Adaptive Immunity

Chapter 17
 The Big Picture

Innate defenses are present at birth and are general

defenses against potential pathogens.
Adaptive defenses are specific defenses that develop upon
exposure to antigens.
Refresh: The Big Picture
The Adaptive Immune System
Adaptive immunity: defenses that target a specific pathogen
• Acquired through infection or vaccination
• Primary response: first time the immune system combats a particular
foreign substance
• Secondary response: later interactions with the same foreign substance;
faster and more effective due to “memory”

Adaptive immunity consists of

(1) Humoral immunity
(2) Cellular immunity

Is vaccination an example of innate or adaptive immunity?

Overview: The Two Adaptive Systems

Humoral Immunity
Targets antigens within the body’s
environment (blood, fluids, tissue, etc.)
Consists of molecules:
Antibodies (immunoglobulins) produce by B
cells

Cellular Immunity
Targets antigens within our cells (e.g. virus
infected cells; tumor cells; intracellular
pathogens)
Consists of cells
T Cells
Animation: Humoral Immunity: Overview
Dual Nature of the Adaptive Immune System:
Humoral immunity
Humoral Immunity

Produces antibodies that combat foreign molecules known as antigens

B cells are lymphocytes that are created and mature in red bone marrow
• Recognize antigens and make antibodies
• Named for bursa of Fabricius in birds

Key: fights invaders and threats outside cells

• Extracellular bacteria and toxins, viruses before they enter a host cell, large
pathogens (e.g. fungi, helminths) that are too big to enter cells
Dual Nature of the Adaptive Immune System:
Cellular Immunity
Cellular Immunity

Produces T lymphocytes (T Cells)

• Recognize antigens processed by APCs
• Mature in the thymus

T cell receptors (TCRs) on the T cell surface contact antigens, causing the T cells
to secrete cytokines instead of antibodies

Key: attacks antigens that have already entered cells

• Viruses, cancer cells, intracellular pathogens
Recall: Cytokines Are Chemical Messengers of Immune Cells

Produced in response to a stimulus

Interleukins (ILs): cytokines between leukocytes
Chemokines: induce migration of leukocytes
Interferons (IFNs): interfere with viral infections of host cells
Tumor necrosis factor alpha (TNF-α): involved in the inflammation of autoimmune
diseases
Hematopoietic cytokines: control stem cells that develop into red and white blood
cells

Overproduction of cytokines leads to a cytokine storm (recall mechanism of a positive

feedback loop)
Summary: Key Cytokines and Their Roles
Review:

Cell most associated with humoral immunity

Cell that serves as the basis for cellular immunity

Humoral Immunity
In Depth
Humoral Immunity
Antibody-based immunity.

Antibodies in blood and tissues bind to foreign molecules (antigens)

present in blood and tissues.

B-cells are stimulated to produce antibodies which bind to antigens

and facilitate their removal. Antibodies also activate other
components of the immune system.

B-memory cells may provide immunity to future infections.

Humoral immunity is not effective against intracellular antigens.

 Antigens (Ag) and Antibodies (Ab or Ig)
Antigen
A molecule capable of inducing an
immune response. Microbes typically
have many antigens.

Epitope
(antigenic determinant) the portion of an
antigen recognized (bound) by an
antibody. Large antigens will contain
several epitopes.
Haptens
The most effective antigens are large and Antigens too small to provoke immune
complex (proteins). responses; attach to carrier molecules
B cells and Antigens
B-cells produce antibodies which
can bind to antigens.
antibodies can be on the cell
surface (Ig receptor) or secreted.
Antibody Structure (For a monomer)

• Globular proteins also called immunoglobulins (Ig)

• Valence is the number of antigen-binding sites on an antibody Variable regions (V) of the heavy
• Bivalent antibodies have two binding sites and light chains are responsible for
antigen binding
Constant regions (Fc) have binding
sites for phagocytic cells and
complement.
Concept: Antigen Specificity

This T Cell recognizes the

same antigen, but a
different epitope.

It will be able to go on to
activate the B cell to
become plasma and
memory cells
IgG
• Monomer
• 80% of serum Abs
• Fix complement
• In blood and lymph
• Cross placenta
• Enhance phagocytosis; neutralize toxins and viruses;
protects fetus and newborn
• Highest affinity for antigens
• Half-life = 23 days
IgM
• Pentamer
• 5–10% of serum Abs
• Fix complement
• In blood, in lymph, and on B cell surfaces
• Agglutinates microbes; first Ab produced in
response to infection
• Half-life = 5 days
IgA
• Dimer
• 10–15% of serum Abs
• In secretions including breast
milk.
• Mucosal protection
• Important in GALT and MALT
• Half-life = 6 days
IgD
• Monomer
• 0.2% of serum Abs
• In blood, in lymph, and on B cells
• On B cells, initiate immune response
• Poorly understood function; very similar
to IgM.
• Half-life = 3 days
IgE
• Monomer
• 0.002% of serum Abs
• Bound by Fc region to mast cells and
basophils.
• Allergic reactions; lysis of parasitic
worms
• Half-life = 2 days
 Antibody
Diversity
B cell repertoire: Our circulating B
cells are capable of producing huge
numbers of different antibodies with
ability to bind huge numbers of
different antigens.
This “repertoire” forms in the bone
marrow during B-cell development. The
antibody genes recombine randomly
such that each B-cell produces an
antibody with unique antigen-binding
capabilities.
Summary of Immunoglobulin Classes
Activation and Clonal Expansion of
Antibody-Producing Cells (1 of 4)
• Major histocompatibility complex (MHC) genes encode
molecules on the cell surface
• Class I MHC are on the membrane of nucleated animal
cells
• Identify “self”
• Class II MHC are on the surface of antigen-presenting
cells (APCs), including B cells
Activation and Clonal Expansion of
Antibody-Producing Cells (2 of 4)
• Inactive B cells contain surface Ig that bind to antigen
• B cell internalizes and processes antigen
• Antigen fragments are displayed on MHC class II molecules
• T helper cell (TH) contacts the displayed antigen fragment
and releases cytokines that activate B cells
• B cell undergoes proliferation (clonal expansion)
 B-Cell Activation

A B-cell becomes activated when it 1) binds to antigen and 2)

gets “help” from a helper T-cell.
Clonal Selection

Only B-cells which bind

antigen are activated to
divide and eventually
make plasma cells and
memory cells.

Clonal deletion
eliminates harmful B cells
 Two kinds of antigens

• T-dependent antigen
• Antigen that requires a TH cell to produce
antibodies

• T-independent antigens
• Stimulate the B cell without the help of T
cells
• Provoke a weak immune response, usually
producing IgM
• No memory cells generated
Animation: Antigen Processing and
Presentation: Overview
Animation: Humoral Immunity: Clonal
Selection and Expansion
 Results of the Antigen-Antibody Interaction

An antigen–antibody complex forms when antibodies bind to

antigens
• Strength of the bond is the affinity
• Protects the host by tagging foreign molecules or cells for
destruction. Mechanisms of action include:
• Agglutination
• Opsonization
• Antibody-dependent cell-mediated cytotoxicity
• Neutralization
• Activation of the complement system
 PROTECTIVE MECHANISM
OF BINDING ANTIBODIES
Agglutination TO ANTIGENS Activation of complement

Reduces number of infectious Causes inflammation and cell lysis

units to be dealt with

Complement

Antibody Bacteria Lysis

Bacterium

Opsonization Antibody-dependent cell-mediated cytotoxicity

Coating antigen with antibody Antibodies attached to target cell

enhances phagocytosis cause destruction by macrophages,
eosinophils, and NK cells
Phagocyte Eosinophil
Epitopes
Perforin
and lytic
enzymes

Large target cell (parasite)

Neutralization

Blocks adhesion of bacteria Blocks attachment

and viruses to mucosa of toxin

Virus

Toxin

Bacterium
Animation: Humoral Immunity: Antibody
Function
Cellular Immunity
In Depth
 Cellular Immunity- T-cells

• T cells combat infected and abnormal cells

• Arise from hematopoietic cells in the bone marrow.
• They travel from the bone marrow to the thymus for “maturation”
• Thymic selection: useless and dangerous T-cells are eliminated.
• Migrate from the thymus to lymphoid tissues
• Attach to antigens via T-cell receptors (TCRs)

• Only recognize antigens bound to MHC.

• 98% are eliminated in the thymus (thymic selection)
Cellular and Humoral Immunity
CD8+ T-cells (cytolytic T-cells)
eliminate infected and abnormal
cells.
CD4 + T-cells (helper T-cells)
activate and control humoral and
cell-mediated immunity.

Cluster of Differentiation (CD) markers are cell surface

receptors on leukocytes used by scientists to identify
cell types.
Types of T-Cells

Helper T-Cells (CD4+). (TH)The central controllers of the immune

response. Required for both humoral and cellular immunity.
• These cells can differentiate into one of several subtypes, including T H1, TH2,
TH3, TH17, and THF which secrete different cytokines to facilitate different
types of immune response.
Cytotoxic T-Cells (CD8+) (CTL). A specialized T cell that destroys
abnormal or infected cells.

Regulatory T-Cells. (Treg)Dampening or suppressing immune responses.

Help to remove cells that recognize self.
 B and T Antigen Binding

B-cells have antibody on their cell surface which binds directly to antigen.
T-cells have the T-cell receptor (TCR) which only binds antigen when it is
“processed and presented” by an antigen-presenting cell.
 T-cell Receptor (TCR)

The T-cell receptor (TCR) is on the surface of all T-cells. The TCR recognizes
antigen that is processed and presented by an antigen presenting cell.
Presentation involves MHC molecules.
 Antigen Processing and Presentation
The most important antigen-presenting cells are Dendritic Cells, Macrophages
and B-cells.

Antigens are “processed” into 10-20 amino acid peptides which are complexed
with MHC molecules and presented to T-cells.
 Major Histocompatibility Complex
A cluster of genes coding for proteins involved in antigen presentation
and self/nonself recognition.

• T-cells will only recognize and respond to antigens complexed with MHC
proteins on the surface of an antigen-presenting cell.
• MHC proteins on cell surfaces serve as signals by which the immune
system distinguishes “self from non-self”.
• MHC molecules are also called “transplantation” antigens because they
are the primary factor determining graft and transplant rejection or
acceptance.
Major Histocompatibility Complex

MHC Class I molecules are on the

surface of all nucleated cells.
MHC Class II molecules appear only
on lymphocytes.
Lymphocytes have both Class I and
Class II molecules on their surface.
T-cell activation step by step
1. An antigen-presenting cell (APC) phagocytizes (or otherwise internalizes) an antigen
2. The antigen is torn apart into 10-20 amino acid fragments (processing).
3. The fragments are combined with MHC molecules and located to the cell surface
4. The MHC-peptide combo is “presented” to a T-cell and bound by the T-cell receptor
(TCR)
5. If the T-cell has is naive (meaning it has never before encountered this antigen), a
second signal is need for activation to occur.
6. Activated T-cells proliferate and produce cytokines which activate other cells of the
immune system.
 Helper (CD4+) T-Cell Activation

Helper T-cells only recognize processed antigen complexed

with MHC class II but activation can only occur if a second
signal is present.
 Helper T-cells (CD4+) are in control

CD4 cells bind MHC II (CD8 bind MHC I) APCs produce IL-12, which activates TH1 cells
Activation of CD4+ cells results in cytokine production (esp. IL-2)
Macrophage
Activation
Macrophages that present
both antigen and
costimulatory molecules
induce T-helper cells to
become activated and
secrete cytokines.
The cytokines (IL-2 and
others) cause the
macrophage to enlarge,
divide, and produce more
lysosomes. They become
“angry killers”.
Cytolytic (CD8) T-Cell Activation

Better than this slide is this animation

Thymic Selection of T-cells

Removal of ‘dangerous’ (high

affinity) and useless T-cells (no
binding).
Retention of T-cells that bind
MHC with ~low affinity.

*We only keep 2% of the T-cells

that we produce- the other 98%
are deemed useless or
dangerous.
Natural Killers (NK cells)
• NKs are lymphocytes lacking
antigen receptors.
• NK cells will often kill cells
that lack the proper
concentration of MHC Class I
molecules (some virus-
infected cells and some
cancer cells).
• Killing is via apoptosis
• Kill cells via ADCC (they bind
to the Fc portion of
antibodies) and release
cytotoxic enzymes
Antibody-dependent cell-mediated cytotoxicity (ADCC)