The document discusses several theories of antibody formation: 1. Side chain theory proposed that cell surface receptors react with complementary antigens. This was later abandoned. 2. Direct template theory proposed antigens directly enter cells and act as templates for antibody production. 3. Indirect template theory proposed antigens generate copies that incorporate into the cell genome to direct antibody formation. 4. Natural selection theory proposed that natural antibodies pre-exist and antigens select for matching antibodies. Clonal selection theory, introduced by Burnet, widely explains the immune response and is based on lymphocytes bearing unique receptors that activate upon antigen binding.

1. Y. Prvaeen Kumar
Msc.Clinical Biochemistry

2. Other theory's
• Side chain theory
• Direct template theory
• Indirect template theory
• Natural selection theory

3. 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)

5. 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

7. Indirect template theory
• Burnet fenner 1949
• A genocopy of antigenic
determinant was in corporated in
antibody producing cell genome
and transmitted to progeny cells

8. 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

10. What clonal selection explains..?
• It explains how the cells of immune
system will react with a specific antigen
that enters body

11. Who introduced it..?
• Australian doctor Frank Macfarlane
Burnet in 1957
• Widely accepted model

12. 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.

13. 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).

14. 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).

15. Cell mediated immune response
cellular immunity
T-cell immunity
many cells
• Lymphocytes
• Macrophages
• Nk cells
• No anti
body's

16. 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

17. 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

18. 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.

19. Humoral immune response
Antibody mediated immunity
B-cell immunity
• Antibodies are secreted into body fluids (blood &
lymph)
• Humours (Latin) = fluid
• It is the major defense mechanism againest
bacterial infection

20. 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

21. • 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)

22. Reference