MICROBIOLOGY

AND
IMMUNOLOGY
OPT 416
HS246
Dr MAIMUNAH MUSTAKIM
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LEARNING OBJECTIVES
AT THE END OF THE LESSON, STUDENTS ARE ABLE TO
EXPLAIN OR IDENTIFY:

I. B lymphocytes and antibody response.

II. Activation of B cells.
III. Primary and secondary responses.
IV. T cells and mechanism of their activations.
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B Lymphocyte and Antibody Response

• Antigen binds to B cell receptor
• Poises (self-control) B cell to respond
• In many cases B cell needs conformation from helper
T (T H ) cells. B cells activated dividing and
differentiating to produce antibodies.
• Antigen (Ag) enters the body and is phagocytized and
processed by macrophages
• These macrophages destroy Ag and present a portion
on the surface of the macrophage
• Macrophages are called antigen-presenting cells (APC)
 B-Cell Activation
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ü Ag binds to a B-cell receptor, the B-cell internalizes the Ag, enclosing

within a membrane-bound vacuole inside the B cell.
ü Ag is degraded into peptide fragments – delivered to proteins MHC
class II molecules that the move to the B-cell surface – process called
antigen presentation (pieces of the Ag is presented for inspection of
TH cells.
ü T cells have on their surface multiple copies of an antigen-specific
receptor called T-cell receptor (analogous to B-cell receptor).
ü TH receptor binds to one the peptide fragments being presented by
the B-cell – activation of B cell.
ü If the TH fails to recognize any of the fragments being presented by
the B-cell – unresponsive to future exposure to the antigen –
tolerance to that particular Ag.
ü However, the above mechanism is important in avoiding erroneous
responses against ‘self’ and other Ag.
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B-Cell Activation
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B-Cell Activation
• https://youtu.be/iIJulGXWm6Q
• https://youtu.be/_qF2jEe7ZWc
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Characteristic of Activated B Cells

Function – to enhance the
immune response:
1. Affinity maturation -
B cells bind Ag for the
longest duration will
proliferate.
Figure shows +++ –
indicate the most “fit”
binding which will
continue proliferation. The
++ will undergo apoptosis.
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2. Class switching – initial

program – secrete IgM.
Switch genetic program –
secrete other class of Ab –
to meet the most effective
mechanism against specific
Ag. Circulating B cells
most commonly switch to
IgG production. B cells in
mucosal associated
lymphoid tissues – switch
to IgA.
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3. Formation of memory cells – some of the

B cells from class switching – form memory
cells – persist in the body for years – sufficient
to give a prompt and effective 2o response
when the same Ag is encountered again later
time.
Ø As Ab clear the Ag, the Ab response is
reduced. The remaining Ag stimulate the
lymphocytes to undergo apoptosis. Memory B
cells – long lived – even in the absence of Ag
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Characteristic of Primary Response

• Lag period of 10 days – 2 weeks occurs before antibody
detection in blood (low amount of Ab).
• During this delay, the individual could very well
experience symptoms of an infection.
• However, the immune system is actively responding
where naïve B cells present Ag to TH cells resulting in B-
cell activation.
• Activated B cells proliferate and differentiate into
increasing numbers of plasma cells as long as antigen is
present – secrete thousand of Ab.
• Net result is slow steady increase in antibody titer
(concentration of Ab)
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Characteristics of
Secondary Response
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1. First response to an antigen – 5. Cytokines trigger
recognized by host B cells. proliferating B cells to
2. B cells divide to form plasma cells – switch from making plasma
begin to synthesize antibodies cells that produce IgG.

Lag 6. As IgM production decreases, IgG

production accelerates then decreases.
period

3. In few days, antibodies begin to appear in the blood plasma, increase

concentration over a period of time of 1 to 10 weeks.
4. First antibodies – IgM – bind directly to foreign substances.
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Secondary Response
7. B cells formed memory cells persist in lymphoid
tissues. They do not participate in initial response,
but they retain their ability to recognize a particular
antigen.
8. When an antigen recognized by memory cells
enters the blood, secondary response occurs.
9. Secondary response react much faster. IgM
(smaller quantities and short period) is produced
before IgG (followed sooner after IgM and in large
quantities)
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Primary & Secondary Immune

Response
• https://youtu.be/qUG4-yZVPUQ
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GENERAL CHARACTERISTIC OF T CELLS

• Have multiple copies of cell receptors on their surface
• T-cell receptor (TCR) consists of two polypeptide chains (either a
set of alpha and beta or gamma and delta)
• Receptors have variable region to recognize a specific antigen
• Role of T cells different from B cells
• T cells never produce antibodies
• T cells armed with effectors that interact directly with other cells
• T cell receptor does not react with free antigen
• Antigen must be present by APC

Disulfide
bond
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T Lymphocytes Antigen Recognition and Response

q During antigen presentation, the peptides from the

antigen are cradled in the groove of major
histocompatibility complex molecule (MHC molecule)
• Two types MHC
• MHC class I binds:
• endogenous antigens – made within the cells
• MHC class II binds:
• exogenous antigen – taken up by a cell
q MHC I – produced by all nucleated cells
q MHC II – produced by APC i.e dendritic cells, B cells and
macrophages
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Endogenous Exogenous
antigens antigens
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MHC
• https://youtu.be/t81EjpkCiss
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T Lymphocytes Antigen Recognition and Response
• Two major function of T cell populations
• Cytotoxic T cells
• Proliferate and differentiate to destroy infected or
cancerous “self” cells
• Have CD8 marker
• Recognize MHC class I (endogenous antigens)
• Helper T cells
• Multiply and develop into cells that activate B cells
and macrophages
• Stimulate other T cells; orchestrate immune response
• Have CD4 marker
• Recognize antigen display by MHC class II
(exogenous antigens)
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Activation of T Cells
Ø Dendritic cells – play crucial role in T-cell activation.
Ø Immature dendritic cells – in peripheral tissues
(beneath the skin) – gather various materials from skin
by phagocytosis and pinocytosis
Ø Dendritic cells – located below mucous membrane –
use tentacle-like projections – send between the
epithelial cells – able to sample materials from the
lumen and intestine.
Ø Dendritic cells travel to secondary lymphoid organ –
mature to a form able to present Ag to naïve T cells.
Ø Upon activation, T cells produce cytokine that
stimulates T-cell growth (IL-2). T cells also produce
adhesion molecules when activated. Acquire their
effector functions.
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T-Cell Activation
• https://youtu.be/JPh9P1aEfMI
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T Lymphocytes
Antigen Recognition and Response

• Functions of Tc (CD8) cells

• Induce apoptosis in “self” cells
• Cells infected with virus or intracellular microbe
• Destroys cancerous “self” cells
• Nucleated cells degrade portion of proteins
• Load peptides into groove of MHC class I molecule
• MHC class I molecule recognized by circulating Tc cell
• Cell destroyed by lethal effector function of
Tc cell
• Tc cells releases pre-formed cytokines to destroy cell
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Cytotoxic T Cell
• https://youtu.be/5TcH3ITMqOM
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• Functions of TH (CD4) cells

• Orchestrate immune response
• Recognize antigen presented by MHC class II molecules
• MHC class II molecules found only on APC
• If TH cell recognizes antigen, cytokines are delivered
• Cytokines activate APC to destroy antigen

Notes:
Cytokines are produced by a broad range of cells, including
macrophages, B lymphocytes, T lymphocytes and mast
cells, as well as endothelial cells, fibroblasts, and various
stromal cells; a cytokine may be produced by more than
one type of cell
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T Lymphocytes Antigen Recognition and Response
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Helper T Cell
• https://youtu.be/RUmmqFZQx9A
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T Lymphocytes Antigen Recognition and Response

• Role of TH cells in B cell activation

• If TH cell encounters B cell bearing peptide:
MHC class II complex
• TH cell responds by producing cytokines
• B cell is activated in response to cytokine
stimulation
• B cell proliferates and undergoes class
switching
• Also drives formation of B memory cells
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T Lymphocytes Antigen Recognition and Response

• Role of TH cells in macrophage activation

• Macrophages routinely engulf invading microbes
resistant to lysosomal killing
• TH cells recognize macrophage with engulfed
microbes resistant to killing
• TH cells activate macrophages by delivering
cytokines that induce more potent destructive
mechanisms
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Lymphocyte Development

• During lymphocyte development, B and T

cells acquire ability to recognize distinct
epitopes (from pathogens)
• Once committed to specific antigen, cells
“checked out” to ensure proper function
• B cells undergo developmental stages in
bone marrow
• T cells go through process in thymus