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The Alternative Complement Pathway

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Presentation on theme: "The Alternative Complement Pathway"— Presentation transcript:

1 The Alternative Complement Pathway
The alternative complement pathway is mediated by C3b, either from the classical or from C3 hydrolysis by water. (Water can hydrolize C3 and form C3i, a molecule that functions in a manner similar to C3b).

2 Activation of the alternative complement pathway begins when C3b (or C3i) binds to the cell wall and other surface components of microbes. Alternative pathway protein Factor B then combines with the cell-bound C3b to form C3bB. Factor D then splits the bound Factor B into Bb and Ba, forming C3bBb.

3 A serum protein called Properdin then binds to the Bb to form C3bBbP that functions as C3 Convertase. C3 convertase capable of splitting hundreds of molecules of C3 into C3a and C3b. The alternative complement pathway is now activated.

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5 Some of the C3b subsequently binds to some of the C3bBb to form C3bBb3b, a C5 convertase capable of splitting molecules of C5 into C5a and C5b.

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8 Antigens Substance that reacts with antibody molecules and antigen receptors on lymphocytes. An immunogen is an antigen that is recognized by the body as non-self and stimulates an adaptive immune response. Both antigens and immunogens are usually referred to as Antigens.

9 Antigens To be Immunogenic, the antigen must possess three characteristics: High molecular weight. Chemical complexity. Foreignness (recognized as nonself by the body).

10 Antigens Chemical nature of antigens
Chemically, antigens are large molecular weight proteins (such as glycoproteins, lipoproteins, and nucleoproteins) and polysaccharides ( lipopolysaccharides). These protein and polysaccharide antigens are found on the surfaces of viruses and microbial cells (bacteria, fungi, protozoans) and human cells.

11 Antigens 2. Epitopes of an antigen
The portions or fragments of an antigen that react with receptors on B-lymphocytes and T-lymphocytes, as well as with free antibody molecules.

12 Antigens Some antigens, such as polysaccharides usually have many epitopes, but all of them of same specificity. Proteins are more immunogenic than Polysaccharides; they are chemically more complex.

13 Antigens A microbe, such as a single bacterium, has many different proteins and polysaccharides on its surface that collectively form its various structures, and each different protein may have many different epitopes.

14 Antigens Therefore, immune responses are directed against many different parts or epitopes of the same microbe. (For example bacterial cell wall alone may contain over 100 different epitopes.) Even simple viruses possess many different epitopes

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16 Antigens 3. Recognizing an antigen as foreign
B-lymphocytes and T-lymphocytes are the cells that carry out the immune responses. The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes and T-lymphocytes by means of epitope-specific receptor molecules.

17 Antigens 4. Substances that act as antigens
In terms of infectious diseases, the following may act as antigens: Microbial structures: Cell walls, Capsules, Flagella, Pili. Viral capsids, Envelope-associated glycoproteins.

18 Antigens B. Microbial toxins
Certain non-infectious materials may also act as antigens if they are recognized as "non-self" by the body. These include: Allergens (dust, pollen, hair, foods, Animal dander, bee venom, drugs, and other agents causing allergic reactions); Foreign tissues and cells (from transplants and transfusions).

19 The body's own cells that the body fails to recognize as "normal self" (cancer cells, infected cells). Hapten: small molecule that by itself is not immunogenic but can act as an antigen when it binds to a larger protein molecule.

20 Antibodies (Immunoglobulins)
Humoral Immunity refers to the production of antibody molecules in response to an antigen. These antibodies molecules circulate in the blood and enter the tissue via inflammation. Antibodies or immunoglobulins are specific glycoprotein produced by B-lymphocytes and plasma cells in response to a specific antigen and capable of reacting with that antigen.

21 Antibody Structure There are 5 classes of human antibodies: IgG, IgM, IgA, IgD, and IgE. The simplest antibodies, such as IgG, IgD, and IgE, are "Y"-shaped macromolecules composed of Four Glycoprotein Chains.

22 Antibody Structure There are two identical Heavy chains (H) having high molecular weight that varies with the class of antibody. In addition, there are two identical Light chains (L) which have lower molecular weight. The four glycoprotein chains are connected to one another by: disulfide (S-S) bonds.

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25 Antibody Structure The area where the top of the "Y" joins the bottom is called the Hinge. This area is flexible to enable the antibody to bind to pairs of epitopes various distances apart on an antigen.

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27 Antibody Structure The two tips of the "Y" monomer are referred to as the Fab portion of the antibody. The bottom part of the "Y", the C terminal region of each glycoprotein chain, is called the Fc portion. The Fc portion is responsible for the Biological activity of the antibody.

28 Antibody Depending on the class and subclass of antibody, biological activities of Fc portion of antibodies include the ability to: Activate the complement pathway (IgG & IgM). Bind to phagocytes (IgG). Bind to mast cells and basophils (IgE). Bind to NK cells (IgG).

29 The 5 Classes of Human Antibodies
IgG (Immunoglobulin G) It makes up approximately 80% of the serum antibodies. It has 7-23 days life time depending on the subclass. IgG has 2 epitope-binding sites.

30 Antibody IgG The Fc portion of IgG can
Activate the classical complement pathway. Bind to macrophage and neutrophils for enhanced phagocytosis. Can bind to NK cells for antibody-dependent cytotoxicity (ADCC).

31 IgG The Fc portion of IgG enables it to Cross the placenta.
(IgG is the only class of antibody that can cross the placenta and enter the fetal circulation.)

32 IgM (Immunoglobulin M)
It makes up approximately 13% of the serum antibodies. The first antibody produced during an immune response. It has about 5 days life. IgM has 10 epitope-binding sites.

33 IgM The Fc portions of IgM are able to activate the classical complement pathway. It is more effective than IgG in bactericidal action and bacterial agglutination but less effective in neutralisation of toxin and viruses. 

34 IgA (Immunoglobulin A)
IgA makes up approximately 6% of the serum antibodies. It has half-life of approximately 5 days. IgA) is found mainly in body secretions (saliva, mucous, tears and milk colostrum as secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment.

35 IgA IgA is made primarily in the Mucosa-Associated Lymphoid Tissues (MALT). The Fc portion of secretory IgA binds to components of mucous and contributes to the ability of mucous to trap microbes.

36 IgD: (Immunoglobulin D)
IgD makes up approximately 0.2% of the serum antibodies. It has 2 epitope-binding sites. Play a role in eliminating B lymphocytes generating self-reactive auto-antibodies.

37 IgE (Immunoglobulin E)
IgE makes up about 0.002% of the serum antibodies with a half-life of 2 days. Most IgE is tightly bound to basophils and mast cells via its Fc region. It has 2 epitope-binding sites.

38 IgE IgE is made in response to parasitic worms and often in response to allergens. The Fc portion of IgE can bind to mast cells and basophils where it mediates many allergic reactions. **Note: Most antibodies have a relatively short half-life (3-5 days) but IgG has a much longer half-life (3 weeks) making it a very useful antibody.

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40 Percentage of serum antibodies
Property IgG IgM IgA IgD IgE Percentage of serum antibodies Life time # Antigen -binding sites Cross the placenta First produced by Immune system Activation of Its FC portion

41 THANKS


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