Transcript Humoral Immunity

Humoral Immunity
Ajith Sominanda
Department of Anatomy
The need of a humoral immunity
• Microorganisms multiply in the fluid
compartments i.e. ECF and blood, therefore
needs a soluble agent to act on !
• Antibodies stick to microorganisms in the fluid
compartments of the body
A magnet coated with iron dust
A bacteria coated with antibodies
Components in the Humoral immunity
Cellular component
• B cells
• Plasma cells
• T cells
• Macrophages
Molecular component
• Immunoglobulins (Antibodies)
• Complement proteins
B cell
• B cells are lymphocytes and mature in the bone marrow.
• Express immunoglobulin receptor (IgM or IgD) on the cell surface
called B cell receptor (BCR).
• Different types of B cells are found (Naïve, Activated,
Memory)
• B cells secrete antigen specific immunoglobulins which circulate as
antibodies.
IgM or IgD
Plasma cell
• Fully differentiated B cells form Plasma cells and
secrete antibodies
• Has a different morphology and adapted to
Secretory function
Antibodies
Structure of a typical antibody (IgG molecule)
1. Globular proteins in the serum are immunoglobulins
2. Typical immunoglobulin molecule consists of
a) 2 heavy chains (450-600 a.acids)
b) 2 light chains (230 a.acids)
3. These are cross linked by disulphide bonds
Immunoglobulin molecule has Two
functional regions
1. Variable region (‘V’ region)
For antigen binding
2. Constant region (‘C’ region)
For effector functions of antibodies
• Complement activation
• Fc receptor activation
• Placental transfer
Antigen binding site
Antigen
CDR
Complementarity determinant Region
Specific B cell produces specific antibodies
against a specific antigen
Process
Specific of
B cell
Somatic
produces
recombination
specific antibodies
in B cell
nucleus against
produces
a specific
this Antibody
antigendiversity
Types (Classes) of antibodies
Comparison of antibody classes
Humoral Immune
Response
(sequence of events in antibody mediated immunity)
Humoral Immune Response
Antigen binding to BCR
&
B cell Activation
Proliferation of B cells (clonal expansion)
Antibody production by plasma cells
Effector mechanisms of antibodies
1. Neutralization
2. Opsonization
3. Complement activation
1. B cell activation
•Antigenic stimulation / Binding
starts the B cell activation
•First signal is sent through BCR
•Second signals are sent through coreceptors (CD 40/40L)
Types of B cell activation
T cell independent
activation
T cell dependent
activation
Signaling that occurs during cell-cell interaction:
comparison between ‘APC-T cell’ and ‘B cell-T cell’
For T cells second signal is
delivered by a professional
antigen-presenting cell such
as dendritic cell.
For B cells (right panel), the
second signal is usually
delivered by an activated T
cell.
2. B cells proliferation and differentiation
1. 1st signalling through Ag-BCR
2. 2nd signalling through CD40-CD40L
3. IL4 drives B cells to proliferate
2. B cells proliferation and differentiation
Cont..
During B cell proliferation, mutations (somatic hyper
mutation) generate many clones of B cells bearing
surface BCRs with different affinities towards the
same antigen
2. B cells proliferation and differentiation
Cont..
In the lymph node germinal centers, high affinity B cells
are selected and differentiated into plasma cells
Primary Immune response
• Immune response which occurs by activation of
naïve B cells by encountering the relevant antigen for
the first time
• Takes some time to mount this immune response (714 days)
• Produces IgM antibodies
• Disappears rapidly
• Produces memory B cells
• Indicates an acute infection
Initial Humoral Immune Response
‘’The Primary Immune Response’’
Antigen binding to Naïve B cells
B cell Activation
Proliferation of B cells (clonal expansion)
Antibody production by plasma cells
Secondary Immune response
• Subsequent encountering of the same antigen
by memory B cells produces antibodies rapidly
and in a larger quantity (titer)
• The type of antibody is IgG (class switching
has occurred)
• Indicates the protective immunity
• May last a longer period
Primary Immune Responses
Naïve B cell
Activated B cell
Plasma cell
Secondary Immune Responses
Memory B cell
Activated B cell
Plasma cell
Primary and Secondary Immune Responses
3. Effector Mechanisms of antigen bound
Antibodies
1.
2.
3.
Neutralization i.e. Toxines
Fc mediated phagocytosis i.e. activation of Macrophages and ploymorpho
nuclear leukocytes
Complement activation
Effector Function:
Fc receptor activation by antigen-antibody complex
Fc receptor
Just before the END
1. IgG
A. is the major type of antibody in serum
B. is a multivalent antibody
C. can activate the complement cascade
D. can cross the placenta
2. IgM
A. is a divalent antibody
B. is the first antibody synthesized in a primary
infection
C. Found on surface of B cell
D. activates complements
3. IgE
A. is at high concentrations in the blood
B. is found on mast cells
C. plays a role in allergic responses
D. produced in parasitic infestation
4. IgA
A. is present in the secretions of mouth and
intestinal tract
B. is a pentavalent antibody
C. can activate the classical complement
cascade
D. both a and c
Q: Discuss the following aspects in
relation to routine childhood
vaccination:
1. Antigens and adjuvents
2. Booseter doses
Good to know stuff
Comparison of B cell and T cell
BCR
TCR
CD19
CD40
CD3
CD40L
Antigen binding
yes
yes
Antigen binding receptor
BCR
TCR
Co-stimulatory molecules
Yes
yes
Co-stimulatory partner
T cell
APC
Cell marker / identity
CD19
CD3
Comparison of Antigen processing and
presentation: B cell as an APC
The end