Humoral immunity antibody mediated
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Humoral Immunity Antibody Mediated. Dr.T.V.Rao MD. 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.

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Humoral Immunity Antibody Mediated

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Humoral immunity antibody mediated

Humoral ImmunityAntibody Mediated

Dr.T.V.Rao MD

Dr.T.V.Rao MD


Humoral immunity

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.

Dr.T.V.Rao MD


What are antibodies

WHAT ARE ANTIBODIES?

  • Antigen 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

  • Secreted form of immunoglobulin's

Dr.T.V.Rao MD


Classes isotypes of immunoglobulins

CLASSES (ISOTYPES) OF IMMUNOGLOBULINS

  • Classes based on constant region of heavy chains

    • Immunoglobulin A (IgA)

    • Immunoglobulin D (IgD)

    • Immunoglobulin E (IgE)

    • Immunoglobulin G (IgG)

    • Immunoglobulin M (IgM)

  • Differentiation of heavy chains

    • Length of C region, location of disulfide bonds, hinge region, distribution of carbohydrate

  • Classes have different effector functions

Dr.T.V.Rao MD


Different classes of antibodies

Different classes of Antibodies

Dr.T.V.Rao MD


Structural configuration of antibody

Structural configuration of Antibody

Dr.T.V.Rao MD


Three dimensional structure of antibodies

THREE DIMENSIONAL STRUCTURE OF ANTIBODIES

  • Antibodies function in setting of infectious process

    • Proteolytic enzymes, salt and pH differences

  • Antibodies remain stable based on

    • Sequence of domains

  • Single domain consists of

    • 100 – 110 amino acids folded into compact and stable conformation

  • Domains

    • Variable (V)

      • Single V domain in H and L chains

    • Constant (C)

      • Single C domain in L chains

      • Three to four (C) domains in H chains

Dr.T.V.Rao MD


Antibodies are produced by b lymphocytes

Antibodies are Produced by B Lymphocytes

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Immunoglobulin Classes

I. IgG

  • Structure: Monomer

  • Percentage serum antibodies: 80%

  • Location: Blood, lymph, intestine

  • Half-life in serum: 23 days

  • Complement Fixation: Yes

  • Placental Transfer: Yes

  • Known Functions: Enhances phagocytosis, neutralizes toxins and viruses, protects fetus and newborn.

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Immunoglobulin Classes

II. IgM

  • Structure: Pentamer

  • Percentage serum antibodies: 5-10%

  • Location: Blood, lymph, B cell surface (monomer)

  • Half-life in serum: 5 days

  • Complement Fixation: Yes

  • Placental Transfer: No

  • Known Functions: First antibodies produced during an infection. Effective against microbes and agglutinating antigens.

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Immunoglobulin Classes

III. IgA

  • Structure: Dimer

  • Percentage serum antibodies: 10-15%

  • Location: Secretions (tears, saliva, intestine, milk), blood and lymph.

  • Half-life in serum: 6 days

  • Complement Fixation: No

  • Placental Transfer: No

  • Known Functions: Localized protection of mucosal surfaces. Provides immunity to infant digestive tract.

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Immunoglobulin Classes

IV. IgD

  • Structure: Monomer

  • Percentage serum antibodies: 0.2%

  • Location: B-cell surface, blood, and lymph

  • Half-life in serum: 3 days

  • Complement Fixation: No

  • Placental Transfer: No

  • Known Functions: In serum function is unknown. On B cell surface, initiate immune response.

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Immunoglobulin Classes

V. IgE

  • Structure: Monomer

  • Percentage serum antibodies: 0.002%

  • Location: Bound to mast cells and basophils throughout body. Blood.

  • Half-life in serum: 2 days

  • Complement Fixation: No

  • Placental Transfer: No

  • Known Functions: Allergic reactions. Possibly lysis of worms.

Dr.T.V.Rao MD


Classes isotypes of immunoglobulins1

CLASSES (ISOTYPES) OF IMMUNOGLOBULINS

  • Additional classification based on light chains

    • Kappa

    • Lambda

  • Each IG has either kappa or lambda, not both

    • IgG kappa

    • IgG lambda

  • No functional differences between light chains

Dr.T.V.Rao MD


B cell receptors for antigens

Antigen-

binding site

Antigen-

binding

site

Disulfide

bridge

V

V

V

V

Variable

regions

Light

chain

C

C

Constant

regions

C

C

Transmembrane

region

Plasma

membrane

Heavy chains

B cell

Cytoplasm of B cell

(a)

A B cell receptor consists of two identical heavy

chains and two identical light chains linked by

several disulfide bridges.

B Cell Receptors for Antigens

  • B cell receptors

    • Bind to specific, intact antigens

    • Are often called membrane antibodies or membrane immunoglobulin's

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Antibodies bond to antigenic determinants

Antigenic determinants are portions of the antigen

Dr.T.V.Rao MD


Antibodies are proteins that recognize specific antigens

Antibodies are Proteins that Recognize Specific Antigens

Dr.T.V.Rao MD


Epitopes antigen regions that interact with antibodies

Epitopes: Antigen Regions that Interact with Antibodies

Dr.T.V.Rao MD


Dynamics of antibody production

Dynamics of Antibody Production

  • Primary immune response

    • Latent period

    • Gradual rise in antibody production taking days to weeks

    • Plateau reached

    • Antibody level declines

Dr.T.V.Rao MD


Secondary response

Secondary Response

  • Second exposure to SAME antigen.

  • Memory cells are a beautiful thing.

  • Recognition of antigen is immediate.

  • Results in immediate production of protective antibody, mainly IgG but may see some IgM

Dr.T.V.Rao MD


Dynamics of antibody production1

Dynamics of Antibody Production

  • Antibody production

    • Initial antibody produced in IgM

    • Lasts 10-12 days

    • Followed by production of IgG

    • Lasts 4-5 days

    • Without continued antigenic challenge antibody levels drop off, although IgG may continue to be produced.

Dr.T.V.Rao MD


Humoral immunity antibody mediated

1

Secondary response to anti-

gen A produces antibodies

to A; primary response to anti-

gen B produces antibodies to B

Day 1: First

exposure to

antigen A

4

Primary

response to

antigen A

produces anti-

bodies to A

2

Day 28:

Second exposure

to antigen A; first

exposure to

antigen B

3

104

103

Antibody concentration

(arbitrary units)

102

Antibodies

to A

Antibodies

to B

101

100

35

28

21

42

49

56

0

14

7

Time (days)

  • In the secondary immune response

    • Memory cells facilitate a faster, more efficient response

Dr.T.V.Rao MD


The primary humoral immune response

THE PRIMARY HUMORAL IMMUNE RESPONSE

  • Immune response initially produces IgM antibodies then switches to IgG antibodies

  • Question

    • Why switch from IgM to IgG?

  • Answer

    • Limited effector mechanisms for IgM

    • Range of effector mechanisms for IgG

  • Mechanism

    • Isotope or class switching

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Humoral (antibody-mediated) Immunity

IL 1

IL 2

Autocrine stimulation

Dr.T.V.Rao MD


Isotype or class switching

ISOTYPE OR CLASS SWITCHING

  • Process by which B cell changes class of IG produced while preserving antigenic specificity

  • Involves somatic recombination which attaches different heavy chain constant region to variable region

  • Occurs only during active immune response

  • Mechanisms involves recombination between

    • Switch sequences (regions)

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Antigen molecules

bind to the antigen

receptors of only one

of the three B cells

shown.

Antigen molecules

B cells that

differ in

antigen

specificity

Antigen

receptor

The selected B cell

proliferates, forming

a clone of identical

cells bearing

receptors for the

selecting antigen.

Some proliferating

cells develop into

short-lived plasma

cells that secrete

antibodies specific

for the antigen.

Some proliferating cells

develop into long-lived

memory cells that can

respond rapidly upon

subsequent exposure

to the same antigen.

Antibody

molecules

Clone of memory cells

Clone of plasma cells

  • Clonal selection of B cells

    • Generates a clone of short-lived activated effector cells and a clone of long-lived memory cells

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Humoral (antibody-mediated) Immunity

Memory Cells

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Benefits of Immunological Memory

Dr.T.V.Rao MD


Humoral immunity antibody mediated

Clonal Selection

Only one type of antibody—and one type of B cell—responds to the antigenic determinant

That cell type then produces a large number of clones

Dr.T.V.Rao MD


Functions and properties of antibody

FUNCTIONS AND PROPERTIES OF ANTIBODY

  • Neutralization

    • Direct inactivation of pathogen or toxin thereby preventing its interaction with human cells

  • Opsonization

    • Coating of pathogens for more efficient phagocytosis

  • Activation of complement

    • More efficient phagocytosis

    • Direct killing

Dr.T.V.Rao MD


D iversification of antibodies after b cells encounter antigen

DIVERSIFICATION OF ANTIBODIES AFTER B-CELLS ENCOUNTER ANTIGEN

  • Mature, naïve B cell has membrane bound IgM and IgD antigen receptors

  • Binding of antigen initiates proliferation and differentiation of B-cells into plasma cells

  • During differentiation, B cells switch from making immunoglobulin to antibody M and D isotypes

  • IgM

    • Produced in large amounts

    • Provides protective immunity

  • IgD

    • Produced in small amounts

    • No known function

Dr.T.V.Rao MD


Diversification of antibodies after b cells encounter antigen

DIVERSIFICATION OF ANTIBODIES AFTER B-CELLS ENCOUNTER ANTIGEN

  • Following antigen activation of B-cells, additional diversification occurs in V domain by

    • Somatic hyper mutation

  • Somatic hyper mutation

    • Introduction of random single nucleotide substitutions (point mutations) throughout V regions of H and L chains

    • Mechanism poorly understood

    • More common in hyper variable regions (CDRs)

Dr.T.V.Rao MD


Outcome of somatic hypermutation

OUTCOME OF SOMATIC HYPERMUTATION

  • Gives rise to some antibodies with higher

    • Affinity for antigen

  • Affinity

    • Strength of binding of one molecule to another by a single binding site

  • Higher affinity antibodies are produced as immune response proceeds

    • Affinity maturation

Dr.T.V.Rao MD


Igm antibody of the immune response

IgM ANTIBODY OF THE IMMUNE RESPONSE

  • First isotype produced in primary response

    • May or may not be produced in secondary response

    • Produced before B cells undergo somatic hypermutation

  • Occurs as pentamer with J chain

    • Found primarily in blood and lymph

  • Multiple binding sites confers high avidity and compensates for low affinity of monomers

  • Highly effective in complement activation

  • Functions as rheumatoid factor

Dr.T.V.Rao MD


Igg antibody of the immune response

IgG ANTIBODY OF THE IMMUNE RESPONSE

  • Second isotype produced in primary response

  • Primary isotype of

    • Secondary immune response

    • Memory immune response

  • Represents approximately 75% of total serum IG

  • Four subclasses (1-4)

    • Different effector functions

  • Transported across placenta

  • Functions as rheumatoid factor

Dr.T.V.Rao MD


Iga antibody of the immune response

IgA ANTIBODY OF THE IMMUNE RESPONSE

  • Two subclasses (IgA1 and IgA2) and two forms (monomeric and dimeric)

  • Monomeric

    • Located in blood and extracellular spaces

    • Predominately IgA1

      • Ratio of IgA1 to IgA2 is 10:1

    • Functions as rheumatoid factor

  • Dimeric

    • Located in mucous membranes and secretions

    • Predominately IgA2

    • Ratio of IgA2 to IgA1 is 3:2

    • J chain like IgM

Dr.T.V.Rao MD


Ige and igd antibodies of the immune response

IgE AND IgD ANTIBODIES OF THE IMMUNE RESPONSE

  • IgE

    • Binds with high affinity to receptors on mast cells, basophils and activated Eosinophils

    • Longer half-life when cell bound

    • Initiates a strong inflammatory reaction to parasites

    • Involved in allergic reactions

  • IgD

    • Antigen receptor on mature B-cells

    • No other known function

Dr.T.V.Rao MD


Humoral immunity antibody mediated

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.

Dr.T.V.Rao MD


Immunological memory continued

Immunological Memory (Continued)

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.

Dr.T.V.Rao MD


Antibodies as diagnostic and therapeutics agents

ANTIBODIES AS DIAGNOSTIC AND THERAPEUTICS AGENTS

  • Based on specificity and affinity of antibodies

  • Both applications require large quantities of identical antibodies

    • Monoclonal antibodies

  • Monoclonal antibodies are produced using hybridoma cell line

  • Hybridoma cell line

    • Derived from single antibody producing cell fused with myeloma cell (neoplastic plasma cell)

Dr.T.V.Rao MD


Humoral immunity antibody mediated

  • Programme Created By Dr.T.V.Rao MD for basic learning for Medical and Paramedical Students in the Developing World

  • Email

  • [email protected]

Dr.T.V.Rao MD


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