The Adaptive or Acquired System:

Specific Generated Host Defenses

Session 10
SCID (severe combined immunodeficiency)

http://www.cbsnews.com/pictures/bubble-boy-40-years-later-look-back-
at-heartbreaking-case/

https://www.youtube.com/watch?v=B84GJOsioSA
Objectives

❑ Outline the elements of the adaptive (or acquired)

immune system
❑ Describe the functions of the adaptive response
❑ List the 5 types of antibodies and their functions
❑ Define serum and plasma
❑ Explain how a defect in T cells can cause
immunodeficiency
❑ Differentiate between necrosis and apoptosis
 Innate Immunity: Non-specific defense

First line of defense against pathogens

• Skin
• Gut Microbiota

• Complement
• Phagocytosis of microorganisms
• Inflammation
Adaptive Immunity: Specific defense
• Specialized Immune Cells
• Specific response
• Self/non-self recognition
• Memory generation

Specificity is based on antigen recognition

Antigen:
• foreign molecule recognized by adaptive immune cells
• elicit an immune response
• most immunogenic antigens are proteins
 Adaptive Immunity: Specific defense

• Takes time to develop (~5-7 days)

• Highly diverse and specific

• Generates memory

• Is why vaccinations work!

• Mediated by:
• B lymphocytes (humoral*)
• T lymphocytes (cell-mediated)
Classical vaccine
response

*Humoral = body fluids, blood and lymph

 Characteristics of
Innate and Adaptive Immunity

Innate Adaptive
❑ Antigen-independent ❑ Antigen-dependent

❑ Immediate response ❑ Lag time response

❑ Not antigen specific ❑ Antigen specific

❑ No memory ❑ Memory
B Lymphocytes
 B lymphocytes

• Produce antibodies in response to

specific antigens to fight infection

• Produce cytokines, chemical signals

that can change the behaviour of other
cells

• Act as Antigen Presenting Cells (APCs)

to activate other immune cells to
combat infection by cellular
mechanisms
http://www.roche.com/pages/downloads/phot
osel/061106/html/detail_3.html
 Terms to be familiar with:
Antigen

Antibody B (no recognition)

Pathogen Antibody A (recognition)

Pathogen Epitope
recognized by Antibody A

• Antigen is a foreign molecule that can be recognized by adaptive immune cells

and elicit an immune response

• Epitope is a specific site on an antigen recognized by immune cells or

antibodies

• Antibody is a protein produced by B cells that recognizes a specific epitope on

an antigen
 B lymphocytes

Production and Maturation

• In the bone marrow
• Antigen-independent

Activation
• Peripheral lymphoid organs (e.g. lymph glands)
• Antigen-dependent

Differentiation
• Plasma cells or Memory B cells
• Peripheral lymphoid organs
• Antigen-dependent
 B cell activation and differentiation
Antigen recognized 2nd encounter Population of memory
by IgM (months later) cells will become
activated at a faster
rate
IgM

Memory cells

Activated
B cell Plasma cells or effector
cells
Rapid cell division and
proliferation:
CLONAL EXPANSION
Antibodies are
All proliferating cells will have secreted
the same:
• B cell receptor (BCR)
• specificity for antigen
 B cell activation
B cell activation depends on the antigen:
• Thymus-dependent (TD) antigens (proteins)
• Thymus-independent (TI) antigens (mostly other
molecules)

TI antigen TD antigen
(e.g. bacterial cell wall components) (requires T helper cell contact)

T helper
B cell B cell cell
 Terms to be familiar with:

Cytokines:
• Soluble proteins secreted by immune cells
• Chemical signals that can change the behaviour of other cells
• Can cause B cell proliferation (clonal expansion) and “class
switching”

Class Switching:
• Changing Ig produced by B cell (e.g. IgM to IgG) with no loss of
antigen specificity
• Produces different antibodies depending on the cytokine
environment around plasma cells
 Plasma B cell proliferation and
antibody class switching
Antibodies
secreted

IgG
IFN-γ
Activated B cell

TGF-β IgA or IgG

IL-4

IL-2
IgE or IgG
IL-2 IL-4
IL-4 Clonal Expansion IL-5
IL-5
IgM

Abbreviations:
IL: Interleukin Plasma Cells
IFN-γ: Interferon gamma
TGF-β: Tumour Growth Factor beta
Basic antibody structure
Fab region:
• Variable region
• Antigen binding sites
• Different combinations at the
variable regions gives rise to a
large repertoire of different
antigen specificity

Fc region:
• Constant region
• Recognized by other immune cells
that have a Fc receptor (binding
site)
 Functions of antibodies

1. Opsonization
2. Complement activation
3. Agglutination
4. Neutralization
5. Antibody-dependent cell-mediated
cytotoxicity
 1. Opsonization

Bacterial cell

Antibodies recognize
bacterial antigens Macrophages have Fc
receptors that bind the
antibody Fc stem
 2. Complement activation
Antibodies bind to the
antigens on a
bacterium = Immune C3b
Complex which
activates classical
complement pathway.
C3b: split product of C
activation binds to
bacterial cell wall
(opsonin)

Formation of MAC
cell lysis
MAC: Membrane Attack Complex
 3. Agglutination

More efficient uptake of pathogens

(more invaders swallowed up by phagocytosis at once)
 4. Neutralization

Toxin

No attachment to host Blocks toxin

 5. Antibody-dependent
Cell-mediated Cytotoxicity

Infected cell

Used primarily by NK cells which

have Fc receptors
The stem of the Y-shaped antibody monomer is
called the

A. Fab region
B. Fc region
C. Variable region
D. Active region
Antibody classes and their functions
 Serum and Plasma

Serum
• Yellow liquid separated from coagulated blood
after centrifugation and fibrin removal
• Rich in proteins
• Mostly used for laboratory testing
• Contains no active blood clotting proteins
http://www.differencebetween.info/sites/default/files/i
mages/6/serum.jpg
Plasma
• Yellow fluid obtained by treating blood with an
anticoagulant
• RBCs removed by centrifugation
Plasma
• Sometimes used for some laboratory tests
• Contains intact blood clotting proteins that have WBC &
not been activated platelets

RBC
 Immunoglobulin G (IgG)

➢ Most abundant class of antibody in serum, 80% of

serum antibodies

➢ Transferred from mother to unborn child via

placenta. Confers immunity on fetus for ~ 6 months
IgG
➢ Highly efficient to activate complement

➢ High affinity for Fc receptors on phagocytic cell

membranes and can readily mediate opsonization
 Immunoglobulin M (IgM)
IgM

➢ 5-10% of serum antibody

Membrane
➢ 1st antibody produced in a primary response bound IgM

➢ 1st antibody to be synthesized by neonates IgM

J-chain
➢ When in membrane bound form (monomeric), it
forms the BCR (B cell receptor)

➢ Plasma cells secrete soluble IgM as a pentamer (5

molecules connected by a Joining chain)
IgM is secreted as
a pentamer
➢ IgM is more efficient to activate complement
 Immunoglobulin A (IgA)
➢ 10-15% of antibody in serum

➢ Predominant antibody in external secretions e.g. J-chain

breast milk, saliva, tears, and mucus in the
bronchial, digestive and genitourinary systems

➢ Exists as a monomer, but dimers can form and

these are held by a J-chain (joining chain) used for
easy transport across mucosal surfaces

➢ Prevents the attachment of bacteria or viruses to

mucosal surfaces, thus prevents colonization

➢ IgA secreted in breast milk protects the newborn

during the first months of life
 Immunoglobulin E (IgE)

➢ Extremely low concentrations in serum

(0.0002% of serum antibodies)

➢ Responsible for allergies

➢ Binds Fc receptors on mast cells and eosinophils

➢ Plays an important role in the neutralization of

parasites

Mast cell
 Immunoglobulin D (IgD)

➢ 0.2% of serum antibodies

IgM
IgD
➢ Expressed at the cell surface of mature B cells,
along with IgM

➢ Biological function not well established but Mature B cell

may be involved in mucosal immunity
The first class of antibody synthesized; especially
effective against microorganisms.

A. IgA
B. IdD
C. IgE
D. IgG
E. IgM
Antibodies that can be transferred from mother
to fetus:

A. IgA
B. IgD
C. IgE
D. IgG
E. IgM
Antibodies that protect mucosal membranes and
are a good reason to breast feed:

A. IgA
B. IgD
C. IgE
D. IgG
E. IgM
Antigen Presenting Cells (APC)
 Antigen Presenting Cells:
Showing what’s inside

MHC: Major Histocompatibility Complex (also

called HLA)

• MHC I: MHC class I

• MHC II: MHC class II
MHC I
MHC II

Exogenous
Self Protein

Endogenous
host Protein
No infection
Antigen Presenting Cells: Presenting
what’s inside

MHC I
MHC II

Exogenous
pathogenic
Virus Protein Protein

Danger!
Infected Cell
 Differences between MHCI and MHCII
MHC Class I MHC Class II

Found on all nucleated cells (self- Found only on APCs

marker)
Presents endogenous peptides Presents exogenous peptides
Activates CD8+ cytotoxic T cells Activates CD4+ helper T cells

CD: Cluster of Differentiation

• different proteins on surface of cells used to
characterize different cell types in the body

FYI: MHC terminology used by immunologists, but it

really refers to the molecule found in mice. In
humans, it is called HLA (human leukocyte antigen).
T lymphocytes
 T lymphocytes

Cytotoxic T Lymphocytes (CTLs): CD8+

• target and directly kill virus-infected cells, tumour cells, or
cells from a tissue graft

Helper T Lymphocytes: CD4+

• produce cytokines that support inflammation and activates
other immune cells
• activate B cells which leads to antibody production
• Activate T cytotoxin cells

Regulatory T Lymphocytes:
• can suppress other immune cells
 T lymphocytes

T cells communicating
with dendritic cells

http://today.uconn.edu/wp-
content/uploads/2014/10/FEI_IM_20130728_Serda_95_immunecell_orig.jpg

T cells attacking tumour cell

Attack!
https://www.mskcc.org/sites/default/files/styles/large/public/node/3
9463/images/t-lymphocytes-and-cancer-cell.jpeg
 T lymphocytes

Development
• Immature T cells travel to the thymus from the bone marrow
• In the thymus, development is dependent on self MHC molecules
and antigen
• Cells are programmed so they don’t auto-react to self

Activation
• In peripheral lymphoid organs (e.g. glands)
• MHC and antigen-dependent

Differentiation
• Become effector cells (Th or Tc) or memory cells
 Cytotoxic T Lymphocyte (Tc) Activation

Needs cell
contact:
“Cellular
Immunity”

T cells can recognize

CD8+ CD8+
foreign antigen due to:
• Infection
• Cancer
Activated T cells produce and secrete effector
molecules to destroy target cells:
• Perforin and granzyme
• Perforin helps granzyme enter the cell and kill
 Cytotoxic T Lymphocyte (Tc) Differentiation

CD8+ CD8+
Effector Cell

Memory Cell

CD8+

Activated Tc cells undergo clonal expansion

• Majority remain in the system as killer cells
• Small percentage become memory cells that can quickly activate after a
second encounter with the same antigen and MHC I
 Helper T cell (Th) Activation

Th1 *Activation of CTLs*

CD4+
Th Th2 *Helpers for B cell
activation*

Activated Helper T cells will secrete

cytokines or act as B cell helpers
 Helper T cell (Th) Differentiation

CD4+ CD4+

Effector cells

Memory Cell
CD4+

Activated Th cells undergo clonal expansion

• majority will remain in the system as helper cells
• small percentage will become memory helper cells, readily activated upon
a second encounter with the same antigen and MHC II
 T lymphocytes: Immunodeficiency

Partial Immunodeficiency
• Loss of function or numbers
• Patients highly prone to infections

Auto-Immunity
• T cells unable to differentiate self from non-self
• Hyper-immune responses

Severe Immunodeficiency
• Severe Combined Immunodeficiency (SCID)
• Fatal if untreated by bone marrow transplant

Acquired Immune Deficiency Syndrome

• HIV hijack Th cells
 How do immune cells kill infected
cells?

Apoptosis:
• Programmed cell death

Necrosis:
• Caused by cell injury, or infection/toxins
 Apoptosis and Necrosis

“Blebbing”
“Blebbing”
 Cell Death
Apoptosis:
• death of cells that occurs as a normal part of
development or as a targeted event
• does not trigger inflammation since “clean up” of
apoptotic bodies is done by phagocytic cells

Necrosis:

• death cell that is triggered by extrinsic factors

• detrimental to host and accompanied by an
inflammatory response
 Summary

• We need both the innate and adaptive immune systems

to maintain health

• The adaptive immune system is composed of humoral

immunity (B cells and antibodies) and cell-mediated
immunity (cytotoxic T cells/T helper cells)

• The two arms of the immune system will interact with

each other (cross-talk) and do not work completely
independent of each other