HTH245 Test 2

Microbiome/ Human Microbiome

microbes that form a community in a particular environment, such as the human digestive system/skin

Symbiosis

association between 2+ species; “living together”

Mutualism

condition in which both species benefit

• e.g. lichen

Commensalism

one species benefits but the other neither benefits nor is harmed

• e.g. normal flora

Parasitism

an association in which the parasite lives at the expense of the other species, the host

• e.g. all microbial pathogens

False; commensalistic

True or false: The human flora is mostly parasitic.

opportunistic pathogen

a normally harmless microorganism that causes disease only when the host's immune system or physical barriers are weakened

Appendix rupturing and E. coli from inside leaking into the peritoneal cavity (peritonitis).

What is an example of how the normal human flora can be opportunistic pathogens?

Parasites

a cause of infectious disease

• live at the expense of the host

• cause damage to the host

Parasitism

results in a constant negotiation between the parasite and the host, as each evolves in response to the other

• (n) dose

• (V) virulence

• (R) resistance

The chance of acquiring an infection depends upon 3 major factors:

• __ - the number of microbes encountered

• __ - virulence factors

• __ host immunity

D = nV/R

Disease = dose x Virulence/ Resistance

What is the formula for the severity of infection?

Infectious dose (ID)

minimal number of microbes necessary for infection

True

True or false: More virulent organisms have smaller IDs than less virulent organisms.

1 million

Infectious dose (ID) of Vibrio cholerae (causes cholera) is __.

10

Infectious dose (ID) of Myobacterium tuberculosis (causes TB) is __.

LD50 (Lethal Dose)

__ is the number of microbes necessary to kill 50% of the animals infected.

Pathogenicity

ability to cause disease

Virulence

a measure of pathogenicity

• encompasses two types of virulence factors - defensive and offensive strategies

Defensive strategies

virulence factor that allows microbes to escape destruction by the host immune system

• e.g. adhesins, capsules, antigenic variation, etc.

Offensive strategies

virulence factor that results in damage to the host

• e.g. exoenzymes, exotoxins, endotoxins, etc.

Adhesins

fixation to host cell surfaces/linings

• defensive strategy

• e.g. Neisseria gonorrhoeae (attachment to urethral lining); Streptococcus mutans (causes tooth decay/sticks to surface of teeth)

Capsules

interfere with uptake of bacteria by host immune defenses (phagocytosis)

• defensive strategy

• e.g. Bacteria that causes anthrax, plague, or streptococcal diseases (scarlet fever, strep throat, pneumococcal infection)

Enzymes

destroy integrity of tissue structure

• offensive strategy

Exotoxins

specific activities that interfere with vital host functions

• offensive strategy

Endotoxins

produces shock-like symptoms like chills, fever, weakness

• offensive strategy

Bacterial uptake

process by which bacteria actively bring in substances from their environment like nutrients, DNA, or other molecules across their cell membranes using specialized transport systems, often involving specific protein receptors to identify/capture the target molecule, allowing it to enter the cell for further utilization

Incubation

period between initial infection/appearance of symptoms; considerable variation among disease

• stage 1 of disease

Prodromal

period in which early symptoms appear; usually short/not always well characterized

• stage 2 of disease

Illness

period during which the disease is most acute/is accompanied by characteristic symptoms

• stage 3 of disease

Decline

period during which the symptoms gradually subside

• stage 4 of disease

Convalescence

period during which symptoms disappear/recovery ensues

• stage 5 of disease

Herpes Simplex Virus 1 (HSV 1)

sometimes referred to as oral herpes/cold sores

Stage 1 — Incubation

HSV 1

• mild symptoms of itching, tingling, burning, and sometimes swelling and redness in the area where the lesions subsequently appear

• infected person is contagious during this stage because the virus is shedding from the skin

Stage 2 — Prodromal

HSV 1

• the infected person has an “outbreak” of visible bumps/blisters, either on or around the mouth

• lesions usually begin as painful, small red bumps or tiny, fluid-filled blisters on a red base

• person is the most contagious during this stage because high concentrations of the virus reside in the fluid within the blisters

Stage 3 — Illness

HSV 1

• about 2-3 days after bumps/blisters appear, they give way to crusts/ulcers

• crusts, as the name implies, are crusty, yellowish granular scabs

• Crusts/ulcers are often itchy and painful. Viral shedding may continue during this time, making the infected person still contagious.

Stage 4 — Decline

HSV 1

• healing occurs as crusts/ulcers are gradually replaced by new tissue

• as with other kinds of skin problems, healing occurs from the outside to the inside, with measurable decreases in diameter and depth

Stage 5 — Convalescence

HSV 1

• In a primary outbreak, the process may take as long as 6 weeks. In recurrent outbreaks, lesions usually resolve within a week.

• Herpes lesions usually heal without scarring.

• Although there is no cure for herpes and the infection can stay in the body for life, the number of outbreaks tends to decrease over a period of years and there are medicines that can prevent/shorten outbreaks.

antiviral medicine

• can shorten an outbreak of herpes

• can also help prevent infected people from spreading the virus

Abreva

There is only one OTC FDA-approved cream called __ which has been clinically proven to speed the healing process of oral herpes.

False

True or false: There is a cure for oral (HSV1) or genital (HSVII) herpes.

Pathogen, reservoir (source) of pathogen, transmission to susceptible host, portal of entry into susceptible host, portal of exit out of susceptible host

What are the factors of the cycle of microbial disease?

Reservoir

a site in nature in which microbes survive (and possibly multiply) and from which they may be transmitted

• all pathogens, to exist, must have 1+ of these

• are prime targets for preventing, minimizing, and eliminating existing/potential epidemics

• humans are the only known __ for pathogens that cause smallpox, gonorrhea, measles, polio, etc.

Active carriers

individuals who have a microbial disease

Healthy carriers

have no symptoms (asymptomatic) and may unwittingly pass the disease onto others

• asymptomatic carriers play a critical role in the transmission of common infectious diseases such as typhoid, HIB, C. difficile, influenzas, cholera, tuberculosis, hepatitis B, herpes, syphilis, and COVID

Chronic carriers

continue to harbor an infectious microbe after recovery

• state can occur indefinitely without recurring illness

Typhoid Mary

Who was the first known asymptomatic carrier in the US?

Zoonoses

diseases of animals that can affect humans

• animals act as reservoirs of pathogen

Transmission

the mechanism by which an infectious agent is spread to a susceptible person

Horizontal transmission

the spread of an infectious agent from one individual to another

• can be direct/indirect transmission

Vertical transmission

spread of an infectious agent from mother to child (via transplacental, vaginal birth, breast milk)

Direct transmission

e.g. of this mode of transmission includes touching, kissing, sexual contact, contact with oral secretions, or contact with body lesions

Indirect transmission

microbes pass from reservoir/source to an intermediate agent and then to a host

• vehicleborne

• airborne

• vectorborne - mechanical/biological vectors

Portal of entry

• can be important in the outcome of infection

• a portal of exit is required for transmission to a new host

Epidemiology

an investigative branch of medicine that deals with the sources of cause and possible control of infectious disease/other public health problems

Epidemiologists

challenged to determine why an outbreak of disease occurred at a particular time and/or particular phase

• investigate the distribution/determinants of disease in populations

• provide the foundations for policies/work to apply this knowledge to the control of health problems

Sporadic

disease only occurs occasionally and in an unpredictable fashions (tetanus, etc.)

Endemic

when disease is regularly found at a steady level in a particular location (common cold, etc.)

Epidemic

when disease causes a sudden increase in morbidity (illness rate) and mortality (death rate) above the norm

• e.g. include the West African Ebola __ of 2014 - 2016 and the Zika virus __ from 2015 - present

Pandemic

epidemics that spread across continents (e.g. 1918 influenza, HIV/AIDS, COVID)

Cholera

What is the world’s longest pandemic?

Common-source epidemics

__ epidemics involve contact with a single contamination source.

• e.g. contaminated water

Propagated epidemics

__ epidemics result from person-to-person contact.

• e.g. mumps/chicken pox

Herd immunity

refers to the proportion of immunized individuals in a population

• The smaller the number of susceptible individuals, the less opportunity for contact between them and infected individuals.

• Public health officials strive to maintain high levels of this.

Reproduction rate (R0 or R-nought)

measure of the potential for transmission

• This must be greater than 1 for spread; if less, it will die out.

12-18

What is the reproduction rate (R0/R-nought) of measles?

<1

What is the reproduction rate (R0/R-nought) of rabies?

Epidemiology of fear

fear of epidemics can reach epidemic proportions

• threat of infectious disease is out of proportion

• awareness, surveillance, common sense precautions, and calmness are predominant

Antigens

harmful microbes

Innate (nonspecific) immune system

inherent immune system, present before infection

• always ready to go, ready to fight immediately

• first line of defense

• e.g. skin, stomach acid, mucus, white blood cells

Adaptive (specific) immune system

immune system that develops in response to infection

• activates when needed and learns from past infections

• special ops

• e.g. B cells (antibodies), T cells (attacking infected cells

• Skin

• Stomach acidity

• Mucous membranes

• Cilia

• Lysozyme

• __ is the first line of defense against microbial infection.

• __ is inhibitory to most microbes.

• __ line the internal body cavities/act as a mechanical barrier.

• __ in airways, propel microbes into the pharynx where they are swallowed/expelled (mucosal-ciliary escalator system).

• __ is an enzyme that destroys cell walls of many bacteria (found in saliva, tears, and sweat).

Innate (non-specific) physiological defenses

__ physiological defenses operate to:

• block microbes from gaining access to the body

• eliminate microbes that have penetrated into the body

• not formed in response to infection (present since birth)

• act against types of microbes, not specific microbes

Phagocytosis

a nonspecific defense mechanism by which monocytes/neutrophils engulf and destroy foreign substances

• critical function of the innate immune response

• “Big Eaters” engulf, swallow, and destroy.

• Professional __: monocytes, neutrophils, and macrophages (located strategically throughout the body).

redness (rubor), heat (calor), swelling/edema (tumor), and pain (dolor)

What are the 4 cardinal signs of inflammation?

Vasodilation

cause of the redness, heat, and edema in inflammation

Chemoattraction

when phagocytes are attracted in large numbers to the inflamed tissue; they migrate out of blood capillaries/phagocytose any microbes encountered, preventing/minimizing infection

When something foreign enters your body (viruses, bacteria, toxic chemicals, etc.) or you’re injured, your immune system activates. Your immune system sends out cells (phagocytes) to trap bacteria and other offending agents/start healing injured tissue. This is the inflammatory response that can result in pain, swelling, bruising, or redness.

What happens during inflammation?

an immunoglobulin, Ig

What is another name for antibodies?

IgM

a very large protein that clears foreign substances from the bloodstream

• these antibodies are part of the body’s general first line of defense against invaders

IgA

antibody found in the secretions of the saliva/mucous

• provides a mucosal first line of defense

• first defenders that a common cold would encounter

IgE

antibody involved in immediate allergic responses and sometimes parasitic infections

• combines with a special cell (mast cell) to release the chemical histamine, which leads to swelling

• e.g. swelling associated with a mosquito bite

IgG

these antibodies are formed in response to specific invaders and they usually last a lifetime — this is why we vaccinate

• take 7-14 days to be produced so unless they were previously present, we can’t rely on them as a first line of defense

IgG

What is the most important immunoglobulin?

Because IgG antibodies take 7-14 days to be produced, so unless they were previously present, they cannot be relied on as a first line of defense.

Why can vaccination not be used as immediate treatment strategies for infection?

placenta

IgG is the only antibody that can cross the __.

False, adaptive immunity

True or false: B and T cells are part of innate immunity.

True

True or false: Phagocytosis is a part of innate immunity.

B cells

• antibody factories

• protective proteins that attach to antigens and neutralize them

• exist since birth

T cells

attackers of infected cells

TH (T-Helper) cells

required to help B cells produce antibodies and do so by releasing stimulatory proteins called cytokines

antigen

large foreign substances associated with microbes, tumor cells, pollen, dust, food, etc. that triggers an immune response

lymphocytes (B or T cells)

The specific (adaptive) immune system produces __ (__) that respond to a foreign antigen.

Humoral (antibody-mediated) immunity

This immunity:

• relies on antibodies, B cells (lymphocytes)

• triggers production of antibodies specific for an antigen

• all antibodies are made by one B cell and bind to the same antigen

Cell-mediated immunity (CMI)

This immunity:

• driven by T cells, not antibodies

• production of T lymphocytes directed against an antigen

• the lymphocytes are said to be “sensitized”

• B cells (lymphocytes); T Helper cells

• foreign antigen

• activated

• plasma

• memory B cells

Antibody-mediated (Humoral) Immunity

• Antibodies are produced by __ (with the aid of __ cells).

• Each antibody binds specifically to a __ on bacterial cells, viral particles, toxins, tumor cells, etc.

• The binding of antibodies to antigens has many outcomes, each leading to the destruction/inactivation of the antigen.

• B lymphocytes are “__” by simultaneous contact with antigen/TH cells to become antibody-producing __ cells.

• Estimates are that a single plasma cell can produce thousands of identical antibody molecules per second.

• In response to antigens, some B-cells develop into long-lived __ cells; these cells frequently provide lifelong immunity to a microbe or vaccine-antigen encountered earlier in life.

Cell-mediated immunity (CMI)

What type of immunity?

• Cytotoxic T cells can kill tumor/infected cells displaying foreign antigens via cell-mediated cytotoxicity.

T Helper cells (TH)

What T cell subset?

• activates B cells to produce antibodies

• activates cytotoxic T cells

• activates inflammatory cells

• CD4 (marker)

Cytotoxic T cells (TC or CTL)

What T cell subset?

• killer cell that targets cells with “foreign” intracellular antigens, including viruses, bacteria, and cancer cells

• CD8 (marker)

T Regulatory cells (TR)

What T cell subset?

• regulatory T cell that turns down immune responses

• CD4 (marker)