INTRODUCTION TO IMMUNOLOGY

(a) Describe the specific (adaptive) and non-specific (innate) immune systems including active and
passive, natural and acquired immunity.

WHAT ARE THE DIFFERENCES BETWEEN INNATE AND ADAPTIVE IMMUNITY?

Innate Adaptive
First line of defence, providing immediate non- 2nd line of defence, adapts to the infection of any
specific protection against a wide variety of pathogen, comes after innate immune response
pathogens
 forms immunological memory

Requires no prior exposure to pathogen Requires prior exposure to pathogens

Non-specific to antigen Highly specific to antigen

WHAT ARE EXAMPLES OF INNATE IMMUNITY?

1. Physical barriers: skin, nose, cilia etc blocks entry of pathogens; shedding of skin cells lower
change of pathogen entry
2. Soluble factors
- Body secretions: saliva, tears, sweat and mucous secretions provide a washing action that
inhibits the colonization of fungi and bacteria
- Lysozyme: an enzyme present in tears, saliva and mucous secretions destroys bacterial cell walls
3. White blood cells: phagocytes, engulf pathogens such as bacteria and viruses
- Macrophages, neutrophils, dendritic cells (act as APCs to stimulate adaptive immunity)
4. Natural killer cells: cytotoxic lymphocyte that circulate throughout the body.
- Recognize the abnormal array of surface proteins, characteristic of virus-infected and cancer cells
- Instead of engulfing them, they release chemicals that leads to cell death
5. Natural fauna and flora: micro-organisms present on body surfaces covered by epithelial
cells and are exposed to external environment
- Prevent colonization of harmful pathogens that cause disease by competing with them

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 PHAGOCYTOSIS

1. Phagocyte recognizes antigens on pathogens as foreign

2. Engulf pathogen
3. Pathogen contained in endocytic vesicle
4. Lysosome fuses with endocytic vesicle
5. Pathogen is digested

FOR ADAPTIVE IMMUNITY, WHAT IS THE DIFFERENCE BETWEEN PASSIVE AND ACTIVE,
ACQUIRED VS NATURAL?

1. Passive immunity: providing antibodies or T cells directly (i.e production of antibodies

outside then introduce into body)
- Immediate and short-lived
- Can be acquired naturally (placental transfer of lgG antibodies; transfer of lgA antidbodies in
breast milk
- Acquired artificially by injection of antibodies or T cells via vaccinations

2. Active immunity: exposing the body to an antigen first to generate a subsequent immune
response (i.e make your own antibodies)
- Long lasting
- Acquired naturally (normal life experiences) by pathogen infections (influenza viruses)
- Acquired artificially by vaccinations using killed pathogens

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 (b) Outline the roles of B lymphocytes, T lymphocytes, antigen-presenting cells and memory cells in
specific primary and secondary immune responses

Summary

1. Antibody response (humoral response): Antibodies produced by B lymphocytes recognise

Cell- and bind to antigens, recruiting phagocytes to engulf pathogens

mediated 2. Generation of CD8 cytotoxic T cells: Cytotoxic T cells release chemicals and molecules to kill
response
infected cells.
3. Delayed type hypersensitivity: monocytes are activated by T helper cellsand mature into
macrophages which engulf pathogen. (not in syllabus)

WHAT CELLS ARE INVOLVED IN SPECIFIC IMMUNE RESPONSE?

- APCs, B lymphocytes, T lymphocytes, Memory cells

WHAT DO APCs DO TO PATHOGENS AND WHAT’S THEIR PURPOSE?

- Involved in antigen production

- Carry surface receptors that recognize common features (peptidoglycan cell wall) of pathogens
- Binding of APC receptor to pathogen stimulates APC to engulf pathogen and degrade inside cell
- Antigens are processed and then displayed on major histocompatibility complexes (MHCs) –
class II molecules
- T cells recognize antigens using T cell receptors
- E.G: dendritic cells, macrophages, B cells

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ANTIGENS: foreign molecules belonging to pathogens like viruses, bacteria

- Single antigen has several different epitopes, binding to a receptor with different specificity.

BACKGROUND OF B AND T CELLS

B and T lymphocytes are WBCs that come from lymphoid stem cells in the bone marrow.

Lymphocytes travel from bone marrow to thymus to mature into T cells. Lymphocytes that remain
and mature in the bone marrow develop as B cells.

WHAT ALLOWS FOR B CELLS & T CELLS SPECIFICITY IN RECOGNISING ANTIGENS

Different B cells and T cells (existing) each produce their own different antigen receptors that can
recognize and bind to specific epitopes by complementary 3D conformation.

- B cells take part in antibody production

- T cells take part in cell-mediated responses involving cytotoxic T cells and delayed type
hypersensitivity

Framework for Mechanism in Acquired Immune Response

1. Recognition and binding

2. Proliferation and differentiation of lymphocytes (to form
effector cells & memory cells
3. Effector cells fights pathogens
4. Memory cells remain in body, activated upon antigen re-
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HOW ARE SPECIFIC CD4-T CELLS ACTIVATED TO FORM HELPER T CELLS?

1. After an antigen-presenting cell (APC) engulfs and degrades a pathogen, it displays antigens
fragments on class II MHC mlc on cell surface
2. A specific CD4 T cell (naïve) binds to antigen via T cell receptor  promotes secretion of
cytokines by APC to CD4 T cells
3. 2nd signal(co-stimulus): interaction of CD28 protein on CD4 T cells and CD80/ CD86 protein
on APCs
4. Stimulated by cytokines, specific T cell undergoes proliferation and differentiation  many
clones of activated helper T cells(Th) and memory helper T cells  process is known as
clonal selection and expansion
5. These cells have same T cell receptors are complementary in 3D conformation to the same
MHC-antigen fragment complex

WHAT IS HELPER T CELLS’ PURPOSE?

1. Cell-mediated response: generation of cytotoxic T cells

- Helper T cells release cytokines  proliferation and differentiation of specific CD8 cells into
effector cytotoxic T cells & memory cytotoxic T cells

2. Antibody/ humoral response

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- Helper T cells bind to antigens presented by specific B cells and release cytokines 
proliferation and differentiation of specific B cells  antibody-producing plasma cells &
memory B cells

FOR ADAPTIVE & IMMUNOLOGICAL RESPONSE: memory T cells remain in the body for a long
time & its receptors have higher affinity for the same antigen  proliferate and differentiate faster
into effector cells

HOW ARE SPECIFIC CD8 T CELLS ACTIVATED TO FORM CYTOTOXIC T CELLS?

1. Antigen fragments (infected host cells) are presented on MHC- class I mlc and displayed on
cell surface, recognized by specific CD8 T cells’ receptors (TcR)
2. Nearby Helper T cells release cytokines
3. Specific CD8 T cells are activated by:
- Cytokines from helper T cells
- Binding to infected cells presenting the same antigen from pathogen
4. Specific CD8 T cells undergo proliferation and differentiation  many clones of activated
cytotoxic T cells and memory cytotoxic T cell (process known as clonal selection and
expansion)
5. These cells have the same T cell receptors that are complementary in 3D conformation to
the same MHC-antigen

WHAT’S CD8 T CELLS’ PURPOSE IN AN IMMUNE RESPONSE?

- Activated cytotoxic T cells (effector cells) kills the infected cell:

1. Secretes perforin, form pores in the infected cell membrane and disrupt membrane integrity
2. Release enzymes, granzymes that break down proteins. Granzymes enter the infected cell by
endocytosis and trigger cell death by apoptosis.

FOR ADAPTIVE & IMMUNOLOGICAL IMMUNE RESPONSE: memory cytotoxic T cells remain in the
body for a long time & its receptors have higher affinity for the same antigen  proliferate and
differentiate faster into effector cells

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HOW ARE SPECIFIC B CELLS ACTIVATED TO
FORM PLASMA CELLS?

1. Antigen on pathogen binds to B cell receptor of specific B cell via complementary shape. B
cell internalizes and displays antigen fragment on MHC- class II mlc
2. Antigen fragment displayed on MHC class II mlc binds to activated T helper cells, with
receptors specific for antigen fragment
3. Cytokines released by T helper cells activate B cell
4. Specific activated B cells undergoes proliferation and differentiation  many clones of
activated plasma cells (effector) and memory B cells (process known as clonal selection
and expansion)
5. These plasma cells produce and secrete antibodies with antigen-binding sites that have
same 3D conformation to specific B cell receptors (bind to same antigen)

WHAT IS PURPOSE OF PLASMA CELLS?

1. Involved in humoral response: antibodies are produced & secreted by plasma cells
2. Bind to specific foreign antigens on pathogens and neutralize them
3. Recruit phagocytes for engulfment (opsonization)

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FOR ADAPTIVE & IMMUNOLOGY IMMUNITY: memory B cells remain in the body for a long time &
its receptors have higher affinity for the same antigen  proliferate and differentiate faster into
effector cells

SUMMARY

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WHAT ARE MEMORY CELLS?

These cells persist in the boy after the infection and will rapidly proliferate to effector cells if the same
antigen is encountered again.

Effector and its forms

B cells Plasma cells

T cells T helper cells and cytotoxic T cells

HOW DO THEY CONTRIBUTE TO SECONDARY RESPONSE?

Secondary response: production of effector cells from memory cells upon subsequent exposure to
same antigen

Secondary immune response becomes faster, of greater magnitude and last longer due to more
antibodies produced by B cells, higher affinity to
antigen

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ANTIBODIES AND DIVERSTIY

Antibodies are secreted by plasma cells (effector cells which B cells differentiate into after activation
by helper T cells)

- Glycoproteins/ Immunoglobins
- 1st antibody produced during primary response is always lgM
- Other antibodies, lgG are secreted during subsequent secondary response
- Bind to specific antigens and mark pathogens for destruction
- Has a quaternary structure which is held tgt by ionic and hydrogen bonds, hydrophobic
interactions and disulfide brides between R groups of amino acids of 2 heavy and light chains/

WHAT ARE THE 2 MAIN FUNCTIONS OF ANTIBODIES?

1. Neutralization
- Antibodies bind to pathogen’s surface proteins and prevent infection of host cell by neutralizing
the function of those surface proteins  agglutination of pathogens, antibodies bind to more than
1 of the same pathogen at multiple binding sites, clumping pathogens together
2. Opsonization
- Binding of antibodies to antigens on surface of pathogens promotes phagocytosis by phagocytes
macrophages and neutrophils)

HOW ARE SPECIFIC COMPONENTS OF ANTIBODY’S STRUCUTRE RELATED TO THEIR

FUNCTIONS?

- Y-shaped molecule consists of 4 polypeptide chains, 2 identical heavy chains, 2 identical light
chains
- Each polypeptide chain consists of constant, C and variable regions, V

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Function of variable region:

- Variable regions of light and heavy chain forms an antigen-binding site

- Antigen-binding site provides a lock-and-key fit for specific binding to epitope of antigen
- Differences in variable regions  different binding sites for binding to different antigens

Function of constant region:

- Determine class of antibody (lgG, lgA, lgM)

- Allows binding to phagocyte (macrophage, neutrophil)
- Amino acid sequences vary little among different B cells

lgG secreted by plasma cells in the blood, able to

cross the placenta into the fetus  passive,
natural immunity
lgA Found in mucous, saliva, tears and breast milk
 passive natural immunity
lgM May be attached to surface of B cell or secreted
into blood, part of primary response

Structure Function
1. Disulfide bridges between chains Links heavy and light chains together
2. Hinge region Provides flexibility to change orientation to bind
to antigen
3. Variable region Determine conformation of antigen-binding
site, hence specificity of antibody
4. 2 identical antigen binding sites Antibody mlc cross link with antigens, ensure
binding is stable
5. Constant regions Allows binding to receptors on phagocytes
(opsonization)

WHAT ARE SEGMENTS IN THE GENES THAT CODE FOR LIGHT & HEAVY CHAINS OF
ANTIBODIES?

ANTIBODY DIVERSITY

- Occurs during B cell development

- Due to somatic recombination, somatic hypermutation, class switching

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HOW DOES SOMATIC RECOMBINATION IN DEVELOPING B CELLS RESULT IN ANTIBODY
DIVERSITY?

Somatic recombination is a form of DNA rearrangement where various gene segments are joined
together randomly and some intervening segments are enzymatically removed followed by
rejoining of remaining sequences. It occurs in in Developing B cell.

At the lg heavy chain gene locus, 1 V segment, 1 D segment and 1 J segment are randomly to
form a single VJ exon.

At the lg the light chain gene locus, 1 V segment and 1 D segment are randomly joined to form a
single VJ exon.

Different combinations of VJ/VDJ gene segments can give rise to different light and heavy chain
regions  increase antibody diversity

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HOW DOES SOMATIC HYPERMUATION IN DEVELOPING B CELLS RESULT IN ANTIBODY
DIVERSITY?

1. Somatic hypermutation is a random point mutation in the rearranged VDJ/VJ regions in

activated B cell. It occurs in activated B cell during clonal expansion.
2. Further diversifies variable regions of antibody for antigen binding
3. B cells that express higher affinity B cell receptors are selected for clonal expansion and
differentiation  plasma and memory cells
4. Outcome: secretion of antibodies can bind better to the same antigen (higher affinity antigen
binding sites)

CLASS SWITCHING

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1. DNA rearrangement at a constant gene segment of heavy chain gene locus in activated
B cells.
2. Variable regions of the heavy stay the same while constant regions changes.
3. Stimulated by cytokines released by T cells
4. Outcome: allows the production of different classes of antibodies, with same antigen binding
site, but different function.

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