© Copyright DCU 2014.

Learning Object 3: Adaptive Immunity

1. Overview of Adaptive Immune System

1.1 Welcome

Notes:

Welcome back everyone. In this learning object we will focus on the adaptive immune
system.

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1.2 Learning Outcomes

Notes:

After taking this learning object, you should be able to:

 Describe the cells and components that make up the adaptive immune system
 Describe how these cells ‘communicate’ with each other
 Understand how these cells and components function in preventing disease
 Understand the role of the Major Histocompatibility complex

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1.3 Section 1 Overview

Notes:

Section 1 covers the fundamental aspects of the adaptive immune system, and highlights
the different phases during the adaptive immune response.

1.4 Brief Recap: Innate & Adaptive Immunity

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Notes:

In the previous learning object, we learned about the innate immune system and how the
receptors that we are born with can recognise pathogenic invaders. We now move to the
adaptive immune system that is not genetically determined and must be developed during
a pathogen invading event.

Here we note some diseases whose resistance is genetically determined.

This includes innate human immunity to canine distemper and murine immunity to
poliovirus. See more in the journal article related to this. (Click the icon to view.)

Acquired or adaptive immunity is developed during the lifetime of the individual.

It is not genetically determined and may be acquired artificially by a vaccine or naturally by
contracting an infection and fighting it off, once immune resistance has been established.

1.5 Question 1

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Feedback when correct:

That's right! Skin, sweat, tears, saliva, mucus, stomach acid, urine, defecation, and vomiting are
examples of physical and chemical barriers used in the body's first line of defence.

Feedback when incorrect:

You did not enter a correct response.

Notes:

Over the course of this learning object, we're going to focus on the 3rd line of immune
defence. But before that, just to check your understanding to date, here's a quick recap
exercise where you're asked to enter one example of a physical barrier - please enter just
one one-word example.

Correct (Slide Layer)

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Incorrect (Slide Layer)

1.6 Question 2

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Feedback when correct:

That's right! That's one of the five signs.

Feedback when incorrect:

You did not appear to enter a correct response.

Notes:

And now cast your mind back to the second line of defence which includes the
inflammation process.
See if you can recall one of the five cardinal signs of inflammation. Please enter just one
one-word example.

1.7 3rd Line of Defence

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Feedback when correct:

That's right! You selected the correct response.

Feedback when incorrect:

You did not select the correct response.

Notes:

Good, we're ready to go ahead and focus on the 3rd line of immune defence.
This is known as the adaptive immune system or specific immunity. It is composed of cell
mediated immunity and humoral immunity. These will now be investigated further.

1.8 Components of Human Immune System

Notes:

The lymphatic system is composed of central and peripheral organs, and connecting
lymphatic vessels.
Naive T and B cells are carried by the blood stream to the peripheral lymphoid organs
(Spleen, lymph-nodes etc.) where they can be activated by antigen.

The lymphatic vessels drain extracellular fluid or lymph from the peripheral tissues and into
lymph nodes.
Lymph then drains into the thoracic duct and empties into the subclavical vein.

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Please click on the icons to find out more about each component.
And if you want the overall view, click the button to view the table of components.

Table (Slide Layer)

1.9 Lymphocytes

Notes:

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The production of lymphocytes is called lymphopoiesis.

Lymphocytes arise from stem cells in the bone marrow. B-cells mature in the bone marrow
and then circulate around the body, while T-cells migrate to the thymus for further
maturation.

The naive T and B cells are then carried by the blood stream to the peripheral lymphoid
organs where they can be activated by antigen presenting cells.

1.10 3 Types of lymphocyte

Notes:

There are three key types of lymphocyte to consider: Naive, Effector, and Memory
Lymphocytes. Click the blue headings under the panels for further information on each type.

Naïve lymphocytes are

 Mature lymphocytes that have not previously encountered antigen.
 They migrate to peripheral lymphoid organs (lymph nodes), the sites where
immune responses start.

Effector lymphocytes are

 Activated lymphocytes capable of performing the functions required to
eliminate microbes.
 Activated helper T cells carry out cytokine secretion and cytotoxic T cells kill
infected cells.
 Effector B lymphocytes are antibody-secreting cells also known as plasma cells.

Memory lymphocytes are long living. They are generally functionally silent but mount rapid
responses to antigen challenge once initiated.

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Naive (Slide Layer)

Effector (Slide Layer)

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Memory (Slide Layer)

1.11 Phases of immune response

Notes:

This diagram displays a typical infection timeline and as you will see, the adaptive immune
response can be divided into phases:

On initial infection, the microbe begins to multiply within the host, as shown by the peach
curve.

When the level of microbe reaches a threshold level (indicated by the pink bar), the

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adaptive immune response is initiated.

When the adaptive immune response is initiated, the infection begins to subside.

On clearance of pathogen, immune memory is established.

If no innate immunity existed, the microbe would multiply exponentially with no chance of
an adaptive immune response.

1.12 Cellular Phases of the Adaptive Immune Reponse

Notes:

There are a number of important cellular functions carried out during the adaptive immune
response.

Take a few minutes now to explore this interaction on the key phases involved.

You can click the green Next button or the highlighted areas to step through each phase.

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2. Adaptive Responses

2.1 Section 2 Overview

Notes:

Section 2 covers the two arms of adaptive immunity: firstly, cell-mediated immunity carried
out by T cells and secondly, antibody mediated immunity, carried out by B cells.

2.2 T cells and Cell-mediated Immunity

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Notes:

T cells and Cell mediated immunity are complex topics and have a number of different
components.

Please hover over each of the circles to find out more. After you've done that, we're going
to move on to find out more about cytokines involved in cell-mediated immunity.

2.3 Cytokines

Notes:

Cytokines are an important part of cell-mediated immunity, they act as chemical messengers
to affect the behaviours of other cells.

Cytokines can be sub-divided into three different groups: interleukins, interferons and
chemokines.

For some examples of Cytokines, please click on the diagram shown.

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Interleukins (Slide Layer)

Interferons (Slide Layer)

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Chemokines (Slide Layer)

Table (Slide Layer)

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2.4 T cell-mediated immunity

Notes:

We are now going to focus on the cells involved in T cell-mediated immunity over the next
number of slides.

2.5 General Role of Helper T Cells

Notes:

In this activity, we will uncover the role of CD4 positive and CD8 positive T cells.
The destruction of intracellular bacteria, parasites and viruses is a process mediated by T
cells, as they cannot be recognised by antibodies. Please explore the diagram to find out
more.

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2.6 Key Types of T Cells

Notes:

We will now explore in more detail the function of each type of T Helper cell.
Please click on a cell to bring you to more information about each cell type.

2.7 CTL Cells 1

Notes:

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 Cytotoxic T cells or CTLs express a CD8 co-receptor. They kill cells harboring cytosolic
pathogens and cancer cells.
 Cytosolic pathogens for example Vaccinia virus, Influenza virus, Rabies virus and Listeria,
infect cells, they are recognised, digested and processed.
 Fragments are displayed on cell surface MHC class I molecules.
 Cytotoxic CD8 positive T cells express CD8 co-receptors and T cell receptors.
 The T cell receptor recognizes MHC I packaged antigenic peptide.
 The CTL releases Perforin which forms a pore on the infected cell causing apoptosis.

2.8 CTL Cells 2

Notes:

Cancerous cells or Cells infected with cytosolic pathogens display antigenic fragments
packaged in MHC Class I molecules on their surface.

Cytotoxic CD8 positive T cells lyse the infected cells by releasing perforin.

Perforin binds to the infected cell.

Ions and water rush into and out of the cell and the cell loses homeostasis. Lysing enzymes
are released and the infected cell is destroyed by apoptosis.

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2.9 TH1 Cells

Notes:

 Phagocytes recognize pathogens (using receptors e.g. scavanger receptor, complement

receptors and Toll-like receptors) and internalize them, the pathogen is lysed and
processed into antigen fragments.
 The fragments are packaged along with MHC class II and presented to T cells on the
surface. Co-stimulatory molecule B7 is also transported to the surface upon pathogen
uptake.
 TH1 cells expressing T cell receptor and CD4 co-receptor recognize processed antigen
fragments presented by MHC II molecules. The T cell becomes activated and induces the
production of co-stimulatory ligand CD28.
 When both signals are present the TH1 cell activates the macrophage to destroy
intracellular pathogens more efficiently, and the T cells specific for bacterial protein
proliferate and differentiate.

You can read more about this via the journal paper highlighted here.

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2.10 TH2 Cells

Notes:

 CD4 positive TH2 cells play an important role in activating B cells.

 The B cell receptor recognizes extracellular antigen, for example Clostridium tetani
and Polio virus, the antigen is internalized, processed and presented on MHC class II
molecules, it also expresses co-stimulatory molecule CD40.
 The T cell receptor on the CD4 positive T Helper 2 cells recognizes the MHC class II
molecule presented fragment. The TH2 cell is induced to expressed CD40L which binds
to CD40 on the B cell.
 The TH2 cell secretes cytokines IL-4, IL-6 and IL-5 driving the proliferation and
differentiation of the B cell into plasma cells. Plasma cells secrete antibody, or develop
into memory B-cells which persist for a long time and facilitate rapid response to
secondary antigen exposure.

You can read more about this via the journal paper highlighted here.

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2.11 Antibody-mediated (humoral) Immunity

Notes:

 Antibody mediated or humoral immunity involves the production of antibodies

against foreign antigens.
 Activated B cells differentiate into plasma cells that actively secrete antibodies.
 Antibodies are found in extracellular fluids and on the surface of B cells and are
involved in defense against bacteria, bacterial toxins, and viruses that circulate freely
in body fluids, before they enter cells.
 Humoral immunity can also cause certain reactions against transplanted tissue.

Click on the words highlighted in blue for further definitions:

Plasma cells: are terminally differentiated B cells whose main function is the antibody
production and secretion. They are found in the medulla of the lymph nodes, in splenic red
pulp and in the bone marrow.
Extracellular fluids: are fluids that are found outside cells, including blood plasma, lymph,
mucus etc.

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2.12 Antibodies are Proteins that Recognize Specific Antigens

Notes:

 A more detailed look at the antibody reveals a number of different sections. The IgG
antibody is made up of 2 heavy chains and 2 light chains, connected by disulphide bonds.
 The heavy and light chains are composed of constant and variable regions.
 The antigen binding region is composed of a variable heavy chain and a variable light
chain.
 Looking closer we can see the variable heavy and variable light domains that form the
antigen binding site, which recognises the epitope or the antigenic determinant of the
antigen.

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2.13 Role of antibodies

Notes:

The production of antibody molecules during acquired immunity has a number of outcomes:
 The antibodies can act as opsonins for enhanced phagocytosis of extracellular pathogens.
 They activate B cells to produce memory and plasma b cells.
 They cause the clumping and inactivation of bacterial and bacterial toxins, rendering them
ineffective.
 They trigger mast cell degranulation and the release of histamine.
 They activate complement
 And finally, they activate antibody dependent cellular activity.

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2.14 Specificity & memory in adaptive immunity

Notes:

 The production of antibody depends on whether it is the primary, secondary or tertiary

immune event.
 Naïve B cells encounter Antigen A,
 They stop circulating and enlarge to form a lymphoblast, creating approximately 1000
identical daughter cells. Activated B cells differentiate into plasma cells which produce
antibody.
 After 4 to 5 days the clonal expansion is complete, and the infection is eliminated.
 Once the antigen is removed, most of the B cells are eliminated, however, some remain
and become memory B cells.
 This is the basis for immune memory.
 Upon reinfection with the same antigen A, the presence of the memory B cells allow a
very rapid and intense secondary immune response, eliminating the pathogen even more
rapidly.
 It is immunological memory that permits successful vaccination and prevents pathogen re-
infection.

Click on the orange icons to find out more about primary and secondary responses.

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2.15 Origin of T Lymphocytes and Cell-Mediated Immunity

Notes:

We will now look at the origin of T lymphocytes and NK cells and how their differentiation
results in various functions in different parts of the body.

Multipotent stem cells are produced in the bone marrow.

Precursor T cells can become NK cells that can kill abnormal cells for example virus infected
cells and tumour cells. They are also important in defense against intracellular pathogens.

Alternatively, T cells can migrate to the Thymus where they undergo further differentiation,
they are released into the blood stream and circulate to the peripheral lymphoid organs.

CD8 positive CTLs are specialized to kill virus-infected cells.

Finally, Th1 cells are specialized to recognize MHC Class II on APCs. They activate the APC to
kill the intracellular pathogen and also secrete cytokines.

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2.16 Recap of acquired immunity

Notes:

In your own time, please carefully review the summary slide and become familiar with the
pathways involved in antibody and cell-mediated adaptive immunity.

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3. Major Histocompatibility Complex

3.1 Section 3

Notes:

Section three explores in more detail the role of the major histocompatibility complex of the
adaptive immune system.

3.2 Acquired Immunity Exercise

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Feedback when correct:

That's right! You selected all the correct responses.

Feedback when incorrect:

You did not select all the correct responses.

Notes:

Now here's a quick recap exercise. Please fill in the blanks to check your understanding of
some of the key terminology in the acquired immune response system. You'll need to get all
the answers right to receive a 'Correct' response.

3.3 Immune Adaptive team

Notes:

We like to think of the immune system as a tough and smart team...

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3.4 Role and Structure of MHC Molecules

Notes:

Let's take some time now to really focus in on the role and structure of MHC molecules. Step
through each of the tabs to find out more.

3.5 The fundamentals of MHC

Notes:

This document outlines the fundamentals of MHC molecules. You might find it helpful to
print it out and read.

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3.6 Section 3 Summary:

Notes:

And so to summarise the key points of this section...

Antigen receptors on T cells are specialized to only recognise antigenic peptide that is
presented by major histocompatibility complexes 1 and 2.

MHC molecules are membrane bound proteins that present peptides to T cells.

MHC Class I collects cytosol derived antigen, that are derived mostly from viruses.

MHC Class II molecules collect antigenic fragments from internalised pathogens that are
present in intracellular vesicles.

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4. Review

4.1 Section 4

Notes:

Section 4 re-addresses the important role of cell-mediated and humoral immunity. This can
be done by completing the exercises and filling in the missing words in the diagrams.

4.2 Quick Summary of Key Cell Types

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Notes:

First, let's start with a quick recap of the key cell types. Please click on each panel to access
further information. Then we'll move on to the questions and exercises.

4.3 Describe two key mechanisms of Lymphocyte communication. You're

advised to keep a record of your answer in your notes or learning journal.

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4.4 Which of the following are involved in lymphocyte communication?
(There may be more than one correct answer.)

Correct Choice

X Cytokines

X Interleukins

X Major Histocompatibility Complex (MHC)

X T Cell Receptors (TCR)

Immunoassays

Erythrocytes

Aptamers

Feedback when correct:

That's right! You selected all the correct responses.

Feedback when incorrect:

You did not select all the correct responses.

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4.5 Antigen Presentation to CD8+ T-cells

Feedback when correct:

That's right! You selected all the correct responses.

Feedback when incorrect:

You did not select all the correct responses. Please review the relevant earlier materials and try
again.

Notes:

Some of the labels in this diagram are missing. Please complete the diagram by filling the
blanks in the red "type your text here" fields. You'll need to get all the correct answers to
get a 'correct' response. You can skip ahead to view the correct answer but it's best to try at
least once before you do!

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4.6 Antigen Presentation to CD8+ T cells: Solution

4.7 Antigen presentation to CD4+ T cells

Feedback when correct:

That's right! You selected the correct response.

Feedback when incorrect:

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You did not select the correct response.

Notes:

Please complete the diagram by filling in the red blanks.

4.8 Antigen presentation to CD4+ T cells

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4.9 Antigen presentation to CD4+ T cells: Fill in the Blanks

Notes:

Please complete the diagram by filling in the blanks highlighted in red.

4.10 Antigen presentation to CD4+ T cells: Solution

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4.11 TH2 Cells

Notes:

And for the last activity of this learning object, please complete the diagram by filling in the
blanks around the red highlighted items.

4.12 TH2 Cells Solution

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4.13 Overall View

Notes:

This simplified diagram shows the relationship between the innate and adaptive immune
systems and provides an overview of the topics covered in this and the previous learning
object.

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