1. Effector Mechanisms of Humoral Immunity
Prof.Dr.Pongsak Utaisincharoen
Department of Microbiology, Faculty of Science

2. Properties of Antibodies that determine effector function
Antibodies function throughout the body and in the lumens of mucosal organs
Protective antibodies are produced during the first (primary) response and in large amounts during subsequent (secondary responses)
Antibodies use Ag-binding (Fab) regions to bind to microbes and Fc regions to activate effector mechanisms that eliminate microbes
Heavy-chain isotype (class) switching and affinity maturation enhance the protective function
Heavy-chain isotype switching: results in the production of Ab with Distinct Fc regions capable of different effector function

3. Antibody isotype Effector functions IgG IgM IgA IgE
Neutraliztion of microbes and toxins
Opsonization of antigens for phagocytosis by macrophages and neutrophils
Activation of the classical pathway of complement
Antibody-dependent cellular cytotoxicity mediated by NK cells
Neonatal immunity: transfer of maternal antibody across placenta and gut
Feedback inhibition of B cell activation
IgM
IgA
Mucosal immunity: secretion of IgA into lumens of gastrointestinal and respiratory tracts, neutralization of microbes and toxins
IgE
Defense against helminthes
Mast cell degranulation (immediate hypersensitivity reactions)
IgM

4. Affinity maturation is induced by prolonged or repeated stimulation
with Ag results in the production of Ag with higher affinity to Ag

6. Where is antibody produced from?
Cells:
B lymphocyte and
plasma cells
Organ:
Lymphoid organs and
bone marrow

7. How antibody is produced ?
Naïve B cell
Differentiation
Ab producing cells (plasma cell)
Memory cells located in lymphoid organ
Ag (e.g. microbe)

9. Heavy-chain class switching:
optimize for combating the microbes
Affinity maturation:
increase binding affinity to Ag by repeated or prolong stimulation

10. Neonatal Fc receptor (FcRN)
- expressed in placenta, endothelium, phagocytes and
few other cells
- protecting IgG antibodies from intracellular catabolism
- found in endosomes of endothelial cells
- once bond to FcRn, IgG is recycled back into the circulation
(avoiding lysosomal degradation)
* This unique mechanism for protecting IgG to have longer half
live than other Ig

11. 8.2

12. Neutralization of microbes and microbial toxins
Ab binds to microbes and prevent them to infect the cells
Ab binds to toxins and bock the toxin to damage the cells

13. 8.3

14. Opsonization and Phagocytosis
Ab coat microbes promote phagocytosis (FcgRI)
major defense mechanism against encapsulated bacteria eg. Pneumococci

15. 8.4

16. FcγRIIB
important not for shutting down antibody production and reduce inflammation (negative feedback inhibition of B cell)
also inhibits activation of macrophages and dendritic cells

17. 8.4

18. Antibody-Dependent Cellular cytotoxicity (ADCC) - FcγRIII on NK cells
8.5

19. Immunoglobulin E and Eosinophil/ mast cells
defense against helminthic parasites
involve in allergic diseases
use FceRI on eosinophil or mast cells
8.6

20. Complement system
a collection of circulating and cell membrane proteins
activation involves sequential proteolytic cleavage of these proteins leading to generation of effector molecules
activated complement proteins covalently attached to the cell surfaces where the activation occurs

21. 8.7

22. 8.7

23. 8.8

24. Function of the complement system
elimination of microbes during innate and adaptive immune response
provide stimuli for the development of humoral immune response

26. 8.9

27. Regulation of Complement Activation
purpose to preventing complement-mediated damage to host cells
Decay accelerating factor (DAF) is a lipid-linked cell surface protein, disrupts the binding of Bb to C3b
Membrane cofactor protein (MCP) serves as a cofactor for cleavage of C3b thus destroying C3b
C1 inhibitor (C1 INH) stop complement activation at stage of C1

28. 8.10

29. 8.10

30. *Inherited deficiencies of regulatory proteins cause uncontrolled and
pathologic complement activation
e.g. Deficiency of C1INH case disease called “hereditary angioneurotic edema” (excessive C1 activation)

31. Inherited deficiencies of complement often
lead to an increase susceptibility to infection

32. Functions of Antibodies at special anatomic sites
- Ab function at any site in the body to which Ab gain access
- Ab serve protective function at two special anatomic sites
1) Mucosa organs 2) the fetus

33. Mucosal Immunity
IgA is produced in mucosal lymphoid tissues, transported across epithelia and bind and neutralizes microbes in the lumens of espiratory or gastrointestinal tract
IgA 60-70% produced daily
The propensity of B cells in mucosal epithelia tissues to produce IgA is influenced by Transforming Growth Factor b (TGF-b) which induces class switching
B-1 cells also can produce IgA (T cell independent)
Poly-Ig receptor important for transport IgA across epithelial cell

34. 8.11

35. Neonatal Immunity
Transported across the placenta to the fetus across the gut epithelium of neonates protecting the newborn from infection
Naturally occurring passive immunity
Neonates acquire maternal IgG by two routes both of which rely on neonatal Fc receptor (FcRN) which help IgG to transport into fetal circulation
FcRN express in the placenta during pregnancy and facilitate IgG to transport into the fetal circulation
After birth neonate ingest maternal Ab from milk and FcRN express in the neonate’s intestinal epithelial cell
IgA from milk provide mucosal immune protection

36. Evasion of Humoral Immunity by Microbes

37. 8.12

38. Vaccination
8.13

39. Vaccine that stimulate Cell Mediated Immunity
To elicite T cell mediated response, the Ag must be delivered to the interior of antigen-presenting cell (APC, DC).
Incorporate microbial Ag into viral vectors which infect host cells and produce the Ag inside the cells
Immunize individuals with DNA encoding a microbial Ag in a bacterial plasmid which will ingested by APC and Ag is produced inside the cells