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Humoral (Antibody-Mediated) Immunity Involves production of antibodies against foreign antigens. Antibodies are produced by a subset of lymphocytes called B cells. B cells that are stimulated will actively secrete antibodies and are called plasma cells. Antibodies are found in extracellular fluids (blood plasma, lymph, mucus, etc.) and the surface of B cells. Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells. Also cause certain reactions against transplanted tissue.
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Page 1: Lecture 14

Humoral (Antibody-Mediated) Immunity Involves production of antibodies against

foreign antigens. Antibodies are produced by a subset of

lymphocytes called B cells. B cells that are stimulated will actively secrete

antibodies and are called plasma cells. Antibodies are found in extracellular fluids

(blood plasma, lymph, mucus, etc.) and the surface of B cells.

Defense against bacteria, bacterial toxins, and viruses that circulate freely in body fluids, before they enter cells.

Also cause certain reactions against transplanted tissue.

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Formation of antibodies by plasma cell

B cells develop from stem cells in the bone marrow

After maturation B cells migrate to lymphoid organs (lymph node).

Clonal Selection: When a B cell encounters an antigen it recognizes, it is stimulated and divides into many clones called plasma cells, which actively secrete antibodies.

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Formation of “Memory” cells Few activated B lymphocyte do not go

on to form plasma cells, but instead form moderate numbers of new B lymphocyte similar to the cell population

They circulate in the body to populate all lymphoid tissue

They remain dormant until activated once again of the same antigen

These lymphocyte are called memory cells

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Clonal Selection of B Cells is Caused by Antigenic Stimulation

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B Lymphocytes

Production of antibodies

Stimulate production of memory cells

Transformed into plasma cells

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Mechanism of activating clone of lymphocyte Activation of B lymphocyte is by

antigen attached to antibody in the cell membrane

Activation of T lymphocyte is by surface receptor proteins (T-cell marker) on the surface of the membrane

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Role of macrophage in activation process

Most invading organism are first phagocytized by macrophages

Macrophages pass these antigens to the lymphocytes

This activates specific lymphocytic clones

In addition, Macrophages secrete special activating substance (interleukin-1) that promote growth and reproduction of specific lymphocyte

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Role of macrophage in activation process

Most invading organism are first phagocytized by macrophages

Macrophages pass these antigens to the lymphocytes

This activates specific lymphocytic clones

In addition, Macrophages secrete special activating substance (interleukin-1) that promote growth and reproduction of specific lymphocyte

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Role of the T cells in activation B lymphocyte

Some of the T cells called helper cells secret substance lymphokines activate B lymphocyte

Without the aid of T helper cells, the quantity of antibodies formed by B lymphocyte is usually low

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Antibodies Immunoglobulins are a group of proteins (gamma

globulins) produced by the body from B lymphocytes and plasma cells in response to presence of foreign bodies (antigens).

They constitute 20% of all plasma proteins Antibody consist of two polypeptide building

blocks, a heavy chain and light chain Each antibody chain has a variable portion

and constant portion

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Classes of antibodies

There are five classes of antibodiesIgM, IgG, IgA, IgD and IgE IgG consist of 75% of the antibodies

of the normal person. IgE involve in allergy IgM effective in protecting the body

against invader

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Antibodies

Immunoglobulin Functions

lgG Main form of antibodies in circulation: production increased after immunization; secreted during secondary response

lgA Main antibody type in external secretions, such as saliva and mother’s milk

lgE Responsible for allergic symptoms in immediate hypersensitivity reactions

lgM Function as antigen receptors on lymphocyte surface prior to immunization; secreted during primary response

lgD Function as antigen receptors on lymphocyte surface prior to immunization; other functions unknown

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Ig E Ig D I g M

Ig A Ig G

184 184 970 160 160 Mass (KD)

trace Less than 1

5-10 10-15 70-75 % of total Ig

NO NO NO NO yes Cross placenta

NO NO NO yes yes In breast milk

NO NO NO yes NO In secretions

yes NO NO NO NO Binding with mast cells

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Mechanism of action of antibodies

1. Direct attack on the invader2. Activation of the complement

system

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Direct action of antibodies on invading agent Agglutination: large particle with

antigen are bound together into clump

Precipitation: Molecular complex of soluble antigen and antibody become insoluble

Neutralization: Antibodies cover the toxin side of antigen

Lysis: Attacking membrane of cellular agent

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Complement system for antibody action

Complement : describes system of about 20 proteins, many of which enzyme precursors

The principal actors in the system are 11 proteins designated C1 through C9, B and D

The enzyme precursors are inactive and they become activated by classic pathway

Classic pathway initiated by antigen-antibody reaction

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Classic Pathway

Opsonization and phagocytosis: Activate phagocytosis by neutrophils and macrophages causing these cells to engulf the bacteria to which antigen-antibody complex are attached

Lysis: The effect is rupturing the bacteria cell membrane

Agglutination: invading organism adhere to one another

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Classic Pathway

Neutralization of viruses: attach the structure of some viruses

Chemotaxis: Initiate chemotaxis of neutrophil and macrophages

Activation of mast cells and basophils: Release of histamine and other products

Inflammatory effects: increase blood flow, increase capillary leakage of proteins

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Consequences of Antibody Binding