Defense System (IMMUNITY)

We are in a long-life war!!!

Innate
Immunity

Passive
Immunity
(maternal)
Natural Active
(infection)
Adaptive
Immunity Passive
(antibody transfer)
Artificial Active
(immunization)
 INNATE IMMUNITY
Non-specific defense mechanisms
Barrier defenses:
• Physical barrier (skin, exoskeleton, hair)
• Chemical defenses:
• Skin: acidic pH
• Saliva, tears, mucous secretion from
epithelia
• Antimicrobial proteins, such as lysozyme
• Mucous traps microbes

In trachea, ciliated epithelial cells

trap microbes (exception, hepatitis A
virus)
 Innate Immunity
Non-specific defense mechanisms
 Innate Immunity
Non-specific defense mechanisms
The inflammatory response:
•Release of chemicals from basophils and mast cells:
•Histamine: dilates and increases capillary permeability
•Prostagladins: increases blood flow, induces fever, pain,
•Facilitates blood clotting
•Enhances migration of phagocytic cells
•Facilitated by release of chemokines secreted from endothelial cells and monocytes
(macrophages)
•Macrophages also clean up damaged cells: formation of pus, dead cells plus fluid and
proteins from capillaries
Widespread inflammation:
– disinfect tissues
– limit further infection
•Certain leukocytes release pyrogens  fever, resetting the body temperature
 Innate Immunity
Non-specific defense mechanisms
Phagocytic cells
Periphearal blood leucocytes
(4.5 – 11.000 cells/ul
- Lymphocytes (~30%)
- Granulocytes (~70%)
• Neutrophils (~60% of total WBC in blood)
• Eosinophils (~3%)
• Basophils (<1%, rare)
• Monocytes (~6%)  Macrophages
- Kupffer cells – in liver
- Dendritic cells
(incl. Microglial cells –
in brain /CNS) https://www.news-medical.net/life-sciences
/What-is-the-difference-Between-a-Phagocyt
e-Macrophage-Neutrophil-and-Eosinophil.as
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 Innate Immunity

Non-specific defense mechanisms

Phagocytes
in the body
 Innate Immunity

Non-specific defense mechanisms

Antimicrobial proteins:
Viral nucleic acid
o Lysozyme: antimicrobial VIRUS
6
enzymes in saliva, tears and 1 Antiviral proteins block
viral reproduction
mucus secretion New viruses
o 20 serum proteins, called the 2

complement system: cascade Interferon genes

turned on
of steps leading to microbial
lysis Interferon
stimulates
5 cell to turn
mRNA Interferon on genes
molecules for antiviral
o Interferons: released by virus- 3 proteins
infected cells; limit cell-to-cell
spread of viruses, activate HOST CELL 1
Makes interferon;
4 HOST CELL 2
Protected against virus
phagocytes is killed by virus by interferon from cell 1
 Innate Immunity
Non-specific defense mechanisms
Natural killer cells
o A type of cytotoxic lymphocyte (a
major component of the innate
immune system)
o Play a major role in fighting tumors
and cells infected by viruses
o Kill the target cells by releasing
small cytoplasmic granule protein
(perforin and granzyme)

https://www.leafscience.org/natural-killer-cells-for-immunotherapy/
 Innate Adaptive Immunity
Immunity Adaptive
Immunity
Active
Immunity (infection)
Natural Passive
(maternal)
Naturally Artificially
Adaptive acquired acquired
Immunity
Active
(immunization)
Artificial
Passive
(antibody transfer)
 Adaptive Immunity

The Human Lymphatic System

 Adaptive Immunity

Generation of Specificity and Diversity

Lymphocytes provide the specificity and diversity of immune
system (circulate through blood and lymph and are concentrated in :
• B cells (bone): secrete antibodies
• T cells (thymus): responsible for cellular immunity
 Specificity originates from the recognition by antibodies (B cells) and T cell receptors of
specific foreign molecules called antigens (from viruses, bacteria, parasites, etc…).
(Antigen= antibody-generators)
All the antibodies from a B cell or T cell receptors from a T cell are identical (about
100,000 per cell)
 Diversity arises from genetic events that occur during early development lymphatic
tissues
 Adaptive Immunity

Antigens interact with specific lymphocytes and induce immune responses

and immunological memory

Selection results in the proliferation and differentiation of lymphocytes (clonal selection)

Two types of clones:
- effector cells : short-lived cells combating the antigen by producing antibody
- memory cells : long-lived cells
Primary immune response : first encounter to antigen:
• takes 10-17 days to produce maximum response (time for lymphocyte division,
production of antibodies and cell-mediated immune response)
Secondary immune response: second encounter to antigen:
• faster response : 2-7 days
• antibodies have greater affinity for antigen
• due to immunological memory
Adaptive Immunity
Clonal selection
 Adaptive Immunity
Immunological memory
 Adaptive Immunity
Distinction between self and non-self

• Lymphocytes originate from bone marrow (or liver in

developing fetus):
- migrating through thymus T cells
- staying in bone marrow B cells
• During maturation, those reacting to self-molecules are
destroyed by apoptosis (programmed cell death): self-
tolerance
- Failure to self-tolerance leads to auto-immune
diseases
Self-tolerance is the immune system's ability to recognize what
is 'self' and not react against or attack it.
 Adaptive Immunity
Major Histocompatibility Complex (MHC) Proteins

• In humans = HLA Complex (Human Leucocyte Antigen)

• Two main classes of MHC proteins:

- Class I MHC proteins : on all nucleated cells
- Class II MHC proteins : on macrophages, B cells, activated T cells, and cells
in the thymus
• MHC proteins responsible for antigen presentation to T cells
• Two main types of T cells:
• Cytotoxic T cells (Tc): respond to antigens presented by Class I MHC
proteins and destroy antigen-infected cells
• Helper T cells (TH) : activated by antigens presented by Class II MHC
proteins
 Adaptive Immunity
The interaction of T cells with MHC proteins

protein protein
 Adaptive Immunity
Immune Responses

Two types of responses:

Humoral immunity:
by B cells and production of
antibodies

Cell-mediated immunity:
by T cells with coordination
between B cells and T cells
 Adaptive Immunity

An overview of the immune responses

 Adaptive Immunity

An overview of the immune responses

 Adaptive Immunity

An overview of the immune responses

 Adaptive Immunity

An overview of the immune responses

 Adaptive Immunity

The central role of helper T cells

APC engulfs a TH cell is activated. Activated TH cell Secreted cytokines

bacterium; The CD4 protein proliferates further stimulate TH cells
A fragment is enhances the activation, and produces cloned and help activate B cells
transported to as does Interleukin-1, activated TH cells and and Tc cells
The surface by a secreted by APC memory TH cells
Class II MHC
molecule
 Adaptive Immunity
The functioning of cytotoxic T cells

An infected cell displays an antigen Activated Tc cell releases Water and ions flow into
fragment perforins which make cells and the cell lyses and
using class I MHC molecule. pores dies.
A Tc cell is activated, and CD8 protein in infected cell.
enhances
the activation as does interleukin-2.
Adaptive Immunity
 Adaptive Immunity

Antibody

• Each molecule of antibody is made of 2 identical heavy chains and 2 identical light
chains
• The variable region is the antigen binding site, while the constant region is responsible
for mechanisms mediating antigen removal
 Adaptive Immunity
Epitopes (antigenic determinants)
A small portion of an antigen that interact with antibodies

A single bacterium can be coated with as many as 4,000,000 antibodies

 Adaptive Immunity
Antibodies are globular serum proteins, called immunoglobulins (Igs)
 Adaptive Immunity

Antibodies mark antigens for elimination

 Adaptive Immunity

The classical complement pathway,

resulting in lysis of a target cell
Monoclonal antibodies Antigen injected
Tumor cells
grown
into mouse in culture

Monoclonal antibodies are

powerful tools in the lab and clinic. B cells
(from spleen) Tumor cells

HOW?
Cells fused to
generate hybrid
cells

Single hybrid cell

grown in culture
Antibody

Hybrid cell culture,

producing monoclonal antibodies
 Innate
REVIEW Adaptive
Immunity Immunity

Active
Immunity (infection)
Natural Naturally Artificially
Passive
acquired acquired
(maternal)
Adaptive
Immunity
Active
(immunization)
Artificial
Passive
(antibody transfer)

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