humoral immunity lksay

HUMORAL IMMUNITY

DR.LAXMI KANTA SAY

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DEFINATION

IMMUNITY-protection against infections,& immune system is the collection of cells & molecules responsible for defending us against pathogenic microbes in our environment.

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FATHER OF IMMUNOLOGYLouis Pasture- Live attenuated vaccine for

fowl cholera, protective role of anthrax vaccine-1881

Jacques Miller –Modern Immunology

Edward Anthony Jenner-Humoral Immunity , small pox vaccine

Ilya Ilyich Menchnikov-Natural Immunity

HISTORY

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NOBEL LAUREATES

2011-Bruce A. Beutler & Jules A. Hoffmann"for the activation of innate immunity“

- Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity“

1984- Niel K. Jerne, Georges J.F. Kohler & Cesar Milstein "for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies

1960-Sir Frank Macfarlane Burnet for discovery of Acquired immunological tolerance

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FIRST LINE DEFENCE or

innate immunity

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ACQUIRED

HUMORAL

CELL-MEDIATED

SECOND LINE DEFENCE

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LYMPHOID ORGANS

INVOLVED

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CELLS INVOLVEDB-Lymphocytes:

Immunocompetency occurs in liver-mid –fetal life, bone marrow -late fetal life

1ST discovered in Birds , preprocessing organ called bursa of Fabricius

Produce Antibodies Conduct Humoral Immunity

T-Lymphocytes: Immunocompetency occurs in thymus Non antibody producing cells Conduct Cellular Immunity

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ANTIGEN

Defination- a substance,protein in nature & sometimes polysaccharide,which when introduced into a living animal evokes specific immune response ,either by producing specific antibody or specially sensitised T-cells or both.

Terms Hapten- (haptein-to grasp)low mol.wt. non protein,unable to

induce an immune response by itself but can become immunogenic when covalently linked to carrier protein. e.g. capsular polysaccharide of pneumococcus,cardiolipin.

Epitope- antigenic determinant-actual molecular structure that interacts with a single antibody molecule

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ANTIGEN PRESENTING CELLS

The cell populations that are specialized to capture microbial & other antigens, display them to lymphocytes, & provide signals that stimulate the proliferation & differentiation of lymphocytes.

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ANTIGEN PRESENTATION

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ANTIBODY

Specialized serum proteins that are formed in response to antigen & reacts specifically with that antigen.

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Structure and function of antibody molecules

Fab (fragment antigen binding) region – part of the antibody molecule where the antibody actually binds to the antigen for which it specific

Fc region – gives each antibody molecule other important biological properties not related to specificity

Five different forms of Fc region – each form is called the molecule’s “isotype”

Figure 4-4

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ENZYMATIC DIGESTION

Porter, Edelman & Nisonoff ,1959-64 develpoed technique for fragmentation of immunoglobulin papain digeston which has led to discovery of 5 main classes of immunoglobulin.

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TYPES

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SYNTHESIS OF B-CELL AND Ig

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B Cell Receptor (BCR)

Is an antibody that remains associated with the cytoplasmic membrane

Each B lymphocyte has multiple copies of a single type of BCR

Antigen binding site is identical to that of the secreted antibody for that particular cell

The randomly generated antibody variable region determines the BCR (it is not formed in response to antigens)

Each BCR is complementary to only one antigenic determinant

The BCRs on all of an individual’s B cells are capable of recognizing millions of different antigenic determinants

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B-CELL RESPONSE TO ANTIGEN

B-cell binds to antigen using antigen-specific receptor

Gets help from a T-helper cell Undergoes rapid cell replication

(“clonal expansion”) Each daughter cell

Produce antibodies of the IgM version

Switch the “isotype” of the antibody produced to the more effective IgG version

Improve its ability to form strong bonds with the antigen (“affinity maturation”)

Become a “Memory” B-lymphocyte

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DEVELOPMENT

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Why are these memory cells important?

When an antigen enters the body the first time, a delayed and rather slow antibody response is produced (called the “primary” response)

When the same antigen enters the body again, the expanded population of “memory” cells produces an almost immediate, more rapid and much more effective response (called the “secondary” response)

Called “memory” cells because the immune system seems to have “remembered” the first encounter with the antigen and “adapts” itself to respond much better the next time

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Consequences of Antibody Binding

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So what do antibodies do?

Isotype of antibody determines the effect the antibody will have after it binds to the antigen for which it is specific

Notice how many different

functions the IgG isotype has

Figure 8.1

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“Neutralization” of pathogens and bacterial toxins

Neutralization simply means preventing the pathogen or toxin from attaching to the body cell that pathogen could infect or the toxin could harm if that attachment was a required step

Simply preventing the attachment renders the pathogen or toxin harmless (has been “neutralized”)

The IgG isotype is particularly effective

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Helping a macrophage to attach (“opsonization”)

If macrophage could not attach using complement fragments or pathogen did not have anything to which the macrophage could attach to directly – can’t carry out phagocytosis

IgG antibodies specific for an antigen associated with the pathogen binds to the pathogen and the Fc part of the antibody binds to an Fc receptor on the macrophage

That binding (using the IgG antibody as a “bridge”) is

sufficient to initiate phagocytosis

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CLASSICAL PATHWAY

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DEFICIENCY OF COMPLEMENT

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CONCEPT OF MONOCLONAL ANTIBODY

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Monoclonal antibodies used in medicine

Standardized, unlimited reagents for diagnosis or therapy (human antibodies or “humanized” antibodies can be made)

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APPLIED DiGeorge Syndrome-congenital absence of thymus

Agamma-globulinemia or hypogamma-globulinemia -B-lymphocytes with absence of plasma cells

CLL-uncontrolled proliferation of B-lymphocytes

Multiple myeloma-malignant proliferation of plasma cells

AIDS-HIV binds to CD4,leads to loss of helper T cells,leads to failure of proliferation of T8 & B lymphocytes, loss of immune functions death from infections & cancer.