Lymphocytes

Question 1

What makes up the adaptive immune system?

Answer 1

Made up of lymphocytes

They come from the common lymphoid progenitor

Question 2

What does the adaptive immune system do?

Answer 2

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

Question 3

What is an epitome?

Answer 3

the portion of an antigen that makes contact with a particular antibody or T cell receptor

Question 4

What are the 2 types of adaptive immune responses?

Answer 4

T cells: kill infected cells (CD8), produce cytokine (CD4)

B cells: the humoral response, produce antibodies

Question 5

How do B and T cells respond to antigens?

Answer 5

T cell recognises linear epitopes in context of MHC- recognise primary structure

B cell recognises structural epitopes- 3D structure of antigen in space- recognised tertiary structure

Question 6

What is clonal expansion?

Answer 6

Each lymphocyte has a single, unique receptor
Interactions between foreign antigen and receptor leads to activation and clonal expansion (multiple copies of the same cell)

Question 7

How is the adaptive immune response specific?

Answer 7

Each antibody or T-cell receptor recognises one antigen only

Thi means we need a large pool of cells with specific receptors that can recognise a huge array of antigens

Question 8

How do we deal with antigen diversity?

Answer 8

10^15 antibodies can be generated but for this we would need this many genes which would be impossible to incode
Therefor functional genes for antigen receptors don’t exist until they are generated during lymphocyte development

Immunoglobulin gene rearrangement: in B cell maturation gene segments are rearranged and brought together to form BCR

Question 9

What are T helper cells?

Answer 9

Have CD4 markers
Activated when they come into contact with antigen presenting cell
Secrete cytokines - Th1, Th2, Tfh, Th17, Treg (Th0)

Question 10

What cytokines do T helper cells secrete?

Answer 10

Th1- proinflammatory, boost cellular immune response, secrete IFN gamma, IL-12, TNF

Th2- proallergic, boost multicellular response- IL-4, IL-5, IL-13

Tfh- Pro-antibody- IL-21

Th17- proinflammatory, control bacterial and fungal infection- IL-17, IL-23, IL-6

Treg (Th0) (CD25, CD4+, FOXP3) - anti- inflammatory, limits immune response- IL-10, TGF beta

Question 11

What are cytotoxic T cells?

Answer 11

Have CD8 markers
Kill infected cell or tumour cells by increasing apoptosis through 3 major mechanisms:

1. Secrete IFN gamma and TNF
2. Production and release of cytotoxic granules
3. FAS-FAS ligand interactions

Question 12

What’s the effect of Tc cells secreting IFN gamma and TNF?

Answer 12

Have antitumor and antiviral microbial effects

Question 13

What happens when Tc cells produce and release cytotoxic granules?

Answer 13

Cytotoxic granules contain 2 families of proteins- perforin and granzymes

1. Perforin forms pore in membrane of target cell similar to MAC of compliment
2. Pore allows granzymes in granules to enter infected or malignant cells
3. Granzymes have serine proteases which cleave proteins inside cells shutting down production of viral proteins and causing apoptosis of target cell

Question 14

What happens during a Fas/ Fas ligand interaction?

Answer 14

1. Activated CD8+ cells express Fas ligand which binds to Fas receptor on surface of target cell
2. This binding causes Fas molecules on surface of target cells to form a trimer which pulls together signalling molecules
3. These signalling molecules lead to activation of a caspase cascade which leads to apoptosis

CD8+ cells carry both Fas/ FasL so can kill each other with this mechanism

Question 15

What is a T cell receptor?

Answer 15

Has 2 Fab regions each made of one heavy (alpha) and one light chain (beta)
Has 1 Fc region made of 2 heavy chains
Has a variable region made by gene reassortment
All TCRs are associated with a CD3 complex (important is signal transduction)
They recognise antigens on APCs
Antigens are presented on the MHC
TCRs have coreceptors e.g. CD4, CD8 which stabilize MHC-TCR complex

Question 16

What is the major histocompatibility complex (MHC)?

Answer 16

Plays a central role in defining self and non-self
Its encoded by HLA genes in humans
It presents antigens to T cells
Its polygenic (has many genes) and polymorphic (has many alleles)
Different genes combine to form different classes (several class I and class II loci)
Lots of different alleles mean MHC can recognise different pathogens

Question 17

What are the 2 families of MHC molecules?

Answer 17

MHC class I and MHC class 2

Question 18

What does MHC class I do?

Answer 18

CD8 cells work with MHC I
MHC I is found on surface of all nucleated cells
Has 1 transmembrane protein
Accommodates shorter polypeptides

Presents intracellular antigens:

1. protein from intracellular pathogen digested by proteasome
2. Antigen peptides transported via TAP (transporter associated with antigen presentation)
3. MHC Class I synthesized in ER
4. In ER, MHC 1- antigen complex forms
5. complex transported to and expressed on cell surface

Question 19

What does MHC class II do?

Answer 19

CD4 works with MHC II
Has 2 transmembrane proteins
Present in professional antigen presenting cells only (DC, macrophages, B Cells)
Accommodates longer polypeptides

Presents extracellular antigens:

1. Extracellular antigen phagocytosed into an endosome
2. Endosome fuses with lysosome and antigen is digested
3. MHC II synthesised in ER- an invariant chain blocks peptide binding groove
4. Vesicle containing MHC II buds from ER and fuses with lysosome
5. MCH II- antigen complex formed
6. Complex transported to and expressed at cell surface

Question 20

What are the different HLAs corresponding to MHC Class I?

Answer 20

HLA-A, HLA-B, HLA-C

Question 21

What are the different HLAs corresponding to MHC Class II?

Answer 21

HLA-DP, HLA-DQ, HLA-DR

Question 22

What are the 3 functions of antibodies?

Answer 22

Neutralisation- antibody prevents bacterial adherence

Opsonization- antibody promotes phagocytosis

Complement activation- antibody activates complement which enhances opsonization and lyses some bacteria

Question 23

How is an antibody structures?

Answer 23

Has 4 protein chains- 2 heavy and 2 light
Made of Fab and Fc regions
Each heavy chain has a variable and constant region:

Constant region- identical in all antibodies of same class/isotype but differs in different isotypes

Variable region- differs depending on B cell that produces it but is same for all antibodies produced by single B cell or B cell clone

Question 24

What are the different classes of antibodies?

Answer 24

IgG (most common), IgA (dimer), IgM, IgE (parameter), IgD

Question 25

What is IgG?

Answer 25

Most prevalent antibody in serum Able to cross placenta to allow maternal protection for newborn Important in cell-mediated cytotoxicity, fighting viruses and toxins Highest opsonization and neutralisation Made by B cells by T helper cells

Question 26

What is IgA?

Answer 26

Main Ig in secretions (saliva, breast milk, tears) and mucosal epithelia Forms dimers after secretions- consists of 2x IgA molecules, J chain and a molecule of secretory component which protects molecule from proteolytic attack and facilitates its transfer across epithelial cells into secretions

Question 27

What is IgM?

Answer 27

Main antibody in early immune response Has a pentametric structure- 5 Ig units held together by J chain and disulphide bonds 10 potential antigen binding sites so very efficient at agglutination of bacteria and activation of complement pathway Made by B cells by microbial constituents

Question 28

What is IgE?

Answer 28

Involved in allergy and protection against parasitic infections Binding of antigen to IgE coupled with Fc receptor on mast cells and basophils triggers an allergic reaction by activation of mast cells and release of mediators such as histamine

Question 29

What is IgD?

Answer 29

Found mainly on surface of B cells as receptor molecules | Involved in B cell activation

Question 30

Where do antibodies come from?

Answer 30

White blood cells Lymphocytes Effector cells of humoral immunity Memory B cells

Question 31

How are B cells produced to have different antibodies?

Answer 31

Somatic recombination- Gene segment rearrangement that occurs to create repertoire of antigen receptors VDJ (variety, diversity, joining) and VJ recombinases are responsible for looping and cleavage of immunoglobulin gene- also randomly add or remove nucleotides to create variable joint between DNA fragments: - Heavy chain undergoes VDJ rearrangement first -Then light chain undergoes VJ rearrangement VDJ recombinase cuts extra genes we dont want and splices together 2 wanted genes

Question 32

What is SCID and what causes it?

Answer 32

Severe Combined Immunodeficiency Disease | Due to mutations in genes coding for VDJ/VJ recombinase

Question 33

How is diversity of B cells achieved?

Answer 33

1. Germline diversity 2. Combinational diversity 3. Junctional diversity 4. Heavy and light chain diversity 5. somatic hypermutation chain diversity- antigen induces point mutations in variable regions

Question 34

What is a B cell receptor?

Answer 34

Membrane bound antibody with accessory immunoglobulin heterodimer to enhance signal transduction

Question 35

How are B cells activated by T helper cells?

Answer 35

1. Membrane bound BCR recognises antigen 2. Receptor- bound antigen is internalised and degraded into peptides 3. peptide associated with "self" molecules (MHC class II) and is expressed at cell surface 4. complex is recognised by matched CD4 T helper cell 5. B-cell activated