antibiotics

some can cause opportunistic infections

Opportunistic pathogen

An infection that does not cause disease in its normal setting but can cause disease when introduced to an unprotected site or the host immune system is compromised

* opportunistic infection
* normal flora organisms that are able to cause disease if the host is compromised
* compromised hosts = immune system defective, break in tissue allows organism access to new site, loss of other microflora allows organism to bloom

Infection

entry of pathogen or parasite

* doesn’t always cause disease
* most eliminated by immune system

Disease

damage or loss of tissue or organ function due to infection

* symptoms are dependent on the changes to the tissue
* severity is dependent on the importance of the effected organ and amount of damage caused by infection
* can be effected by host factors

primary pathogen

non-normal flora organism that are able to infect and cause disease

Pathogenicity

measure of ability of organism to cause disease

* determined by genetic makeup of organism

Infectious dose (ID50)

number of organisms to colonize 50% of host

* varies greatly between organisms
* sometimes dependent on host factors

virulence

the measure of the severity disease caused by an organism

* rate of lethal infections

Lethal dose (LD50)

number of organisms to kill 50% of hosts

* highly pathogenic organisms are not necessarily highly virulent

Virulence Factors

pathogen metabolites that allow for organisms to cause disease in host

* toxins, attachment/adhesion proteins, capsules, secretion systems
* attenuation

attenuation

the decrease or loss of virulence due to mutation or deletion of virulence genes

Follow the Pathogen

1. encounter -→ patient encounters organism from outside or endogenous source
2. entry -→ how the organism gains access to the host and its initial sites of colonization
3. spread -→ how the organism moves from one tissue to another tissue
4. multiplication -→ most disease requires pathogen to replicate
5. damage -→ due to pathogen factor, host response or both
6. outcome -→ the result of disease, manipulated by diagnosis and treatment

Infection cycle

route of dissemination and intimately associated with encounter

Direct transmission

person to person dissemination of the organism

* virus passed from person to person through direct physical contact
* contaminated hands, sexual contact, kissing, saliva, other secretions

Indirect transmission

dissemination via an intermediate

* contact with fomites (inanimate objects)
* reservoir for disease organism
* virus transferred or carried by an intermediate to host
* air, vector (bite), ingestion, vehicle (fomites)

Phagocytosis

specialized immune cells engulf and destroy the invading bacteria

* requires interaction between phagocyte surface receptor and bacterium or opsonin
* mediated through receptors that recognize PAMPs receptor that recognizes C3b or receptor that recognizes bound antibody
* interaction triggers cytoskeletal changes allowing engulfment and take up of microorganism
* microorganism in compartment = phagosome

complement system

a system of proteins that binds the surface bacteria, causing lysis or promoting phagocytosis


1. promotes inflammation response
2. opsonize an invader (bind to invader, enhancing recognitions by phagocytes and promoting phagocytosis)
3. lyse the invader by forming a pore protein in the membrane of the invading bacteria

antibodies

proteins that bind the surface of bacteria or bacterial products, neutralizing the bacteria/products and promoting phagocytosis

capsules

inhibit phagocytosis and bind of complement system proteins and antibodies

* can aid in attachment

toxins

can damage immune cells or damage other cells allowing for spread of the infection

* bacterial products that directly harm tissue or trigger destructive biological activites

pili

allow for attachment, can inhibit phagocytosis and complement binding

Exotoxin

proteins secreted by bacteria that damage the host

* ex. cholera toxin, tetanus toxin, pertussis toxin
* 5 categories
* cause host cell membrane leakage (ex. S. aureus alpha toxin) = cytolytic toxins
* proteases that cleave host cell proteins ex. Clostridium tetani Tetanospasmin)
* block protein synthesis (ex. Shiga toxin from Shigella dysenteriae)
* block 2nd messenger pathways (ex. choleria toxin)
* superantigens over activate the immune system (ex. S. aureus toxic shock syndrome toxin)

endotoxin

bacterial products or compenents that are released by bacteria and illicit an immune response

* low concentrations lead to productive immune response (activation of inflammation and innate and adaptive immunity
* high concentrations lead to excessive response that overpowers the host and results in shock and sometimes death
* ex. LPS and LTA

AB toxins

2 proteins components


1. B subunit binds to host cell -→ delivers A subunit to cell


1. often 5 B subunits form a pore for A entry
2. A subunit has toxic activity

Targeted killing

cells infected with intracellular pathogens (viruses and some bacteria) can be targeted for destruction

Neutrophils

phagocytose and kill bacteria

Antigen

foreign material that promotes production of antibody

APC (antigen presenting cells)

phagocytose and kill bacteria

* present antigen to T-cells via Class II MHC proteins
* derive from monocytes

macrophage

found in tissue, spleen, lymph nodes and other organs

* initiate inflammatory response

dendritic cells

lymph nodes and tissue

* most potent APC
* initiates and modules T-cell response

B-cells

produce antibody

* internalize antigen, process antigen and present antigen to T-cells to expand immune response
* develop into memory cells and plasma cells
* can present antigen via MHC II
* inactivated pre cells produce surface bound IgM and IgD antibody
* activated by direct interaction with T helper cells

Memory cells (b-cells)

circulate until activated by a specific antigen

plasma cells (b-cells)

produce large amounts of antibody

CD-4 (T-cells)

control, suppress (when necessary) and activate immune and inflammatory response by cell-cell interaction or release of cytokines

CD-8 (t-cells)

release cytokines but known for their role in recognizing virally infected cells, tissue transplant and tumor cells (cytotoxic killer T-cells)

Natural killer cells

innate immune cells but derive from lymphoid precursor

* large granular lymphocytes that kill antibody decorated cells, virus infected, or tumor cells

Basophils

release histamine

eosinophils

phagocytic cells but do not play a role in response to bacterial pathogens

Lymphatic/lymph system

a network of organs, lymph nodes, lymph ducts, and lymph vessels that make and move lymph from tissues to the bloodstream

* maintains fluid balance of the tissues
* absorbs fats and fat soluble vitamins from the small intestine and deliver them to tissues
* production and transport of immune cells

lymph

fluid composed of water and immune cells

* collects bacteria, fats, proteins, and cell waste
* enters lymph system via lymphatic capillaries
* pumped by smooth muscle contraction up vessels to lymph organs and trunks
* drains into circulatory system at lymph ducts

Lymph system at work

1. M cell samples intestinal track
2. M cell present antigen to B cell, T cell and/or macrophage
3. stimulated immune cells migrate to the peyer’s patch stimulating resident B and T cells
4. cells travel through lymph system to the blood stream

systemic response can result from local challenge

PAMPS (pathogen associated molecular patterns)

activates innate protections

* repetitive structures of the microbial surface or genome
* LPS, LTA, flagellin, peptidoglycan

pyrogens

causes fevers

* exogenous = chemicals originating from the invading microorganism
* endogenous = cytokines originating from the host

Basic inflammatory responses

5 cardinal signs = redness, warmth, pain, edema (swelling) and altered function at the affected site

immunogen

a protein or carbohydrate that is recognized and sufficient to illicit an immune response

* may contain one or more antigens

innate immune response

* initial response to invader
* includes -→ physical barriers to infection, antimicrobial molecules, complement protein cascade, cells of the innate immune response
* protections activated by PAMPs

Adaptive immune response

* secondary response -→ specific to a specific pathogen
* immune systems reacts to specific immunogens
* retains “memory” of antigens
* humoral immunity -→ production of antibody proteins, each binds a different antigen
* cellular immunity -→ T cells that bind different antigens, control antibody production, kill intracellularly infected cells

clonal expansion

reproduction of B cells that respond to the specific antigen

* activated T cells undergo --- ---
* activated T cell is stimulated to grow and divide via mitosis
* each t cell division increases the number of T cells that recognize specific antigen
* activated t cells can produce CD4 T helper cells, cytolytic CD8 T cells and memory T cells

Antibody response

primary antigen exposure

* disease or vaccination
* antibodies appear in serum after several days
* B cells that bind antigen activate make IgM antibodies
* class switch occurs after T help cell interaction
* some differentiate to plasma cells
* other b cells differentiate to memory B cells

secondary antigen exposure

* pathogen or booster due
* antibodies appear in blood within hours
* mostly IgG antibodies

Antigen presentation

* MHC I presents proteins from cytoplasm
* cell, viral and intracellular bacterial proteins
* loaded in endoplasmic reticulum
* trafficked via vesicles to cell surface
* MHC II present exogenous proteins
* antigens acquired via phagocytosis
* fusion of digestive vacuole with vesicle containing MHC II
* loading occurs in vesicle
* antigen present cells APC only

T cell development

* occurs in thymus
* similar to B cell development
* receptor rearrangements
* education
* exit the thymus as naive cells
* cannot recognize native protein
* must be presented on MHC

perfoin

forms pores in the membrane of infected cells

granzymes

proteolytic enzymes released into the cytoplasm via the newly formed pores

epidemiology

the study of the occurrence, distribution, and determinants of health and disease in a population

* trace the spread of disease to identify its origin and mode of transmission
* in developed countries -→ infectious diseases cause fewer deaths than noninfectious diseases
* worldwide infectious disease accounts for 25% of all deaths

chain of infection

term used in hospital with regard to the control and prevention of infectious diseases

* portal of exit
* portal of entry
* various ways to break

Susceptible host

* pregnant women
* immune-supressed
* new borns -→ passive immunity from mothers
* elderly -→ become more vulnerable as immune system declines with age
* Exceptions
* 1918 Influenza A
* Herpesvirus
* Shingles

Acute infections

infections that arise suddenly and are characterize by rapid and dramatic disease onset

* new pathogens sometimes emerge for which the host, population, or species has no resistance

chronic infection

long term infections where the pathogen lives in balance with the host, taking what it needs for existence and causing minimal harm to the host

* both host and pathogen survive, unless the host immunity is compromised
* ex. Herpes virus, Hepatitis Virus, Pseudomonas infection of cystic fibrosis patients

Epidemic

occurrence of a disease in a large number of people in a population than would typically be expected in that population

* limited to a population demographic or geographic region
* aka outbreak (refers to smaller geographic area)

pandemic

epidemic disease that is widespread usually distributed worldwide

* cases spread throughout multiple regions and populations

endemic

a disease that is constantly present in a population usually at low incidences

incidence

the number of new cases of the disease in a given period of time

(number of new cases) / (total number of susceptible persons)

prevalence

total number of new and existing cases in a population in a given time

* influenced by recurrence and mortality

(total number of cases in a population) / (total number of persons in population) x 100%

prevalence rate

measure of total disease in a population

ex. a measurement of HIV is taken in a population of 40000 people and 1200 were recently diagnosed with HIV and 3500 are living with HIV then the ---- of HIV is 0.118 (or 11,800 per 100000 persons)

incidence rate

number of new cases of a disease divided by the number of persons at risk for the disease

ex. over the course of 1 year, 5 men are diagnosed with lung cancer, out of a total male study population of 200 (who do not have cancer at the beginning of the study period) then we would say the ---- of lung cancer in this population was 0.025 (or 2500 per 100000 men-years of study)

subclinical infections

diseased individuals who show no or mild symptoms

aka carriers

mortality

the number of deaths in a population due to a disease

morbidity

any departure from a state of physiological well-being encompassing disease, injury and disability

* characterize the number of persons in a population who become ill (incidence) and are ill at a given time (prevalence)

herd immunity

resistance of a group to infection due to immunity of a high proportion of the group

* if a high proportion of individuals are immune to an infection, then the whole population will be protected
* immunized people protect nonimmunized people because the pathogen cannot be passed on and the cycle of infectivity is broken
* if majority of population is protected from a disease through immunization or genetic resistance, the chance of a major epidemic is highly unlikely

reservoir

natural host or habitat of a pathogen

source

organism or object from which the microbe is actually acquired

carrier

a living reservoirs

* an individual who inconspicuously shelters a pathogen and spreads it to others without any notice

\

communicable disease

when an infected host can transmit the infectious agent to another host and establish infection in that host

* direct or indirect

communicable period

time period when an infected individual or animal is contagious and can directly or indirectly transmit to/infect another person, animal, or arthropod

common source epidemic

usually arises from contamination of water or food

* ex. cholera

host to host epidemic

disease show a slow progressive rise and a gradual decline

* ex. influenza and chicken pox

Ro

a measure of the potential for transmission or the reproduction rate of an infectious disease

* when >1, isolation measure are required to prevent transmission

zoonosis

any disease that primarily infects animals but is occasionally transmitted to humans

* control of ---- diseases in human population may not eliminate the disease as a potential public health problem
* certain infectious diseases have complex life cycles involving obligate transfer from non human host to human followed by transfer back to the non human host
* ex. malaria

surveillance

observation, recognition, and reporting of diseases

pathogen eradication

goal is to remove all of a pathogen from any reservoirs (ex. smallpox, polio, and potentially rabies, leprosy, and others)

Vaccines and antiviral targets

* activated B cells make antibodies to neutralize live virus
* activated T cells to lyse virally infected cells

vaccination

exposing a person to material that is antigenic but not pathogenic

* stimulate the immune system to protect against future exposure to a virulent pathogen
* low level of adverse side effects
* protect against the pathogen
* T and B cell memory
* not require numerous boosters
* inexpensive and easy to administer

killed or inactivated pathogen -→ influenza, polio

live attenuated pathogen -→ MMR

Acellular or subunit (toxoid) -→ Tetanus, diptheria, HPV

recombinant -→ Hep B series, Hib

* only licensed and produced if they are safe and effective

smallpox

arrived in new world in 1520s

* native americans had no preexisting immunity
* within a few generations, around 20 million people died -→ 90% of the native american population

good candidate for eradication

* narrow host range
* no carriers
* no animal reservois
* highly effective and inexpensive freeze-dried vaccine was available
* surveillance of disease = easy (centrifugal rash)

natural immunity

acquired through the normal life experiences of a human and is not induced through medical means

active (natural) immunity

consequence of a person developing his own immune response to a microbes infection