Humoral Immunity Flashcards

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1
Q

What is the definition of immunoglobulins

A

• Definition: Glycoprotein molecules that are produced by plasma cells in response to an immunogen and which function as antibodies

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2
Q

What is general functions of immunoglobulins, Ag binding and effector

A

• Ag binding
– Can result in protection
– Valency

• Effector functions
– Fixation of complement
– Binding to various cells

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3
Q

what is the basic immunoglobulins structure

A

• Immunoglobulins - heterogeneous
• Myeloma proteins - homogeneous immunoglobulins

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4
Q

What is antigen

A

Antigen - “anything that can be bound by an antibody“ or
that can elicit an immune response (immunogen). Eg: simple chemicals, sugars, small peptides to complex protein complexes such as viruses.

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5
Q

what is haptens ?

A

Small antigens (haptens) are not immunogenic – they need to be coupled to a carrier to elicit an IR.
Antibodies interact specifically small parts of antigen molecules. These are known as antigenic determinants or epitopes.

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6
Q

what is isotypes, allotypes and idiotypes

A

• ISOTYPES - antigenic determinants characterizing classes & subclasses of heavy chains, types and subtypes of light chains.

• Allotypes - antigenic determinants specified by allelic forms of the Ig genes -slight differences in the amino acid sequences of heavy or light chains
light chain allotypes – Km (Inv) heavy chain - Gm

• Idiotypes - unique antigenic determinants present on individual antibody molecules or on molecules of identical specificity – specific antibody molecules have the exact same hypervariable regions

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7
Q

What is the immunoglobulins structure

A

• Heavy & Light Chains
• Disulfide bonds – Inter-chain – Intra-chain
• Variable & Constant Regions
– VL & CL
– VH & CH
• Hinge Region
• Domains – VL & CL
– VH & CH1 - CH3 (or CH4)
• Oligosaccharides( carbo on CH2)

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8
Q

what is the immunogobulin fragments

A

Ag binding
Complement binding ite
Placenta transfer
binding to fe receptor

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9
Q

immunoglobulins fragments, Fab and Fc

A

• Fab
– Ag binding
– Valence = 1
– Specificty determined by VH and VL
• Fc
– Effector functions
• F(ab’)2

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10
Q

Human Immunoglobulins Classes ,5

A

• IgG - Gamma heavy chains
• IgM - Mu heavy chains
• IgA - Alpha heavy chains
• IgD - Delta heavy chains
• IgE - Epsilon heavy chains

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11
Q

Human Immunoglobulin Subclasses (Heavy Chain)

A

• IgG Subclasses
– IgG1 - Gamma 1 heavy chains
– IgG2 - Gamma 2 heavy chains
– IgG3 - Gamma 3 heavy chains
– IgG4 - Gamma 4 heavy chains
• IgA subclasses
– IgA1 - Alpha 1 heavy chains
– IgA2 - Alpha 2 heavy chains

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12
Q

Human Immunoglobulin (Light Chain)

A

• Kappa
• Lambda
Subtypes
• Lambda 1
• Lambda 2
• Lambda 3
• Lambda 4

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13
Q

Structure of IgG

A

• Structure - 7S Monomer

• Properties
– Major serum Ig
– Major Ig in extravascular spaces
– Placental transfer – No Ag binding required ( IgG2)
– Fixes complement (IgG4)
– Binds to Fc receptors (IgG2, IgG4)
• Phagocytes – opsonization, K cells - AD

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14
Q

Structure of IgM

A

• Structure
– Pentamer (19S)
– Extra domain (CH4)
– J chain(tgh tgh)

• Properties
– 3rd highest serum Ig
– First Ig made by fetus and B cells
– Fixes complement
– Agglutinating Ig
– Binds to Fc receptors
– B cell surface Ig

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15
Q

Structure of IgA

A

• Structure
– Serum - monomer – Secretions (sIgA)
• Dimer (11S)
• J chain
• Secretory
component

• Properties
– 2nd highest serum Ig
– Major secretory Ig (Mucosal or
Local Immunity) Tears, saliva, gastric & pulmonary secretions
– Does not fix complement
– Binds to Fc receptors on some cells

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16
Q

Structure IgD

A

• Structure
– Monomer
– Tail piece
• Properties
– 4th highest serum Ig
– B cell surface Ig
– Does not bind complement

17
Q

Structure IgE

A

• Structure
- Monomer
– Extra domain (CH4)
• Properties
– Least common serum Ig – Binds to basophils
& mast cells
– Allergic reactions
– Parasitic infections (Helminths)
• Binds to Fc receptor on eosinophils – Does not fix complement

18
Q

Effector function of antibodies

A

• Neutralisation. block biological activity of their target molecule e.g a toxin binding to it’s receptor

• Opsonisation. interact with special receptors on various cells, - macrophages, neutrophils, basophils & mast cells allow them to “recognise” & respond to the antigen b

• Complement Activation. cause direct lysis by complement recruitment also enhances phagocytosis

19
Q

What is B cell Antigen Receptor (BcR)7

A

BCRs enable the cell to bind to & be activated by and respond to an epitope on molecules of a soluble antigen. The response ends with descendants of the B cell secreting vast numbers of a soluble form of its receptors. These are antibodies.

20
Q

What is B cell Antigen Receptor (BcR)

A

• Are integral membrane proteins
• Are present in thousands of identical copies exposed at
the cell surface.
• Are made before the cell ever encounters an antigen
• Are encoded by genes assembled by the recombination of
segments of DNA
• Are very similar to TCRs

21
Q

How antibodies are produced ?

A

• BCRs bind soluble antigens

• Bound antigen molecules are engulfed into B cell by
receptor- mediated endocytosis

• Antigen is digested into fragments

• Then displayed at cell surface nestled inside a class II histocompatibility molecule

• Helper T cells specific for this structure bind the B cell and secrete lymphokines
- stimulate the B cell to enter the cell cycle and develop into a clone of cells with identical BCRs
- switch from synthesizing their BCRs as integral membrane proteins to a soluble version
- differentiate into plasma cells to secrete these soluble BCRs, which we now call antibodies.

22
Q

How clonal expansion process

A

The mature B-cells have antibody molecules on their surface. When a surface bound antibodies binds to the antigen for which it is specific, this stimulates that B-cell to divide (clonal expansion) and mature into a population of clonal plasma cells that produce large quantities of uniquely specific soluble antibodies.

23
Q

Immunoglobulin Isotype switching

A

Reconfiguration of genes for IgM to IgA with same antigen binding specificity.
Switch sites combine,
intervening DNA is looped out and deleted.
IgA antibody gene containing VDJ genes and C-alpha gene is formed
CS occurs by - Class Switch Recombination (CSR) binding.

24
Q

Mechanism of generation of diversity

A

• Ig Gene Rearrangements
Random joining of VDJ genes (in HC), VJ (LC) – around 107 possibilities
• Somatic hypermutations – Point mutations in VDJH & VJL
• Affinity maturation
• Antibody Function : Isotype switching, existence of Abs as membrane bound or secreted form