Immunology and Drug Discovery Lecture Notes

Comprehensive vocabulary flashcards covering immunology basics, antibody engineering, diagnostic performance metrics, and medical, and global health ethics based on the CH279 Drug Discovery lecture.

Immunological recognition

The immune system's role in recognizing the presence of pathogens and infection.

Self regulation

The requirement that the immune system does not attack the self; failure in this process results in autoimmune diseases.

Immunological memory

The immune system's ability to provide a stronger response the next time the body encounters the same pathogen.

Cytokines

Proteins secreted by macrophages upon pathogen detection that call for the release of specific effector cells to the site of infection.

Chemokines

Proteins released by macrophages that promote cell migration and activation.

Phagocytosis

The process by which macrophages or other cells consume pathogens.

Antigen-presenting cell

A cell, such as a macrophage or dendritic cell, that presents components of a pathogen on its cell surface to facilitate the immune response.

Complement system

Arrays of proteins and protein fragments in the blood that complement phagocytic cells, antibodies, promote inflammation, and attack pathogens.

Effector cells

Cells released by the innate immune system and recruited by macrophages to kill pathogens.

Neutrophils

Effector cells that perform phagocytosis and activate bactericidal mechanisms to kill bacteria.

Eosinophils

Effector cells that kill antibody-coated parasites.

Basophils

Effector cells that promote allergic responses and augment anti-parasitic immunity.

Mast cells

Cells that release granules containing histamine and other active agents.

Natural killer cells

Cells that kill host cells infected by viruses.

B cells

Cells that produce antibodies through recombining segments of their genes; they proliferate and produce specific antibodies when an antigen binds to them.

Proliferate

The rapid multiplication of immune cells, such as B cells, through cell division.

Immunoglobulins

Another name for antibodies, sometimes abbreviated as Ig.

Complementarity determining regions (CDRs)

Six unique regions (3 light and 3 heavy) that comprise an antigen binding site at the tips of an antibody.

Antibody isotypes

Different classes of antibodies (e.g., IgA, IgG) that share the same basic Y shape but have different stems adapted for different environments.

Affinity

The strength of binding between an antigen epitope and an antibody paratope, measured through a dissociation constant $k_D$.

Dissociation constant ($k_D$)

A measure of how easily an antigen-antibody complex is separated; a smaller value implies higher affinity. Typical values range from $10^{-7}$ to $10^{-11} \text{ mol } dm^{-3}$.

Avidity

The total binding strength of a polyvalent antibody to a polyvalent antigen.

Affinity maturation

The process by which the immune system naturally generates antibodies that bind more tightly and specifically over time through controlled rapid mutations and screening.

Polyclonal antibodies

A heterogeneous mix of antibodies where each antibody is recognized by a different epitope; typically produced via animal immunization.

Monoclonal antibodies (mAbs)

Antibodies derived from a single B cell parent clone targeting only one epitope per antigen.

Phage display and biopanning

A method to screen a large number of antibody domains against a target antigen without animal immunization, isolating DNA from specific phages for production.

Immunogenicity

The ability of a molecule to trigger an immune response.

Murine

Relating to mice or rats.

Humanization

The process of increasing human protein content in monoclonal antibodies, often by transplanting DNA encoding murine CDRs into a human genetic sequence.

Fragment antigen binding (Fab) regions

The arms of an antibody containing variable and constant regions of one heavy and one light chain, isolated by cleaving the hinge with papain enzyme.

Single chain fragment variable (scFv)

A protein containing only the variable regions of heavy and light chains joined by an engineered flexible peptide linker.

Nanobodies

Recombinantly expressed antigen binding VHH domains for heavy chain IgG found in camelids.

Peptidomimetics

Peptide mimics designed to remove, alter, or disguise the peptide nature of a compound while maintaining biological activity.

Truncation studies

A strategy to identify the minimal sequence responsible for a peptide's bioactivity.

Alanine scan

A strategy where amino acids are replaced one at a time with D,L-alanine to recognize key pharmacophores responsible for biological activity.

Molecular diagnostics

The analysis of biochemical markers (biomarkers) like DNA, RNA, or proteins to determine the presence of diseases.

Specificity

A measure of the incidence of negative persons found to be free of disease, calculated as $\text{Specificity} = \frac{TN}{TN + FP}$.

Sensitivity

A measure of the incidence of positive results in patients found to have the disease, calculated as $\text{Sensitivity} = \frac{TP}{TP + FN}$.

Positive Predictive Value (PPV)

The percentage of all positive tests that are true positives, calculated as $\text{PPV} = \frac{TP}{TP + FP} \times 100$.

Negative Predictive Value (NPV)

The percentage of all negative results that are true negatives, calculated as $\text{NPV} = \frac{TN}{TN + FN} \times 100$.

Subclinical disease

A disease or infection physically present in the body but not causing any noticeable symptoms.

Limit of Detection

The lowest concentration of analyte that can be consistently detected with sufficient statistical confidence.

rtRT-PCR

Real time Reverse Transcription Polymerase Chain Reaction; a test that amplifies viral genetic material using sequence-specific dyes.

Threshold cycle ($C_t$)

The number of cycles in RT-PCR after which the concentration of dyes is high enough to be observed by the machine's camera.

LAMP

Loop-mediated isothermal amplification; a fast DNA amplification process that occurs at a constant temperature without heating and cooling cycles.

ASSURED acronym

WHO guidelines for POCT design: Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Delivered to end user.

Equity

Providing various levels of support depending on specific needs to reach an equal outcome.

Equality

Providing the same level of resources, opportunity, and assistance to all segments of society.

Orphan drug

A drug for a condition affecting fewer than 5 in 10,000 people, or one that would not justify investment without incentives.

QALY

Quality-Adjusted Life Year; one year of life in perfect health used to quantify life quality free from pain and mental disturbance.

DALY

Disability-Adjusted Life Year; a measure of healthy years lost due to premature death, ill-health, and disability.

Equipoise

A state of honest professional disagreement or uncertainty among experts about preferred treatment.

Beneficence

The ethical pillar of acting in the best interests of the patient.

Non-maleficence

The ethical pillar of 'first, do no harm' or minimizing harm.

The 3Rs

Principles to reduce animal testing: Replacement (mathematical/cell models), Reduction (minimum animals), and Refinement (minimizing pain).