virology lec.8 host resistance to viral infections Cont’d

Adaptive immunity

• Specific immune responses tailored to the pathogen (adapted or required immunity) require days to weeks before induced or effective in clearing viruses

• Antibody (humoral) response and cytolytic T lymphocyte (CTL) response (cell-mediated immunity) used to neutralize, control, and eliminate viruses

Lymphocytes

B and T lymphocytes

• Lymph supplies lymphocytes to the bloodstream

• Lymphocytes congregate in the lymph nodes and exit

through the outgoing lymph vessels

• B lymphocytes (B cells) are born and mature in the

bone marrow

• T lymphocytes (T cells) mature in the thymus gland. Made in bone marrow too

Humoral response: antibody production

Mature B cells patrol the lymphatic system

When B cells encounter viruses:

• Any B cell that produces antibodies that can bind to epitopes of the virus is activated

• Activated B cells differentiate into clones of plasma cells and memory cells to express correct antibody

What viral structure do B cells recognize?

B cells recognize whole protein antigens

What viral structure do T cells recognize?

• T cells recognize cells that contain foreign antigens

(virally infected cells, tumor cells, foreign tissue grafts)

Two populations of T cells defined

• Cytotoxic T cells (TC)

• T helper cells (TH)

define B cells

• Originating and maturing in the bone marrow, B cells express surface B cell receptors (BCRs) that directly recognize native antigens. Upon activation—often aided by helper T cells—they differentiate into plasma cells and memory B cells.

Define plasma cells

Specialized, high-output effector B cells that secrete large quantities of antigen-specific antibodies (immunoglobulins: IgM, IgG, IgA, IgE, IgD) into the bloodstream and mucosal tissues.

Describe T helpers (CD4 T) cells

produced in the bone marrow and mature in the thymus gland.

type of white blood cell (lymphocyte) that act as the master coordinators of the adaptive immune system. They do not kill pathogens directly; instead, they signal and activate other immune cells to fight infections

They display a surface protein called CD4, which binds to MHC class II molecules on antigen-presenting cells (such as macrophages, dendritic cells, and B cells).

Describe cytotoxic T cells (CD8 T cells)

originate from stem cells in the bone marrow and mature inside the thymus.

adaptive immune white blood cells that destroy virus-infected cells, damaged cells, and tumor cells

Viral evasion strategies

Viruses use several different mechanisms to evade elimination by the host:

• Rapid mutation, thereby escaping neutralizing antibodies and the Tc cell responses

• Latency and molecular mimicry

• A few viruses synthesize excessive soluble viral antigens that bind all of host’s neutralizing antibodies

• Inactivating cytokine signals

• Inactivating immune cells

• Blocking cellular pathways (apoptosis, complement, IFN pathways)

Emil von Behring and Shibasaburo Kitasato’s 6-step process for developing therapeutic serum

• passive antibody serum therapy

1. Growing bacteria that cause diptheria or tetanus in pure culture

2. Inactivating the bacteria with a disinfectant

3. Injecting the attenuated/killed bacteria into healthy rats, guinea pigs, or rabbits

4. Collecting the serum produced by inoculated/injected animals

5. Injecting the serum into nonimmunized animals that were previously infected with the fully virulent bacteria

6. Injecting the animals with immune serum or control serum from nonimmunized animals

Sometimes the terms immunization and vaccination are

used interchangeably, but they do not mean the same

thing

Vaccines cause immunization

• Some infections result in immunization after individual recovers from infection

• Ex: Unvaccinated person who recovers from a measles virus naturally would be immunized

Passive immunity

Immunity from vaccines (injected with survival antibody’s) and no memory

Active immunity

when a person's own immune system responds to an infection or vaccine and creates long-term protection

Vaccines

• Vaccination mobilizes the host immune defenses to prevent viral infections- immune memory

• Vaccination breaks the chain of transmission

• Traditional vaccines:

• Killed or inactivated vaccines- target nucelic acid, use UV light

• Live, attenuated viruses

Disadvantages of traditional vaccines

• Not all viruses can be cultivated

• May not be adequately inactivated or attenuated

• Reversion of attenuated viruses

• Low yields of vaccine strains

• Shelf-life limitations

• Not all viruses can be prevented with traditional vaccines (Ex: HIV, Hepatitis C)

Innactivated virus vaccine

Inactivated viruses cannot replicate inside the host. The viral antigens are “preserved” by chemicals or ultraviolet radiation and can act as an immunogen.

Attenuated virus vacccine

The pathogenic viruses are grown in human cell cultures and then passaged many times in other nonhuman cell lines such as monkey cells.

The serial passage of the virus in monkey cells causes the virus to accumulate adaptive mutations suited for replication in monkey cells and not human cells.

use a weakened, living version of a germ to build a strong and long-lasting immune defense

• selective pressure, force virus to grow in unusual cell. Modifying receptors

• Ex;measles, mumps, rubella- MMR vaccine

• chickenpox- varicella

• yellow fever, rotavirus

New generation of vaccines

Made using recombinant DNA methods

• Usually safer (uses parts rather than whole viruses)

• Recombinant subunits

• Peptides

• Live vectors

• Reassortant viruses

• Naked DNA

• Edible plants

Recombinant subunit vaccines

Ex; Hepatitis B (HBV)

Peptides

– less effective vaccines and most expensive

Recombinant Live vectors

Genes coding for surface proteins of pathogenic viruses inserted into safe viruses

• ex; Rabies vaccine

Naked DNA vaccines

• Consist of plasmid DNAs that have been manipulated to contain a gene encoding a specific viral antigen

• DNA vaccines have been tested in animal model for viral infections caused by West Nile virus, SARS-Cov, Ebola virus

• two viruses containing segmented genomes infect same cell (Rotavirus and Influenza strain A)

Immunocompromised hosts where use of live vaccines are not recommended

• transplant patients on immunosuppressive drugs to prevent organ rejection

• HIV- infected individuals

• Cancer patients receiving intensive therapy

List some vaccine issues

• Vaccine additives

• Adjuvants

• Side effects

• Vaccine delivery

Describe vaccine additives

Sulfites or thimerosal (mercury) as preservatives

Adjuvants

Aluminum hydroxide added to stimulate immunity

• Illicit better immune response

Side effects

Localized reaction: swelling, redness, pain at the site of the injection

• Rare side effect: allergic responses

Vaccine delivery issues

• New ways to deliver under consideration (nasal sprays, skin patches, time-release pills)

• Needle-and-syringe systems inadequate for global vaccination programs

Economics of vaccines

Finite number of vaccine companies

• Daily pharmaceuticals more profitable

• Majority of individuals in need of vaccines are children located in impoverished countries

• UNICEF major consumer of vaccines

• Global Alliance for Vaccines and Immunization