BIOM-3070 Week 6 - Transmission, Immunization and Immune Disorders

Transmission

From a reservoir or a portal of exit to another host's portal of entry.

Three groups of transmission

Contact transmission, vehicle transmission, and vector transmission.

Portals of exit

Pathogens leave hosts through portals of exit, often the same as portals of entry, in materials the body secretes or excretes.

Direct contact transmission

Usually involves body contact between hosts. Transmission within a single individual can also occur.

Indirect contact transmission

Pathogens are spread from host to host by fomites.

Droplet transmission

Spread of pathogens in droplets of mucus by exhaling, coughing, and sneezing.

Airborne transmission

When pathogens travel more than 1 m via an aerosol. Aerosols arise from sneezing, coughing, air-conditioning systems, and sweeping.

Waterborne transmission

Important in the spread of many gastrointestinal diseases. Fecal-oral infection.

Foodborne transmission

Spread of pathogens in and on foods, including inadequately processed, cooked, or refrigerated foods, which may be contaminated with feces.

Bodily fluid transmission

Bodily fluids such as blood, urine, and saliva can carry pathogens. Prevent contact with conjunctiva or breaks in the skin or mucous membranes.

Biological vectors

Transmit pathogens and serve as host for some stage of the pathogen's life cycle. Biting arthropods transmit many diseases to humans.

Mechanical vectors

Passively transmit pathogens present on their body to new hosts.

Disease classification

Diseases can be classified by taxonomic categories, the body system affected, longevity and severity, how they spread to their host, and effects on populations.

Epidemiology

The study of where and when diseases occur and how they are transmitted.

Incidence

Number of new cases of a disease in a given area during a given period of time.

Prevalence

Number of total cases of a disease in a given area during a given period of time.

Epidemiology reporting

Epidemiologists report data as cases per 100,000 population, number of deaths per age category, and percentage of cases per month.

Endemic

A disease normally present in a region.

Sporadic

A disease which occurs rarely or sporadically and infrequently.

Epidemic

A disease present in higher frequency than is usual.

Pandemic

An epidemic disease occurring in more than one continent at a given time.

Nosocomial infections

Healthcare-associated infections. Types are exogenous, endogenous, iatrogenic, and superinfections.

Exogenous healthcare-associated infection

Pathogen acquired from the health care environment.

Endogenous healthcare-associated infection

Pathogen arises from normal microbiota within the patient.

Iatrogenic infection

Results from modern medical procedures.

Superinfection

Use of antimicrobial drugs inhibits some resident microbiota, allowing other microbes to thrive.

Public health education

Diseases transmitted sexually and through the air are difficult to control (for example Covid). Public health agencies campaign to educate the public on healthful choices to limit disease.

Active immunization

Administration of antigens so the patient actively mounts an adaptive immune response.

Passive immunotherapy

Immunity acquired through the transfer of antibodies formed by an immune individual or animal.

Variolation

In 12th century China, children who recovered from smallpox did not contract it again, so children were infected with material from a smallpox scab to induce immunity. It spread to England and America but was stopped due to risk of death (1-2 percent).

Edward Jenner (1796)

Discovered vaccination by inoculating children with pus from cows infected with cowpox (related to smallpox), which protected them from smallpox.

Louis Pasteur (1879)

Developed a vaccine against Pasteurella multocida (avian cholera).

Antibody transfer (1890)

Developed when it was discovered vaccines protected through the action of antibodies (passive immunotherapy).

Vaccine impact

Vaccines work: massive drop in pathogen infections in the past 75 years (smallpox, measles, polio, whooping cough). Hundreds of millions of lives saved in the past 60 years, called the greatest public health innovation in human history.

Vaccine gaps

3 million children die globally every year from diseases with available vaccines, many developing nations do not receive vaccines, and effective vaccines are not developed for some pathogens (HIV, malaria).

Anti-vaccination beliefs

Have led to recent measles epidemics.

Poliovirus

An RNA virus which infects neural cells and causes paralysis of organs (for example lungs). Patients were treated in iron lungs in the 1940s-50s, which allowed them to breathe until they could breathe on their own.

Salk vaccine

Dr. Jonas Salk (University of Pittsburgh) used a killed version of poliovirus grown in human cells in culture. First available 1955-1962. Last case in the Americas in 2022, only 418 polio cases worldwide in 2024, and polio is expected to be the next virus eradicated after smallpox (1980).

Attenuated (modified live) vaccines

Use pathogens with reduced virulence (attenuation). Can result in mild infections, stimulate a strong immune response, and provide contact immunity, but modified microbes may retain enough residual virulence to cause disease in susceptible individuals.

Inactivated (killed) vaccines

Safer than live vaccines. Whole agent vaccines use inactivated but whole microbes, while subunit vaccines use antigenic fragments of microbes.

Subunit vaccines

Antigenic fragments of microbes. Often require multiple doses to achieve full immunity and often contain adjuvants.

Adjuvants

Chemicals added to increase effective antigenicity.

Toxoid vaccines

Chemically or thermally modified toxins used to stimulate active immunity. Useful for some bacterial diseases, stimulate antibody-mediated immunity, and require multiple doses because toxoids possess few antigenic determinants.

Combination vaccines

Simultaneous administration of antigens from several pathogens.

Recombinant DNA vaccines

Recombinant DNA techniques used to improve vaccines, in research attempts to make vaccines more effective, cheaper, and safer.

Vaccine types summary

Four main types: attenuated (modified live), inactivated (killed), toxoid, and combination vaccines, plus recombinant DNA approaches.

Immune disorders

Conditions resulting from defective immune mechanisms. Three general types: hypersensitivities, primary immunodeficiency diseases, and acquired immunodeficiency diseases.

Hypersensitivity

Any immune response against a foreign antigen exaggerated beyond the norm.

Four types of hypersensitivity

Type I (immediate, the only one discussed in the course), Type II (cytotoxic), Type III (immune complex-mediated), Type IV (delayed or cell-mediated).

Primary immunodeficiency diseases

Result from a genetic or developmental defect and develop in infants and young children.

Acquired immunodeficiency diseases

Develop as a direct consequence of some other recognized cause and develop in later life.

Type I hypersensitivity

Localized or systemic reaction from release of inflammatory molecules in response to an antigen. Develops within seconds or minutes following exposure and is commonly called allergies. The antigens are called allergens.

Type I two-step process

Sensitization upon initial exposure to an allergen, then degranulation of sensitized cells.

Mast cells

Distributed throughout the body in connective tissue, with granules containing inflammatory chemicals. Degranulation releases histamine, kinins, proteases, leukotrienes, and prostaglandins.

Localized allergic reactions

Usually mild and localized, with the site depending on portal of entry. Inhaled allergens may cause hay fever, small inhaled allergens may reach lungs and cause asthma, and some allergens cause hives (urticaria) of the skin.

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.