Y. Prvaeen Kumar

Msc.Clinical Biochemistry

Other theory's

• Side chain theory

• Direct template theory

• Indirect template theory

• Natural selection theory

Side chain theory

• Ehrlich (1900)

• Cells have surface receptors which have capability to react with substances having complementary side chains

• This theory is abandoned when Landsteiner explained

Antibodies could be formed against not only natural antigens but also against various synthetic chemicals (riboflavin, estradiol & L-thyroxine)

Direct template theory• Breinl & haurowitz

• Alexander

• Mudd

• The antigen enters antibody forming cells and acts as a template so that antibodies are formed with complimentary combining sites to antigen

• Pauling 1940 specificity was determined by folding of the antibody to form tertiary structure fitting antigen molecule

Indirect template theory

• Burnet fenner 1949

• A genocopy of antigenic determinant was in corporated in antibody producing cell genome and transmitted to progeny cells

Natural selection theory• Jerne 1955

• Million globulin molecules are formed in embryonic life with full range of antigenic specificities ( natural antibodies)

• Antigen when enters it combines with nearly matching

• This move on to the antibody producing cells they get activated and produce same kind of antibody

What clonal selection explains..?

• It explains how the cells of immune system will react with a specific antigen that enters body

Who introduced it..?

• Australian doctor Frank Macfarlane Burnet in 1957

• Widely accepted model

Postulates

1. Each lymphocyte bears a single type of receptor with a unique specificity (by V(D)J recombination).

2. Receptor occupation is required for cell activation.

3. The clone cells derived from an activated lymphocyte will bear receptors of identical specificity as the parental cell.

4. Forbidden cells will be deleted at an early stage.

Primary responseFirst exposure to a foreign antigen, a lag phase occurs in which no antibody is produced, but activated B cells are differentiating into plasma cells. (The lag phase can be as short as 2-3 days, but often is longer, sometimes as long as weeks or months.)

• The amount of antibody produced is usually low.

• Antibody level declines to the point where it may be undetectable.

• The first antibody produced is mainly IgM (although small amounts of Ig G are usually also produced).

Secondary Response• second dose of the same antigen is given days or even

years later, an accelerated immune response (IR) occurs. (This lag phase is usually very short (e.g. 3 or 4 days) due to the presence of memory cells.)

• The amount of antibody produced rises to a high level.

• Antibody level tends to remain high for longer.

• The main type of antibody produced is IgG (although small amounts of IgM are sometimes produced).

Cell mediated immune responsecellular immunityT-cell immunity

many cells

• Lymphocytes

• Macrophages

• Nk cells

• No anti body's

Antigen presenting cells

• This induces the invaded microorganism to release the antigenic materials…& this antigenic material is presented to T-cells

• Types

1. Macrophages (major role) present in all lymphoid tissues

2. Dendritic cells

a) Dendritic cells of spleen( filter blood)

b) Follicular dendritic cells lymph node (trapping ag)

c) Langerhans dendritic cells in skin (traps skin contact organisms

B-lymphocytes antigen receiving & presenting

Entry of micro organism

Phagocytosis or APC

Antigen is digested into peptides

Digested peptide binds with HLA in class II MHC molecule present on APC

TCR on T-cell recognizes the antigen and

T-cell activated

Activated T-cell proliferates

Enters circulation

interleukin also released from macrophages

T-cells types & role• Helper T-cells (CD4)

TH1…IL-2 activates other t cells and gamma interferon it increases the phagocytic activity

TH2…IL4 & 5 B-cell activation, proliferation of plasma cells, & antibodies by plasma cell

• Cytotoxic T-cells (CD8)(killer T-cells)

Releases cytotoxic substances (lysosomal enzymes)

Destroys own body tissue affected by foreign bodies

• Suppressor T-cells (regulatory T-cells)

Suppress the activity of T-cells (CD8 & CD4)

• Memory T-cells

Not enters circulation remains in tissue.

Humoral immune responseAntibody mediated immunity

B-cell immunity

• Antibodies are secreted into body fluids (blood & lymph)

• Humours (Latin) = fluid

• It is the major defense mechanism againestbacterial infection

Entry of micro organism

Phagocytosis or APC

Antigen is digested into peptides

Digested peptide binds with HLA in class II MHC molecule present on APC

BCR on B-cell recognizes the antigen and

B cell activated

B-cell proliferation

Plasma cells memory cells

interleukin also released from macrophages

• Plasma cells 2000 antibodies/sec (immunoglobulins)

• Memory cells

present in all lymph nodes in in-active form until the body is exposed with same antigen

second exposure to same antigen results in rapid production of antibodies…. ( This is the principle in vaccination)

Reference