Last edited: 8/8/2021
1. ADAPTIVE IMMUNITY
Immunology: Adaptive Immunity
OUTLINE
I) HUMORAL IMMUNITY
II) B-LYMPHOCYTES
III) T- LYMPHOCYTES
IV) CELL MEDIATED IMMUNITY
V) NATURAL KILLER CELLS
VI) REVIEW QUESTIONS
VII) REFERENCES
I) HUMORAL IMMUNITY
The antigens are exogenous
o Antigens outside the cell trigger the B-cell
proliferations
(A) CELLULAR EVENTS
Before entering the lymph nodes, there are cellular
events happening in order to bring the antigens inside the
lymph node
(1) Macrophages
o In macrophages the antigens that were pulled away
from bacterial microbe may be expressed on MHC II
molecules on cell surface → these macrophages are
referred to as Antigen Presenting cells (APCs) →
these APCs then interact with T-helper cells
o Antigen Presenting cells (APCs)
 Macrophages
 Dendritic Cells
 B-cells
(2) Neutrophils
o In neutrophils these antigens are exocytosed into
interstitial fluid and then carried to nearby lymph
nodes
o This is the free antigen
II) B-LYMPHOCYTES
Lymph nodes contain germinal centers which contains
large amount of B-cells/ B-lymphocytes
B-lymphocytes contains specific types of receptor on their
membrane which is called the B-cell receptors
o Designed to be IgD antibody
o The B-cell receptors are formed through
recombination. This means like the DNA inside the B-
cell, the MHC II molecules on cell membrane undergo
shuffling producing different types of binding domains
o Hence, each receptor can bind different types of
antigen
 Example: Square antigen binds with the square
receptor and the circular antigen binds with the
circular receptor
(A) NAÏVE B-LYMPHOCYTE
Before the binding, the B-lymphocyte is technically naïve
since it hasn’t gone any immunogenicity response →
activation happens when the free antigen circulating
inside the lymph node, by random chance binds onto the
B-cell receptor which was perfectly designed to fit that
antigen → activates the B-cell through signaling
mechanisms → the B-lymphocytes, now more mature,
undergo receptor mediated endocytosis of antigen-
antibody complex into B cell → chromosome number 6 of
the B cell produce MHC II molecules which fit perfectly to
the antigen → fused on to the cell membrane
ADAPTIVE IMMUNITY
Medical Editor: Dr. Sofia Suhada M. Uzir
(B) ACTIVATED B-LYMPHOCYTE
Have B-cell receptors (usually IgD antibodies) including
the MHC II molecules with the foreign antigen on its
membrane → important to make more specific types of
antibodies specific to the antigens
It still cannot undergo proliferation
(C) PROLIFERATION OF THE B-LYMPHOCYTES
Occurs when there is a stimulus: the macrophages
(APC) → interacts with T-helper cell
(1) Interactions of APC and T-cell
Before interacting with the antigens, the T helper cell is a
naïve T-helper cell → have receptors which can respond
to the molecule but still not activated and unspecific
Remember:
On the membrane of the macrophages, there are:
o MHC I molecules with some type of self-antigen
 All nucleated cells must have this molecule
o MHC II molecules which expresses the antigen
Signals sent to the nucleus of naïve T-cells for activation
include:
(i) Primary signal
MHC II molecules on cell membrane of macrophages
o Which interact with CD4 molecule on T helper cells
Antigen which is expressed on the MHC II molecule
o Interact with T-cell receptor specific to that antigen
on T-helper cells
o Like the B-cell, due to recombination, every T-cell
have different types of receptors specific to the type
of antigens
o This interaction sends primary signals to the nucleus
(ii) Secondary signal
Co-stimulation B7 molecules
o Which interact with CD28 on naïve T helper cells →
send secondary signal/co-stimulation to the
nucleus
(iii) The third signal
The macrophages secrete IL-1 molecule
o Binds to specific receptor on the naïve T-helper cells
→ this sends the third signal to the nucleus
Activation of the T-cell leads to the production and
secretion of IL-2 → IL-2 can bind on the T-cell
(autocrine) → activation of the cell sends signal to the
nucleus again to produce IL-4 and IL-5
Note:
Autocrine: Binding to the same cell that secretes it
(2) B-cell proliferation – cytokines released
The B-cell and T-helper cell interaction as listed above
triggers T-helper cells to release cytokines:
IL-4 and IL-5 → converts naïve T cell into TH2 cells
(i) IL-4
activates B-cells to start proliferating (clonal expansion)
→activated B-cells will ↑ →immunocompetent
IMMUNOLOGY: Note #1. 1 of 4
 o This B-cell have specific B-cell receptor to the specific b. IL-4 → converts naïve T cell into TH2 cells (anti-
foreign antigen and MHC II molecules with the foreign inflammatory pathway)
antigen, expresses on its membrane → can c. IL-12 → ↑converts naïve T cells into TH1 cells (pro
recognize any types of antigens due to the specific B- inflammatory pathway)
cell receptor d. TGF-beta, IL-1/IL-6/IL-23→↑converts naïve T cells
into TH17 cells
(ii) IL-5 e. TGF-beta → converts naïve T cells into T
↑ differentiation of proliferated B cells into memory B regulatory cells
cells and plasma cells T regulatory cells → promotes self-tolerance
Prevents autoantibodies → reducing autoimmune
(iii) IL-5/IL-6 reactions via TGF-beta and IL-10 release
↑ plasma cells to produce antibodies against specific
(1) TH2 Cells
antigens on pathogens
o Neutralization Stimulated by IL-4
 The antibodies bind to all the surface antigens on Genes to be activated
the pathogen → block the antigen from attaching o IL-2
to healthy host cell which can cause damage o IL-4
o Precipitation reaction o IL-5
 Antibody bind to the freely circulating antigen → Fight extracellular pathogens
causes precipitation → enhance opsonization
 Free antigen-antibody complexes may deposit into (i) Stimulate B cell pathway via IL-4/ IL-5
tissues causing type 3 hypersensitivity
o B cells → Plasma cell → ↑antibody production (IgE)
o Lysis
 Antibodies binds to the same pathogen → this (ii) Stimulates pathogen killing by activating
produces different types of proteins which
eosinophils
produces membrane attack complex → this
causes lysis of the cell (2) TH1 Cell
o Agglutination
Stimulated from IL-12
 When there’s a mismatch/incompatible blood →
Genes to be activated
antibodies bind to the antigen on the RBCs
o Gamma interferon (IFN-gamma)
o Opsonization
o Tumor necrotic factor
 When the pathogen is marked for destruction by
the antibody → the pathogen will be destroyed by Fight intracellular pathogens
the macrophages either through the antibody-
dependent cellular phagocytosis or complement- (i) Stimulates macrophages via IFN-gamma
dependent cytotoxicity o ↑ phagocytosis of pathogens
o ↑ MHC-II expression
III) T- LYMPHOCYTES
(ii) Stimulates B cell pathway via IL-2 and IFN-
Antigen presenting cells like macrophages, B-cells and
dendritic cells present antigens on their MHC II molecules
gamma
and then present the antigen to T-helper cells o Triggers IgG antibody production from plasma cells

(iii) Stimulates infected cellular killing via NK cells,

cytotoxic T cells
(3) TH17 Cells
Regulates inflammation and fights extracellular
pathogens
Regulates Inflammation response (pro and anti-
inflammatory) through use of neutrophils via IL-1/ IL-21
release

Figure 1. T-cell [Biology Dictionary]

(A) NAÏVE T-HELPER CELLS

Contains CD3 molecules
o Signaling molecule inside the cell
It can be activated into → TH1 cell or TH2 cell
Naïve T helper cells expresses:
o CD4 molecules that binds to the MHC II molecule on
the antigen presenting cells
o T-cell receptor that binds to the antigen expressed
on the MHC II molecule of antigen presenting cells
o CD28 molecules that bind to B7 molecules on
antigen presenting cells
The antigen presenting cell and T-helper cell interaction
as listed above activates T-helper cells to release the
following cytokines:
a. IL-2 → ↑T cell proliferation

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 IV) CELL MEDIATED IMMUNITY V) NATURAL KILLER CELLS

Triggered by endogenous antigen It is not a part of the adaptive immunity, only the
o The antigen is inside the cell causing damage to the mechanism of action is very similar to cytotoxic T-
cell cells
Mediated through the cytotoxic T-cells NK cells are large agranular lymphocytes
The activated natural killer cells release Perforins and
Granzymes which trigger apoptosis of viral infected cells
They can kill by 3 ways:
(1) Absent MHC I molecule expressed on the surface
All nucleated cells must have MHC I molecule expressed
on the surface
If a viral pathogen infects tissue cells → virus induces
abnormal MHC I complex or inhibit MHC I formation
This foreign MHC I or Absent MHC I due to viral infection
→ activates natural killer cells
(2) Different type of MHC I expressed on the surface
(MICA)
MICA doesn’t contain beta 2 molecule
Structure of MHC I molecule contains the
o Alpha 1, alpha 2, alpha 3 and beta 2 molecule
This foreign MHC I like molecule activates natural killer
Figure 2. Humoral vs cellular [Socratic] cells
(3) Through IgG mechanism
(A) CYTOTOXIC T-CELLS
Via antibody dependent cell mediated cytotoxicity
Kills virus infected cells and neoplastic (cancerous) cells If IgG antibodies made by plasma cells bind viral antigens
When cells are infected by virus or are cancerous this expressed on MHC-I complex this allows natural killer
o The virus can get integrated into the DNA → creates cells to bind to Fc portion of IgG antibody via their CD-16
viral proteins → endogenous proteins → can get protein this activates the natural killer cells→ the
integrated into the self-peptide → leads to expression activated natural killer cells then release Perforins and
of viral antigen or cancer antigens on MHC-I complex Granzymes which trigger apoptosis of viral infected cell
o MHC-1 complex of infected or cancerous cells interact
with CD8 molecule on cytotoxic T cell
The cancerous or viral antigen on infected or cancerous
cells interact with T cell receptor on cytotoxic T-cell
o Once cytotoxic T-cells are activated they release
perforins and granzymes
(i) Perforins
o This creates pores in infected or cancerous cells
(ii) Granzymes
o Moves through the pores and activates pro-apoptotic
gene → production of BAX proteins → which
removes BCL-2 from mitochondrial membrane which
allows cytochrome C to leak into cytoplasm → which
activate proteolytic enzymes called caspases →
which leads to cell destruction (apoptosis)

Figure 3. Cytotoxic T-cell [VectorStock]

ADAPTIVE IMMUNITY IMMUNOLOGY: Note #1. 3 of 4

 VI) REVIEW QUESTIONS VII) REFERENCES
The specific targeted responses constitute the third ● Humoral vs Cellular response. Socratic Q&A 2017 [digital
image] https://socratic.org/questions/what-are-examples-of-
line of defense in response to an infectious agent is humoral-immunity
called ● Biology dictionary. Helper T-cell [digital image]
a. Third line of defense https://biologydictionary.net/helper-t-cell/
b. Adaptive immunity ● Cytotoxic T-cell. Vector Stock [digital image]
https://www.vectorstock.com/royalty-free-vector/cytotoxic-t-cell-
c. Acquire immunity vector-23523146
d. All of the above ● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for
the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017
● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
The characteristics of adaptive immunity include Pearson; 2020.
a. Specificity ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
b. Immunologic memory ● Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB,
Campbell NA. Campbell Biology. New York, NY: Pearson; 2020.
c. Discrimination of self from non-self-molecules ● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL,
d. All of the above Loscalzo J. Harrison's Principles of Internal Medicine. New York
etc.: McGraw-Hill Education; 2018.
● lberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P .
Which of the cells are involved in adaptive Molecular Biology of the Cell. New York, NY: Garland Science;
immunity? 2002
a. B cells and T cells ● Murphy K, Weaver C. Janeway's Immunobiology. Garland
Science; 2016
b. B cells only
● Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology.
c. T cells only Lippincott Williams & Wilkins; 2012
d. Macrophages and NK cells ● Levinson W. Review of Medical Microbiology and Immunology.
Lange; 2012
T cell mediates
a. Humoral immunity
b. Non-specific defense
c. Cell mediated immunity
d. None of the above

The ratio between T cells and B cells is

a. 3:1
b. 1:3
c. 1:1
d. 1:2

B cells and T cells are originated from

a. The spleen
b. Thymus
c. Bone marrow
d. Lymph node

Injection of anti-venom against snake bite is an

example of
a. Active immunity
b. Passive immunity
c. Non-specific immunity
d. Phagocytic immunity

Which of the following statement are true regarding

adaptive immunity?
a. Prior exposure to antigen is essential
b. Prior exposure to antigen is not essential
c. It is a non-specific defense mechanism
d. Macrophages are the major cells involved

Active immunity involves

a. Contact with foreign antigens
b. Immunologic memory
c. Slow primary response
d. All of the above

Active immunity is produced by

a. Clonal section
b. Clonal expansion
c. Both A and B
d. All of the above

CHECK YOUR ANSWERS

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