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Adaptive Immunity

Innate immunity, by itself, may not be sufficient to protect a host


against an invading pathogen or to prevent disease from occurring.
However, if innate immunity fails, the organism may yet be
detected and attacked by the mechanisms of adaptive immunity.
The innate and adaptive immune responses both function to protect against
invading organisms, but they differ in a number of ways.

(2)The innate immune system is constitutively present and reacts


immediately to infection. The adaptive immune response to an invading
organism takes some time to develop.

(2) The innate immune system is not specific in its response and reacts
equally well to a variety of organisms, whereas the adaptive immune system
is antigen-specific and reacts only with the organism that induced the
response.

(3) The adaptive immune system exhibits immunological memory. It


“remembers” that it has encountered an invading organism (antigen) and
reacts more rapidly on subsequent exposure to the same organism. The
innate immune system does not possess a memory.
How Acquired by Host Examples

Natural: Antibodies are produced


Active Immunity As a result of exposure to an by the host in response to the
infectious agent or one of its infectious agent itself (e.g.
products (antigens) recovery from the disease).

Artificial: immunization
(vaccination) with some product
derived from the infectious agent
(e.g. toxoid, killed cells, structural
components of cells, inactivated or
attenuated viruses, etc.).

Natural: Transplacental transfer of


As a result of the acquisition of antibodies from mother to fetus;
antibodies which have been transfer of antibodies from mother to
Passive Immunity produced in another animal (by infant in milk by nursing.
active means) or derived from cells
grown in tissue culture (e.g. Artificial: Injection of immune serum
monoclonal antibodies) from an individual previously
immunized or recovered from disease,
e.g. hepatitis; injection of serum from
an animal hyperimmunized with
tetanus toxoid.
Immunological Response

B-lymphocytes T-lymphocytes

Antibody-secreting plasma cells. (1) mediation of the B-cell response to antigen;


The plasma cells synthesize large (2) ability to recognize and destroy cells bearing
amounts of immunoglobulins foreign Ag on their surface; and
(antibodies) which will react (3) production of a variety of diffusible compounds
stereochemically with the stimulating called cytokines and/or lymphokines, which
antigen. include substances that are activators of
macrophages, mediators of inflammation,
chemotactic attractants, lymphocyte mitogens,
and interferon.
Immunological Response

Specificity Immunological Tolerance

An antibody or reactive T-cell Tolerance is brought about


will react specifically with the Memory in a number of ways, but
antigen that induced its formation; basically the immunological
it will not react with other Once the immunological system is able to distinguish
antigens. response has reacted to "self" antigens from "non-
produce a specific type of self" (foreign) antigens; it
antibody or reactive T-cell, it will respond to "non-self"
is capable of producing more but not to "self".
of the antibody or activated T-
cells rapidly and in larger
amounts.
4 Postulates of Clonal Selection Theory

1. Each lymphocyte bears a single type of receptor with a unique


specificity.

3. Receptor occupation is required for cell activation.

6. The differentiated effector cells derived from an activated


lymphocyte will bear receptors of identical specificity as the
parental cell.

9. Those lymphocytes bearing receptors for self molecules will be


deleted at an early stage.
Clonal Selection Theory
Mucosal-Associated Lymphoid Tissue

The mucous membrane lining of the digestive, respiratory and urogenital


systems are defended by a group of organized lymphoid tissues known as
MALT.

•Lymphoid cells in the Lamina Propria of intestinal villi

•Tonsils and appendix

•Peyer’s patches
Cutaneous Associated Lymphoid Tissue

The epidermal layer of the skin is composed largely of specialized epithelial


cells called keratinocytes. These cells secrete a number of cytokines that may
function to induce a local inflammatory reaction. These can express class II
MHC molecules and may function as antigen-presenting cells. Scattered
among the Langerhans cells, a type of dendritic cell, internalizes the Ag by
phagocytosis. These cells then migrate to the regional lymph nodes where they
function as potent activators of naïve T-helper cells.
Dendritic Cells
Granulocytes

Basophils
Neutrophils
Eosinophils

Agranulocytes

Lymphocytes Monocytes
Regulation of Hematopoeiesis

•Control of the levels and types of cytokines produced by bone-marrow


stromal cells.

•The prodcution of cytokines with hematopoietic activity by other cells,


such as activated T cells and macrophages

•The regualtion of the expression of receptors for hematopoietically


active cytokines in stem cells and prgenitor cells

•The removal of some cells by the controlled induction of cell death


Antigens
Factors influencing Immunogenicity
• Foreignness -

• The less a molecule is like a self-molecule, the more immunogenic it is likely to be.

• Conversely, if a pathogen produces a surface molecule that is very like one of your
own molecules, you will have a much harder time recognizing and responding to it
(like a wolf in sheep's clothing.)

• Even worse, if a pathogen produces a protein that resembles one of your own, you
may produce antibodies to your own protein when you develop immunity to the
pathogen.

• If your immune system does not get exposed early on to one of your own tissue
components, it will be able to produce an immunogenic response to it (lens
crystallins, for example).
2. Molecular Size

• Generally, the bigger the molecule, the more likely it is to trigger an immune
response.

• Usually it takes the equivalent of a peptide of 50 to 100 amino acids or so

1. Chemical Constitution

• A molecule seems to need a definite, interesting shape.

• If something is not a protein, but still has a definite, interesting conformation

• The molecule must also be something that can activate a T cell


Properties of the Biology of the Response that Affect Immunogenicity
1. Genotype of the Individual.

3. Nutritional Status.

5. Dosage

• Too little, and you don't mount a response.

• Oddly, too much may make the system unresponsive.

• Series of doses more effective than a single one (immunization series and booster
shots).

11. Routes of administration - matters how you expose

• GI tract least effective - although you may have had Sabin vaccine.

• Other routes (IV, IM, IP) will expose different immune organs first.

Different anatomic sites have different kinds of sentinel dendritic cells, macrophage
sub-types, and different kinds of circulating lymphoid cells.
Properties of Adjuvants

•Prolong antigen persistence

•Enhance co-stimulatory signals

•Induce granuloma formation

•Stimulate lymphocyte proliferation nonspecifically


Properties of B- Cell epitopes

•Nature of the antigen-binding site on the antibody molecules displayed


by B cells.

•On native proteins they are generally composed of hydrophilic amino


acids on the protein surface that are topographically accessible to
membrane-bound or free antibody.

•They can contain sequential or non-sequential amino acids.

•They tend to be located in flexible regions of an immunogen and display


site mobility.

•Complex proteins contain multiple overlapping B- cell epitopes, some of


which are immuno-dominant.
Properties of T- Cell epitopes
•Antigenic peptides recognized by T cells form tri molecular complexes
with a T-cell receptor and an MHC molecule.

•The antigen-binding cleft on an MHC molecule interacts with various


oligomeric peptides that function as T- cell epitopes.

•Antigen processing is required to generate peptides that interacts


specifically with MHC molecules.

•Epitopes recognized by T cells are often internal.

•Immuno-dominant T- cell epitopes are determined in part by the set of


MHC molecules expressed by an individual.
Superantigens

Superantigens are molecules which short-circuit the immune system,


resulting in massive activation of T-cells rather than the usual,
carefully controlled response to foreign antigens. It is believed that
they do this by binding to both the variable region of the beta-chain
of the T-cell receptor (V-beta) and to MHC II molecules, cross-
linking them in a non-specific way
• This results in polyclonal T-cell activation rather than the usual situation
where only the few clones of T-cells responsive to a particular antigen
presented by the MHC II molecule are activated.

• The over-response of the immune system produced results in


autoimmunity, as rare clones of T-cells which recognise self antigens are
activated.

• Immune suppression, as the activated cells subsequently die or are killed


by other activated T-cells. It is possible that such superantigens might also
induce apoptosis (pronounced "apotosis"), or 'programmed cell killing'
Immunoglobulins
Structure and Types
Structural basis of the FcRn–IgG interaction
Hybridoma Technology
Monoclonal Antibodies
The Discoverers

Cesar Milstein Georges Kohler


Selection of hybrid cells
Production of monoclonal antibody
Human Monoclonal antibody against HIV
Name Function Expression

All nucleated cells. MHC class I


proteins contain an α chain & β2-
Encodes heterodimeric peptide-
micro-globulin(not part of the
binding proteins, as well as
MHC class I MHC). They present antigen
antigen-processing molecules such
fragments to cytotoxic T-cells via
as TAP and Tapasin.
the CD8 molecule and also bind
inhibitory receptors on NK cells.

Encodes heterodimeric peptide-


On antigen-presenting cells MHC
binding proteins and proteins that
class II proteins contain α & β
modulate antigen loading onto
chains and they present antigen
MHC class II MHC class II proteins in the
fragments to T-helper cells by
lysosomal compartment such as
binding to the CD4 receptor on the
MHC II DM, MHC II DQ,
T-helper cells.
MHC II DR, and MHC II DP.

Encodes for other immune


components, such as complement
MHC class III region components (e.g., C2, C4, factor B) Variable
and some that encode cytokines
(e.g., TNF-α) and also hsp.
HLA-Genes of MHC molecules
MHC class- I molecule
X-Ray crystallography structure

Peptide
Ag presentation on MHC class-I molecule
MHC class- II molecule
X-Ray crystallography structure

Peptide
Ag presentation on MHC class-II molecule
Diagram showing MHC
class I-peptide binding
motif:-
Diagram showing MHC
class II-peptide binding
motif:-