L5-6 - Specific Antigen Receptors and Genes Flashcards by Asheton Mcinerney

What is the role of B and T cell receptors?

Recognise and bind antigen

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What happens to the first antibodies made by a new B cell?

They are inserted into the cell membrane as B cell receptors

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What is the structure of an antibody/B cell receptor?

2x antigen binding sites
2x heavy chains
2x light chains
Fab domain ('fork')
Hinge region
Fc domain ('stem')

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What is the difference in structure between a B cell receptor and an antibody?

BCRs have a transmembrane domain and a cytoplasmic ‘tail’

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What does the hinge region on an antibody do?

Allows the space between the two antigen binding sites to vary
Allows cross-linking and formation of antibody-antigen complexes of varying shapes and sizes

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What are immunoglobulins classified based on?

The type of heavy chain they have (e.g. alpha, delta…)

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What are the two types of light chain that can be part of an antibody? How many of each can an antibody contain?

Kappa and lambda

Can either have 2 kappa or 2 lambda, cant have one of each

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Describe the structure of IgM

5 subunits (Pentameric) linked by a J (joining) chain, giving 10 antigen binding sites

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What is the first Ig secreted in response to infection?

IgM

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What occurs when IgM binds an antigen?

Activates complement system - this can kill pathogen or mark it for phagocytosis

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What are the two Immunoglobulins expressed on naïve B cells?

IgM then IgD

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What are thought to be the roles of IgD?

B cell activation and differentiation by acting as an antigen receptor

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What is the major class of Ig seen in the blood?

IgG

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How many different subclasses of IgG are there?

4 - IgG1-4

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What are the roles of IgG?

Activate complement

Bind to Fc receptors on macrophages and neutrophils to facilitate phagocytosis

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What are Fc gamma receptors (FcγRs)?

Receptors on the surface of various cell types that bind to IgG

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What are the roles of Fc gamma receptors (FcγRs)?

Regulation of cellular responses
Uptake of antigen-antibody complexes
IgG transport

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What is FcRn? What does it do?

Fc γ neonatal receptor - allows IgG to be transferred from mother to neonate via placenta

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What immunoglobulins are monomeric, dimeric and pentameric?

Monomeric - IgG, D, and E
Dimeric - IgA
Pentameric - IgM

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Describe the structure of IgA

2 subunits (dimeric) in secretions linked by J (joining) chain

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Where is IgA mostly found?

External secretions - saliva, tears, milk, respiratory and intestinal secretions

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What is the role of IgA?

Protects mucosal surfaces from pathogens

What does the constant domain of IgE bind to?

What does this do?

Fc epsilon receptors on mast cells and basophils

Can act as passive antigen receptors - when bound to antigen, stimulates secretion of cytokines and amines (e.g. histamine)

What are the roles of IgE?

Activate mast cells and basophils

Dilate blood vessels to allow movement of immune components

Which Ig is responsible for allergic reactions?

IgE

What is a T cell receptor and what does it do?

Receptor of the surface of T cells that binds to MHC molecules on antigen presenting cells

What are the two types of T cell receptors?

Alpha:beta T cells - receptors have 1 alpha and 1 beta chain Gamma:delta T cells - receptors have 1 gamma and 1 delta chain

What is the problem with the T cell receptor cytoplasmic tail? How is this problem overcome?

It is small, making it difficult to activate signalling cascades Forms a complex with CD3 and CD247 (zeta chain) to carry out signal transduction in its place

How many complementarity determining regions are there in a T cell receptor?

3 each in the alpha and beta chains

What are the roles of the complementarity determining regions (CDRs) in a T cell receptor?

CDR1 - interact with N/C terminals of antigen CDR2 - interacts with MHC CDR3 - main CDR for recognising antigen CDR4 (beta chain) - doesn't come into contact with antigens, but interacts with super-antigens

What are the two lineages of B cells?

B1 and B2 cells

Give three key differences between B1 and B2 cells

B1 - innate, produced before birth in liver, low affinity for many antigens B2 - adaptive, produced throughout life in bone marrow, high specificity for certain antigen

What are the two general phases of B2 cell development? Where in the body do these occur?

Antigen independent - produced in bone marrow, mature in spleen Antigen dependant - peripheral lymph nodes

What are the names of the cells produced in the antigen independent phase of B cell development? (6)

Haematopoietic stem cell > pro-B cell > pre-B cell > immature B cell > T1 immature B cell > T2 immature B cell

What are the key stages of B2 cell development in the antigen independent phase? (5)

1. Pro-B cells arise from haematopoietic stem cells in bone marrow 2. BCR heavy chain gene re-arrangement - pre-B cell 3. BCR light chain gene re-arrangement 4. Immature B cell enters spleen for maturation 5. B cell activation factor (BAFF) signalling triggers transition from T1 to T2 phase

How is BCR diversity created during B cell development?

Gene rearrangement of the heavy and light chains

Describe the stages of heavy chain gene rearrangement of the B cell receptor (3)

DJ recombination - one D segment and one J segment join, everything between is deleted VDJ recombination - one V segment joins the DJ segment Constant segment - added at the end during transcription

Describe the stages of light chain gene rearrangement of the B cell receptor (2)

VJ recombination - one V segment and one J segment join, everything between is deleted Constant segment - added at the end during transcription

What is the major difference between heavy and light chain gene rearrangement in the BCR?

Light chain has no D segments, so has one less recombination event

What triggers the change from T1 phase to T2 phase in the spleen in B cell development?

B cell activation factor (BAFF) signalling

What is the name of B cells after they leave the bone marrow?

Immature B cells

What is the name of B cells after they leave the spleen?

Mature naïve B cells

What happens to naïve mature B cells in the periphery before entering the lymph node?

They become exposed to antigen, process it and present it in MHC class II

What are the key stages of B2 cell development in the antigen dependent phase? (6)

1. Naïve mature B cells pick up antigen and migrate to lymph node 2. Activate through interaction with Th cells 3. Become centroblasts that form germinal centre 4. Develop hypermutated IgG in dark zone 5. Move to light zone and become centrocytes - checked for autoreactiveness and interact with Th to promote survival 6. Class switching and differentiation

What occurs within the dark zone of the germinal centre in B cell development?

Centroblasts develop IgG that have been hypermutated to produce BCRs of varying specificity to the antigen

What occurs within the light zone of the germinal centre in B cell development?

Centrocytes with negative mutations undergo apoptosis, and those with positive mutations undergo differentiation and class switching

What is antibody class switching?

The daughter cells of a B cell produce antibodies with the same variable region but different constant region than the mother

How does class switching occur in B cell development?

Class switch recombination - mu or delta heavy chain segments are deleted and replaced by gamma, alpha or epsilon

What CDs do progenitor t cells have?

They are CD4 and CD8 negative

Where are progenitor T cells produced?

Bone marrow

Where do progenitor T cells go after leaving the bone marrow?

Thymus

What occurs in the thymus during T cell development?

Random recombination of alpha and beta chains to produce CD4+ and CD8+ T cells, and central tolerance mechanisms

What are the central tolerance mechanisms in place during T cell development? What do they do?

Positive and negative selection - ensures T cells are functional and not autoreactive