BIOL1110 From Molecules to Cells

Module 4: Biotechnology in environment, food and medicine

Lecture 8: Immune response
 Outline

• Innate vs. adaptive immune response

• Antibodies
• Vaccines

(Tortora Microbiology Ch15-19)

 How microorganisms enter a host?
Portals of Entry:
• Mucous membranes at respiratory tract, gastrointestinal track, genitourinary
tract and conjunctiva
• Skin (hair follicles, sweat gland ducts or intact skin)
• Parenteral route – directly into the tissues beneath the skin or into mucous
membranes when these barriers are penetrated or injured (injections, bites,
cuts, wounds, surgery)

The preferred portal of entry is a

prerequisite to their being able to cause
disease. If they gain access to the body
by another portal, disease might not
occur.

E.g., Salmonella typhi cause all typhoid

fever’s sign and symptoms when
swallowed. If the bacteria are rubbed
on skin, no reaction or only very slight
inflammation.
https://www.quora.com/What-are-the-portals-of-entr
y-for-pathogens
Some other factors that determine if the pathogen causes diseases?

• Number of microbes
• Adherence – attachment to host through adhesins/ligands (e.g., glycoproteins
or lipoproteins) that bind specifically to complementary surface receptors
• Biofilms – microbe community that comes together in masses, cling to surfaces
(e.g., dental plaque)
 How Bacterial Pathogens Damage Host Cells?
• Using host’s nutrients
• Direct damage (rupture host cells)
• Production of toxins

E.g., Enzymes;
Botulinum toxin
 Why we need an immune system?
• To defend our body against invasion by foreign substances or antigens (e.g., bacteria,
viruses, fungi, etc.)
• Our immune system is broadly divided into two parts:
1. Innate or non-specific immune system (Present at birth)
2. Specific (adaptive or acquired) immune system
Innate vs adaptive immunity
 Innate immune system
• The function of innate immune system is to provide our body the first line of
defense against various pathogens.

• Characteristics:
– Present intrinsically (i.e., in-born)
– Quick response (hours)
– Non-specific
– No memory
A “hungry” macrophage.

• It consists of 4 types of defense barriers:

1. Physical (e.g., skin and mucous membrane)
2. Chemical (e.g., oil and sweat have an acid pH 3-3.5 to discourage microbes;
Saliva and tears contain lysozyme to digest bacterial cell walls)
3. Physiological (e.g., temperature, pH, normal microbiota, etc.)
4. Phagocytic (e.g., macrophages)
 Phagocytic cells in innate immunity
• Phagocytosis = A process in which particulate • Phagocytic cells: Macrophages (in
foreign substances (e.g., bacteria) are ingested tissues)
by phagocytes and then destroyed by
intracellular enzymes (e.g., lysozymes and
proteases).
Neutrophils

Monocytes

Macrophages
 Adaptive immune system
• The adaptive immune system works in an antigen-specific manner to provide for the elimination of
the antigen and prolonged protection for its future challenge.

• Characteristics:
– Specific for a particular antigen  specialized response for best protection
– Diverse in specificity  protection against maximum no. of pathogens
– With memory  enhanced response with repeated exposure
– Capable of distinguishing between self and non-self  ↓ autoimmunity
– Slow response (days)

• Two major components:

1. Lymphocytes: T cells, B cells, and antibody-producing plasma cells
2. Antigen-presenting cells: Macrophages, B cells, and dendritic cells (DC)

DC
macrophage
 Antibody function in humoral immunity
• Humoral – body fluid-related
• The major function of an antibody: it binds specifically to an antigen and enhances the inactivation and
elimination of the antigen.
• The variable region of the antibody is responsible for antigen binding, whereas the constant region of heavy
chain (Fc region) can be recognized by other immune cells (e.g., neutrophils) for antigen elimination.
• There are five classes of immunoglobins (Ig): IgM, IgD, IgG, IgE, and IgA.
• Produced by B cells (plasma cells), usually require the assistance of a T helper cell for antibody production.
 Major histocompatibility complex (MHC) molecules

• MHC proteins are important for our immune system to

discriminate self from non-self.

• T cells recognize an antigen with their specific T cell receptor,

but they only respond to the antigen presented in the context
of MHC.

• MHC class I:
– Located on the surface of all nucleated cells.
– Presents peptides derived from intracellular antigens.
– Recognized by CD8+ cytotoxic T cells.

• MHC class II:

– Located on antigen presenting cells (e.g., B cells,
macrophages, and dendritic cells).
– Presents peptides derived from extracellular antigens
(e.g., bacteria in tissues).
– Recognized by CD4+ helper T cells.
 How activated cytotoxic T cells kill virus-infected and cancer cells?
• Activated cytotoxic T cells bind to and kill infected cells by releasing their granules (perforins and
granzymes) onto the surface of an infected cell.

• Perforins can create pores on the cell membrane of the infected cell, which allows the passage of
granzymes (proteolytic enzymes) into the cell and induce cell killing.
 Humoral immunity: Antigens and the role of B cells in antibody production

- Million of B cells circulate in the blood and lymph or reside in lymphoid tissues.
- B cells respond to two different types of antigens: T-dependent antigen and T-independent antigen.
1) T-dependent antigens:
- Mainly peptide antigens.
- Digested and presented on class II MHC.
- Recognized by helper T cells, which secrete cytokines (e.g., IL-2) to stimulate B cells to proliferate
and differentiate into antibody-producing plasma cells and long-lived memory cells .
 Humoral immunity: Antigens and the role of B cells in antibody
production

2) T-independent antigens:
- Mainly polysaccharide or lipopolysaccharide
antigens with long arrays of repeating units.

- Repeating units can bind to a large number

of B-cell receptors (antibodies), providing a
strong stimulus for B cell to proliferate and
differentiate into plasma cells without the
help of helper T cells.

-IgM antibodies are produced.

- No memory B cells are generated.

 Cell-mediated immunity: the role of T cells in cell-mediated
immune response
• Two major types of T cells: helper T cells and cytotoxic
T cells.

• Helper T cells (CD4+):

- Primary regulators of immune responses.
- Operate indirectly by secreting cytokines that
enhance the activity of:
(i) Macrophages and natural killer cells (innate immune
response)
(ii) B cells, cytotoxic T cells, and helper T cells
themselves (specific immune response).

• Cytotoxic T cells (CD8+):

- Responsible for killing cells infected by viruses,
bacteria, and other abnormal cells (e.g., cancer cells
and transplanted cells).
 Vaccination
• Honor Edward Jenner’s work (1788) on smallpox and cowpox
• Latin vacca meaning cow
• Vaccine – a suspension or organisms/viruses or fractions that is used to induce immunity

https://tophat.com/marketplace/science-&-math/biology/textbooks/surveying-the-immune-system-wendy-tamminen-
liliana-clemenza/3190/112641/
 Vaccination

(weakened)

weakened

(killed)

http://www.nature.com/scitable/content/types-of-dengue-virus-vaccines-22405302
Vaccines for COVID-19
Inactivated/live-attenuated vaccines:
dead/weakened version of the virus (Sinovac
and Sinopharm vaccine, Covaxin vaccine)

Adenovirus vector vaccines: put the gene for

coronavirus spike protein to a chimpanzee
adenovirus (cannot replicate in human cells).
The adenovirus pushes its DNA into the nucleus
where the spike gene can be transcribed into
mRNA (Oxford-AstraZeneca vaccine and Sputnik
vaccine)

Subunit vaccines: present one or more

antigens, often proteins (Novavax vaccine)
From New York Times (Jonathan Corum and Carl Zimmer)

mRNA vaccine: the first time any mRNA vaccine

has been approved for human use. The delivery
mRNA vaccine with
is achieved by a lipid nanoparticle carrier which
carrier molecules. Nature
protect the RNA and help their absorption into Reviews Drug Discovery
cells (Pfizer-BioNTech and Moderna vaccines) volume 17, pages261–
279 (2018)
 Vaccines for COVID-19

https://www.youtube.com/watch?v=WOvvyqJ-vwo
 Question T/F
1. The break down of the cell wall of gram-negative bacteria release endotoxin.

2. In an antibody, only the light chain interacts with the antigen.

3. The interaction between the toll-like receptor and the peptidoglycan in the cell
wall of the bacteria is an example of adaptive immune response.

4. The MHC class II molecules are present in the surface of helper T cells.

5. Helper T cells secrete cytokines to enhance both innate and adaptive immune
responses when interacting with antigens presented by MHC class II.

6. In vaccine using adenovirus as vector, the adenovirus is engineered in a way that

their DNA cannot be transcribed.