Complex of proteins on T cell surface Variable region is made by gene reassortment - Recognises antigen fragments presented by other cells in the context of MHC

Lymphocytes Flashcards by Elizabeth Akeju

Why do we need adaptive immunity?

Protects us from repeat infections with the same pathogens

Absence of which would lead to the inability to clear infections

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What are benefits/characteristics of adaptive immunity?

Improves efficacy of the innate immune response
Focuses a response on the site of infection and the organism responsible
Had memory
Needs time to develop

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What type of immunity are T cells a part of?

Cell-mediated response

Produce cytokines to help shape immune response (CD4)
Kill infected cells (CD8)

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What type of immunity are B cells a part of?

Humoral response

-Produce antibodies

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What is specificity of B and T cells due to?

Their respective BCRs and TCRs

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Define epitope

Region of an antigen which the receptor binds to

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What structure of epitopes do T cells recognise?

Linear epitopes in the context of an MHC molecule - Primary structure

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What structure of epitopes do B cells recognise?

Structural epitopes - the 3D structure of the antigen in space

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What is an antigen?

Molecule that induces an adaptive immune response (mostly protein)

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Explain the process of clonal expansion

Each lymphocyte bears a single, unique receptor
Interaction between a specific foreign molecule and that receptor leads to activation and clonal expansion (multiple copies of same cell)
Differentiated effector cells of that lineage will bear the same receptor

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Explain the antigen receptor diversity problem

We need to encode a large Repertoire of specific lymphocyte receptors
We need 10^15 different genes for each different antibody, but we only have 25000 genes total for all functions

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How is antigen receptor diversity generated?

Each BCR chain is encoded by separate multi-gene families on different chromosomes.
During B cell maturation these gene segments are rearranged and brought together.
This process is called Immunoglobulin gene rearrangement.

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What is a TCR?

Complex of proteins on T cell surface
Variable region is made by gene reassortment

Recognises antigen fragments presented by other cells in the context of MHC

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What is the role of an MHC?

To bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells
Critical in surgery and donor matching

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What presents antigens to T cells?

Major Histocompatibility Complex (MHC) - critical in surgery and donor matching

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Describe the structure of MHCI and where are they found?

Single variable alpha chain plus a common beta-microglobulin

On all nucleated cells

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Describe the structure of MHCII and where are they found?

2 chains - alpha and beta

Normally only on “professional” antigen presenting cells

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What gene in humans encodes for MHC?

Human leukocyte antigen (HLA) genes

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How are MHC genes expressed?

MHC is polygenic - 3 class I and 3 class II loci
Co-dominant (maternal and paternal both expressed)
Each person can have up to 6 of each gene if completely heterozygous 
More than 17,000 MHC variants

Which MHC is presented to CD8 T cells?

MHCI

Which MHC is presented to CD4 T cells?

MHCII

Where are extracellular MHC/TCR interactions processed?

Endosomes

Where are intracellular MHC/TCR interactions processed?

Cytosol

Explain what CD4 T helper cells do

They produce cytokines (family of inflammatory mediators)

Influence the outcome of the immune response

List all 5 CD4 T helper cell classes

``` Treg (Th0) - limits the immune response Th1 - boosts cellular immune response Th2 - boosts multicellular response Th17 - controls bacterial and fungal infection Tfh - pro-antibody ```

Which CD4 T helper cells are pro-inflammatory?

Th1 and Th17

Which CD4 T helper cell class includes interleukins 4,5 and 13?

Th2

Which CD4 T helper cell is pro-allergic?

Th2 - help fight off multi-cellular organisms such as worms

Which class of CD4 T cells includes interleukins 6, 17 & 23?

Th17

How do cytotoxic T cells (CTL) kill their target cells?

Apoptosis

How is apoptosis characterised?

Fragmentation of nuclear DNA

What do CTLs store and then release after target recognition?

Perforin, granzymes, granulysin (all in cytotoxic granules)

How is apoptosis carried out by CD8 T-cells?

CD8 T cell makes Perforin hole (pore) in the infected cell Injects granzymes into the cell Granzyme triggers cascade of events within target cell which leads to cell death and kills anything inside of target cell

Outline the process of how CD8 cells kill cells once they are infected

1. Virus infects the cell and releases its contents 2. Cell now starts making viral proteins 3. Displays these as non-self MHC 4. CD8 cell detect non-self MHC and attacks 5. CD8 cell kills the virally infected cell

What is the main purpose of B cells?

To make antibodies

What are the 3 core protective roles of B cells?

- Neutralisation - antibody prevents bacterial adherence to host cell - Opsonisation - promotes phagocytosis - Complement Activation - enhances opsonisation and lyses some bacteria

List all of the antibody classes

- IgA - IgD - IgE - IgG - IgM

Which antibody class is involved in type I hypersensitivity?

IgE

Which antibody class is expressed in mucosal tissue?

IgA

Which antibody class has highest opsonisation activity?

IgG

Which antibody class has highest neutralisation activity?

IgG

Where does B cell generation and maturation occur?

In bone marrow in the absence of antigen

What do mature B cells migrate into from the bone marrow?

Circulation (blood, lymphatic system) and lymphoid tissues

What is the portion of antigen that the BCR binds to, called?

Epitope / Antigenic determinant

What do naïve B cells require to be activated?

Accessory signal: 1. Directly from microbial constituents (Thymus-independent, only IgM) 2. From a T helper cell (Thymus-dependent)

Describe the Thymus-independent activation of B cells

Thymus independent antigens (often polysaccharide, repetitive structure) directly activate B cells without help of T cells Second signal is provided by microbial PAMP, e.g. LPS

Outline the process by which B cells are activated by T cells (Thymus-dependent)

1. Membrane bound BCR recognises antigen 2. Receptor-bound antigen is internalised and degraded into peptides 3. Peptides associate with "self" molecules (MHC class II) and are expressed at the cell surface 4. This complex is recognised by matched CD4 T helper cell that was activated by dendritic antigen presenting cell 5. B cell activated