Humoral Immunity

Ajith SominandaDepartment 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 immunoglobulins2. 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

CDRComplementarity determinant Region

Specific B cell produces specific antibodies against a specific antigen

Process of Somatic recombination in B cell nucleus produces this Antibody diversity Specific B cell produces specific antibodies

against a specific antigen

Types (Classes) of antibodies

Comparison of antibody classes

Humoral Immune Response

(sequence of events in antibody mediated immunity)

Humoral Immune ResponseAntigen binding to BCR

&B cell Activation

Proliferation of B cells (clonal expansion)

Antibody production by plasma cells

Effector mechanisms of antibodies1. Neutralization2. Opsonization3. 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 co-receptors (CD 40/40L)

Types of B cell activation

T cell independent activation

T cell dependent activation

For B cells (right panel), the second signal is usually delivered by an activated T cell.

For T cells second signal is delivered by a professional antigen-presenting cell such as dendritic cell.

Signaling that occurs during cell-cell interaction: comparison between ‘APC-T cell’ and ‘B cell-T cell’

2. B cells proliferation and differentiation

1. 1st signalling through Ag-BCR2. 2nd signalling through CD40-CD40L3. IL4 drives B cells to proliferate

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

2. B cells proliferation and differentiation Cont..

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 (7-14 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

Memory B cell Activated B cell Plasma cell

Secondary Immune Responses

Primary and Secondary Immune Responses

1. Neutralization i.e. Toxines2. Fc mediated phagocytosis i.e. activation of Macrophages and ploymorpho nuclear leukocytes3. Complement activation

3. Effector Mechanisms of antigen bound Antibodies

Effector Function: Fc receptor activation by antigen-antibody complex

Fc receptor

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1. IgGA. is the major type of antibody in serumB. is a multivalent antibodyC. can activate the complement cascadeD. can cross the placenta

2. IgMA. is a divalent antibodyB. is the first antibody synthesized in a primary infectionC. Found on surface of B cellD. activates complements

3. IgEA. is at high concentrations in the bloodB. is found on mast cellsC. plays a role in allergic responsesD. produced in parasitic infestation

4. IgAA. is present in the secretions of mouth and intestinal tractB. is a pentavalent antibodyC. can activate the classical complement cascadeD. 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

CD40

BCR

CD19

TCR

CD3

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

CD40L

Comparison of Antigen processing and presentation: B cell as an APC

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