This document discusses antigens, antibodies, and the complement system. It defines antigens as substances that stimulate antibody production when introduced into the body. It describes the structure and classes of antibodies, which recognize and bind to specific antigens. It then explains the three pathways that make up the complement system - the classical, alternative, and lectin pathways - which are activated by antigen-antibody binding or pathogen recognition and help clear antigens from the body.

1. ANTIGEN & ANTIBODIES,
COMPLEMENT
DR.KEERTHIKA.V
1 ST YEAR
PERIODONTICS AND IMPLANTOLOGY

2. ANTIGEN
An antigen is any substance which, when introduced
parenterally into the body, stimulates the production of an
antibody with which it reacts specifically and in an
observable manner.

3. Types
 Immunogenicity –[induction of an immune response]
 Immunological reactivity-[Specific reaction with
antibodies or sensitised cells]

4. Determinants of antigenicity
 Size
 Chemical nature
 Susceptable to tissue enzymes
 Foreignness
 Antigen specificity
1. Isospecificity
2. Autospecificity
3. Organ specificity
 Hetrogenetic specificity
1. Frossman antigen

5.  Weil-felix reaction-typhus fever
 Paul –Bunnell test-infectious mononucleosis
 Cold agglutinin test in primary atypical pneumonia

6. Biological classes of Antigens
 T cell-dependent[TD] antigens
 T cell-independent[TI] antigens

7. SUPER ANTIGEN

8. PATHOGEN RECOGNITION RECEPTORS
 Toll like receptors

9.  Scavenger receptors
 Mannose receptors

10. ANTIBODIES
Antibodies are glycoprotein molecules that recognise a
particular epitope on an antigen, bind specifically to it
and finally facilitate the clearance of that antigen.

11. Immunoglobulin chain
 Two identical heavy chain[H]
 Two identical light chain [L]
 Heavy chains are Five types
Alpha
Delta
Epsilon and
Mu
 L-chain are similar in all classes of immunoglobulins.

12. Structure of immunoglobulin molecule

13. Immunoglobulin classes

14. Abnormal immunoglobulins
 Mutiple myeloma
 Heavy chain disease
 Cryoglobulinemia

15. ANTIBODY DIVERSITY
 CLINICAL SIGNIFICANCE:
Immunoglobulin genes has made it possible to develop
engineered antibodies to treat various lymphomas and
autoimmune disease.
In HIV the genetic variation and mutability of the virus has
created a plethora of constantly changing antigens which
generate diverse immune responses.

16. COMPLEMENT SYSTEM
The term ‘complement [C] refers to a system of factors
which occur in the normal serum and are activated
characteristically by antigen-antibody interaction and
subsequently mediate a number of biologically
significant consequences.

17. ACTIVATION OF COMPLEMENT
SYSTEM & CELL LYSIS
 ACTIVATION OF COMPLEMENT SYSTEM IS
DONE BY THREE PATHWAYS;
 CLASSICAL PATHWAY-Activated by antibody-
antigen reaction.
 ALTERNATIVE PATHWAY-Activated on microbial
surface.
 LECTIN PATHWAY-Activated by plasma lectin that
binds to mannose residues on microbes.

18. FUNCTION
 Membrane Attack Complex (Terminal Complement Complex
C5b-9)
 Complement triggers the following immune functions:
 Membrane attack – by rupturing the cell wall of bacteria.
(Classical Complement Pathway)
 Phagocytosis – by opsonizing antigens. C3b has most important
opsonizing activity. (Alternative Complement Pathway)
 Inflammation – by attracting macrophages and neutrophils.
(Lectin pathway)

19. Classical pathway
 The classical pathway is triggered by activation of the
C1-complex. The C1-complex is composed of 1
molecule of C1q, 2 molecules of C1r and 2 molecules of
C1s, or C1qr2s2. This occurs when C1q binds
to IgM or IgG complexed with antigens.
 A single pentameric IgM can initiate the pathway, while
several, ideally six, IgGs are needed. This also occurs
when C1q binds directly to the surface of the pathogen.
Such binding leads to conformational changes in the
C1q molecule, which leads to the activation of
two C1r molecules.

20.  C1r is a serine protease. They then cleave C1s (another
serine protease). The C1r2s2 component now splits C4
and then C2, producing C4a, C4b, C2a, and C2b
(historically, the larger fragment of C2 was called C2a
but is now referred to as C2b).
 C4b and C2b bind to form the classical pathway C3-
convertase (C4b2b complex), which promotes cleavage
of C3 into C3a and C3b. C3b later joins with C4b2b to
make C5 convertase (C4b2b3b complex).

21. ALTERNATIVE PATHWAY
 The alternative pathway is continuously activated at a low
level, analogous to a car engine at idle, as a result of
spontaneous C3 hydrolysis due to the breakdown of the
internal thioester bond (C3 is mildly unstable in aqueous
environment). The alternative pathway does not rely on
pathogen-binding antibodies like the other pathways. C3b
that is generated from C3 by a C3 convertase enzyme
complex in the fluid phase is rapidly inactivated by factor
H and factor as is the C3b-like C3 that is the product of
spontaneous cleavage of the internal thioester.

22.  In contrast, when the internal thioester of C3
reacts with a hydroxyl or amino group of a
molecule on the surface of a cell or
pathogen, the C3b that is now covalently
bound to the surface is protected from factor
H-mediated inactivation. The surface-bound
C3b may now bind factor B to form C3bB.
This complex in the presence of factor D will
be cleaved into Ba and Bb. Bb will remain
associated with C3b to form C3bBb, which is
the alternative pathway C3 convertase.

23.  Pathogens, in general, don't have complement regulatory proteins
(there are many exceptions, which reflect adaptation of microbial
pathogens to vertebrate immune defenses). Thus, the alternative
complement pathway is able to distinguish self from non-self on the
basis of the surface expression of complement regulatory proteins.
 Host cells don't accumulate cell surface C3b (and the proteolytic
fragment of C3b called iC3b) because this is prevented by the
complement regulatory proteins, while foreign cells, pathogens and
abnormal surfaces may be heavily decorated with C3b and iC3b.
Accordingly, the alternative complement pathway is one element
of innate immunity.

24. LECTIN PATHWAY
 he lectin pathway is homologous to the classical
pathway, but with the opsonin, mannose-binding
lectin (MBL), and ficolins, instead of C1q. This
pathway is activated by binding of MBL to
mannose residues on the pathogen surface, which
activates the MBL-associated serine proteases,
MASP-1, and MASP-2 (very similar to C1r and
C1s, respectively), which can then split C4 into
C4a and C4b and C2 into C2a and C2b. C4b and
C2b then bind together to form the classical C3-
convertase, as in the classical pathway. Ficolins
are homologous to MBL and function via MASP
in a similar way.

25.  Several single-nucleotide polymorphisms have been
described in M-ficolin in humans, with effect on ligand-
binding ability and serum levels. Historically, the larger
fragment of C2 was named C2a, but it is now referred to
as C2b.
 In invertebrates without an adaptive immune system,
ficolins are expanded and their binding specificities
diversified to compensate for the lack of pathogen-
specific recognition molecules.