Shafqat

Where are antibodies found?

1. Free in serum

2. Free in secretions (mucous, milk, saliva, tears)

3. Surface of cells

Function of Antibodies

To binds to antigens with a complimentary shape and neutralise them.

Basic Antibody Structure

2 light chains

2 heavy chains

2 antigen binding sites

2 types of light chain

Kappa and Lambda

5 types of heavy chain

-Gamma

-Delta

-Epsilon

-Alpha

-Mu

How is diversity in an antibody produced

Through rearrangement of genes in the variable regionWhat

What binds chains together

disulphide bonds

what is the function of the hinge region

provide flexibility when binding to the antigen

What is a CDR

Complimentary Determining Regions

-Binds to antigens

Structure of Variable Region

Forms a beta-sheet structure to hold hypervariable regions in place

Stability of variable region?

More stable amino acid sequence than CDR

CDR interactions with antigen

1. Hydrogen bonding

2. Electrostatic Forces

3. Van Der Waals Forces

4. Hydrophobic Forces

5 antibody classes

1. IgG

2. IgD

3. IgE

4. IgA

5. IgM

Type of chains in each

IgA has alpha chains, IgD has delta chains etc.

IgA Structure

Dimer of 2 antibodies joined by a J polypeptide chain

IgM Structure

Pentamer of 5 Ig molecules with Mu chains

Functions of Antibodies

1. Immobilisation

2. Agglutination

3. Neutralisation

4. Opsonisation

5. Activation of Complement

Immobilisation of Bacteria (Antibodies)

Antibodies specific to flagella and cilia cause them to clump , preventing movement

What is agglutination?

The clumping of antibodies to antigens forming a large co

Benefits of agglutination? (2)

1. easier to dispose of antigens

2. antigen-antibody complexes are easily phagocytosed

What is the basis of blood group tests?

Haemagglutination

What is neutralisation (antibodies)

Bind to pathogens to disarm them and prevent toxins from entering the cell.

Disarmed pathogens are then phagocytosed

What is opsonisation?

1. Fab region binds to antigen

2. Fc region binds to receptors on phagocytic cells

Activation of Compliment by antibodies

Antibodies bound to pathogen act as a receptor for the first protein of the compliment system

What is ADCC and ADCP?

1. ADCC = Antibody Dependent Cell-Mediated Cytotoxicity

2. ADCP = Antibody Dependent Cell-Mediated Phagocytosis

Process of ADCC/ADCP?

1. Fab region binds to infected cell

2. NK cell binds to Fc region

3. Perforin released

4. Granzymes pass through pores and destroy cell cytoskeleton causing apoptosis

What type of antibody is produced first in the immune response?

IgM

4 phases of antibody response to infection?

1. Lag phase

2. Exponential phase

3. Steady State

4. Declining Phase

3 Facts about secondary immune response.

1. Lag phase is shorter due to presence of memory cells

2. Antibody levels are higher for longer

3. Less IgM and more IgG

What is class switching?

genetic rearrangement allowing B-cells to stop producing IgM and produce other types of antibodies.

DOES NOT CHANGE ANTIGEN SPECIFICITY

What is affinity maturation?

B-cells produce antibodies with progressively higher affinity for an antigen

Where dos affinity maturation occur?

Germinal centres

What is somatic hypermutation?

Rapid point mutations in the variable regions of immunoglobulin genes.

• enhances antibody diversity and specificity

Where does somatic hypermutation occur

In B-cells within germinal centres after antigen exposure

What is the function of a B-cell receptor?

binds to membrane bound and free-floating receptors

What is the function of a T-cell receptor?

Only binds to membrane bound receptor when antigen is attached

Shape of BCR and TCR

BCR is a Y shape, TCR is an I shape

What does MHC stand for?

Major Histocompatibility Complex

What does HLA stand for?

Human Leukocyte Antigen

What is the function of MHC?

Recognises foreign substances

Difference between class1 and class2 MHC?

Class 1 has 1 heavy chain, class 2 has 2 heavy chains

What is an antigen?

Any substance that can elicit an immune response

What is a Complimentary Determining Region (CDR)?

Determine an antibodies specificity to an antigen an bind directly to it.

Sections of an immunoglobulin heavy chain (3)

Variable, Diversity, Joining segments

What are immunoglobulins?

hypervariable

T-cell rearrangement?

same as in B-cells as both are hypervariable

what is CD4?

T-helper cell

What is CD8?

cytotoxic T-cell

Where is MHC class 1 found?

on almost all nucleated cells

Where is MHC class 2 found?

1. B-cells

2. macrophages

3. dendritic cells

Differences of MHC classes

Function of MHC class 1

Function of MHC class 2

What marks a cell as self?

presence of MHC

What is the antigen presented on in an APC?

Antigen presented on MHC like a flagpole

Types of antigen presenting cell?

1. macrophages

2. Dendritic cells

3. B-cells

How is MHC1 presented?

1. Protein chopped by proteosome into peptides

2. Peptides passed from TAP to TAPBPR by tapasin

3. Tapasin makes peptides wait until TAP has processed them

4. Peptides processed by TAPBPR

5. MHC1 transferred to surface with peptide attached

   

How is MHC2 presented?

1. Antigens degraded by proteases

2. Clip holds them in place when degraded

3. HLA-DM degrades CLIP allowing the peptide to bind .

4. HLA-DO removes HLA-DM which allows MHC class 2 to be presented with the peptide on the cell surface.

   

What do CD4 T-helper cells secrete to activate CD8 T-cells?

IL-2

How are T-cells activated?

1. MHC-peptide-TCR interaction

2. Co-stimulatory signals from CD80/86 with CD28

3. Cytokine signals

4. Inhibitory Signals via PD-L1-PD-1 OR CTLA-4 --CD80/86