Download IMMUNOLOGY (Ms. Lucky Juneja)

IMMUNOLOGY
Ms. Lucky Juneja
Lecturer, School of
Biotechnology, DAVV
Immunity—the state of protection from infectious disease
Via both a non-specific and specific component.
The less specific component, innate immunity, provides the
first line of defense against infection, that are not specific to a
particular pathogen.
Phagocytic cells, such as macrophages and neutrophils,
barriers such as skin, and a variety of antimicrobial
compounds synthesized by the host all play important roles in
innate immunity.
Adaptive immunity, does not come into play until there is an
antigenic challenge to the organism.
Adaptive immunity responds to the challenge with a high
degree of specificity as well as the remarkable property of
“memory.”
Anatomoic Barriers
 Tend to prevent the entry of Pathogen .
 Mucous membranes lined at the alimentary, respiratory and
urogenital tracts.
 Many pathogens enter the body by binding to and penetrating
mucous membranes.*ex-saliva, tears, and mucous secretions
act to wash away potential invaders, contain antibacterial or
antiviral substances
 In the lower respiratory tract,it is covered by Cilia,hair like
protrusions of epithelial cell membrane.
 The movement of cilia propel mucus caused the entrapped
micro from these tracts.
Some organism escaping these defense mechanisms and are
able to invade the body through mucous membranes.e.g
Infuenza Virus.
Normal flora compete with microbes for attachment sites and
nutrients.
Adherence of bacteria to the mucous membrane due to the
interaction b/w hair like protusion on bacteria that is
Fimbriae/Pili.
Certain Glycoprotein or Glycolipid that experessed only by
epithelial cell of mucuos membrane of particular tissue.*
Physiologic Barrier
It include Temperature,Low pH,Chemical mediators.
Normal body temperature inhibits growth of some pathogens.
E.g. Chicken have innate immunity to Antrax due to high body
temp.
Acidity of stomach contents kills most ingested microorganisms.
Therefore newborns are susceptible to some diseases their
stomach contents are less acid than those of adults.
Lysozyme,Interferon,Complement are Soluble factor that
contribute to innate immunity.
Lysozyme are found in mucous secretion,tears.*
Interferon induces antiviral state in uninfected cells.*
Complement lyses microorganisms or facilitates phagocytosis.*
Phagocytic/Endocytic Barrier
Inflammatory Barrier
Adaptive Immunity
 Unlike innate immune responses.
 The adaptive immune system is composed of highly
specialized, systemic cells and processes that eliminate or
prevent pathogenic challenges.
 The adaptive or "specific" immune system is activated by
the “non-specific” and evolutionarily older innate immune
system.
 Adaptive immune responses are not the same in all
members of a species but are reactions to specific antigenic
challenges.
 Adaptive immune responses exhibit four immunologic
attributes:specificity, diversity, memory, and self/nonself
recognition.
 The antigenic specificity of the immune system permits it to
distinguish subtle differences among antigens.
 Antibodies can distinguish between two protein molecules that
differ in only a single amino acid.
 The immune system is capable of generating tremendous
diversity in its recognition molecules,allowing it to recognize
billions of unique structures on foreign antigens.*
Cells of immune system
 An effective immune response involves two major groups
of cells: lymphocytes and antigen-presenting cells.
 Lymphocytes are types of white blood cells produced in
the bone marrow by the process of hematopoiesis.*
 It display antigen binding cell-surface receptors, therefore
lymphocytes mediate the defining immunologic attributes
of specificity, diversity, memory, and self/nonself
recognition.
 B-Lymphocytes (B-cells), T- Lymphocytes (T-cells).
ANTIGEN-PRESENTING CELLS
 Activation of both the humoral and cell-mediated branches of
the immune system requires cytokines produced by TH cells.
Antigen Selection of Lymphocytes Causes
Clonal Expansion
 Clonal selection provides a framework for understanding the
specificity and self/nonself recognition that is characteristic of
adaptive immunity.
Antigens
• Antigen.*
• Immunogenicity/Antigenicity.*
• Factors that influence immunogenicity.*
Contribution of the immunogen to immunogenicity
•
•
•
•
Foreignness.
Molecular size. *
Chemical composition.
Complexity.
Foreignness
 When an antigen is introduced into an organism, the degree
of its immunogenicity depends on the degree of its
foreignness.
 The greater the phylogenetic distance between two species,
the greater the structural difference between them.
 Ex- BSA is not immunogenic when injected into a cow but is
strongly immunogenic when injected into a rabbit.
 BSA would be expected to exhibit greater immunogenicity in
a chicken than in a goat, which is more closely related to
bovines.
Chemical composition
• Size and foreignness are not, by themselves, sufficient to make
a molecule immunogenic.
• Synthetic homopolymers (polymers composed of a single
amino acid or sugar) tend to lack immunogenicity regardless of
their size.
• Copolymers composed of different amino acids or sugars are
usually more immunogenic than homopolymers of their
constituents.
• These show that chemical complexity contributes to
immunogenicity.
• Therefore, it is clear that all four levels of protein organization
contribute to the structural complexity of a protein and hence
affect its immunogenicity
SUSCEPTIBILITY TO ANTIGEN PROCESSING
AND PRESENTATION
 Large, insoluble macromolecules are more immunogenic
than small, soluble ones because the larger molecules are
more readily phagocytosed and processed.
 Macromolecules that cannot be degraded and presented
with MHC molecules are poor immunogens.
 Ex-polymer of D-amino acids, which are stereoisomers of
the naturally occurring L-amino acids.*
GENOTYPE OF THE RECIPIENT ANIMAL
 The genetic constitution (genotype) of an immunized animal
influences the type of immune response the animal manifests,
as well as the degree of the response.*
ADJUVANTS
 Adjuvant are substances , when mixed with an antigen and
injected with it, enhance the immunogenicity of that antigen.
 The antibody response of mice to immunization with BSA can be
increased fivefold or more if the BSA is administered with an
adjuvant.
They appear to exert one or more of the effects:1. Antigen persistence is prolonged.
2. Co-stimulatory signals are enhanced.
3. Local inflammation is increased.
4. The nonspecific proliferation of lymphocytes is stimulated.
Aluminum potassium
persistence of antigen.
sulfate
(alum)
prolongs
the
When an antigen is mixed with alum, the salt precipitates
the antigen.
 Injection of this alum precipitate results in a slower
release of antigen from the injection site, so that the
effective time of exposure to the antigen increases from a
few days without adjuvant to several weeks with the
adjuvant.
Epitopes
 Epitopes are the immunologically active regions of an
immunogen that bind to antigen-specific membrane receptors
on lymphocytes or to secreted antibodies.
 Paratope.
 B cells recognize soluble antigen.*
 T cells recognize only peptides combined with MHC
molecules on the surface of antigen-presenting cells.
Properties of B-Cell Epitopes Are Determined
by the Nature of the Antigen-Binding Site
 The B-cell epitopes on native proteins are composed of
hydrophilic amino acids on the protein surface that are
topographically accessible to free antibody.
 Amino acid sequences that are hidden within the interior of a
protein often consist of hydrophobic amino acids, and cannot
function as B-cell epitopes unless the protein is first
denatured.
 Antibody binds to an epitope by weak noncovalent
interactions.
 The antibody’s binding site and the epitope must have
complementary shapes that place the interacting groups near
each other.
 The size of the epitope recognized by a B cell can be no larger
than the size of the antibody’s binding site.
 Complex proteins contain multiple overlapping
epitopes, some of which are immunodominant.
 Immunodominant epitope*.
B-cell
Properties of T-cell epitopes
• Gell and Benacerraf compared the humoral (B-cell) and cellmediated (T-cell) responses to a series of native and denatured
protein antigens.
• Antigenic peptides recognized by T cells form trimolecular
complexes with a T-cell receptor and an MHC molecule.*
Hapten and Antigenicity
 Karl Landsteiner in the 1920s and 1930s created a simple,
chemically defined system for studying the binding of an
individual antibody to a unique epitope on a complex
protein antigen.
 When multiple molecules of a single hapten are coupled to
a carrier protein, the hapten becomes accessible to the
immune system and can function as an immunogen.
 Landsteiner found that the overall configuration of a hapten plays a
major role in determining whether it can react with a given antibody.
 For example, antiserum from rabbits immunized with aminobenzene
or one of its carboxyl derivatives (o-aminobenzoic acid, maminobenzoic acid, or p-aminobenzoic acid) coupled to a carrier
protein reacted only with the original immunizing hapten and did not
cross-react with any of the other haptens