The Humoral Immunity in adaptive defense system

ARBAMINCH UNIVERSITY
SCOOL OF POST GRADUATE STUDY
Immunology of Infectious diseases (PVEDC 622)
Medical Entomology and Vector controlMedical Entomology and Vector control
By:
Abate Waldetensai
Mathewos Garsho
Silabat Aschalew
Wondwossen Jemal
June, 2018
25-Jun-18Immunology of Infectious diseases1

The Role Of Humeral Immunity in
Adaptive Defense System (Seminar)

Outline
o General Overview of immunity
o Adaptive Immunity
o Seminal Review Methods
o Humeral ImmunityHumeral Immunity
o Mechanisms of Humeral Immunity
o Structures and roles of Humeral immunity
o B lymphocytes (B cells)
o Summary

General overview of Immunity
o The responses given by the host to the pathogenic microbes
could be classified into two, innate and adaptive.
o In innate immunity, recognition of molecules is expressed
broadly on large number of cells and also circulationbroadly on large number of cells and also circulation
o Innate immunity is non specific

Cont..
Adaptive Immunity
o Host defenses that are specific to a particular infectious agent
o Most specific immune responses improve with repeated
exposures to the infectious agent or antigen (Frank, 2002).
o Adaptive Immunity can be classified into two
• Humoral
• Cell-mediated
25-Jun-18Immunology of Infectious diseases
5

Cont….
The main objectives of this seminar paper was:
o To understand the Role of Humoral Immunity in Adaptive
defense system through reviewing different journal Articles

Review Methods
This seminar was prepared in group through:
o All journal articles published between 2000 and 2018 were
reviewed
o From 80 collected articles, about 36 best documents were
selected and reviewed

Cont…
o The reviewed documents were:
o Review articles
o Full Research papers
o Abstract
Abstract
o Manuscripts
o Resently published books

Humoral Immunity
Definition:
 A component of adaptive immunity
 Generated by circulating antibodies to specific immune
responses to a particular foreign material
(Rameyer et al, 2000)

Mechanisms in Humoral Immunity
o Humoral immunityTriggers the B cells
o The B cells transform into plasma cells during activation of
adaptive immune system by innate immune system
o The plasma cells then secrete large amounts of antibodies
o The antibodies circulate in the lymph and the blood streams
(Nauta, 2011).

Cont..
o B cells (B lymphocytes) are “born” in the bone marrow
o Lymphoid stem cell precursor differentiates into pre-B cell
o Young B cells express membrane-bound antibodies on their
surface (Wols et al., 2005).
o Each B cell makes a different antibody
o (i.e., an antibody with a different variable region that can
specifically bind to a different antigen (Chaplin, 2010)

Cont…
o Antibody on the surface of a B cell encounters the antigen it
is specific for
o The antigen binds to the membrane-bound antibody
o The B cell is activated (Warrington et al., 2011).o The B cell is activated (Warrington et al., 2011).
o Antigen stimulation leads to Clonal expansion:
o The one B cell that produces the correct antibody multiplies
into many identical B cells, all producing the right antibody
(Krause et al., 2018).

Cont…
Expanded B cell clones then will either:
1. Differentiate into Plasma Cells
 Plasma cells are mature B lymphocytes which synthesize and
secrete massive quantities of the needed antibody or, with
the help ofTH (T helper) lymphocytes,
 2. Become B memory cells (Trkola et al., 2018).
 Memory cells are long-lived. If these cells encounter the
antigen again in the future, the humoral immune response is faster
& more vigorous (secondary or anamnestic response) (Helmberg,
2017).

Clonal selection
Antigen
specificity
Diversity
Memory
Central tolerance Peripheral tolerance
(Greenland science, 2008)

Structures and Roles
 The humoral immunity system is characterized by the
activity of B cells
 The main lymphocyte is the B lymphocyte, produced from germ
line DNA in the bone marrow (Zarnitsyna et al., 2015).line DNA in the bone marrow (Zarnitsyna et al., 2015).
 It is the rearrangement, recombination of these genes that
help to create the diversity of antibodies at our disposal
(Tetsuhiro, 2011).

B Lymphocytes (B cells)
o B cells are lymphocytes (leukocytes of the lymphoid
lineage) matured in bone marrow
o Subsequently, they circulate/reside in blood & various
lymphoid tissues (Wols et al., 2005).lymphoid tissues (Wols et al., 2005).
 Each expresses a unique antigen-binding receptor on its
membrane (Carroll et al., 2012).
o This antigen-binding or B-cell receptor is a membrane-
bound antibody molecule (William et al., 2008).

o The B cell receptor has one pair of heavy and light chains
connected by disulfide linkages
(William et al., 2008; Panawala, 2017)

B cells Roles
o Antibody (production)
o Antibody-antigen interaction
o Response

Cont..
o In B cells, the challenging antigen provokes the humoral
immune response
o In contrast, plasma cells exhibit a small, dense, eccentric
nucleus, voluminous cytoplasm containing prominent
amounts of RER and enlarged Golgi (William et al., 2008;
Panawala, 2017).
 Plasma cells are synthesizing large amounts of Ig and may
not exert much energy in secreting cytokines readily available
to them in the surrounding microenvironment (Work et al.,
2000).

Are proteins that have
highly specific binding
sites for antigen
Each individual antibody is
Antibodies
specific for ONE antigen
Carroll et al., 2012

Generation of Antibodies
o Antibody genes are constructed individually in each B cell by
recombination of gene parts
o Gene bits for the variable region are randomly mixed and
“intentionally” mutated to generate a spectacular number of
genetically unique B cell clones
o Antibody diversity is randomly generated before antigen
exposureexposure
o When antigen enters the body, appropriate antibodies are
selected from the pool of B cells with membrane-
bound antibody on their surface
o Selected B cells proliferate, differentiate
(Simon et al., 2015).

Isotypes of Antibodies
Based on the Fc (constant)fragment 5 classes of Ig
o IgG - peripheral
o IgA - gut/mucosal
o IgM - surface & secreted
o IgD - surface
o IgE - allergies - worms
(Speirs et al., 2009).

Function of Antibodies
o Evolved to handle different types of antigens produced
during the stimulation of B cells
o Antibodies attack the invading pathogens differently
o Bind to the antigens and mark the pathogens for destructiono Bind to the antigens and mark the pathogens for destruction
by phagocytes
o Recognizing a uncommon antigen and hence neutralizing
particular pathogens
(Wols et al., 2005)

Cont…
o Activate the complement, serum proteins able to destroy
pathogens or to induce the destruction of pathogens
o Neutralizing antibodies are antibodies that bind to
antigens so that the antigen can no longer recognize hostantigens so that the antigen can no longer recognize host
cells, and infection of the cells is inhibited.
(Radbruch, 2007)

Cont…
o IgG, IgM and IgA, are involved in defense against viruses,
bacteria and toxins
o IgE is involved in allergies and defense against parasites
o IgD has no apparent role in defenseo IgD has no apparent role in defense
(Panda et al., 2018).

Prominent in blood
•Main antibody of memory (secondary)
immune responses
•Acts as an opsonin
•Activates complement (classical pathway)
•Crosses the placenta from mother to
fetus and found in milk
IgG Binds to antigens and
Serves as mature B-cells
receptor
Ig D
Binds to antigens, Bridging two IgE on cell membranes triggers mast
IgE
Binds to antigens, Serves as
memory B-cell receptor,
Protects areas of mucosal
secretions
Binds to antigens, Bridging two IgE on cell membranes triggers mast
cell degranulaton and Serves as memory B-cell receptor, mediates
allergic reactions and provides immunity against parasites IgA
Secreted as a pentamer (5 “Y” units connected together; ten
antigen binding sites), First class of antibody secreted, especially
during primary immune responses; high levels indicate recent
exposure to antigen,Activates complement
•Causes very strong agglutination reactions (clumping microbes helps
to eliminate them
IgM
(Carroll et al., 2012)

Antibody-antigen interactions
Opsonization
o Microbes or particles coated with antibodies - similar to C3b
o Enables macrophages to recognize and phagocytize microbe
NeutralizationNeutralization
o Antibody binds to the microbe or virus receptor and
Antigenic site of a molecule (Eg. Exotoxin)
o Prevents further binding of microbe (no cell entrance for
virus) or toxin
(Krause et al., 2018)

Cont…
Complement fixation (Activation)
o Antibodies interact with complement proteins - activate
complement cascade (Eg. Classical pathway)
o Lysis of microbial cell
(Zimmerman et al., 2013)

Responses
Primary responses
o First exposure
o Latent period - initial response to Ag
o Synthesis of antibodies
Slower response - less antibody generatedo Slower response - less antibody generated
o IgM first
o Followed by IgG
o The primary humoral immune response is usually weak and
transient, and has a major IgM component (Sahu et al., 2011).

Responses ….
Secondary Response
o Re-exposure to the same immunogen
o Antibody synthesis, titer, and length of antibody persistence
is rapid and amplified
o Due to presence of memory cells
o The secondary humoral response is stronger and more
sustained and has a major IgG component
(Niki et al., 2015).

Primary and secondary responses to antigens
(Panda et al., 2018).

Summary
o The humoral immunity is mediated by B cells and acts on the
extracellular microbes and their toxins.
o The plasma B cells secrete antibodies and immune response is rapid.
o The secondary humoral response is stronger and more sustained
o Memory B cells provide the potential to react fast
o Antibodies attack the invading pathogens differently.
o Bind to the antigens and mark the pathogens for destruction by
phagocytes

The Humoral Immunity in adaptive defense system

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