BIOM-3070 Midterm 2

Urticaria (hives)

Inflammation of the skin in an allergic reaction; a histamine response.

Systemic allergic reactions

Many mast cells degranulate at once, releasing large amounts of histamine and inflammatory mediators. Acute anaphylaxis or anaphylactic shock can result, with clinical signs of suffocation, and must be treated promptly with epinephrine. Common causes include bee stings and certain foods (seafood, nuts).

Epinephrine

Neutralizes many mechanisms of anaphylaxis: relaxes smooth muscle and reduces vascular permeability. Used in emergency treatment of severe asthma and anaphylactic shock.

Treatment of type I hypersensitivity

Administer drugs that counteract inflammatory mediators. Antihistamines neutralize histamine, and asthma is treated with a glucocorticoid and a bronchodilator.

Prevention of type I hypersensitivity

Identification and avoidance of allergens. Food allergens identified using an elimination diet. Immunotherapy (allergy shots) is a series of injections of dilute allergen, repeated every two to three years, and is not effective in treating asthma.

Hygiene hypothesis (1989, Dr. Strachan)

A lack of exposure to microbes, viruses, and parasites predisposed children to develop allergies later in life. Recommendations: natural childbirth, breast feeding, more outdoor activities, less time indoors, better diet, and controlled antibiotic use.

Microflora hypothesis (2003, Graham Rook)

Also called the old-friends hypothesis or microbiome depletion hypothesis. Alteration in human microbiomes since hunter-gatherer societies leaves the immune system searching out risks different from those historically present.

Acquired immunodeficiency causes

Severe stress (excess corticosteroids suppress cell-mediated immunity), malnutrition and environmental factors (inhibit production of B cells and T cells), and AIDS.

AIDS definition

Not a disease but a syndrome, defined as certain opportunistic or rare infections along with HIV infection, or a severe decrease in helper T cells plus a positive HIV test.

HIV

An enveloped, +ssRNA retrovirus that uses reverse transcriptase to make a DNA copy of its genome. Two major types: HIV-1 prevalent in the United States and Europe, HIV-2 prevalent in West Africa.

gp120

The primary attachment molecule of HIV on the viral envelope, with antigenic variability during prolonged infection.

gp41

Promotes fusion of the viral envelope to the target cell.

Origin of HIV

Likely arose from mutation of simian immunodeficiency virus (SIV) and may have emerged in the human population around 1930.

HIV latency

Reverse transcriptase transcribes dsDNA from ssRNA, antigenic variants arise from transcription errors, dsDNA provirus enters the nucleus, viral integrase inserts it into a human chromosome, and it is passed to progeny cells. Provirus can remain dormant for years, and macrophages and monocytes are major reservoirs.

HIV release and maturation

HIV exits at lipid rafts in the cytoplasmic membrane, lipid raft components become the viral envelope, capsomeres form an immature capsid outside the cell, and viral protease releases proteins producing a mature virus. Protease inhibitors are used to treat HIV.

HIV pathogenesis

Only humans replicate HIV. HIV destroys the immune system, and destruction of helper T cells relates to the course of AIDS.

HIV transmission

HIV in blood, semen, saliva, vaginal secretions, and breast milk can cause infection. Blood and semen are more infective than other secretions, and infected fluid must be injected or encounter a tear or lesion in skin or mucous membranes.

AIDS first recognized

First recognized in young male homosexuals in the United States; now found worldwide.

AIDS diagnosis

Based on symptoms, low levels of CD4 lymphocytes, and presence of antibodies against HIV. A positive test does not indicate presence of AIDS.

Long-term nonprogressors

Do not develop AIDS. Possible reasons: defective virions, poor binding of HIV to cells, or well-developed immune systems.

Antiretroviral therapy (ART)

A cocktail of antiviral drugs currently used to reduce viral replication. It does not cure the infection but inhibits replication, and patients can live relatively normal lives on treatment.

HIV vaccine challenges

A vaccine must generate antibodies and cytotoxic T cells, induction of IgG can be detrimental, numerous HIV variants exist within an individual, HIV can spread directly from cell to cell, HIV infects cells important to combating infections, and vaccine testing involves ethical and medical concerns.

Skin: two main layers

Epidermis and dermis

Skin functions

Prevents excessive water loss, regulates temperature, sensory phenomena, assists vitamin D formation, barrier against microbial invaders

Wounds

Trauma to any tissue: cuts, scrapes, surgery, burns, bites. They allow microbes to infect deeper tissues, and can result in severe or fatal disease

Skin microbiota: normal role

Normally harmless microbes on skin that compete with potential pathogens for nutrients and space, and cannot be completely removed by cleansing

Skin microbiota: where do they grow?

Typically in moist areas of the skin; their waste products cause body odor

Skin microbiota: yeast example

Malassezia

Skin microbiota: bacterial examples

Staphylococcus, Micrococcus, and diphtheroids such as Propionibacterium acnes

Propionibacterium acnes: effect

Produces propionic acid, which lowers the pH of the hair follicle

When do skin microbiota cause disease?

If they penetrate the epidermis, or if the immune system is suppressed

Folliculitis: what is it?

Infection of the hair follicle, often called a pimple

Folliculitis at the eyelid base

Called a sty

Furuncle

Spread of folliculitis infection into surrounding tissues

Carbuncle

Multiple furuncles growing together

Folliculitis: most common pathogen group

Staphylococcus: facultatively anaerobic, Gram-positive cocci typically arranged in clusters, tolerant of salt and desiccation

Two Staphylococcus species commonly found on skin

Staphylococcus epidermidis and Staphylococcus aureus

Folliculitis: transmission

Direct contact or by fomites; infection can spread into blood and move to organs beyond the skin

S. epidermidis vs S. aureus: disease

S. epidermidis lacks virulence factors and rarely causes disease; S. aureus transiently colonizes skin or mucous membranes of most people

Folliculitis: diagnosis

Isolation of Gram-positive bacteria in grapelike clusters from pus

Folliculitis: treatment

Mupirocin or dicloxacillin; vancomycin for resistant strains

Folliculitis: prevention

Hand antisepsis and proper hospital procedures to minimize MRSA infections

Staphylococcal Scalded Skin Syndrome (SSSS): signs

Skin becomes red and wrinkled and forms blisters; outer epidermis peels off in sheets

SSSS: pathogen and virulence factor

Some Staphylococcus aureus strains; one or two exfoliative toxins that target desmoglein 1, the desmosome cell attachment protein

SSSS: why no scarring?

Dermis is unaffected

SSSS: epidemiology

Occurs primarily in infants; transmitted by person-to-person spread

SSSS: diagnosis and treatment

Diagnosed by characteristic sloughing of skin; treated with antimicrobial drugs; death is rare, most often due to secondary infections

SSSS: prevention difficulty

Widespread presence of S. aureus makes prevention difficult

Impetigo: signs

Red patches form on the face and limbs

Erysipelas: signs

Infection spreads to the lymph nodes

Impetigo and erysipelas: pathogens

Most cases caused by S. aureus; some cases caused by Streptococcus pyogenes

S. pyogenes virulence factors in impetigo

M protein (attachment to host cells), hyaluronic acid (protects from phagocytosis), pyrogenic toxins (can induce inflammation)

Impetigo: complication if infection spreads to kidneys

Acute glomerulonephritis

Impetigo: who gets it most?

Mostly children; erysipelas can also occur in the elderly

Impetigo: diagnosis

Presence of vesicles is diagnostic

Impetigo: treatment

Oral and topical antimicrobials and careful cleaning of infected areas

Erysipelas: treatment

Penicillin

Impetigo and erysipelas: transmission and prevention

Person-to-person contact or via fomites; prevent with proper hygiene and cleanliness

Necrotizing fasciitis: signs

Redness, intense pain, and swelling at infection site; fever, nausea, malaise, and possible mental confusion

Necrotizing fasciitis: pathogen

Most cases caused by Streptococcus pyogenes, which enters through breaks in the skin

Necrotizing fasciitis: virulence factors

Various enzymes facilitate tissue invasion; exotoxin A and streptolysin S damage cells and tissues

Necrotizing fasciitis: mortality and treatment

Death in about 20% of patients; treat with clindamycin and penicillin; early diagnosis is difficult because symptoms are nonspecific

Cat scratch disease: signs

Fever, malaise, localized swelling at infection site

Cat scratch disease: pathogen

Bartonella henselae, a Gram-negative aerobic bacillus; endotoxin (LPS) is the primary virulence factor

Bartonella henselae: where does it grow?

Inside red blood cells and in cells lining blood vessel walls

Cat scratch disease: transmission

Cat bites or scratches, and by blood-sucking arthropods

Cat scratch disease: diagnosis and treatment

Diagnosed with serological testing; treated with antimicrobials

Spotted fever rickettsiosis: most severe form

Rocky Mountain spotted fever

Spotted fever: signs

Non-itchy spotted rash on trunk and appendages (hemorrhages called petechiae); organ failure can occur in severe cases

Spotted fever: pathogen

Rickettsia rickettsii, a Gram-negative intracellular parasite that needs a host cell to divide and grow

Rickettsia rickettsii: nutrient and toxins

Does not use glucose as a nutrient, and does not secrete any toxins

Spotted fever: transmission and area

Bite of an infected tick; prevalent in the Appalachian Mountains

Spotted fever: diagnosis, treatment, prevention

Serological testing; various antimicrobials; tick repellents and avoidance of tick-infested areas

Gas gangrene: signs

Death of muscle and connective tissue, blackening of infected muscle and skin, presence of gas bubbles

Gas gangrene: pathogens

Several Clostridium species, anaerobic endospore-forming bacilli; C. perfringens is most often isolated; vegetative cells secrete 11 toxins

Gas gangrene: how do endospores enter?

A traumatic event must introduce endospores into dead tissue; it was a major cause of death in World Wars

Gas gangrene: mortality and treatment

Mortality exceeds 40%; rapid treatment is crucial: surgical removal of dead tissue, antitoxin, and antimicrobials; prevent with proper cleaning of wounds

Poxviruses that cause human disease

Smallpox, cowpox, and monkeypox (rare in humans)

Smallpox: historical importance

Caused over 100 million human deaths, and was the first human disease to be eradicated

Poxviruses: type and spread

DNA viruses that produce proteins interfering with the immune response; smallpox spreads by inhalation, other poxviruses by direct contact

Smallpox: pathogen

Orthopoxvirus, variola virus; infection spreads from the respiratory tract throughout the body

Smallpox: stocks and vaccination today

Variola virus stocks are maintained in US and Russian labs for research; vaccination program discontinued in the 1970s, with some military and health care personnel still vaccinated

Chickenpox: signs

Highly contagious; lesions on the back and trunk that spread across the body

Shingles: cause and signs

Reactivation of varicella-zoster virus; lesions localized to skin along an infected nerve; pain may last after lesions heal

Chickenpox and shingles: pathogen

Varicella-zoster virus (VZV)

VZV: latency

Virus becomes latent within sensory nerves / nerve ganglia after chickenpox

Chickenpox: epidemiology

Occurs mostly in children; VZV infected 90% of children prior to immunization; disease is more severe in adults

Shingles: risk

15 to 20% of people who have had chickenpox develop shingles; risk increases with age

Chickenpox vaccine

Varivax, an attenuated vaccine, available since 2000

Shingles vaccines

Zostavax, a live attenuated vaccine; Shingrix, a recombinant vaccine, 2 doses separated by 3 to 6 months; given to people over 50

Chickenpox in Canada: age statistic

About 99% of people over 40 years old in Canada have had chickenpox

Rubella: signs in children vs adults

Children develop a mild rash; adults may develop arthritis and encephalitis

Rubella: congenital infection

Can result in birth defects or death of the fetus

Rubella: pathogen

Rubella virus, a (+) single-strand RNA virus; infection spreads from the respiratory tract throughout the body via blood

Rubella: transmission and host

Spread by respiratory secretions; infects only humans

Rubella: diagnosis and vaccine aim

Diagnosis by observation of rash and serological testing; vaccine is aimed at preventing rubella infections in pregnant women

Measles (rubeola): characteristic sign

Koplik's spots, oral lesions

Measles: pathogen

Measles virus, a (-) single-strand RNA virus; adhesion and fusion proteins help it avoid immune recognition

Measles: pathogenesis

Immune response to infected cells causes most symptoms; disease can be fatal in children

Measles: transmission and host

Highly contagious, spread via respiratory droplets; humans are the only host