The document discusses adaptive humoral immunity and the antibody-mediated immune response in fish. It notes that adaptive immunity relies on generating diverse repertoires of B and T cell receptors. Upon exposure to an antigen, B cells produce antibodies that are specific proteins that bind the antigen. Memory B cells are also produced to facilitate a faster secondary response upon re-exposure. Fish have three main antibody classes - IgM, IgD, and IgT, with IgM being the predominant systemic antibody and IgT playing an important role in mucosal immunity. The structure and function of antibodies in fish are generally similar to those in mammals.

1. ADAPTIVE IMMUNE
SYSTEM IN FISH:
HUMORAL IMMUNITY
Harapriya
behera
DPHFM

2. IMMUNE SYSTEM:

4. INTRODUCTION:
Adaptive immunity relies on the generation of random and highly diverse
repertoires of T and B-lymphocyte receptors encoded by recombinant
activation genes (RAGs) and contributes to a more specific and efficient
response against infections (McGuinness et al., 2003; Medzhitov, 2007)
Adaptive immune recognition is mediated by antigen (Ag) receptors, with
random but narrow specificities.
Adaptive or combinatorial system, characterized by the presence of Ig, T cell
receptors (TCR) and products of the MHC that allow clonal selection of B and
T cells.

5. COMBINATORIAL IMMUNE
RESPONSE
All jawed vertebrates possess the genetic elements essential for the function
of the adaptive/combinatorial immune response (Marchalonis et al., 2006).
The combinatorial immune system (CIS) consists of Ag-recognizing
lymphocytes, immunoglobulins (Abs and Ig-family TCR), MHC products, and
recombination activating (RAG) 1 and 2 genes.
The overall shape of the molecules and the recombination mechanisms that
create junctional diversity in TCRs and Igs are similar in fish and mammals
(Du Pasquier, 2001).
Naturally occurring Abs whether in serum or on lymphocytes as receptors for
Ag are also essential to the selective basis of combinatorial/adaptive
vertebrate immunity

6. Specific immunity
Specificity
• Memory
• Ability to distinguish b/w self vs
non-self
• T and B cell

7. Adaptive humoral immunity Results in production of proteins
called “immunoglobulin's” or “antibodies”.
• Body exposed to “foreign” material termed “antigen” which
may be harmful to body: virus, bacteria, etc.
• Antigen has bypassed other protective mechanisms, ie,
first and second line of defense.
Antibodies are specific proteins produced by plasma cells
Belong to immunoglobulin superfamily Located in blood and
extravascular tissues, secretions and excretions
Bind pathogenic microorganism and their toxins in
extracellular compartments

9. ANTIBODIES ARE PROTEINS
THAT RECOGNIZE SPECIFIC
ANTIGENS

10. THE INNATE IMMUNE SYSTEM
ACTIVATES ACQUIRED
IMMUNITY
• Cells of the innate immune system activate the
specific immune response.
• A group of cells called Antigen presenting cells
(APC) activate the acquired immune system. Ex-
Macrophages, Dendritic cells and B-cells.
• APCs turn on the acquired immune system by
activating T-Helper cells (TH-cells).
• TH-cells in turn activate either the cell mediated or
the humoral immune system.

11. SPECIFIC DEFENCE
MECHANISM
Lymphocyte, is the immunocompetent cell.
Which is responsible for initiating and mediating the :
1. Humoral immunity- production of soluble antibody
[immunoglobulin]
2. Cell-mediated immunity (CMI) responses which are
mediated by a variety of cells including lymphocytes and
macrophages.
3. Immunological memory constitutes an adaptive change in
the lymphoid cell populations.

12. INDUCTION OF B CELLS
Ags an be classified into TI or TD.
For induction of Ab response for TI Ags the auxillary assistance of
macrophage or monocyte are required.
And for induction of Ab response for TD Ags, The Ag must be
processed by an accessory cells (macrophage) and be presented
on the cell surface to T cell, which in turn helps in B cell
differentiation.
 B cell differentiate into plasma or effector cell which produces Abs
and memory cells which carries Ag for recognition property.
Myelopoiesis generally occurs in the head kidney (HK) and/or
spleen, whereas thymus, kidney and spleen are the major lymphoid
organs
HK exhibits morphological similarities with the bone marrow of
higher vertebrates and also serves as a second lymphoid organ (a
lymph node analogue), and in the clearance of soluble and
particulate Ags from the circulation. Furthermore, it is also the major

14. Only one type of antibody and one type of B cell responds to the antigenic determinant That cell
type then produces large number of clones

15. IMMUNOLOGICAL MEMORY
Antibody Titer: The amount of antibody in the serum. Pattern of
Antibody Levels During Infection
Primary Response:
– After initial exposure to antigen, no antibodies are found in serum for
several days.
– A gradual increase in titer, first of IgM and then of IgG is observed.
– Most B cells become plasma cells, but some B cells become long
living memory cells.
– Gradual decline of antibodies follows.

16. SECONDARY RESPONSE:
– Subsequent exposure to the same antigen displays a faster and more
intense
antibody response.
– Increased antibody response is due to the existence of memory cells,
which rapidly produce plasma cells upon antigen stimulation.

18. IMMUNOGLOBULINS
(Ig)
3 immunoglobulin classes IgM, IgD, and IgT in
bony fishes.
1. IgM constitutes the main systemic
immunoglobulin,
2. IgT plays the prevalent role in mucosal
surfaces.
3. IgD in fish immunity is also present.
Both IgM and IgD are co-expressed in B cells
found both in systemic and mucosal lymphoid
areas, where as IgT is uniquely expressed by a
B-cell subset.

19. (Ig)s present in different types of
fishes
Bony fish are the only animals that produce IgT/Z.
Rainbow trout (IgT) and zebra fish (IgZ).
IgT, a monomer in trout serum but a tetramer in mucous, is able
to pass through the mucosal epithelium using a fish polymeric
immunoglobulin receptor (pIgR).
IgT and IgM are also found in Thunnus orientalis (Pacific blue fin
tuna)
 B cells extensively populate teleost SALT (skin associated
lymphoid tissue) and are responsible for secreting polymeric IgT
into the skin mucus to protect the skin from infectious microbes.

20. MUCOSAL IMMUNITY
First line of humoral defence, where pathogens get
blocked and neutralized is the mucosal surface.
Enterocytes of secondary gut segment appears to
have evolved the specialized function of antigen
uptake and processing of antigen.
Carp mucosal intraepithelial lymphoid cells are
composed of sIg- cells NK cells, sIg+ (B cells) and Ig
binding APCs.
Specific antibody secreting cells were detected in both

21. STRUCTURE OF
ANTIBODY
Antibody (Ab) also know as
Immunoglobulin (Ig) is the large Y
shaped protein produced by the
body’s immune system when it
detects harmful substances, called
antigens.
The tetramer structure of fish Ig is
composed of four monomeric units,
two identical heavy (H) chains (70 kD)
and two light (L) chains (25 kD).

22. CONT,,

23. Antibody (Ab) also know as Immunoglobulin (Ig) is the
large Y shaped protein produced by the body’s
immune system when it detects harmful substances,
called antigens.
The B cells producing these Igs appear to be
mutually exclusive, at least for IgM and IgT
production.
Ig also exists in mucus secretions of the skin and gut,
and in the bile in the form of IgT.
The number of VH families varies tremendously
between different teleost species

24. The functional B-cell receptor is a multi-protein complex consisting of an antigen binding
subunit and a signaling subunit.The BCR is composed of membrane immunoglobulin (mIg)
molecules and associated Igα/Igβ (CD79a/CD79b) heterodimers (α/β). The mIg subunits
bind antigen, resulting in receptor aggregation, while the α/β subunits transduce signals
to the cell interior. BCR aggregation rapidly activates the Src family kinases Lyn, Blk, and
Fyn as well as the Syk and Btk tyrosine kinases. This initiates the formation of a
'signalosome' composed of the BCR, the tyrosine kinases, adaptor proteins such as CD19
and BLNK, and signaling enzymes such as PLCγ2, PI3K, and Vav. Signals emanating from
the signalosome activate multiple signaling cascades that involve kinases, GTPases, and
transcription factors. This results in changes in cell metabolism, gene expression, and
cytoskeletal organization. The outcome of the response is determined by the maturation
state of the cell, the nature of the antigen, the magnitude and duration of BCR signaling,
and signals from other receptors such as CD40, the IL-21 receptor, and BAFF-R. Many
other transmembrane proteins, some of which are receptors, modulate specific elements
of BCR signaling. A few of these, including CD45, CD19, CD22, PIR-B, and FcγRIIB1
(CD32), are indicated here in yellow. The magnitude and duration of BCR signaling are
limited by negative feedback loops including those involving the Lyn/CD22/SHP-1
pathway, the Cbp/Csk pathway, SHIP, Cbl, Dok-1, Dok-3, FcγRIIB1, PIR-B, and
internalization of the BCR. In vivo, B cells are often activated by antigen-presenting cells
that capture antigens and display them on their cell surface. Activation of B cells by such
membrane-associated antigens requires BCR-induced cytoskeletal reorganization. Please
refer to the diagrams for the PI3K/Akt signaling pathway, the NF-κB signaling pathway,
and the regulation of actin dynamics for more details about these pathways.

25. ANTIGEN TRAPPING:
The (MMCs) of the haemo-lymphopoietic organs of teleost fish
trap and retain antigens and are closely associated with
immunoglobulin-secreting cells .
B memory cells are specific for the antigen trapped.
These structures are considered to be involved in the execution
and/or establishment of immune memory.
antigen and immunoglobulin become trapped within the reticulin
fibres of the splenic ellipsoids and then subsequently also on the
surface of the cells within the MMC. . The antigen is probably
trapped as an immune complex. Ag coexist with Ig.

26. LYMPHOID ORGANS OF BONY
FISH:
Lymphoid organ
Organised tissues in which
lymphocytes interact with non lymphoid
cells sites of maturation & initiation of
adaptive immune responses
Central lymphoid organs- T cell
maturation
head kidney
Thymus
Peripheral lymphoid organs – B cell
maturation
Spleen

27. The thymus, a primary lymphoid organ and a major site of T-cell
development in teleosts. Basically, thymus can be considered as
an encapsulated aggregation of MFs that processes the
proliferation of T cells.
The gut-associated lymphoid tissue (GALT) of teleosts consists
principally of different sized lymphocytes, plasma cells and MFs,
as well as several types of granulocytes, PAS positive cells and
eosinophil granular cells (Zapata and Amemiya, 2000).
In teleosts, gut intraepithelial lymphocytes are largely
considered as T cells, whereas lymphoid cells in the lamina
propria are mainly as B lymphocytes
IgM can be present in serum and secretions of fish, including
cutaneous and gut mucus.
The Ab response and serum concentration of IgM may vary

28. ANTIBODY EFFECTOR
MECHANISM
1. Neutralisation
2. Precipitation /agglutination
3. Opsonization
4. Complement activation
5. Hypersensitivity responses

29. 1. Neutralisation- blocks
the entry of antigen
into the cell.
2. Precipitation- when
soluble Ag binds to Ab
3. agglutination – when
particulate Ag get bind
with Ab

30. 3. Opsonization- is the process
by which a pathogen is marked
for ingestion and eliminated by a
phagocyte.
4. Hypersensitive reaction-skin in
perciform fish do EGC contain
histamine.
Skin sensitivity responses in the
plaice have been associated
with C-reactive protein mediating
degranulation of mast cells and,
as fish possess the C3a and
C5a components of
complement, these may mediate

31. COMPLEMENT ACTIVATION
Complement is amongst the main mechanisms involved in the initiation of the innate
response and further mounting of an adaptive response.
.

34. FACTORS AFFECTING IMMUNE
RESPONSE
1. Temperature
2. Antigen dose
3. Nature of antigen
4. Route of administration
5. Adjuvants and immunostimulant
6. Seasonal effect
7. Environmental effects

35. REFERENCES
1. Fish Immunoglobulins Sara Mashoof1 and Michael F. Criscitiello1,2,* Brian
Dixon, Academic Editor
2. Fish Pathology FOURTH EDITION Edited by Ronald J. Roberts
3. Basic immunology by Gregory Heath BSc (Hons), MCOptom, Dip. Clin. Optom
4. The fish immune system by George Iwama
5. Fish immune system. A crossroads between innate and adaptive
responses L. Tort, J.C. Balasch, S. Mackenzie
6. The innate immune response of finfish e A review of current knowledge Shona K.
Whyte*Centre for Aquatic Health Sciences, Department of Health Management,

36. Than
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