IMMUNE SYSTEM

CHARACTERISTICS
The cells that function in Adaptive Immune System are the
Lymphocytes (T-cells and B-cells). And these cells have these major
characteristics:
- TOLERANCE- ability to distinguish “self” from “non-self”
- SPECIFICITY - refers to cell-surface receptors specific for a certain
fragment of an antigen (epitope)
- MEMORY - refers to the ability of these cells to respond much
faster repeated antigen exposure
LYMPHOID ORGANS
Primary Lymphoid Organs

Secondary Lymphoid Organs

LYMPHOID ORGANS
Primary Lymphoid Organs/
Central Lymphoid Organs

Bone Marrow Thymus

✓ Bone Marrow – Site of B cell
Maturation

✓ T cells– Site of T cell maturation

LYMPHOID ORGANS
Primary Lymphoid Organs/
Central Lymphoid Organs

Bone Marrow
✓ Equivalent to Bursa of Fabricius in birds

✓ Origin of ALL BLOOD CELLS

✓ Centre of ANTIGEN INDEPENDENT

LYMPHOIESIS

✓ Contains PLURIPOTENTIAL HEMATOPOIETIC

STEM CELLS
LYMPHOID ORGANS
Primary Lymphoid Organs/
Central Lymphoid Organs

Thymus
✓ Site of T cell development

✓ DIMINISHES IN SIZE as a person

aged

✓ Progenitor T cells from BM migrate

to the thymus and enter via the
HEV
LYMPHOID ORGANS
SECONDARY LYMPHOID ORGANS

SPLEEN
LYMPHOID ORGANS
SECONDARY LYMPHOID ORGANS

Lymph nodes
✓ Collects LYMPH FLUIDS from adjacent tissues
✓ Traps antigens in the TISSUES

✓ Cortex – contains MACROPHAGES and naive B

cells
✓ Secondary follicles – contains ANTIGEN
STIMULATED B cells
✓ The paracortex – contain T lymphocytes which are
in close proximity to interdigitating dendritic cells
✓ The medulla – contains T cells, B cells,
macrophages, and plasma cells
LYMPHOID ORGANS
SECONDARY LYMPHOID ORGANS

Lymph Nodes

LYMPHADENOPATHY
LYMPHOID ORGANS
SECONDARY LYMPHOID ORGANS

Mucosa Associated Lymphoid Tissues

ADAPTIVE IMMUNITY
BASIC CONCEPTS

Component of the immune system that

ADAPTS – depending on the antigen
encountered.

Considered as the 3rd line of defense

Result from exposure of immunogens.

ADAPTIVE IMMUNITY
BASIC CONCEPTS

COMPONENTS:
Cellular
- Lymphocytes (T helper cells and Cytotoxic Cells)
Humoral
- Cytokines and Antibodies
ADAPTIVE IMMUNITY
BASIC CONCEPTS
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY
MATURE T CELLS

Antigen fragment

Zeta chain Zeta chain

Bigger view of TCR

CD4 + T cell CD8 + T cell
for better
(T helper) (T cytotoxic)
understanding
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

PRE- THYMIC PHASE

✓ Sites of origin of LYMPHOID PRECURSOR
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCAPSULAR REGION)

✓ Progenitor T cells LACK THE SURFACE
MOLECULES of a mature T cell

✓ CD2, CD3, and CD7 are – the FIRST T CELL

specific surface molecule is expressed, and
are considered as Pan-T markers

✓ Immature, DOUBLE NEGATIVE CD3 TCR

complex -, CD4/8- thymoyctes
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCAPSULAR REGION)

✓ Double Negative thymocytes 1 (DN1)
• Expression of adhesion molecule
CD44

• Genes encoding the β chain of the

TCR are in the germline
configuration
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCPSULAR REGION)

✓ Double Negative thymocytes 2 (DN 2)

• Expression of adhesion molecule

CD44

• Expression interleukin receptor

CD25
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCPSULAR REGION)

✓ Double Negative thymocytes 3 (DN 3)

• Reduced expression of CD44

• Rearrangement of the gene coding

for the β chain occur
Note: DN3 cells that fail to make
successful rearrangement of the
gene for β chain remain in the DN3
stage!!!
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCPSULAR REGION)

✓ Double Negative thymocytes 3 (DN 3)

• Expression of the β chain paired

with a surrogate α chain (PRE-TCR
or the pT α) together with CD3
molecules

• Expression of the pre TCR arrests

further β chain rearrangement

PRE-TCR
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCPSULAR REGION)

✓ Double Negative thymocytes 3 (DN 4)

▪ Expression of the pre-TCR on the surface of DN3

thymocytes leads to the cessation of Beta chain
rearrangement and proliferation of DN3
thymocytes into Double Negative thymocytes
stage 4 characterized by complete absence of
CD44 and CD25 expression
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (SUBCPSULAR REGION)

✓ Double Positive thymocytes

• Pre-TCR is still expressed

• Expression of both CD4 and CD8

molecules
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

THYMIC PHASE (CORTEX)

✓ Double Positive Thymocytes

• Rearrangement of the gene coding

for the α chain of the TCR

• Expression of the complete α: β

TCR
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

SCREENING TESTS
✓ DEATH BY NEGLECT

• Thymocytes lack TCR signal

under apoptosis
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

SCREENING TESTS
✓ POSITIVE SELECTION

• T cells with functional α: β

TCR are given proliferation
signal
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

SCREENING TESTS
✓ NEGATIVE SELECTION

• Thymocytes with STRONG TCR

signals are deleted (apoptosis)
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

MATURE T CELLS
• Survivors of the selection processes
exhibit only ONE TYPE of marker
➢ CD4
➢ CD8
• Express other receptors: CD2, CD3, CD7
• Thus: CD8 + T cell
o T helper cells: CD4+, CD3+, CD7+, α:βTCR CD4 + T cell (T cytotoxic)
o T cytotoxic cells: CD8+, CD3+, CD7+, α:βTCR (T helper)
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ONTOGENY

MATURE T CELLS

• Migrate to the medulla and leave the

thymus via the HEV and go the secondary
lymphoid organs

CD4 + T cell CD8 + T cell

(T helper) (T cytotoxic)
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION
Breached Physical Barrier

Activated dendritic cell

External Interstitial Blood

environment space vessel
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

Antigen Fragment

Dendritic cell migrates

Chemokine receptor 7 (CCR7)

ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

• Upon arrival in the lymph node, naïve T helper cells interact with the
antigen displayed on MHC class 2 through the TCR with the help of the
CD4 costimulatory molecule that binds to the B2 region of MHC class 2

This doesn’t end here as there is a need to stabilize the binding

of your T helper cells and dendritic cells so they can interact
efficiently.

In the lymph nodes

ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

▪ Leukocyte Function Antigen (LFA) – major

integrin on Th cells

▪ Intracellular Adhesion Molecule 1 (ICAM-1)

– LFA ligand on dendritic
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

▪ B7-1 (CD80) and B7-2 co stimulators – also

are important signals needed for efficient
interaction
B7 costimulation
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

▪ CD40 ligand or CD154 on T helper cells and its CD40

on dendritic cell stimulates it to express more B7
ligands thereby improving the strength of signaling
APC
between the two cells making your APCs better in
stimulating your T helper cells.
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

▪ Once efficient binding successfully occurs, your

previously naïve T cells activate and transform into
cytokine producing T helper

▪ Activated T-helper cells increase its expression of high

affinity IL-2 receptor

IL-2 – first cytokine produced by activated T helper cells 1-

2 hours after activation.
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION

Clonal Expansion in the Lymph Nodes

CLONAL EXPANSION

Th memory

Effector Cells
 ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION
Differentiation of CD8 + T cells into Cytotoxic T lymphocytes (CTL)

MHC II CTL and Memory

MHC I
Steps… 1 2 3
ADAPTIVE IMMUNITY
CELL MEDIATED IMMUNITY:T CELL ACTIVATION
Differentiation of CD8 + T cells into Cytotoxic T lymphocytes (CTL)

Nucleated Target cell acting also as non-

professional APC

Activated CTL

Target cell
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELLS
Critical difference between B-cells and T-cells is how each
lymphocyte recognizes its antigen

T cell Receptor

B cell Receptor B-cell Receptor Complex

ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELLS
Basic Antibody Structure

Variable region

Constant region
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ONTOGENY

Pro-B cell
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ONTOGENY

Pre- B cell
Expressed u chain with
surrogate light chain
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ONTOGENY

Immature B cell
Complete IgM molecule
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ONTOGENY

Immature B cell

CENTRAL TOLERANCE
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ONTOGENY

Mature B cell

PERIPHERAL TOLERANCE
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ACTIVATION
T cell dependent B cell activation

Cross linking

Start here…
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ACTIVATION
Plasma cells

▪ Plasma cells are antibody secreting B cells that produce

antigen specific antibodies that bind and neutralize
microorganisms.

▪ Antibodies work with other components such as

phagocytes and complement to kill foreign cells.
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ACTIVATION
Memory B cells

▪ Memory B cells are one step closer to become plasma

cells
▪ Survive decades and in the event of reinfection, can
produce an accelerated and robust antibody-mediated
immune response
ADAPTIVE IMMUNITY
HUMORAL IMMUNITY: B CELL ACTIVATION
References

Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory Perspetive. FA
Davis.

Abbas, A. K., Lichtman, A. H., & Pillai, S. (2019). Basic Immunology E-Book: Functions and Disorders
of the Immune System. Elsevier Health Sciences.

Janeway Jr, C. A. (2020). Immunobiology.

IMMUNE SYSTEM