Year 2 Immunology Flashcards

Question

Describe what hypervariability within the heavy/light variable chains are.

Answer 1

Heavy/light variable regions have 3 regions of hypervariability each. We label them HV1, HV2, HV3. The total 6 regions from each region are grouped together and are called the complementarity determining regions. These complementarity determining regions are important to the way antibodies actually make contact with the antigen, as these regions lie in loops on edges of the structure allowing for interactions to be made.

Answer 2

B cell receptors must fit the shape of the antigen exactly. The antigen can bind in pockets, grooves or extended surfaces in the binding site of B cell receptor/antibodies. B cell receptors only recognise 3D shapes of antigens.

Answer 3

Immunoglobulins refer to structure more, and antibody refers to function more. Immunoglobulins that are attached to B cells are called B cell receptors, however if they are floating around, they're antibodies. Immunoglobulins are also known as glycoproteins, proteins with sugar stuck on them that function as antibodies.

Answer 4

IgG, IgM, IgA, IgD, IgE

Answer 5

T cell receptors resemble a membrane bound fragment antigen binding region. They also have regions of hypervariability. It has 2 cytoplasmic tails that stick into the cell, go through the membrane and hold it into the cell. T cells receptors only bind to linear peptides and are always membrane bound (not secreted like in B cells). There are carbohydrates on every region, for stability. Stalk segment is between the bottom of the T cell receptor and the membrane. 1 disulfide bond between the chains. The T cell receptor is encoded by a completely different set of gene segments.

Answer 6

For a good immune system, we need activation of both B cells & T cells. Both B and T cells can get activated by the same antigen, but different parts of it. The different parts are called epitopes. 3 X 3D B Cell Receptor epitopes and 2 X linear T Cell Receptor epitopes in egg white lysozyme.

Answer 7

T cell receptors can only see its matching antigen if it's presented by a specific MHC molecule. There are two types of MHC molecules: Class 1 and Class 2. MHC molecules look different from person to person. In organ transplants, we have to match the MHC molecules as best as possible to reduce chance of rejection. Class 1: alpha chains are membrane bound, beta chain isn't membrane bound. You get different side chains sticking off the alpha helices which affect which antigen peptides it can interact with. MHC Class 1 binds peptides via the ends of their backbone via hydrogen bonds and ionic interactions. As the peptides need to fit in the MHC, peptides can only be 8-10 amino acids long. MHC Class 1 will be more domed. Anchor residues are amino acids on the MHC which are always in the same position as its preferred by MHC class 1 for binding, it gives good affinity. Each MHC Class 1 structure will have a different allele specific binding motif compared with another MHC 1 structure, hence it can interact with a wide range of different peptides. Class 2: both alpha and beta chains are membrane bound separately. Again, you'll get different side chains sticking off, causing variation. MHC Class 2 binds peptides along the length. It interacts with peptide backbone via hydrogen bonds & ionic interactions. Peptide length can be longer because its open from both ends, hence lengths can be 13-17aa in length. It's harder to identify the allele specific binding motifs because they can occur anywhere along the amino acid sequence of the peptide, but they still do have them. MHC class 2 will have a flatter shape.

Answer 8

MHC Class 1 is found on any nucleated cell. MHC Class 2 is only found on (Antigen presenting cells): B cells, macrophages, dendritic cells, epithelial cells. MHC Class 1 is unlikely to be found on immunoprivileged sites - places where inflammation would be more harmful than beneficial such as they eyes. Red blood cells have no MHCs. T cells are likelier to have MHC class 1 rather than MHC class 2 in their resting state.

Answer 9

T cells also express either CD4 or CD8 surface proteins. These proteins stabilise the binding of T cell receptor to MHC:peptide complex. These proteins also have the anti-parallel beta sheets all folded over with the disulfide bonds holding them together. T cells are only able to express CD4 or CD8, not both. CD4 and CD8 also have a signalling role to help stimulate T cells to become effector T cells that have immune functions. CD4 is 4 chained domains. A single molecule that hooks into the membrane too. Works with MHC Class 2. Works with T helper cells that activate B cells. CD8 is either a heterodimer (alpha/beta) or homodimer (alpha-alpha/beta-beta). It works with MHC Class 1. It works with cytotoxic T cells.

Answer 10

We need the peptides to get into the binding groove of the MHC class 1 or 2 so the T cell receptor can see it. The MHC molecule & peptide in it are recognised by the T cell as an entire complex.

Answer 11

1. Combinatorial diversity during segment recombination 2. Junctional diversity during segment recombination 3. Combinational diversity driven by different combinations of heavy & light chain. 4. Somatic hypermutation.

Answer 12

Variable region genes are constructed from somatic recombination of separate gene segments, depending on if they are in the light/heavy chain. Germline DNA --> D-J rearranged DNA joined --> V-J/V-DJ joined rearranged DNA. It's made of Variable (V), Diversity (D) and Joining (J) and Constant (C) regions. The variable light has only VJ segments, and one constant region. The variable heavy has VDJ segments, and many constant regions. Segments are brought together via somatic recombination & then splicing occurs to form mRNA that's translated into polypeptide chains. There are many VDJ regions on each variable gene. There's a small 'L' exon at the front of the gene segment that encodes a leader peptide that directs the protein into the cell secretory pathway, and its cleaved off, its not part of the final antibody structure. Light chains can be either kappa (Chrm 2) or lambda (Chrm 22). Heavy chain is on Chrm 14. The variable segment is is usually most diverse, joining/constant is less diverse.

Answer 13

Lambda light-chain: J&C not separated. L & V near the start, J1 &C1 alternate till the end, 23 --> 12. Kappa light-chain: J&C separated. L&V near the start, then J and lastly C, 12 --> 23. Heavy chain locus: L&V near the start, D next separated, J next separated, C last, 23 --> 12, 12 --> 23. Colon is just representing all of the ones in between.

Answer 14

We want random selection for diversity, but we must still have the segments in order: V -> D -> J -> C. The rearrangements is guided by flanking DNA sequences called recombination signal sequences (RSS). Two main types of RSS: 12 bp spacer OR 23 bp spacer. You get a specified heptamer (7) which is conserved, then 12/23 bp RSS random combination nucleotides, and lastly specified nonamer (9) which is also conserved. 23bp sequence can stretch around DNA double helix twice, 12bp sequence can stretch around DNA double helix once. To transcribe the gene segment, everything must be in the right orientation; for 2 segments to be transcribed, they must be in the same transcriptional direction. It always goes from heptamer to the nonamer.

Answer 15

1. Check if following 12/23 rule. 2. If yes, check if it's in right orientation. 3. Alignment of Recombination Signal Sequences regions, loops out intervening DNA. Looking like this: Ω. 4. Enzymes cuts at the recognition signal sequences. 5. V-J brought together and ligated. DNA loop is lost. You have the same orientation.

Answer 16

1. Check if following 12/23 rule. 2. It's not the right orientation (direction). 3. Recombination signal sequences try to align, forming a coil structure. 4. Enzymes cut at the recognition signal sequences. 5. Inverted region is retained on the same chromosome, and V-J brought together & ligated. 6. Same orientation now!

Answer 17

1. RAG1/RAG2 complex will bind to the recognition signal sequence. 2. Other RSS is found & brought to RAG1/2 complex. You end up with synapsis. 3. RSS's are cleaved precisely by RAG's endonuclease capacity. 4. After RSS removal, DNA ends join back on themselves and form a hairpin loop, as they bind to whichever thing they match up to resulting in blunt ends: coding/signal joints. 5. Coding joints (we want) have blunt ends. Ku70/Ku80 form heterodimer rings to recruit other proteins to come fix the blunt ends too. 5. Signal joints (DNA lost) will be bound by Ku70/Ku80 proteins. 6. DNA-PK:Artemis proteins open hairpins at random sites. 6. DNA ligase:XRCC4 protein comes along and ligates DNA ends forming an extra loop. Precise signal joints made. 7. Tdt (contributes to diversity of third hypervariable region) processes the open DNA ends by adding in upto 20 nucleotides - junctional variation. 8. DNA ligase:XRCC4 will ligate the DNA end together, resulting in an imprecise coding joint.

Answer 18

If the hairpin is opened in a way that forms a tail (by DNA-PK:Artemis) you might get a palindrome (sequence reads the same back and forwards) nucleotide sequence.

Answer 19

The random bases that TdT adds are called N-nucleotides because they are non-templated. After N-nucleotides are added, the stands try to pair up. Any unpaired nucleotides are removed by an exonuclease. The gaps are filled by DNA synthesis & ligation to form coding joints.

Answer 20

Disadvantages of TdT is that if bases aren't added in threes, you might get a frameshift mutation. So this process is brilliant, but dangerous.

Answer 21

The T cell receptor gene segments are arranged in a similar pattern to Ig gene segments and are rearranged by the same enzymes. Germline DNA --> Rearranged DNA --> Protein TCR. The alpha chain has 1 recombination event (VJ) , beta has 2: DJ first, then V. Alpha-Beta TCR are common in mature TCR. Gamma-Delta TCR is more during embryonic development & have fewer diversity segments. 12/23 rule & orientation also apply here. RSS's help keep orientation. TCR also affected by TdT, and have P/N nucleotides. TCR diversity is concentrated in third hypervariable region (CDR 3) as this region makes contact with the antigen peptide.

Answer 22

TCR has greater diversity than BCR as there are more linear peptides to interact with compared to 3D chunks that BCR works with. TCRs also have to interact with MHCs and require more diversity than BCR to do so. They also need to interact with CDR's too.

Answer 23

One type of MHC can bind thousands of peptides, even if they are slightly different as they will share anchor residues that allow it to fit.

Answer 24

There are 2 major intracellular compartments, separated by membranes: cytosol and vesicular system. Some bacteria thrive in cytosolic environments, others in extracellular environments.

Answer 25

Cytosolic pathogens get broken down inside the cell, and displayed on the cell surface by MHC Class 1. CD8+ cytotoxic T cells recognise MHC Class 1. Intravesicular pathogens/extracellular pathogens (cells that can phagocytose) are broken down, displayed on surface by MHC Class 2 and CD4+ T cells recognise the antigen.

Answer 26

This pathway is used for intracellular pathogens. 1. Partly folded MHC Class 1 alpha chain is bound to calnexin until the beta-microglobulin binds. 2. MHC Class 1 complex is released from calnexin then binds to a complex of calreticulin (chaperone proteins) and ERp57. 3. Old cytosolic proteins & defective ribosomal products (<30%) are degraded to peptide fragments by proteasome enzyme. 4. TAP protein across the ER membrane delivers peptide fragments to the ER. 5. Chaperone/MHC C1 complex bound to TAP protein via tapasin for proximity. 6. Peptide fragments bind to MHC C1 via ERAAP & completes folding. 7. MHC C1 complex is release from TAP complex & is exported to cell membrane.

Answer 27

It's got proteosome activator (PA28) on both ends. It's got the alpha-annulus on the inside of both of these PA28's. Right in the middle, it has the beta catalytic chamber. The alpha annulus opens up after PA28 activation. An immunoproteosome has an added hydrophobic C terminal, allowing it to bind better into the MHC C1 groove.

Answer 28

It's actually TAP1/TAP2 structure. The longer parts is hydrophobic transmembrane domain, and the circle part is ATP-Binding Cassette domain. The TAP protein is heterodimeric & different combinations of the polypeptides make some things easier to enter than others - selectivity. Peptide fragments can be from pathogens or old self peptides.

Answer 29

Many viruses produce immunoevasions that interfere with antigen presentation by MHC C1. Eg. Adenoviruses produce E19 protein that competes with tapasin & inhibits peptide fragment loading on MHC C1 protein in ER lumen.

Answer 30

1. Antigen is taken up from extracellular space into intracellular vesicles. 2. In early endosomes of neutral pH, endosomal proteases are inactive. 3. H+ is pumped into vesicles and pH decreases, this activates proteases that degrade antigens to peptide fragments. 4. Vesicles containing peptides fuse with vesicles containing MHC C2.

Answer 31

To stop anything from binding to MHC C2 groove before it meets antigenic cargo, it must be blocked by invariant chain: Ii. It has 2 major roles: prevents peptides with coincidental matching anchor residues from fitting into groove; it has a cytoplasmic tail for signalling role to make sure vesicle moves towards outer membrane. It's a transmembrane protein. The invariant chain sits as a trimer bounds to 3 MHC C2's simultaneously in ER.

Answer 32

1. pH change in vesicles cleaves at the ends of invariant chain until your left with the bit in the groove - CLIP. 2. Both the MHC C2 vesicles & antigen vesicles fuse. 3. HLA-DM protein binds to MHC C2 to release CLIP and allows other peptides to bind, then the MHC C2 travels to surface.

Answer 33

Cross presentation allows exogenous protein to be presented by MHC C1/2 by a restricted set of antigen presenting cells. If a virus doesn't infect an antigen presenting cell a type of dendritic cell will phagocytose the dying host cell, break down the viral cell to peptide fragments; but even though it should go down the MHC C2 pathway, it sheds vesicle contents into the cytoplasm to switch to the MHC C1 pathway. We don't know how. MHC C2 can also be loaded with cytosolic proteins (should go to MHC C1) via autophagy. Autophagy is when some damaged organelles & cytosolic proteins are delivered into endosomes by autophagosomes for proteolytic breakdown. The peptides can be expressed in the context of MHC C2. We don't know how.

Answer 34

It's called the HLA - human leukocyte antigen receptor. HLA-B/C/A code for heavy alpha chain of MHC C1. LMP (proteosomal protein)/ TAP (TAP protein) TAPBP codes for tapasin. DP (B,A) / DQ (B,A) / DR (B, B, A) are genes for MHC C2 alpha and beta chains. DM plays role in HLA-DM in MHC C2 pathway. DOA/DOB regulate HLA-DM expression.

Answer 35

Both polymorphism (2+ different variations of a specific gene in a population) and polygeny (trait controlled by 2+ genes) contribute to the diversity of the MHC and are all expressed co-dominantly. If 1 MHC 1 can house 1000 different peptides with same anchor residues, then as we have 6 MHC (3 from each parent) we can house 6000 different peptides. 3 different MHC loci on gene from each of both parents. It's 12 segments on MHC 2, we have 6-8 different MHC 2's on every cell, leading to high diversity.

Answer 36

MHC plays a role in tissue transplantation, tissue matching and tissue typing.

Answer 37

There are certain points along the TCR/BCR polypeptide where we see lots of variation. These points are majorly centred in the points in the binding groove. MHC1 - The variation points are all along the alpha and beta parts. MHC2 - The variation points are more along the beta region than alpha. There is very high specificity between the TCR on phagocytic/APC cells and MHC:antigen complex. If T cells recognise self proteins, we'd end up with autoimmune disease.

Answer 38

Some antigens that don't abide by the specificity rule are called superantigens = very large antigens. Bacterial superantigen (eg. Staph) binds both MHC & TCR regardless of if there's a peptide inside. This creates a bridge. It causes a massive immune response (toxic shock syndrome) - fatal. You'll get a mass stimulation of clones of T cells.

Answer 39

Some TCRs will work, some wont.

Answer 40

The development capability is reduced in elderly, hard to fight disease. This means they rely mainly on memory cells.

Answer 41

1. T cell precursor rearranges its TCR in bone marrow and migrates to the thymus. 2. Immature T cells that recognise self MHC will get signals to survive. Those that interact & get activated when interacting with self, are removed. 3. Mature T cell encounter foreign antigens in peripheral lymphoid organs & are activated. They proliferate and eliminate the pathogens.

Answer 42

2 lineages of T cells are made in the thymus: CD4+ and CD8+

Answer 43

When T cells go into the thymus, they're CD3-4-8-. CD3 is a supporting molecule. This means they don't express anything. In early embryonic development - T cells are likely to go down the gamma/delta route as we get older they go down alpha/beta. Gamma/delta T cells are bad at shuffling genes so they get limited variation. They make their way to mucosal surfaces in newborns to allow a first kind of humoural response, also to the gut. As we get older, we lost the gamma/delta portions of DNA during gene rearrangement so we are pushed down the alpha/beta route. They first become alpha/beta CD4+8+ cells: 'double positive', and after more development, these double +ve cells go through a series of tests to determine whether the cells develops further to be a single-positive thymocytes. Thousands of cells go into the thymus, but only ~100 come out. Rigorous process.

Answer 44

Thymus is situated above the heart, the cortex (specifically the cortical epithelia cells) is a dense-filled with thymocytes. The medullary region (local dendritic cells) has less cells. Cortex - deciding if they want to be CD8/4+ in medulla test themselves to see if they recognise the self/non-self MHCs or not. If they don't interact with any MHCs, they don't get survival signals & hence apoptose/phagocytose. If the binding is too strong/light we also kill them off. After becoming CD4/8+ after cortex, they go to medulla for testing.

Answer 45

+ve selection: MHC1/MHC2 or CD4/CD8. -ve selection: self/non-self recognition.

Answer 46

As beta chain is being made, a surrogate alpha chain goes out and joins beta chains so it can go out & be expressed onto cell surface. Leads to pre TCR half made = pre-TCR at DN3 stage. DN1/2/3 has DJ recombination, and then VDJ recombination. There is proliferation at the DN4 stage. Double +ve stage gets VJalpha rearrangement too. Once that's rearranged successfully, we kick off the surrogate alpha chain production too & it goes to join the beta chain too. We express CD3 as it supports CD4/8. To become single +ve, the double +ve shakes hands with the thymic epithelial cells to decide to be CD4/8.

Answer 47

As T cells mature, they move towards medulla of thymus.

Answer 48

In the lower medullary region, we test the receptor against particular self protein. If it recognises it, we must destroy, done via -ve selection. +ve selection is to help make sure the TCR can actually interact with the self MHC1/2. In the cortex, beta chain segments rearrange first, then alpha chain rearranges.

Answer 49

1. DN1/2 - Germline gene configuration 2. DN2/3/4 - D(Beta)-J(Beta) rearrangement. 3. DN3/4 - V(Beta) - DJ(Beta) rearrangement in frame. Beta chain is produced. 4. DN4 - V(Beta) - DJ(Beta) rearrangement in frame. Beta chain is produced.

Answer 50

Early double +ve: surface expression of beta chain with surrogate alpha chain. Beta chain rearrangement stops, cell proliferates, CD4/8 induction and alpha chain transcription starts. Late double +ve: V(Alpha)-J(Alpha) rearrangement. Surface expression of alpha/beta/CD3/4/8. Selective events begin. CD3 supports TCR. Multiple alpha chain gene rearrangements can take place to rescue non-productive joins.

Answer 51

MHC restriction takes place on thymic cortical epithelial cells, for +ve selection. Normally thymic cells express both MHC1&2, depending on which the new T cells interact with, they become CD4/8 +ve. We make some of both. If we have class 2 -ve mutant thymic cells (only express MHC1) we can only make CD8 +ve. Adding that missing gene back results in both CD8/4 +ve cells being made, but adding a faulty version of that gene back in results in only CD8+ as MHC2 isn't expressed.

Answer 52

-ve selection occurs in both thymic cortex & medulla. Driven by APCs. TCR that interact too strong with self are deleted, it prevents inappropriate activation. TCR that interact with every self antigen-deleted in thymus - prevent autoimmunity.

Answer 53

It finds its way to a lymph node. In the lymph nodes, we have dendritic cells (Antigen presenting cells) which show T cell different antigens to ask 'do you recognise this bro?' and then get stimulated to differentiate into different T cell types.

Answer 54

T cells can become either cytotoxic t cells (CD8+) or T helper 1/2/17 and T reg. For CD4+ T cells to know what to become, the dendritic (APC) will give it a message in the form of a cytokine, to drive it down a specific pathway.

Answer 55

- CD8+ cytotoxic t cell = kill virally infected cell. Eg. viruses/intracellular bacteria. - CD4+ TH1 cell = Macrophage activation and inflammation. - CD4+ TH2 cell = Help B cell class switch, especially to IgE. Eg. helminth parasite. - CD4+ TH17 cell = Enhance neutrophil recruitment & protect mucosal barriers. - T follicle helper cell = Helps B cell class switch, to make antibodies. - T regulatory cell = Suppresses T cell responses, when there's no infection. It uses interleukin 10.

Answer 56

For CD4+ T cell to know what to become, the dendritic (APC) will give it a message in the form of a cytokine, to drive it down a specific pathway.

Answer 57

T cells migrate to peripheral lymphoid organs where they sample the antigens on offer. If they recognise it, they stay, proliferate and differentiate. If not, they carry on their way. Lymph fluid contains debris from any infection & dendritic cells take in the antigen debris & put it on their surface as MHC1/MHC2. This is how they interact. After proliferation T cells can't leave the lymph nodes, only activated effector cells leave the lymph node. T cells that don't encounter their antigen exit via cortical sinus of lymph node.

Answer 58

It enters via the high endothelial venules. Entry us regulated by selectins, adhesion molecules, chemokines, chemokine receptors.

Answer 59

1. All naive T cells will express L-selectin that recognise addressins (on lymph endothelial venules) such as CD34 to bind T cells weakly to the endothelial surfaces, to slow them down via rolling interaction. 2. Integrins on naive T cell surfaces (Eg. LFA1 - activated by chemokines in extracellular matrix) binds to adhesions molecules on endothelial venule cells (Eg. ICAM-1) to activate it to stabilise binding to APC/endothelia. The binding is stronger. 3. T cell migrates into the lymph node by diapedesis (squeeze between cell walls). LFA1:ICAM1 is the initial low affinity interaction. Subsequent binding of TCR signals LFA1 to change shape to increase affinity, and prolong cell-cell contact. This gives a nice, rigid & secure connection & activation of T cell.

Answer 60

Dendritic cells process antigens to present to T cells from a wide variety of pathogen. MHC1 presentation: Viral infection, cross presentation after phagocytosis, transfer between dendritic cells. MHC2 presentation: Receptor mediated phagocytosis, macro-pinocytosis.

Answer 61

1. Specific interaction between TCR & MHC & antigenic peptide using LFA1 to help. 2. Co-stimulatory interaction between B7 on APC & CD28 on T cell to provide a survival & proliferation signal. It's a danger signal. 3. Cytokines that provide differentiation signals for T cell (what kind of T cell it will become) Eg. TRL's or Interleukins. It's important to have all 3 signals because its like a safety mechanism. The co-stimulatory signal provided by CD28:B7 binding on the activated T cell means it starts to express an alpha chain next to the interleukin 2 receptor to give high affinity for interleukin 2 to trigger growth, differentiation & proliferation.

Answer 62

The differentiation signal allows T cells (CD4+) to differentiate & acquire different effector function. If there's no infection, lack of B7:CD28 interaction drives T reg development. Partial signalling (not all 3 signals) results in functional inactivation or anergy. You won't get a reaction.

Answer 63

Signal from APC - TGF-Beta Transcription Factor - FoxP3 Products of cell - TGF-Beta, Interleukin 10

Answer 64

Signal from APC - Interleukin 6 Transcription Factor - Bcl6 Products of cell - Interleukin 21, ICOS

Answer 65

Signal from APC - TGF-Beta, Interleukin 6 Transcription Factor - RORγT Products of cell - Interleukin 6, Interleukin 17

Answer 66

Signal from APC - Interferon γ, Interleukin 12 Transcription Factor - T-bet Products of cell - Interleukin 2, Interferon γ

Answer 67

Signal from APC - Interleukin 4 Transcription Factor - GATA3 Products of cell - Interleukin 4, Interleukin 5

Answer 68

Activation of cytotoxic T cells is a 2 step process. 1. CD4+ T cell & APC interact to activate T cell to make CD40L and interleukin 2. CD40L binds to CD40 receptor on the APC to increase B7 & make 4IBBL. 2. 4IBBL binds to 4IBB on CD8+ T cell & B7:CD28 binding gives co-stimulatory signal to T cell & more interleukin 2 production. Interleukin 2 is a growth factor that promotes Tc differentiation.

Answer 69

1. B cell precursor rearranges its immunoglobulin genes. 2. IgM is made first. Immature B cells bound to self-antigen are removed. -ve selection. 3. IgD is made second, mature B cell bound to foreign antigen is activated. 4. Activated B cell -> Plasma Cells -> Memory cell.

Answer 70

It's dependent on stromal cells in bone marrow. 1. Multipotent progenitor cell - CXCLI2 cytokine keeps FLT3 (B cell) attracted to FLT3 ligand on stromal cell. 2. Common lymphoid progenitor - more cell adhesion molecules. 1 & 2 = Germline H&L chains. 3. Early pro-B cell - Start to see B cell characteristics. D(H)J(H) rearrange. Germline L chain. 4. Late pro-B cell - V-DJ (heavy). Germline L chains. 5. Pre-B cells - Surrogate light chains (VpreB & lambda5) accompanies the heavy chain to the surface, and then we get V-J(L) rearrangement. 6. Immature B cell - Release from stromal cell & production of IgM receptor. 7. Mature B cell - IgD & IgM made from alternate splicing of H chain regions.

Answer 71

They are supporting molecules that sit next to the BCR and have cytoplasmic tails that transduce signals into the cell. Linked signalling by Ig alpha & Igbeta (allelic exclusion) prevent further H chain rearrangement because we only want 1 class of antibody to be made eventually (the one that's most effective at tackling the antigens).

Answer 72

Non productive light chain rearrangements can be rescued by further rearrangements. The gene rearrangements can happen on the first chromosome, and if it's a non-productive join, it can happen on second chromosome. Then we tie kappa/lambda light genes on the first/second chromosome and it turns out that we have lots of chances to fix non-productive joins via further rearrangements. We want to try and make it work as much as possible before we have to destroy the B cell.

Answer 73

The educative route is based on what they interact with. - No self reaction -> Ideal, migrate to periphery. - Lots of self reaction -> Apoptosis/reshuffle light chain - Reaction to soluble self-molecule -> Migrate to periphery but are generally lost because there aren't many soluble self-molecules to react with. - Low affinity for binding -> Migrate to periphery, becomes clonally ignorant mostly, but can rarely become autoimmune.

Answer 74

After activation, the mature B cells express antibodies. Antibodies can neutralise (prevent adherance); opsonize (promote phagocytosis), activate complement cascade. But to be activated, it needs antigen & T helper cells. Antibodies themselves don't clear infection, but its the complex that they form with that particular antigen. These complexes need to be gotten rid of, if they aren't removed and destroyed properly, they can get trapped in places like synovial joints or in your kidney and can lead to inflammation.

Answer 75

All B cells need 2 signals to be activated regardless of its its doing it in the thymus or not. First signal - Delivered when immunogolobulin on surface of B cell binds its antigen. Second signal - Delivered by T helper cell recognising degraded fragments of same antigen via MHC2 & involves interaction between CD40/CD40L and release of cytokines.

Answer 76

Once the B cell has had its 2 signals, then they start to divide. Collectively they produce monoclonal antibodies. If another B cell recognises a different epitope of the antigen, they will produce slightly different variations of the same antibody that are fighting the same infection (polyclonal antibody response). Some of the B cells need to become memory cells, so rather than being active they might go back to being in the bone marrow for reinfection.

Answer 77

When the T cells adhere to the B cells and begins to synthesize interleukin 4 & CD40 ligand. The T helper cell reorients its cytoskeleton & secretory apparatus towards the B cell. It releases cytokines via gaps in the synapses in a directional way. Naive B cell activation and conversation with T cell in lymph nodes. B cells in the germinal centre will have to move through an area with lots of T cells that have been activated.

Answer 78

High endothelium venule is where they first come in. They then go through the T cell region where some are activated. The ones that are activated form a cluster called the primary focus which starts pumping out IgM antibodies. Later on during first infection, we'll get IgG antibodies being made. During 2nd infection, we'll get IgG made straightaway. Some T cells that are activating B cells help them go towards germinal centres and create an area where somatic hypermutation occurs.

Answer 79

Germinal centres are active sites of B cell proliferation. They mainly consist of B cells but also have 10% antigen specific T cells which continue to help the differentiating B cell. Outside the germinal centre, there is unstimulated and resting B cells, this is called a mantle zone. At the mantle zone, they're called centrocytes.

Answer 80

Centroblasts (active B cells) undergo somatic hypermutation in the dark zone of germinal centres. They are tested for antigen binding ability by cycling into the light zone of the germinal centres. Testing involves contacting the follicular dendritic cells bearing the antigen. If the testing is successful, they go and become plasma cells and if not, they go back to dark zone for another round of editing. Re-entry mechanism (for top part of the antibody): Centrocytes carry chemokine receptor CXCR5 but not CXCR4. They gain and lose CXCR4 to let them re-enter the dark zone, by attraction to CXCL12. Editing bottom region of antibody mechanism: AID introduces uracil base into a specific switch region in constant gene segments to create dsDNA breaks and allow rearrangement of constant gene segments to class switch.

Answer 81

IgM -> Activates complement system & expressed early. IgD -> Expressed early but we don't know what it does. IgG1 -> Can cross placenta, diffuse into extravascular sites, important for oposonisation, highest concentration of antibody type. IgG3 -> Important for complement system. IgA -> Found as a monomer, but dimerises when in use, support mucosal system as it transports across epithelia, good at neutralising, found in secretion via milk. IgE -> Sensitisation of mast cells.

Answer 82

Interleukin 4 induces IgG1 & IgE. Interleukin gamma induces IgG3 & IgG2. Some of us are genetically likelier to produces more interleukin 4 which pushes us to make more IgE which predisposes you to have allergies. This is called atopic.

Answer 83

Antibodies are good at binding to a specific toxin before they have a chance to damage cells. Antibodies can stop viruses from binding to cells to cause infection. Antibodies binding can also attract a specific component of the complement cascade to trigger proper complement cascade, or flagging for macrophage engulfment.

Answer 84

1. Small antigen/antibody complexes form in circulation. 2. Complement receptor on RBCs bind onto complexes via complement component. 3. Take complex to spleen where it dies along with the old RBC that was going to die anyways OR simply remove the complex from RBC in spleen and liver.

Answer 85

They form a complex structure often with restricted tissue distribution which aid the destruction of antibody coated pathogens. Fc receptor binds onto the tail of the antibody. The Fc receptor and complement receptors on phagocytes trigger phagocytosis. Antibody coated target cells are killed by natural killer cells in antibody dependent cellular cytotoxicity (opsonisation).

Answer 86

IgE can bind to outside of mast cell, once antigen is recognised, the IgE's will cross link and cause the mast cell to release inflammatory mediators. It can lead to allergies, IgE helps battle against worm infections.

Answer 87

The mucosal immune system is an important compartment of the immune system which protects internal surfaces. We focus on the GALT (Gut-associated lymphoid tissue).

Answer 88

1. Protection of mucosal membranes through colonisation, difficult for pathogens to squeeze in due to sheer amount of commensal bacteria. 2. Protect against uptake of antigens derived from food (food intolerance) 3. Regulates appropriate immune response to appropriate antigen & stop it while staying balanced to prevent things like irritable bowel syndrome.

Answer 89

Mucosal immune system includes lymphoid organs associated with the intestine, respiratory tract & urogenital tract and associated glands. It's protected by commensal bacteria/microorganisms that are good for the host. The colon is most heavily colonised. Types of food you're exposed to determines a a person's gut microbiota. We have ~1012 organisms/ml.

Answer 90

1. Anatomic features that distinguish it from systemic immune system. 2. Effector mechanisms - unique to the gut. 3. Immunoregulatory environment which has unique characteristics.

Answer 91

Close association between mucosal epithelia & lymphoid tissues. Discrete compartments of diffuse lymphoid tissue & more organised structures such as Peyer's patches, isolated lymphoid follicules, and tonsils. Specialized antigen uptake mechanisms, eg. M cells in Peyer's patches and tonsils.

Answer 92

Activated/memory T cells predominate even in the absence of infection. Multiple activated 'natural' effector/regulatory T cells present all times even without pathogenic infection. IgA sit on surface of mucosal cells. Presence of microbiota.

Answer 93

There's active downregulation of immune responses to innoculus antigens (pollen). There are lots of inhibitory macrophages & tolerance - inducing dendritic cells.

Answer 94

Drawing - look at immunology L10. Antigens in the gut lumen need to move into Peyer's patch. This is done via M (microfold) cells that are non-selective. 1. M cells take up antigen by endocytosis & phagocytosis. M cell has a highly folded surface. 2. Antigen transported across M cells via vesicles & released below to dendritic cells. 3. Antigen bound by dendritic cells that may express danger signals (if pathogenic) to activate T cells.

Answer 95

Once T cells are activated, they drain from the lymph node, into lymphatics, then back to circulation. They then either go to lamina propria of villi or surface epithelia of villi depending on cell type.

Answer 96

B cells Macrophages Dendritic Cells Mast Cells T cells (CD8/CD4) with specific addressins.

Answer 97

T cell (CD8) with specific addressin labels. E - Cadherin is the specific adhesion molecule.

Answer 98

1. T cell enter Peyer's patches from blood vessels, directed by homing receptors. 2. T cells in Peyer's patch encounter antigen that has been transported, they become activated by dendritic cells. 3. Activated T cells drain to thoracic duct & return to gut via blood. 4. Activated T cells expressing alpha4:beta7 integrin and CCR9 allows it to come close to the lamina propria.

Answer 99

- Non specific transport across epithelium via M cells. - Fc receptors on endothelial cells binds to IgA containing antigen, transport triggered. - Virally-infected/stressed cell undergo apoptosis near dendritic cell, transfers. - Microprocesses on dendritic cell goes up to mucosal surface, grab a hold of things and pull it through to the Peyer's patch.

Answer 100

The proportion of T cells CD4:CD8 is a 3:1 ratio. TH17 cells maintain a constant low level immune response in the mucosa. TH1 and TH2 is found in lower quantities, but in the presence of danger signals their quantities increase. CD4+ T cells secrete lots of cytokines like IL-17 (drives TH17). The mucosa, especially the colon, is the only place in a healthy body where TH17 is found. The TH17 cells cause inflammation in other areas in the body, but they are balanced by Treg cells which secrete IL10. During infection, regulatory activity lessens and effector activity increases. Lamina propria contains innate-type lymphocytes produces IL-22 which are somewhat like natural killer cells.

Answer 101

Gut epithelia contains intraepithelial lymphocytes (located here at birth) which are CD8+ T cells. These cells push their way between the epithelial cells.

Answer 102

They are activated in the ABSENCE of infection. There are 2 types: - Type A: Normal CD8+ Tc cells that have good T cell receptors. These have a perforin, granzyme pathway to allow destruction of cells. It tries to tackle viral infection. - Type B: Less functional gamma/beta T cells that don't have good T cell receptors (as they have restricted VDJ usage). It looks for stress signals. Intraepithelial lymphocytes express binding integrin to be able to bind to the endothelium.

Answer 103

1. Virus infects the mucosal epithelium of the cell. 2. Infected cell displays antigen to intraepithelial cell via MHC 1. 3. Activated intraepithelial kills infected cell by perforin or granzyme dependent pathways.

Answer 104

Example: gliadin is a component of gluten that isn't broken down in the gut - it's a toxic peptide. Some people have a much stronger inflammatory response (celiac disease). Here is the normal mechanism of the Type B cells without the stronger inflammatory response. 1. Epithelial cells of gut are stressed due to toxic peptide, express MIC-A/MIC-B. 2. NKG2D on intraepithelial cell bind to MIC-A/MIC-B and activate cells. It also binds TL. 3. CD8+ T cell bind MIC-A/MIC-B, and TL and become activated to go down the perforin pathway.

Answer 105

1. IgA bound to receptor on base surface of epithelial cells. 2. Endocytosis & then transcytosis to top surface of epithelial cells. 3. Release of IgA dimer at apical face of epithelial cell.

Answer 106

- External neutralisation -> Stop microorganisms from even entering the epithelial cell. - Internal neutralisation -> Neutralise antigens as they're coming into the cell via endosomes. - Export -> IgA can export toxins from the lamina propria out of the villi structure.

Answer 107

We get a constant response due to commensals having PAMPs of their own.

Answer 108

Gut pathogens will lead to and generate the first immune inflammatory response which is usually sufficient for elimination. Pattern Recognition Receptors (PRRs) like Toll Like Receptors (TLRs) are important for this. Binding to PRR like TLR stimulates release of cytokines & chemokines which attracts monocytes, eosinophils and T cells out of the blood into gut tissue to release antimicrobial peptides. Local lazy dendritic cells are also attracted and are responsible for displaying the viral particle on cell surface for T cells.

Answer 109

Pathogens like salmonella can target the M cells to enter the lamina propria and infect macrophages here. Typically, when we have a gut infection in the gut, we can increase the number of M cells in the gut epithelial layers so innate immune cells can come into lamina propria faster.

Answer 110

The intestine has to make a decision of whether it's been infected by a pathogen of it's something we've just eaten.

Answer 111

Majority of antigens in the intestinal tract are from food/commensals. They don't raise an immune response even though they should be considered non-self as they aren't in the thymus when T cells are educated. This is oral tolerance and this process has been tried to use to treat autoimmune disease.

Answer 112

You either get protective immunity against the pathogen or mucosal tolerance. We can produce IgA's for commensals and food antigens to make sure they don't cross the gut lining.

Answer 113

1. Mice fed with ovalbumin for 7 days - egg protein, other mice are fed with normal protein (control). 2. Inject ovalbumin with adjuvant to stimulate immune system. Mice with ovalbumin had low immune response, hence they had peripheral tolerance. 3. Control group had a big response to ovalbumin. Hence, oral route of antigens can lead to tolerance, peripheral tolerance.

Answer 114

Enterocytes.

Answer 115

Wherever commensal bacteria are - prostaglandins are made. They inhibit dendritic cell maturation. Immature dendritic cells give weak signals and induce CD4+ T cells to become T regulatory cells.

Answer 116

They activate dendritic cells as there are more danger signals present during infection. The dendritic cells have more ligands expressed on the surface and induce CD4 + T cells to differentiate into TH17/1/2 cells. As a result, B cells are stimulated to make and release IgA to target toxins.

Answer 117

Commensal and food antigens don't carry danger signals: PRRs don't recognise anything. No inflammatory response means that there are no immune responses. Prostaglandins also inhibit response. T regulatory cells generate anti-inflammatory cytokines and stimulate anti-inflammatory local IgA response via class switch recombination.

Answer 118

- Producing oral/mucosal tolerance increases TGF-beta which is an immunosuppressant. - Generating mucosal tolerance in animal models shows protective property for those diseases. - Trials haven't been so promising yet.

Answer 119

1. Inflammatory Response: Due to activation of macrophages, cytokines like TNFalpha released. 2. Cytokine release increases the amount of P & E selectin adhesion molecules on surface of endothelial cells for lymphocytes so cells stick to the blood vessel walls and penetrate into the tissue. 3. Local dendritic cells become activated. They carry the antigen in a complex with MHC on the surface to the nearest secondary lymphoid system. 4. Dendritic cells will stimulate T cells resulting in adaptive immune response. 5. T helper cells will help stimulate B cells for humoral response.

Answer 120

Whilst we don't know how much infection is cleared by the innate immune system, mice knockout experiments show that a lack of innate immune system means adaptive immune responses can't be stimulated properly. RAG1/RAG2 deficiencies in mice lead to limited BCR and TCR production as the gene cannot be rearranged. SCID affects humans and its a mutation in the DNA protein kinase that repairs breaks in DNA during rearrangement.

Answer 121

Dendritic cells change the cytokines they produce in response to if there's an infection or not. No infection will mean increased amounts of TGF-beta being released by dendritic cells, and then increase in T regulatory cell development. Each type of T helper cell makes a set of cytokines that negatively regulate other T helper cell subset development. This affects nature of immune responses made.

Answer 122

Protective immunity result from a combination of preformed immune reactants and immunological memory.

Answer 123

Primary response will show mainly IgM, low affinity of antibody and low somatic hypermutation. Secondary response in immunised individuals show mainly IgG and IgA, high affinity of antibody and lots of somatic hypermutation.

Answer 124

Memory T cells live longer than memory B, this is important because the thymus gets smaller with time (involution) and you're less able to add to your T cell repertoire as a result. Memory T cells express survival molecules to help them survive for longer. They have fewer adhesion surface molecules to let them survive for longer.

Answer 125

1. Antigenic variation. 2. Antigenic Drift & Shift 3. Persistence & Reactivation

Answer 126

1. Antigenic variation (eg. strep pneumonia): Bacteria can have different serotypes (diff antigen on surface). Antibodies against one serotype don't protect against another serotype. Pathogens simply change the proteins on their coat. 2. Antigenic variation (eg. trypanosomes): Gene conversion brings a new gene to active site of expression once effective antibody is generated against trypanosome. The new gene has different immunological properties to evade existing antibody. You'll get waves of infection.

Answer 127

Influenza introduces mutations on segmented genome coding for haemagglutinin so antibodies can't recognise as well so flu can infect. Exchange of genomes between 2 influenza can make major changes to haemagglutinin so we can't recognise. Major changes cause pandemics and epidemics.

Answer 128

It's hiding. Herpes Simplex Virus enter latent state where they don't make viral proteins and aren't eliminated. Things that reactivate the virus: stress, hormonal changes, sunlight. HSV also have virally encoded FC receptors that bind onto antibodies and stop complex formation with antigens. HSV makes a protein that bind complement and stops complement cascade. HSV impairs MHC 1 expression.

Answer 129

Hypersensitivities (allergic reactions) are when adaptive immune response are generated against harmless antigens that aren't associated with pathogens. They have a genetic & environmental components.

Answer 130

Immune disorders generally involve more than one gene, there are regions within these genes that are associated with different disorders. Sometimes disease genes are clustered around certain loci, or sometimes they can be spread across many loci.

Answer 131

- Type 1: IgE response mainly, it reacts to soluble antigen, it leads to mast cell activation. - Type 2a: IgG response mainly, cell/matrix associated antigen which activates complement. - Type 2b: IgG response, involves cell surface receptors that have altered signalling. - Type 3: IgG response to soluble antigen which activates complement pathway and phagocytosis. - Type 4a: TH1 cells respond to soluble antigen, activates macrophages. - Type 4b: TH2 cells that respond to soluble antigen and produce IgE that activates eosinophils. - Type 4c: CTL respond to cell associated antigens, leading to cytotoxicity. It's more common in graft rejections.

Answer 132

Cause: IgE response (normally clear worm infections) is produced by innocuous antigen, subsequent exposure to allergen triggers activation of mast cells and basophils. Some individuals have predisposition to develop allergic reactions known as 'atopy'. Development of atopy has both genetic and environmental components. Atopic allergic disease is increasing worldwide due to changes in exposure to animal and soil micro-organisms and changes in intestinal microbiota.

Answer 133

Counter-Regulation hypothesis suggests that general immune response protects against atopy. This produces interleukin 10 and TGF-beta which downregulates TH1 and TH2 cells. Having some immune response will mean that some Treg cells will always be there, suppressing atopic responses.

Answer 134

The symptoms depend on the site of mast cell degranulation (granzyme), the symptoms can be systemic (anaphylaxis which is systemic is dangerous), flared, seasonal hay fever, asthma and food allergy.

Answer 135

1. Der p 1 is taken up dendritic cells for antigen presentation and TH2 priming. 2. TH2 cell (also produces IL-4 to drive more TH2 cells production) induces B cells to switch to IgE production. 3. IgE binds to receptors on mast cells. 4. Mast cell granule contents cause allergic symptoms. IgE secreted plasma cells binds to a high-affinity Fc receptor on mast cells. Activated mast cells provide contact and secreted signals to B cells to stimulate IgE production. Mast cell also releases more interleukin 4 that helps B cells to class switch to IgE even more.

Answer 136

- Proteins: Induce T cell responses. - Low dose: Favours activation of IL-4. - Low molecular weight: Allergens diffuse into mucosa. - High Soluble - Stable: Allergen can survive in a damaged particles. - Has peptides that bind MHC 2.

Answer 137

- GI tract: Increased fluid secretin, vomiting, diarrhoea. - Eyes/Nose/Airways: Decrease diameter, and increased mucus secretion, congestion and swelling. - Blood vessels: Increased permeability, increased blood flow and potential oedema.

Answer 138

It occurs when an antigen is infected straight into the blood because mast cells are activated. Mild activation - urticartia. Severe activation - anaphylactic shock and huge loss of blood pressure of death.

Answer 139

- Immature mucosal immune systems. - Early introduction to solid food. - Poor commensal microbiota. - Deficient IgA production.

Answer 140

- Induce Treg cells: via desensitization therapy by injecting small doses of antigen. - Antigen-inflammatory effects: Corticosteroids. - Prevent IgE from binding to Fc receptor on mast cell: via anti-IgE antibodies.

Answer 141

- Type 2 - caused by drugs like penecillin which bind to RBC surfaces and induces a response that can result in anaemia. - Type 3 - arise via soluble antigens. Deposition of soluble antigens can be harmful depending on where in happens. Eg. serum sickness. - Type 4 - arise from T cell responses, release of cytokines. Eg. coeliac disease. Some harmful cytokines that are made: chemokines, IFN-gamma, TNF-alpha, IL-3.

Answer 142

It's a Type 4 hypersensitivity. It's the allergy to gluten. It's caused due to loss of intestinal villi, inflammation of gut, increased intestinal lymphocytes. MHC 2 will bind peptides that contain glutamic acid specifically. Mechanism: 1. Normal gluten peptides don't bind to MHC2. 2. tTG modified gluten peptide so it binds to MHC 2. 3. Bound peptides activate gluten-specific CD4+ T cells. 4. Activated T cells kill mucosal epithelial cells and creates inflammation in the gut. The innate immune system will activate intraepithelial lymphocytes. Gluten peptides activate non-classical MHC molecules, recognised by TCR and they try to kill the epithelial lining of the gut.

Answer 143

Hypersensitivities are overreaction of immune response to a foreign antigen. It's normally harmless. Autoimmune diseases see our own antigens as foreign in a threatening way.

Answer 144

Normally, TCR and BCR are generated by recombination events and screened for self-tolerance. Autoimmunity results when self tolerance stops. A variety of different mechanisms, act as checkpoints to generate self-tolerance and normally prevent autoimmunity.

Answer 145

They are influenced by genetic and environmental components. Psoriasis - T cells attack the skin, they're itchy. Type 1 Diabetes - T cells attack pancreatic cells islets and we can't make insulin.

Answer 146

Organ specific autoimmune disease: Type 1 diabetes, multiple sclerosis, Crohn's disease, psoriasis. Systemic autoimmune disease: Rheumatoid Arthritis.

Answer 147

1. Genetic factors along with infection & environmental exposure. 2. Lead to changes in immune regulation. 3. Leads to autoimmune disease.

Answer 148

Certain types of MHC molecules predispose certain people to hold certain proteins on their binding grooves, which can cause a big immune response. These rearrangement of the HLA gene introduces the susceptibility. Other genetic evidence: - Overexpression or under-expression of cytokine signalling/production. - Mutation in genes involved in 1 or more mechanisms of tolerance, inability to clear antigen, leading to abnormal Treg development. - There are a few examples of point mutations causing disease.

Answer 149

1. Disruption of cell/tissue barrier that releases antigen that immune system doesn't normally see. 2. Molecular mimicry is when you get molecules that are similar to the self. Immune system will act on the foreign ones, but then since our own look so similar, the immune system acts on the self ones that look similar to the foreign ones.

Answer 150

Release of sequestered antigen especially from immunopriviledged sites that don't normally interact with immune cells leads to autoimmunity. Antigens from these special sites are carried to lymph nodes when ruptures and activate T cells-causing immune response. Existing T cells will never have had a chance to interact with the self antigens, which raises autoimmunity.

Answer 151

We get types 2, 3, 4 hypersensitivities and autoimmunes too, but no type 1 autoimmunes. Type 2 antibody antibody against cell surface or matrix antigens. Type 3 antibody against immune complexes. Arthritis = immune complexes stuck in joints. Type 4 antibody is T cell mediated disease.

Answer 152

Graves Disease: leads to hyperthyroidism. B cells make antibodies against TSH receptor so since there is no negative feedback to say we have enough TSH in circulation and to stop producing more, we get too much TSH and hence hyperthyroidism. Myasthenia Gravis: Antibodies bind to post synaptic vesicles on neurons, prevent acetylecholine from binding to the receptor. This means lack of conduction of impulse, a progressive muscle paralysis occurs.

Answer 153

Type 1 diabetes. T cells attack beta cells in pancrease until they're destroyed and can't make insulin to regulate glucose levels anymore. Genetic aspect is that normal people have 2.5% of the DS3/4 gene, whilst affected people have 39% of this gene. And if there's aspartic acid at position 57 in DR3/4 in the beta chain is normal, but susceptible individuals will have valine/serine/alanine instead. The change will lead to loss of salt bridge, altering salt bridge formation and changing the antigens it binds to, making it predisposed to altering MHC and changing the antigens that it can bind with.

Answer 154

Manipulating the immune system and its responses using pharmacological modulators to benefit the host. It dates back to 'variolation' which means giving a person small amounts of material from a diseased person to give rise to milder illness with lower mortality chances.

Answer 155

Rapamycin disrupts signalling of cytokines involved in lymphocyte growth and differentiation. Antihistamines block histamine receptors. Iboprufen blocks inflammatory mediators that cause pain. Alum is a type of adjuvant used to stimulate and activate immunity in vaccines.

Answer 156

Hormones, Cytokines, Antibodies, Fusion Proteins, DNA vaccines, Subunit vaccines, conjugate vaccines.

Answer 157

- Inactivated vaccines: poliovirus. - Live Attenuated vaccines: MMR vaccine - Adoptive Cell Transfer: Chimeric antigen receptor (CAR) T cells have the engineered CAR protein on the surface that is modified by modifying the gene segment that codes for the protein, then it binds to the antigen of target cells.

Answer 158

Radiation, bone marrow transplants.

Answer 159

Rheumatoid Arthritis is both a type 3 and type 4 autoimmune disease. It's systemic, inflammatory disease that affects joints and organs in 1-2% of the population. Swollen joints will get damaged. It's likely to occur at 35-60 years old, and likelier in females. The HLA DR4 gene is at a higher percentage in rheumatoid arthritis, and is linked to increasing the risk of getting rheumatoid arthritis. Environmental factors like smoking, air pollution, infections (E. Coli) are also linked to increased incidence.

Answer 160

It's hard to diagnose as many things can cause joint stiffness. We use blood tests like erythrocyte sedimentation rate (how fast RBCs fall to bottom of tube, high rate in ppl with autoimmune diseases), C reactive protein test (checks level of inflammation which is higher in people with rheumatoid arthritis), full blood count. We can check rheumatoid factor - IgM antibodies against the Fc portion of the IgG antibodies. 50% + of people with rheumatoid arthritis have high rheumatoid factor. Anti-CCP antibodies indicate rheumatoid arthritis, if you have these you have rheumatoid arthritis. We can also use scans like MRI and X-Rays to detect rheumatoid arthritis.

Answer 161

1. Dendritic APC's have the HLA - DR4 variant and display the rheumatoid arthritis peptide. 2. T cells randomly match with it, and become activated. 3. B cell is activated, and differentiates into plasma cells that release rheumatoid factor antibodies that are deposited around the body. 4. T cells activate macrophages which release chemokines that activate chondrocytes (degrade cartilage) and osteoclasts (erode bone).

Answer 162

We target tumour necrosis factor alpha because it: - induces production of inflammatory cytokines. - Stimulates joint cells to break down the matrix that surrounds them. - Stimulates macrophages to make metalloproteinases that degrade the matrix. - Stimulates further recruitment of cells to the joint.

Answer 163

There's no cure for rheumatoid arthritis, so we simply try to reduce the pain and stop/slow further damage. First line medicine: pain managements like opiods Second line medicine: Disease modifying drugs like methotrexate which inhibits enzymes that breakdown adenosine (has anti-inflammatory effects). Side effects: Sickness, Hair loss, Headache, Diarrhoea. Newer treatments are biological (cell-based).

Answer 164

'mab' = antibody treatment. 'cept' = antibody fusion protein. All of these work with TNF-alpha: 'Infliximab' = chimeric monoclonal antibody 'adilumab' = monoclonal antibody 'etanercept' = fusion protein

Answer 165

Systemic Lupus Erythematosus.

Answer 166

It's a chronic systemic autoimmune disease which affects women 20-40 years old. It's frequent in african-american and hispanic females. Auto antibodies cause the symptoms. It results from the overproduction or defective clearance of immune complexes, or both. The main antigen targeted by autoantibody is proteins and nucleic acids wrapped around histones. It's classed as a type 3 hypersensitivity reaction.

Answer 167

They arise due to excessive complement activation. Neutrophils are activated on smaller blood vessels which causes blockages. Mild SLE symptoms: Joint and skin problems, tired. Moderate SLE symptoms: Inflammation of skin and organs (lungs/heart/kidney) Severe SLE symptoms: Inflammation causes severe / deathly damage to lungs, heart or kidney. Symptoms can come in waves, you get bad flare ups and settling back into remissions.

Answer 168

Some is genetic = MHC genes, and some is environmental = stress.

Answer 169

We discuss history, we look at anti-nuclear antibody test to see if your body is likely to make anti-antibodies of lupus. +ve result from this means you have SLE. We can also do skin/kidney biopsies, and scans to check organs.

Answer 170

Sunscreen to reduce environmental risk, anti-inflammatories, steroid tablets, hydroxychloroquine, biological medicines, immunosuppressants.

Year 2 Immunology Flashcards

To learn Immunology perfectly. (195 cards)