IMMUNE DEFENCE MECHANISM

BLOK 3.1

Betty Suryawati
MD, MBiomedSc , PhD

Faculty of Medicine Universitas Sebelas Maret

4/09/2018
 Immunity

All the mechanisms used by the body as protection against

environmental agents that are foreign to the body

Microorganisms
Microorganism’s products
Foods
Chemicals
Drugs
Pollen
Animal hair, etc

Immunity may be innate or acquired

 Cells involve:
T Cell, B Cell,
Antigen
Presenting Cell
(macrophages,
dendritic cells)

• Specificity
• Adaptiveness
• Discrimination
between self
and nonself
• Memory

Figure 1. Immune defence mechanism

Taken from: http://sphweb.bumc.bu.edu/otlt/mph-modules/ph/ph709_defenses/ph709_defenses2_print.html

 Innate and Acquired Immunity
• Innate immunity
– Physical and chemical barrier
– Phagocytosis: macrophages, Neutrophils, NK cells
– Engulf and digest recoqnize “foreign” cells-molecules
– Inflammatory response
• Acquired immunity: Antigen specific response
– Activates T-cells : direct attack
– Activates B-cells to become
• Memory cells: immune response to the antigen
• Plasma cells : antibody attack to the antigen
Innate and adaptive immune response

Figure 2. Innate and adaptive immune response

 Organs involved in immune defence

• The key primary lymphoid organs of the immune

system include the thymus and bone marrow,
secondary lymphatic tissues including spleen, tonsils,
lymph vessels, lymph nodes, adenoids, skin, and
liver.
• Primary lymphatic organs are where lymphocytes are
formed and mature. They provide an environment
for stem cells to divide and mature into B- and T-
cells
Overview of immune defence organs

Figure 3. Organs involved in immune defence

Cells involve in immune defence
• Lymphocytes: helper, plasma, cytotoxic and
natural killer (NK)
• Basophil
• Mast cells
• Monocytes
• Macrophages
• Neutrophils
• Eosinophil
Figure 4. The derivation of the key cells involved in the innate and adaptive immune systems

Taken from: http://sphweb.bumc.bu.edu/otlt/mph-modules/ph/ph709_defenses/ph709_defenses2_print.html

 Dendritic Cells
• Dendritic cells (DCs) are antigen-
presenting cells of the mammalian immune
system.
– Located in the skin, mucosa and lymphoid tissues.
– Act as messengers between the innate and the
adaptive immune systems.
• Function :
– To process antigens and present them to T cells to
promote immunity to foreign antigens and tolerance to
self antigens.
– To secrete cytokines to regulate immune responses.
 Picture taken from http://www.biology-pages.info/D/DCs.html

Figure 5. Two dendritic cells (arrows) from the spleen of a mouse. Compare their
smooth surface with that of the two macrophages visible at the upper left.
 Dendritic cells in immune systems

Figure 6. The immune system

consists of innate and
adaptive immunity. Dendritic
cells (DCs) are a crucial
element of the immune
system, bridging innate and
adaptive immunity. Upon
stimulation with PAMPs, DCs
secrete cytokines that activate
natural killer (NK) cells and
also help to differentiate
CD4+ and CD8+ T cells.

Picture taken from http://www.mdpi.com/1424-8220/9/9/6730/htm

 Maturation of Dendritic Cells
• At the onset of an inflammatory response, DCs
undergo a process of “maturation”
– Forming the long dendritic processes that give this
cell type its name, an up-regulation of cell surface
MHC and co-stimulatory molecules, redistribution
of proteins involved in antigen processing, and
secretion of a number of cytokines such as IL-12
which collectively induce the activation of naïve T
cells.
 Dendritic cells maturation process

Figure 7. DC progenitors that carry sensing pathogens travel from bone marrow to
lymphoid and non lymphoid tissues. The ‘maturation/danger’ signal together with
components of pathogens, cytokines and other molecules from the inflamed or
damaged tissues are being released. Upon getting the signal, the immature DCs
transform to mature DCs. In order to respond productively with T-cells, the mature
DCs have higher peptide-loaded MHC class II, CD80 and CD86.

http://dendritic-cells-research.com/index.php?request=maturation_process
 Figure 8. Dendritic cell
activation. Immature DCs
reside in non-lymphoid
tissues where they survey for,
capture, and process
antigens. When DCs come
into contact with
proinflammatory cytokines or
bacterial products,
maturation is induced and
the cells migrate to
secondary lymphoid tissues
where they stimulate naïve T
cells and B cells to initiate
and shape the immune
response.

(M-macrophage, NK-natural
killer cell, E-eosinophil)

Picture was taken from https://www.researchgate.net/figure/Dendritic-cell-activation-Immature-DCs-reside-in-non-lymphoid-tissues-

where-they-survey_fig12_8074608
Figure 9. The dendritic cell finds antigens and hauls it back to a lymph
node to show it around to all the T cells there. The APC processes antigen
and shows it to a T cell inside an MHCII molecule, while also having co-
stimulatory molecules present on the APC surface. MHCII + antigen (and
CD80/86 on the side) → activates the T cell TCR, and thereby activates the
T cell.
 Maturation vs. Tolerogenic
development of DCs

• Exposure of DCs to antigen in the presence of immune

stimulatory molecules such as LPS leads to maturation
of DCs and subsequent immune responses.
• However, in the absence of immune stimulatory
molecules DCs develop a tolerogenic phenotype upon
antigen exposure.
Figure 10. Dendritic cells (DCs) maturation

https://tolerogenics.lu/home/technology/tolerizing-ps-liposomes/
 Dendritic Cells Function in Immunity
• DCs play an essential role as regulatories to secrete
cytokines which can develop Th1 or Th2 effector cells
that respond to immune system and also provide link
in between innate and adaptive community.
• DCs also respond to 'danger' signal and act as inducers
to T-cells response. By activating macrophages, natural
killer (NK) cells, NK-T cells and eosinophils, DCs can
respond to attack infectious agents.
• DCs are the major source of Interferon (IFN) -a and -b,
such as plasmacytoid DCs (P-DCs).
 T-Cell

• T cells : predominantly produced in the thymus.

• T cell is a type of lymphocyte (a subtype of white
blood cell) that are important for adaptive
immunity.
• T cells have unique cell surface receptors that
are generated by randomly assorting genes.
These receptors allow T cells to sense and
respond to diverse types of infection.
 T Lymphocyte-Cell (T cell)
• T cells recognize foreign particles (antigen) by a
surface expressed, T cell receptor (TCR).
• There are two major types of T cells: the helper T
cell and the cytotoxic T cell.
• Helper T cells ‘help’ other cells of the immune
system, whilst cytotoxic T cells kill virally infected
cells and tumors.
 Figure 11. Blood cell
development.
A blood stem cell
goes through
several steps to
become a red blood
cell, platelet, or
white blood cell.

https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022044/
 The different kinds of T cells

T cells have a number of variants that perform differing roles

within the immune system.
• Effector: These are relatively short-lived activated cells that
defend the body during the immune response. The
category of effector T cells includes helper, killer,
regulatory, and potentially other T cell types as well as B
cells.
• Helper: The helper T cells support other white blood cells
with immunologic processes, including the maturation of B
cells into plasma cells and memory B cells along with the
activation of cytotoxic T cells and macrophages. These cells
are also called CD4+ T cells because they express the CD$
glycoprotein on their surfaces.
– T cells detect fragments of protein antigens that have
been partly degraded inside the APC. These peptide
fragments are carried to the surface of the APC on
special molecules called MHC proteins, which then
allow the T cells to detect them and become
activated.
– These cells can differentiate into one of several
subtypes (TH1, TH2, TH3, TH17, TH9, or TFH), which
secrete different cytokines for different kinds of
immune responses. The signaling from the APC
determines what subtype a helper T cell becomes
• Cytotoxic T Cell/ killer T cells : known as CD8+ T cells, since
they express the CD8 glycoprotein at their surfaces.
– These cells are designed to seek and destroy pathogens,
including viruses and bacterial invaders, and tumors. Killer T
cells detect these threats by sensing antigens (toxins or other
foreign substances) when encountering a threat.
• Natural killer T cell: Natural killer T cells (NKT cells) are
different from natural killer cells of the innate immune
system, as they link the adaptive system and the innate
immune system.
– Similar to regular T cells, which recognize certain antigens, these
cells detect a different set of antigens (glycolipid antigens); once
activated, they can function in a double capacity, as if they were
T helper and T killer cells combined into one.
https://www.leafscience.org/t-cells/
Figure 14. Cytotoxic T cell and Helper T cell in immune response
• Memory: Memory T cells are a type of antigen-specific T
cell that remains long after an infection has resolved.
– When they encounter an antigen associated with a pathogen
they encountered in the past, they quickly expand to large
numbers of effector T cells capable to destroy the pathogen.
This provides the immune system with a “memory” against past
infections and allows a faster response to attack. For example, if
you had an illness such as chickenpox or the mumps as a child,
you are much better able to fight off any future occurrences, as
your immune “memory” can identify them faster.
• Regulatory: These T cells are crucial for the upkeep of
immunological tolerance, ensuring that there is no immune
response to self-antigens and for suppressing excessive
immune responses damaging to the host.

https://www.leafscience.org/t-cells/
Figure 15. Schematic representation of the two major pathways of T cell differentiation:
the Th and Tc populations and their subsets. Following uptake and processing of an
antigen by an APC shown in the figure as a dendritic cell, peptide is presented either to
the CD8 population in the context of MHC-I or to the CD4 subpopulation in the context of
MHC-II following which a cascading set of cellular lymphoproliferative and differentiative
steps are initiated under the inductive influence of cytokines that ultimately determine
their effector functions.
[Immunology IV: Clinical Applications in Health and Disease. I Care Press, Bethesda, MD, 2012]
Various types of antigen-presenting cells
 B-Cells
• B cells, also known as B lymphocytes, are a type of white
blood cell of the lymphocyte subtype.
• They function in the humoral immunity component of the adaptive
immune system by secreting antibodies.
• B-cells are activated by the binding of antigen to receptors on
its cell surface which causes the cell to divide and proliferate. Some
stimulated B-cells become plasma cells, which secrete antibodies.
Others become long-lived memory B-cells which can be stimulated
at a later time to differentiate into plasma cells.
• The B-cell receptor (BCR) is an immunoglobulin molecule forming a
type I transmembrane protein on the surface of B cells. The BCR
transmits activatory signals into the B cell following its recognition
of a specific antigen.
 Figure 18. When naïve or memory B
cells are activated by antigen (and
helper T cells—not shown), they
proliferate and differentiate into
effector cells. The effector cells
produce and secrete antibodies
with a unique antigen- binding site,
which is the same as that of their
original membrane-bound
antibodies that served as antigen
receptors.

Molecular Biology of the Cell. 4th edition, https://www.ncbi.nlm.nih.gov/books/NBK26884/

 • Plasma cells are B cell antibody-secreting that protect
individuals against invading pathogens.
• Memory B cells are a B cell sub-type that are formed
within germinal centers following primary infection and are
important in generating an accelerated and more robust
antibody-mediated immune response in the case of re-
infection (also known as a secondary immune response).

Figure 19. B lymphocytes are the cells of

the immune system that make antibodies
to invading pathogens like viruses. They
form memory cells that remember the
same pathogen for faster antibody
production in future infections

Picture taken from https://en.wikipedia.org/wiki/Memory_B_cell

EVERY ENDING IS REALLY JUST A NEW BEGINNING