L16 - Engineering of Immunity

Human Life Expectancy

1. Aging problem will be caused by long life expectancy
2. More elderly
3. Less work force
4. Higher tax rate

Public Health Interventions

• Vaccines
  • Biomedical and chemical engineers
  • Methods for the mass production of safe vaccines
• Clean water
  • Civl and environmental engineers
  • Water sanitation systems

Doctors washing hands in between when they saw patients had remarkable effect on reducing transmission of infectious diseases

Vaccines

• Enhancing the function of the immune system
• Safe and effective
• Eradicate diseases

Working Principle

Administration of an antigen to stimulate a protective immune response

Immune Response

• Antibody response (B Cells)
• Cell-mediated response (T cells)

Protective Responses

1. Infection
2. No. of responding immune cells $\uparrow$
3. Apoptosis (cells death)
4. Anamnestic response (memory, rapid respond, more cells in shorter time)

p.15

Antibody

• Y-shaped protein
• Bind to an antigen or specific chemical
• Binds to chemical targets on the surface of pathogens
• Produced by white blood cells (B cells)
• $\sim 10^{10}-10^{12}$ in our body

Strong immune system makes antibodies that will bind to foreign antigens

Monoclonal Antibody (mAb)

• From a single antibody producing B cell
• Only bind with one unique binding domain (epitope)
• Variable region (tip of Y)
  • Responsible for binding to specific target, guiding the bullet to the right place
• Constant region (body of Y)
  • Responsible for the biological effects of a particular type of antibody, enabling the destruction of target

Antibodies use in treating disease was limited by the inability to produce large quantities with a desired specificity. This barrier was eliminated with the development of a method for p producing mAb.

Polyclonal Antibody

• Collection of antibodies from different B cells
• Bind with multiple binding domains (epitopes) on the same antigen
• Each individual antibodies recognizes a unique epitope that is located on that antigen

Polyclonal	Monoclonal
Cheap	Expensive
Mixed population	Single species
Bind to different area	Bind single specific site
Higher overall antibody affinity	High specificity to a single epitope
For general research applications, diagnostic manfatcuring	For therapeutic

Antigen

• Protein, polysaccharide, small molecules that is attached to a larger carrier
• Foreign substance

Pathogens

• bacteria, viruses, transplanted organs, etc

Final: which vaccine need the most additional doses

Bioprocess

Upstream

• cell cultures
• fermentations

Model of Cell Growth

$$\begin{array}{rl}& X=X_0{e}^{\mu t}\\ & \\ & t_D=\frac{\ln 2}{\mu }\end{array}$$

$\mu$	Specific growth rate
$q_p$	Specific production rate
$t_D$	Doubling time

No. of passage refers to how many time the cell culture has been subcultured

Downstream

• Isolation of product and its formulation

1. Solid Liquid Separation
2. Purification

$$\begin{array}{rl}& \text{Yield}=\frac{\text{Amount of product produced}}{\text{Amount of product in feed}}\\ & \text{Purity}=\frac{\text{Amount of product}}{\text{Amount of product plus impurities}}\end{array}$$

Reason for Multiple Steps

• Orthogonal methods for isolating the product
• Product is minority, to be selected from different biomolecules and cell debris
• Similarity between product and junks
• Regulations require high product purity

Overall Product Yield

$$Y=(1-L{)}^n\cdot 100\%$$

$L$	Step loss
n	Number of processing steps

Lower product yield $\to$ higher cost

Criteria for Evaluating Bioprocess

• Purity
• Cost
• Scalability
• Reproducibility and ease of process
• Robustness