Science of Living System: BS10003

Host Defense and Prevention of Diseases

Story: H.G. Wells

Direction: Steven Speilberg

Mainak Bose| School of Bioscience

email: mainak29@[Link]
 Human Diseases

1. Infections (caused by bacteria, virus, fungi etc)

2. Autoimmune diseases (Failure of our immune

system in recognition of self vs non-self)

3. Immunodeficiency (lack/defect in immune system)

4. Cancers (several known and unknown reasons)

 Challenges of the Immune System
⮚ Pathogen-induced diseases:

⮚Autoimmune diseases: When ‘self’ is attacked by the immune system

⮚Cancer: Failure of Immune system to attack defective cells

⮚Immune deficiency: A component of immune system is absent/defective

 Immunology: The Beginning

• In 15th century dried crusts from small pox were

either inhaled or inserted into small cuts in the
skin (Variolation).

• In 1796, Edward Jenner demonstrated that

inoculation with cow-pox protects against small
Edward Jenner: pox, a lethal disease at that time. A process he
father of termed Vaccination
Immunology

• Louis Pasteur’s hypothesis: Weakened or attenuated strain could be

administered to protect from that specific strain causing disease - Vaccine
The Immune System: Body’s Defense Mechanism

▪ The main objective is to

seek, identify and kill
invaders

▪ A complex system that encompasses every organ and

compartment of the body
▪ Highly adaptable (can act against pathogens ranging from ~
30nm to ~100 cm)
▪ Distinguishes between self and foreign and respond against
only foreign while preserving self (‘us’ vs ‘them’)
 The immune system
❑ A functional system – NOT an organ system:
A very complex system that includes:

⮚ Skin – physical barrier

⮚ Lining of mucus membranes – physical barrier

⮚ Secretions – tears, mucus etc - antimicrobial

⮚ Blood cells and vasculature – White blood cells (WBCs)

⮚ Bone marrow—source of Hematopoietic Stem Cell (HSC)

⮚ Lymphatic system and lymphoid organs

⮚ Most tissues – have resident immune cells

 Our immune system generates almost
infinite variety of cells and substances

Foreign Recognition

Effector Response Memory

▪ To eliminate or neutralize ▪ Upon second exposure produces
foreign particle enhanced response

⮚ Active immunity: Immunity that

will generate long term memory

⮚ Passive immunity: Immunity that

will generate short term memory
 Passive and Active Immunity
❑ Passive immunity: Immunity ❑ Active immunity: Immunity
that will generate short term that will generate long term
memory. Examples: memory. Examples:
⮚ Natural: when an infant ⮚ Natural: when a person
receives mother's antibodies becomes infected by a disease,
during pregnancy through the body builds immunity
placental transfer or through against the disease
breastfeeding
⮚ Artificial: a person can build a
⮚ Artificial: when antibodies are resistance to a disease after
administered (gamma globulin vaccination
injection), e.g. after a snake bite
 Distribution of the Immune System
Red: Primary lymphoid organs
Blue: Secondary lymphoid organs

T cells are matured

in the thymus

The bone marrow contains

blood-forming Stem cells,
and makes B cells, innate
immune cells, and all other
blood cell types
 Two modes of immunity

In response to pathogens, vertebrate immune

systems use two interconnected systems:

Innate immunity: inborn

Adaptive immunity: acquired during the life-span
Innate vs Adaptive Immunity

Innate Immunity Adaptive Immunity

Rapid Slower
Non-specific Specific
Halts Infection Clears Infection
No Memory Memory
 First insights into mechanisms of immunity
Emil von Behring ❑ 1880’s- Metchnikoff discovered
phagocytic cells that ingest
microbes and particles-
⮚ cells confer immunity

❑ 1890- von Behring and Kitasato

discovered blood sera could
transfer immunity-
⮚ liquid of blood confer immunity

Elie Metchnikoff ❖ What confers immunity…

⮚ cells or serum?

S. Kitasato
Components of immune system in Blood

Centrifugation of blood Immune component

Antibodies and others

WBCs
Blood cell types and their origin
Immune system defends against infection
Innate immune system

[Link]
Innate immune system
 Mechanical Factors

❑ Skin

❑ Mucous

❑ Flushing action of saliva, tear, urine

 Chemical factors
Antimicrobial
HCl in stomach Lysozyme in tears /saliva
Peptides in sweat
 Biological factors

❑ Symbiotic (commensal) microbial flora:

⮚ microbes in many parts of the body
⮚ > 1000 species of bacteria
⮚ competes with pathogens for nutrients
and space
Phagocytosis
 Epithelial Barriers:
what happens after a breach?
Inflammatory response: A fundamental type of response by the body
to injury/localize infection is characterized by the classical signs of :
Increase in diameter of
1. Vasodilation the blood vessels Heat and Redness

2. Vascular Leakage of fluid

permeability from blood vessel & Swelling, Pain
increases influx od phagocytes

Inflammation: Heat, Redness, Swelling, Pain

WBCs enter the tissue from the local blood vessels and halts
or clears the potential threat
Inflammatory response
Components and Mechanisms of the
Adaptive Immune Response

An image of immune cell communication, showing dendritic cells interacting with T

cells, taken using an FEI microscope, magnification 16,000x. (Rita Serda/FEI Image)
Adaptive Immunity: Our most powerful defense

▪ More tuned to subtle molecular differences

▪ Specificity: antigen specific response

▪ Takes more time to develop

▪ Outcome: gradual resolution of infection; depends on B and T cells

▪ Able to better recognize, eliminate, & remember the invading

pathogen
▪ Development is dependent upon earlier innate pathways

▪ Adaptive immunity provides a second & more comprehensive line of

defense based on the struggles of innate immunity
Adaptive Immunity: Our most powerful defense
 Antigen Presenting Cells (APCs)
Big eaters/Always hungry

Antigen presentation Phagocytosis

Antigen Presenting Cells (APCs)

❑ Proteins eaten by APCs are broken down to small pieces (peptides),

which are loaded on special receptors (MHCs) and transported to the
cell surface. Peptides loaded MHC complex can be recognized by T
cells and that interaction can lead to adaptive immune response.
Antigen Presenting Cells (APCs)
 Adaptive Immune Response: Role of T cells
Antigen presented by APC (via MHC)

T Cells

Cytotoxic T Cell Helper T Cell

Virus Infected/abnormal cell B Cell

(with antigenic peptide loaded on MHC
II) Plasma cell
(antibody producing B cell)

Killing of infected cell

Antibody

• Neutralization
• Induction of phagocytosis
Activation of B Cell and production of Antibody

1. Each B cell can recognize only one antigen

2. That B cell gets activated and differentiated into numerous plasma cells
3. All of these plasma cells produce same antibody in a very efficient manner
4. These antibodies are then utilized in the clearing of initial antigen/antigen
providing microorganisms, which was initially detected by B cell
B cell differentiation after activation
Structure of an Antibody
molecule
B cells and T cells must recognize epitopes of the same
molecular complex in order to interact

1 3

2
4
‘Professional’ Antigen Presenting Cells (APCs)
express both MHC class I and class II molecules

Examples of APCs:
1) Dendritic cells
2) Macrophages
3) B cells
 Adaptive Immune Response: Key Points

• Initiated by innate system

• Diverse set of receptors

• Recognizes pathogen-specific epitopes (immune specificity)

• Immune memory
Innate vs Adaptive : Differences at a glance
Innate vs Adaptive
Timeline after infection
 Innate vs Adaptive
Which immunity confers more protection?

• Losing the Innate arm of the immune system results in more disastrous
outcome than losing the acquired arm
Vaccination (Immunization)

[Link]
 Drug vs Vaccine

• Concept of Drug
– Kills invaders or foreign pathogens
– Inhibits the growth of pathogens

• Concept of Vaccine
– Trains immune system to face existing disease
causing agents
– Generates memory against specific pathogens
 Vaccination: an ongoing global effort
❑ Vaccination has yielded some of the most successful stories in
alleviating worldwide mortality rates
❑ The last case of naturally acquired case of small pox was
reported in 1977
❑ Consequence of eradication: universal vaccination not
required any more
❑ Some vaccines may carry slight risk to the person vaccinated
❑ Herd immunity: In many cases, its not necessary to
immunize every person to protect most of the population. If a
critical mass of people acquire protective immunity they can
serve as buffer for the rest
 Immunological Memory & Vaccination
• Natural infections:
1st infection 🡪 memory 🡪 2nd infection
slow response fast response
pathogens multiply pathogens disposed
Symptoms/disease no disease

• Vaccination 🡪 memory 🡪 natural

infections
no disease fast response
pathogens
disposed
Vaccination protects us from infection by inducing the adaptive
no disease
immune response, bypassing the need for a natural infection
 Covaxin vs Covishield
❑ Covaxin:
• An inactivated viral vaccine. This vaccine is developed with Whole-Virion
Inactivated Vero Cell-derived technology. They contain inactivated viruses,
which can not infect a person but still can teach the immune system to prepare a
defense mechanism against the active virus.
• These conventional vaccines have been in use for decades now.
• There are vaccines for some other diseases as well which are made using the
same technology. These diseases are –
⮚ Seasonal influenza, Rabies, Polio, Pertussis, and Japanese encephalitis

❑ Covishield:
• Prepared using the viral vector platform which is a totally different technology.
A chimpanzee adenovirus – ChAdOx1 – has been modified to enable it to carry
SARS-CoV2 spike protein coding gene into the cells of humans. This cold virus
is basically incapable of infecting the receiver but can very well teach the
immune system to prepare a mechanism against such viruses.
• The exact technology was used to prepare vaccines for viruses like Ebola.
For More information you might visit following links:

[Link]
[Link]

[Link]
 References
▪ Janeway’s Immunobiology
▪ Kuby’s Immunology
▪ [Link]