Vaccination and Immune System Overview

Vaccination History and Development

• Smallpox was a deadly disease that killed one in three infected individuals.
• Vaccination efforts and global health initiatives led to its eradication, with the last natural case reported in 1977.
• Polio was nearly eradicated globally, with the last U.S. case reported in 1986.
• Measles, mumps, and rubella, saw a significant reduction in cases between the years 1994 and 2014; resulting in the saving of 732,000 lives.

Cell-Mediated Immunity

• Any cell can display an antigen on the MHC receptor protein on its surface.
• A cytotoxic T-cell with a TCR that recognizes the antigen (stabilized by CD8) becomes activated,
• which in turn causes the cells to become memory T cells.
• Cytotoxic T cells kill infected cells.

T-cell Receptor Function

• T-cell receptors develop in the thymus.
• Positive selection: T-cells that interact with MHC-peptide complexes in the thymus survive.
• Negative selection: T-cells that interact too strongly with MHC-self peptides die.
• In the thymus, self-reactive T cells are removed to prevent autoimmunity.

Lymphoid Tissues and Circulation

• Lymphoid precursors differentiate into B or T cells in the bone marrow or thymus.
• Immature lymphocytes travel to peripheral lymphoid organs, where they can interact with specific antigens.
• This enables maturation, ensuring the lymphocytes are equipped to respond to pathogens.

Dendritic Cells and Activation

• Immature dendritic cells reside in peripheral tissues.
• Dendritic cells migrate through lymphatic vessels to regional lymph nodes.
• Mature dendritic cells activate naive T cells in lymphoid organs like lymph nodes.

Transplant Suppressing Cytotoxic T cells

• Cytotoxic T cells can attack the transplanted organ because they recognize it as non-self.
• Medication that suppresses cytotoxic T cells is necessary to reduce potential organ rejection.

Humoral Response

• The humoral response is mediated by B cells and antibodies.
• Antibodies neutralize toxins and pathogens.
• The system generates pathogen-reactive B and T cells through a random process.

Cell-Mediated Response

• The cell-mediated response relies on T cells.
• Cytotoxic T cells kill infected cells.
• Helper T cells activate B cells.

Vaccine Design Considerations

• A safe antigen is necessary for a vaccine.
• How pathogens evolve plays a key role in vaccine efficacy.
• Duration of the memory response is significant when developing a vaccine.
• Understanding pathogen biology is crucial to design an effective vaccine.

mRNA Vaccines

• mRNA vaccines rely on the production of viral proteins within the body's cells.
• mRNA technology requires significant academic breakthroughs across several fields, including the understanding of RNA structure, function, decay, etc.

Vaccine Types

• Whole-cell or whole-virus vaccines use inactivated or live-attenuated microbial agents.
• Acellular or subunit vaccines use purified macromolecules or portions of the virus.
• Toxoid vaccines use inactivated toxins.
• Conjugated vaccines link a weak antigen to a strong antigen.
• Recombinant vector vaccines use a benign microbe to provide a significant protein of the original microbe.

Vaccine Development Stages

• Vaccine development requires multiple stages, including research and pre-clinical trials in animals, and clinical trials in humans.
• Clinical trials progress through phases to evaluate safety and efficacy in different groups of participants.

Placebo-Controlled Trials

• Placebos are used in clinical trials to establish a baseline for vaccine efficacy.
• Researchers compare the rate of infection between vaccinated and placebo groups to determine the vaccine's effect.

Herd Immunity

• Partial immunization of a population can protect the whole population, even those who cannot be vaccinated.
• Contagious disease spreads through the population, but is reduced significantly if enough people are vaccinated and thus immune/protect others.

Summary of Vaccine Studies

• Vaccines exploit the adaptive immune system's memory function.
• Generally, antigens from a pathogen are used to prime the immune system.
• Antigens can come from the whole pathogen cell, or from a pathogen fragment, such as the spike protein.