3.

Adaptive immunity
• Unlike innate immune system it does not come into play until
there is an antigenic challenge to the organism.
• responds to the challenge with a high degree of specificity as
well as the remarkable property of “memory.”
•silent and responds (or “adapts”) to the presence of infectious
microbes by becoming active, expanding, and generating potent
mechanisms for neutralizing and eliminating the microbes.
• displays four characteristic attributes:
i. Antigenic specificity
ii. Diversity
iii. Immunologic memory
iv. Self/non-self recognition
• Requires Cooperation between Lymphocytes and Antigen-
Presenting Cells (APC).
3.1 The lymphoid system
• Lymphocytes are one of the many types of WBC that are
produced in the bone marrow and circulates in the blood and
lymphatic systems, and finally reside in various lymphoid
organs.
• Lymphocytes produce and display antigen binding cell surface
receptors.
3.1.1 B lymphocytes and humoral immunity
• when they leave bone marrow, each expresses a unique
antigen-binding receptor (antibody) on its membrane.

antigen binding receptor

B lymphocyte
• Antibodies are glycol-proteins that consist of two identical heavy
polypeptide chains and two identical light polypeptide chains.
- Bind by disulfide bonds.
- The amino-terminal ends are the sites where antigen binds.
• When a naive B cell encounters the antigen that matches its
membrane bound antibody, then the cell divide rapidly
forming memory B cells and effector B cells called plasma
cells.
• Memory B cells have a longer life span than naive cells and
express the same membrane-bound antibody as their parent B
cell.
• Plasma cells produce the antibody in a form that can be
secreted and have little or no membrane-bound antibody.
Figure 3.3 Maturation and clonal selection of B lymphocytes
3.1.1.1 Antigen and antibody recognition
• Host defense requires different recognition systems
• The antigen-recognition molecules of B cells are the
immunoglobulins (Ig).
• Ig are proteins produced by B cells in a vast range of antigen
specificities.
• All Ig molecules have certain common characteristics like
recognition and binding to foreign antigen.
3.1.1.2 Antibody structure
• Antibodies are the first specific product of the adaptive immune
response to be identified.
• found in the fluid component of blood (plasma) and in
extracellular fluids.
• Y-shaped molecules whose arms form two identical antigen-
binding sites

Figure 3.4 Y shaped antibody structure

• Existes in five different classes – Isotypes
• Antibodies - bind specifically to molecules from the pathogen that elicited
the immune response
- recruit other cells and molecules to destroy the pathogen
Eg. neutralizes viruses and marks pathogens for destruction by
phagocytes and complement
• The antigen binding region varies extensively between
antibody molecules - V region.
• The region of the antibody molecule that engages the effector
functions – C region
• C region remains inserted in the membrane of the B cell.
3.1.4. Classes of immunoglobulin
- Different classes of immunoglobulin can be distinguished by
amino acid sequence of their C region
• Five different classes – IgM, IgD, IgG, IgA and IgE.
• IgG, IgA and IgM have been further divided into subclasses by
relatively minor differences in their CH regions.
• Their heavy chains are denoted by the corresponding lower-
case Greek letter (μ, δ, γ, α,).
• IgG- the only antibody class that cross the placenta & provide
humoral immunity to the infant.
– Most abundant immunoglobin 80% of serum Ig
– ~10mg/mL
– IgG1,2,3,4 (decreasing serum concentration)
– IgG1, IgG3 and IgG4 cross placenta
– IgG3 Most effective complement activator
– IgG1 and IgG3 High affinity for FcR on phagocytic cells, good for
opsonization
• IgM
- An antigen receptor on B cells and the first antibody produced in an
immune response
– 5-10% of serum immunoglobulin
– 1.5mg/mL
– Pentameric version is secreted
– High valence Ig (10 theoretical), 5 empirical
• IgA
- First line of defense against microbes entering through mucosal surfaces
– 10-15% of serum Ig
– Predominant Ig in secretions
• Milk, saliva, tears, mucus
– 5-15 g of IgA released in secretions!!!!
– Serum mainly monomeric, polymers possible but not common
• IgE
– Allergic reactions are predominantly associated with IgE
– Very low serum concentration, 0.3g/mL
– Participate in immediate hypersensitivities reations. Ex. Asthma,
anaphylaxis, hives
– Binds Mast Cells and Blood Basophils thru FcR
– Binding causes degranulation (Histamine Release)
• IgD
– This immunoglobulin functions primarily as an antigen receptor on B cells
andis probably involved in regulating B cell function when it encounters
antigen.
– Low serum concentrations, ~30g/mL
– IgM and IgD, Expressed on B-cell Surface
• The immunoglobulin heavy chains cause the various
isotypes to differ which include
- the number and location of inter-chain disulfide bonds,
- the number of attached oligosaccharide moieties,
- the number of C domains, and the length of the hinge region
- IgM and IgE heavy chains contain an extra C domain that
replaces the hinge region found in γ, δ, and α chains. The
absence of the hinge region does not imply that IgM and IgE
molecules lack flexibility; electron micrographs of IgM
molecules binding to ligands show that the Fab arms can
bend relative to the Fc portion. However, such a difference in
structure may have functional consequences that are not yet
characterized.
- Different isotypes and subtypes also differ in their ability to
engage various effector functions.
Structural organization of the main human
immunoglobulin isotype monomers.
3.2. T-lymphocytes (T-cells) and CMI

• CMI is due to the direct action of T cells, which

distinguishes it from immunity mediated by antibodies
(humoral immunity).
• T cells have evolved to protect us against intracellular
microbes (viruses and some bacteria) and to help B cell
responses.
• During its maturation within the thymus, the T cell comes
to express a unique antigen-binding molecule, called the
T-cell receptor, on its membrane.
• Unlike antibodies that recognize the three-dimensional
shape of antigens, the T cell antigen receptor (TCR)
only recognizes linear antigens (peptides) bound to
MHC molecules,
• Helper (CD4+) T cells recognize peptide antigens in the
context of MHC class II molecules that are expressed by
dendritic cells, macrophages and B cells.
• Cytotoxic (CD8+) T cells recognize peptides associated with
MHC class I molecules.
• Types of MHC molecules:
i. Class I MHC molecules
-expressed by nearly all nucleated cells of vertebrate species
- consist of a heavy chain linked to a small invariant protein
called beta-2 microglobulin.
ii. Class II MHC molecules
- consist of an alpha and a beta glycoprotein chain
- expressed only by antigen-presenting cells.
• When a naive T cell encounters antigen combined with a MHC
molecule on a cell, the T cell proliferates and differentiates
into memory T cells and various effector T cells.
• Subpopulations of T cells:
T helper and T cytotoxic cells can be distinguished from one
another by the presence of either CD4 or CD8 membrane
glycoproteins on their surfaces.
the regulatory T cells (Tregs) formerly known as suppressor T
cells, are other subpopulation of T cells which modulate the
immune system, maintain tolerance to self antigens, and
prevent autoimmune disease.
- Tregs express the biomarkers CD4, FOXP3, and CD25 and are
thought to be derived from the same lineage as naïve CD4
cells.
- Because effector T cells also express CD4 and CD25, Tregs
are very difficult to effectively discern from effector CD4+,
making them difficult to study
Figure 5.7 T cell bearing CD4 functioning as TH cell and T cell bearing
CD8 functioning as TC cell, respectively.
• After a TH cell recognizes and interacts with an antigen–
MHC class II molecule complex, the cell is activated
becoming an effector cell that secretes various growth factors
known collectively as cytokines.
• The secreted cytokines play an important role in activating B
cells, TC cells, macrophages, and various other cells that
participate in the immune response.
• Under the influence of TH-derived cytokines, a TC cell that
recognizes an antigen–MHC class I molecule complex also
proliferates and differentiates into an effector cell called a
cytotoxic T lymphocyte (CTL).
• the CTL generally does not secrete many cytokines and
instead exhibits cell-killing or cytotoxic activity.
Kinds of T helper cells

 Th1 lymphocytes
- recognize antigens presented by macrophages and function
primarily to activate and heighten cell-mediated immunity by
producing cytokines such as IL-2, IFN-gamma and TNF-beta.
• These cytokines enable T8-lymphocytes to proliferate and
differentiate into cytotoxic T– lymphocytes
- capable of destroying infected host cells and mutant cells;
- activate cytotoxic T– lymphocytes and NK cells;
- activate macrophages enabling them to destroy intracellular
pathogens;
- stimulate the production of opsonizing and complement-
activating antibodies for enhanced attachment during
phagocytosis; activate neutrophils; stimulate increased
production of monocytes in the bone marrow; and function as
chemoattractants for phagocytes.
Th2 lymphocytes

- recognize antigens presented by B-lymphocytes.

- produce cytokines such as IL 2, 4, 5, 10, and 13 that
promote antibody production.
- these cytokines enable activated B-lymphocytes to
proliferate, stimulate activated B–lymphocytes to
synthesize and secrete antibodies, promote the
differentiation of B-lymphocytes into antibody– secreting
plasma cells, and enable antibody producing cells to
switch the class of antibodies being produced.
- Another major function of the cytokines produced by
Th2 cells is to enable B– lymphocytes to activate
eosinophils and produce increased amounts of IgE against
helminths.
Figure 5.8 T helper cells following uptake of a microbe, APCs produce IL-
12, and present microbial-derived peptides to specific Th0 cells. In the
presence of IL-12 and IFNg, Th0 cells differentiate into Th1 cells
whereas in the presence of IL-4 and other Th2 cytokines the Th0 cells
Comparison of antigen recognition by T cells and B cells
 Reading assignment

 Cytokines and their role in CMI