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IMMUNOLOGY Flashcards

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1
Q

Key factors that determine the process of producing T cells

A

Stem cell factors
Cytokines - Il-7 and IL-3
Tissue specific signals - notch and thymic stromal cells - in commitment stage

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2
Q

Stages of T cell maturation

A
  1. Growth factor mediated commitment, proliferation - receptor gene rearrangment
  2. Selection of cells that express pre-antigen receptors
  3. Selection of repertoire and acquisition of functional competence - avoid self antigens too
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3
Q

Journey of T cells through development

A
  1. Precursors move from bone marrow to thymus
  2. Notch signals by thymic stroma commit to T cell lineage and differentiate into early precursors of T cell
  3. Notch signals induce GATA3 - commit to T cell lineage - intense proliferation
  4. Cells leave the thymus to APC in lymph node and spleen and become activated cells that can carry out function - activate macrophages or kill viral infected cells
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4
Q

MHC Class I

A

Peptides mounted on MHC I originate from inside the cell - CD8 binding site
Expressed in all cells except erythrocytes

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5
Q

MHC Class II

A

Peptides mount on MHC II originate from extracellular space - CD4 binding site
Expressed on APC

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6
Q

MHC peptide interactions

A

Each MHC has 1 cleft that binds 1 peptide at the time but can bind different peptides - peptides share structural features that increase binding.

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7
Q

TCR properties

A

1 form of TCR expressed on T cells - clone
Has only 1 antigen binding site
An infinite number of different TCR - unique antigen binding sites

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8
Q

TCR gene rearrangement

A

TCR gene segments arranged like Ig gene segments - Rag 1 and Rag 2 enzymes rearrange it.
Lead sequence
Junctional diversity
Successful beta rearrangement - signal to thymus and sent to the surface = pre-TCR

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9
Q

Lead sequence (T cell generate)

A

Modified chain tell the cell where to put polypeptide chain

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10
Q

Junctional diversity (generate T cell)

A

During joining of different gene segments - addition/removal of nucleotides = new seq. at junction
Mediated by TdT

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11
Q

Allelic exclusion - what is it and why does it occur

A

A completed beta chain - pre TCR will suppress the expression of RAG genes.
No more rearrangement = allelic exclusion
Occurs so that there is only 1 TCR beta chain gene expressed

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12
Q

Alpha chain rearrangements

A

Successful signalling of pre-TCR = halt further beta chain rearrangements and induce expression CD4 and CD8 - initiate alpha chain rearrangement

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13
Q

Difference in antigen recognition between γδ T cells and αβ T cells

A
  • Specific receptors - skin, gut uterus
  • Do not recognise MHC presented peptides - not MHC restricted.
  • Antigen recognised directly - like antibody
  • Ligands for the γδ TCR are self-proteins - highly regulated under stress conditions
  • Circulating γδ recognise phospholipid antigen mycobacterium TB
  • And play a role in cancer surveillance
    BUT MAKE UP 10% OF T CELLS
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14
Q

Negative selection

A

DP thymocyte looks for MHC molecules in thymus - binds to target and decrease regulation of another CD molecule - BUT binding must be strong.
If it is weak = apoptosis/neglect

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15
Q

Self reactive T cells

A

Epithelial stromal cells in medulla - self protein infiltrated dendritic cells - express self antigens and present to T cell with TCR.
Strong binding = T cell become self reactive - autoimmunity - DANGEROUS = APOPTOSIS.
Weak binding = cell is not a danger = conventional T cell

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16
Q

Positive selection

A

DP T cell found functional TCR bind to MHC molecules in thymus.
CD4 to MHC II = down regulate CD8 and vice versa

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17
Q

What is AIRE

A

Autoimmune regulator - transcription activator gene.
Allows the expression of different genes that are not expressed by thymus = called promiscuous gene expression.
Thymus does not represent all self-antigens.

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18
Q

What do Regulatory T cells - CD25 and Foxp3

A

Do not proliferate in response to MHC self peptide complexes - accumulate in Hassal corpuscles to tissues.
Main role = dampen T cell response - regulate it.

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19
Q

What happens after T cell selection

A
  • T cell pass both +/- selection - become conventional T cells.
  • Migrate to secondary lymphoid organs looking for target antigen - immunological synapse between T cell and antigen
  • If they encounter specific antigen = activate = proliferate = effector T cells/memory T cells
  • If they do not find a target they eventually die by apoptosis after a period of circulation.
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20
Q

Naive T cell circulation

A

Released into the blood circulation and moves freely through the blood - enters lymph node through high endothelial venules.

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21
Q

Naive T cell circulation with no antigen

A

Cell migrates between lymph node via lymphatics till antigen is found.

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22
Q

Naive T cell circulation with antigen

A

Binds to antigen - T cell activated.
Receives signals by dendritic cells = activated T cell = circulation via thoracic duct in vena cava to site of infection.

Antigen picked up by DC - enter lymph node via afferent lymphatic vessels

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23
Q

Signal 1 for T cell activation - explain

A

Antigen recognition
Signal initiate immune response - TCR recognises the antigen with MHC.
But not enough to activate T cell

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24
Q

Signal 2 for T cell activation - explain and give an example.

A

Co-stimulation
Co-stimulatory signal required to activate naive T cell.
B7:CD28
B7 expressed on APC, CD28 on T cell - confirm activation

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25
Q

What happens in T cell APC signalling.

A

T cells recognise antigen with/without B7 = express CD40 on T cells
CD40L bind to CD40 on DC - express B7 - secrete cytokines = stimulate T cell proliferation

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26
Q

Negative co stimulation - what does it do

A

Inhibit downstream effector processes initiated by TCR MHC/peptide interaction - decrease inflammation after infection gone.

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27
Q

Example of negative co-stimulation

A

CTLA-4
Stop T cell from getting activated
Bind to CD80/CD86 - competes with CD28
Has a higher affinity/avidity for CD80 - opposes the effects to CD28

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28
Q

How is IL-2 regulated

A

Important to sustain T cell activation and proliferation.
T cell activated = produce IL-2 = autocrine signal to proliferate
T reg cells - High level of receptors for Il-2 - block IL-2 and proliferation

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29
Q

Function of CD69

A

Retention in lymph node

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30
Q

Function CD25

A

proliferation

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31
Q

Function CD40L

A

Activation of DC, macrophages, B cells

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32
Q

Function of CTLA-4

A

Control of response

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33
Q

TH1 cells function

A 
Activate macrophages - enahnce ability to destroy intracellular pathogens.
Stimulate B cell - complement binding
Opsonising IgG antibodies - class switching
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34
Q

TH2 cells function

A

Produce IL-4, IL-5, IL-13 and recruit cells important for anti-parasitic responses
Support production of antibodies - allergies and anti-helminth response.

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35
Q

TH17 cells function

A

Act on specific tissue cells and recruit neutrophils.

Inflammation

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36
Q

TFH cells function

A

Provide signal to B cell to differentiate and produce antibodies

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37
Q

Treg cell function

A

regulation, suppression of immune and inflammatory response

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38
Q

Cytokines and TH1 cells

A

IFNg - amplify TH1 differentiation

T-bet = master transcription factor - controls differentiation

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39
Q

Cytokines and TH2 cells

A

IL-4 activate STAT 6 - increase GATA3 transcriptional activator of IL-4 and IL-13 gene.
Support B cell - IgE - degranulation mast cell.
IL-4, IL-13 change peristalsis of gut to remove parasites.
IL-5 activate eosinophil - release granules to destroy helminths

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40
Q

Antibody functions

A
  1. Variable fragment can bind to pathogens preventing pathogen host binding - or bind to activate sites of toxins
  2. Opsonisation + ADCP - tagging of pathogen - visible ot ther immune cells - NK cells
  3. Recruit NK cell to perform opsonisation + ADCC - antibody dependent cellular cytotoxicity
  4. Antibodies can form immune complexes - clump antibody and pathogens - agglutinate and be removed by other cells - complement
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41
Q

Complement molecules and antibody binding to pathogen

A

Antibody set to fixed complement = inflammation, phagocytosis and formation of MAC - punch hole in cell membrane = lysis

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42
Q

Signals involved in class switch recombination

A
  1. Cytokine signal
  2. Switch regions
  3. AID and DSB repair proteins - recombo occur between switch regions
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43
Q

Steps of Antigen independent life cycle of B cells

A
  1. Pro B cell – heavy chain variable region – D toJ and V to DJ recombination + µ constant region
  2. Pre-B cell – variable region expressed on heavy chain – V to J recombination code in LIGHT chain variable – IgM expressed on immature B cell
  3. Immature B cell – additional diversity via junctional flexibility – P and N nucleotide addition
  4. When they express IgM and IgD on surface via differential splicing = mature B cell circulate
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44
Q

Process of VJ recombination of kappa light chain genes

A

Chromosome 2
40 variable segments
5 joining segments
1 constant region
Leader segments before V segments - V and J segments randomly chosen and transcribed to mRNA
Then translated - Leader segments cleaved off when protein reaches destination

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45
Q

Process of VDJ recombination of gamma heavy chain genes

A 
chromosome 14
51 variable
27 Diversity segments
6 joining segments
1 constant region
1st recombo = D to J.
Then V to DJ transcribed into mRNA and splicing.
Cµ = IgM
Cδ = IgD
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46
Q

VDJ recombination mechanism

A

Recombination signal sequences - conserved sequences upstream and downstream of gene segment.
12/23 rule - recombo only occurs between a segment with a 12bp spacer and a 23bp spacer

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47
Q

Methods for antibody diversity

A

Multiple germline V,D,J gene segments
Combination VJ and VDJ joining.
Junctional flexibility
P-nucleotide addition
N-nucleotide addition
Combinatorial association of heavy and light chains
Somatic hypermutation during affinity maturation

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48
Q

Junctional diversity - humoral immunity

A

Created by junctional flexibility during VDJ recombination, P and nucleotide additions.
Bad = non-productive rearrangements - incorrect reading frame - wasteful process

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49
Q

Hair pin mechanism for junctional diversity - major and minor hair pin opening and joining

A

Hairpin form after processing Rag 1 and Rag2 - need to open by enzyme Artemis - have overhanging ends.
DNA processed by other enzymes like exonucleases, TdT - add or remove bases.
Ends join together by a series of enzymes.

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50
Q

P nucleotides

A

Artemis nick strands = break the strand

P nucleotides will fill in the overhanging areas.

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51
Q

N nucleotides

A

Add nucleotides to 2 ends before chains are ligated - TdT

Mostly in heavy chain

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52
Q

Junctional flexibility

A

Removal of nucleotides between gene segments during VDJ recombination
Invovles exonucleases - remove mismatched nucleotides

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53
Q

Steps of antigen dependent life cycle of B cells

A
  1. Activated B cell migrate to germinal center - undergoes affinity maturation = increase affinity to bind to pathogen
  2. B cells receive information of what pathogen - class switch to appropriate effector region
  3. Majority B cell differentiate into plasma cells = secrete antibody. Whilst this occurs B cell coding IgM differentiate into plasma cells - secrete IgM as 1st line defence
    4 - after infection - some B cell = memory B cell
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54
Q

T cell independent B cell activation

A

Pathogen invades - B cell partially acitvated - binds to antigen = clonal expansion
clones become 1st line of defense - secrete IgM and other clones migrate to lymph nodes to wait for T cell activation

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55
Q

T cell dependent B cell activation

A
  • Requires 3 signals
  • Antigen binding to BCR - internalise antigen and present on surface via MHC II receptor.
  • CD40 and CD40L confirm it is T helper cell.
  • Co stimulation by activated TH cell specific to same antigen - TCR is activated - recognise antigen due to DC attaching to pathogen.
  • TH cell derived cytokines - activated B cell undergo affinity maturation and class switching.
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56
Q

Affinity maturation

A

Improve affinity of antibody to antigen - binds to antigen at low affinity.
B cell activated - affinity maturation - generate mutations in variable region genes - select the antibody with the high affinity.

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57
Q

Where does affinity maturation occur and what helps affinity maturation to occur

A
  • Occur in germinal centre of lymph node
  • T follicular helper cells – can enter germinal centre
  • Follicular dendritic cells – not norm. dendritic cell – present antigens in germinal centre
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58
Q

Process of affinity maturation

A
  1. activated B cell will go through clonal expansion
  2. AID - point mutations in variable regions of DNA - somatic hypermutation
  3. Mutation - hypermutated B cell go into light zone and undergo selection - follicular dendritic cell present antigen to surface. B cells compete for antigen on FDC = present to Tfh cell.
  4. Give B cell a survival signal - goes back to dark zone and repeat process - increase affinity - survival of the fittest.
    NO survive signal = apoptosis
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59
Q

IgM function

A

Involved in primary response for immune complexes

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60
Q

IgD function

A

Only antibody not released because B cell is mature

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61
Q

IgG function

A

Fc binds to phagocytes - antibody of secondary response - IgG form after affinity
Neutralise toxins or opsonisation

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62
Q

IgA function

A

Form after affinity maturation - secreted into mucus membrane of respiratory tract
in saliva or tears

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63
Q

IgE function

A

Fc binds to mast cells, basophils - allergy and large parasite infections - good at recruit basophils for infections

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64
Q

α-defensins

A

secreted mainly by neutrophils and Paneth cells

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65
Q

β-defensins

A

secreted by broad range of epithelial cells – esp. respiratory tract, skin, and urogenital tract

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66
Q

Complement pathways

A

Classical - activated by antibodies
Lectin - activated by NBL and carbohydrates
Alternative - activated by specific pumps on surface of bacterial cells

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67
Q

Complement functions

A
  • Opsonisation and phagocytosis - microbe detected by C3b = phagocyte recognises = phagocytosis
  • Stimulation of inflammatory reactions - C3b bind to microbe = reelase C3a and C5a = recruitment and activation of leukocytes by C5a, C3a = microbe destroy
  • Complement mediated cytolysis - C3b bind = poylmerisation of MAC = punch hold in membrane, lyse bacteria
68
Q

Role of complement receptors in phagocytosis

A

Macrophages have high expression of complement receptors
Bacteria tagged by complement molecules - detected by complement receptor = phagocytosis.
Detect bacterial component = PAMP through TLRs - produce cytokines

69
Q

How does PRR and PAMPs interaction lead to phagocytosis and cytokines

A
  1. PAMP binding by PRRs activated phagocytes
  2. Phagocytes ingests microbes, enlarges, and increase metabolic activity
  3. Activated phagocytes elevate antimicrobial activity
    Cytokines, chemokines released
70
Q

Neutrophils and bacterial infection

A

Phagocytosis and degranulation of granules – intracellular killing of bacteria
Phagocytosis and oxidative burst kill the bacteria
Neutrophils can also kill bacteria phagocytosing bacteria – neutrophils extracellular traps (NETS)

71
Q

Adaptive immunity triggering complement cascade

A

IgM bound to surface of bacteria - complement = classical pathway
Bacterial cell surface is coated in C3b - facilitate phagocytosis

72
Q

Innate immunity reaction to intracellular bacteria

A

MHC II pathway presents bacterial antigens derived from extracellular infections to helper CD4 T cell.
Peptides bound to MHC II - in phagolysosome - export to surface to T cell

73
Q

Classical pathway of complement system

A

Antibody antigen complex - IgG/IgM bind to C1q = C3 covertase = C5 convertase = C5b-9 membrane attack complex

74
Q

Lectin pathway of complement system

A

Bacteria PRR bind to mannose binding lectin = cascade

75
Q

Alternative pathway of complement system

A

Bacteria coated with C3b - opsonin binds the bacteria

76
Q

Roles of complement

A 
Induce inflammatory response
Promote chemotaxis
Increase phagocytosis by opsonisation 
Increase vascular permeability
Mast cell degranulation
Lysis of cell membrane
77
Q

Pathogens mechanism to overcome complements

A

Failure to trigger complement - LPS, capsules
Inhibit binding of complement to surface - coat with IgA, capsule block C3b binding
Disrupt regulation - Factor H sequestrian - down regulate complement - bound H factor = complement not activated
Block/expel MAC - C5a proteases, blebbing - degrade complements

78
Q

Pathogens mechanism to overcome phagocytosis

A

Produce toxin = leucocidin. - Kills cell - produced by staphylococcus
Prevent opsonisation - Staphylococcus have Protein A on surface. Has high affinity for Fc component of Ig
Blocks contact - have specialised capsules that avoid being bound by macrophages

79
Q

Intracellular pathogens mechanism to prevent macrophages from killing them

A

Promote own uptake - express mannose lectin, enter macrophage via different pathways - without stimulating marophage killing mechanism
Prepare cell for invasion - shigella - bind surface of macrophage and inject proteins - prevent activationa dn macrophage can’t go through normal route.
Negative P-L fusion - no phagolysosome formation or acidification
Escape P-L to cytoplasm - produce toxins damage phagosome
Resist oxidative killing - produce catalses/peroxidases - neutralise killing process

80
Q

Viruses mechanisms to conceal antigens or control the way immune responses present antigens - adaptive immunity

A

Concealment of antigen
Immunosuppression
Antigenic variation
Persistence/latency/reactivation

81
Q

Viruses concealment of antigen

A

Hide inside cells
Block MHC antigen presentation
Surface uptake of host molecules

82
Q

Viruses immunosuppression in adaptive immunity

A

Decrease MHC, receptors
Apoptosis
Cytokine switch
IgA proteases

83
Q

How does streptococcus pneumonia evade immunity

A

Capsule - bypass defence, not recognised, protects itself.
SIgA proteases
By pass surfactants - Produce pneumolysin toxin - damages epithelial layer and endothelial cells - can escape phagocytosis.
LEAD TO meningitis + septicaemia

84
Q

Viral immune evasion

A 
Latency
Decrease antigenic presentation
Decrease MCH expression - block recruitment of immune responses
Mutation of epitopes
Antigenic diversity/polymorphisms
Antigenic variation
85
Q

Antigenic diversity/polymorphisms

A

Genetically stable - alternative forms of antigens

86
Q

Antigenic variation

A

Successive expression of alternative forms of an antigen in specific clone or progeny
Phase variation - on/off antigen at low freq occurs - during course of infection in an individual host, during spread in community

87
Q

Gonorrhoea pathogenesis and immune evasion

A

Infect mucosal surfaces - columnar epithelium - survive in neutrophil, undergo antigenic variation
Dysuria, redness, swelling and pain on urination
Go through phase variation - components are on/off

88
Q

Influenza virus and evading immune system

A

Haemagglutinin and neuraminidase on surface of virus - rapid mutation - no proof reading ability = antigenic drift
Antigenic shift - virus reassort the genome - new combination of haemagglutinin and neuraminidase = new virus

89
Q

CD8 T cells

A 
Cytotoxic adaptive immune cells
Kill virally infected targets
Kill tumour cells
Controlled by T cell receptor recognition, with CD8 acting as a co-receptor
Highly specific
90
Q

Natural killer cells

A 
Cytotoxic innate immune cells
Kill virally infected targets
Kill tumour cells
Controlled by a balance of signals between different activating and inhibitory receptors on their surface
Broad specificity
91
Q

Why do we need more than more than 1 type of cytotoxic lymphocyte

A
  1. Combat infection in the period before T cell response develops
  2. To provide an alternative system when a tumour of infected cells evades cytotoxic T cell response
  3. To provide an additional mechanism for killing infected targets via antibody recognition
92
Q

How are intracellular proteins presented at cell surface by MHC I - (viruses)

A

Virus infect cells
Viral proteins synthesised in cytoplasm
Proteases break down proteins - peptide fragments of viral proteins bound by MHC I in ER
Bound peptide transported by MHC I to cell surface
Cytotoxic T cell recognises complex of viral peptide with MHC I and kill infected cells

93
Q

Pathogens may prevent presentation by MHC-I

A 
Inhibit MHC-I transcription (adenovirus)
Block peptide transport into ER (HSV)
Retain MHC I in ER (adenovirus, HCMV)
Target MHC I for disposal from ER (HCMV)
Downregulate MHC I from cell surface (HIV)
94
Q

Missing self mechanism

A

KIR recognise MHC I they inhibit NK cells from releasing lytic granules.
But if target does not express MHC I = no KIR inhibition - lytic granules released to lyse target

95
Q

Natural cytotoxicity receptors

A

Provide activating signals to NK cells

Target cell death or survival depends on balance of activating and inhibitory signals

96
Q

NKp46

A

Bind to viral haemagglutinin

97
Q

NKp44

A

Binds a ligand that expressed on tumour cells and upregulated by viral infection

98
Q

NKp30

A

Stress induced protein = activate NK cells

99
Q

Antibody dependent cell mediated cytotoxicity

A

Recognition of antibody complexes on target cells.
Virus bud out of cell - antibody bind to cell surface = NK cells target cell.
NK cell express receptor that recognise Fc portion of antibodies
Delivers strong activating signal when it recognises antibodies = result in lysis of target cell

100
Q

Mechanism of lysis - cytotoxic granules

A

NK cells and T cells carry granules filled with cytotoxic proteins.
Release cytotoxic granules at site of contact with target cell

101
Q

Action of perforin

A

Granules of cytotoxic T cells.

Aid delivering contents of granules into cytoplasm of target cell

102
Q

Action of Granzymes

A

Serine proteases - activate apoptosis once in cytoplasm of target cell

103
Q

Action of granulysin

A

Antimicrobial actions and can induce apoptosis

104
Q

immunological synapse

A

T cell receptors an co-receptors cluster at site of cell-cell contact.
This polarises the T cell to effector molecules at point of contact

105
Q

CD8 triggering apoptosis mechanism

A

Fas/FasL interaction to trigger apoptosis.
Fas ligand on T cell engages Fas on target cells to trigger apoptotic pathway (pro-caspase 8)
Fas/FasL triggered apoptosis is used to dispose of unwanted lymphocytes.
Loss of Fas = autoimmune lymphoproliferative syndrome (ALPS)

106
Q

Autologous transplant

A

Transplant biological material from individual to another part of the individual
e.g. skin graft

107
Q

Syngeneic transplant

A

Transplant biological material from donor to another individual - genetically identical e.g. transplant from 1 twin to another

108
Q

Allogenic

A

Donors are recipients are from the same species but genetically different - immune system reacts

109
Q

Xenogeneic

A

Donor and recipient are different species

110
Q

What causes immune responses for transplants

A

Genetic differences between donor and recipient

Differences between antigens forming MHC

111
Q

Allo-recognition

A

T cell activated to response to transplanted material - direct/indirect

112
Q

Live vs dead donor

A

Recipients from dead will have history of disease that can lead to inflammation - inflammatory response
Organs from deceased donors - inflammed condition due to ischaemia
Live transplants are less sensitive to MHC mismatch - inflammatory response is absent

113
Q

3 rejection mechanisms

A

Hyperacute rejection
Acute rejection
Chronic rejection

114
Q

Hyperacute rejection

A

Within few hours of transplant
Commonly seen in vascularised organs e.g. kidney
Requires pre-existing antibodies - ABO blood group antigens or MHC I proteins

115
Q

Steps in hyperacute rejection

A

Antibodies binds to endothelial cell - complement fixation - accumulation of innate immune cells - endothelial damage, platelet accumulate, thrombi develop - tissue death = fail transplant.
(Fc region is recognised - complement activation)

116
Q

Acute rejection

A

Inflammation results in activation of organs resident dendritic cells
T cell response develops because of MHC mismatch

117
Q

Mechanism of acute rejection

A

Direct allorecognition of foreign MHC - DC migrate to secondary lymphoid tissue - encoutner effector T cells.
Macrophage and CTL increase inflammation and destroy transplant

118
Q

Chronic rejection

A

Occur months or years after transplant - blood vessel walls thicken, lumina narrow = decrease blood supply

119
Q

Mechanism of chronic rejection

A

Allo-antibodies bind to antigens on endothelial cells of transplanted organ - recruit effector cell - induce damage - decrease blood supply to organ - indirect recognition
Donor derived cells die - membrane fragment contain donor MHC taken up by DC
Donor MHC processed - peptides - presented by host MHC
T cell and antibody responses generated to the peptide derived from processed donor MHC

120
Q

Graft vs host disease (GVHD)

A

WHen transplanted tissue is immune cell themselves - risk of donor immune cells attack host.

121
Q

3 phases of immunosuppression

A

Induction
Maintenance
Rescue phases of treatment

122
Q

Immunosuppressants for transplants can be

A

General immune inhibitors - corticosteroids
Cytotoxic - kill proliferating lymphocytes - mycophenolic acid
Inhibit T cell activation - cyclosporin

123
Q

Cyclosporin

A

Block T cell proliferation and differentiation

Next generation of cyclosporin - low toxicity and effective at low doses

124
Q

induction regimes

A

Antibody induction therapy = lymphocyte derived from rabbit - ATG bind to T cells - prevent proliferation and activation
Triple drug regime - calcineurin inhibitor, antiproliferative agent, corticosteroid - high dose

125
Q

Maintenance regime

A

Triple drug regime at low doses

126
Q

Rescue phases of treatment

A

T cell mediated rejection (TCMR) is treated with ATG and steroids
B cell mediated rejection may be treated with intravenous immunoglobulin or anti CD20 antibody and steroids
Both have corticosteroids involved

127
Q

Immunosuppressive therapy monitoring

A

Currently no immunosuppressive that will prevent transplant rejection whilst maintaining other immune responses
Transplant patients more susceptible to infection and malignancy
Immunosuppressive drug toxicity leading to organ failure e.g., cyclosporin nephrotoxicity in kidney transplant

128
Q

Type I allergy

A

IgE - allergen = have Ig binding epitopes

Lead to mast cell activation and degranulation - receptors receive Fc and hold Ig molecules on the surface

129
Q

Immediate hypersensitivity reaction

A

Inject allergen into skin - mast cells activated, release immune reactive molecules leading to wheal and flare reaction

130
Q

Type II cytotoxicity hypersensitivity

A

IgG/IgM – anti-drug antibody
drug coated – platelet/RBC coat drug - activate immune response - macrophages/complement
Then antibody bound cells cleared by FcγR+ cells

131
Q

Type III serum sickness/arthus reaction

A

IgG - soluble antigen - immune complex cleared by phagocytosis

132
Q

Arthus reaction

A

Antigen injected to arm - forms immune complexes leading to activation of complements - muscle activation and recruits other immune cells
Platelets accumulates causing occlusion of small blood vessels, haemorrhage and appearance of purpura

133
Q

Type IV delayed hypersensitvity - Th1 reaction

A

TUBERCULIN REACTION = Th1 - antigen - activate Th1, producing IFN-γ - macrophage activation - granuloma

134
Q

Type IV delayed hypersensitivity - Th2 reaction

A

ALLERGIC CONTACT DERMATITIS = Th2 - antigen - eosinophil activation - granuloma - localised tissue damage from eosinophil degranulation

135
Q

Mantoux test

A
  1. Localised injection with PPD - derived from M.tuberculosis into skin.
  2. Th cell recognise tuberculin - Th1 activated and release molecules attracting other immune cells
  3. Development of localised swelling and granuloma over 24-72 hrs
136
Q

Production of specific IgE

A

Th2 response - cytokines IL-4 and IL-13 cause B cells to switch to produce IgE.
IgE coat mast cells

137
Q

Mast cell activation in GI tract

A

Increase fluid secretion, peristalsis, vomiting diarrhoea

138
Q

Mast cell activation in airways

A

Decrease diameter
Increase mucus secretion
Congestion and blockage of airways - swelling and mucus secretion

139
Q

Mast cell activation in blood vessels

A

Increase BF, permeability, flow of lymph to lymph node.
Increase cell and protein in tissues
Increase effector response in tissues

140
Q

Eosinophils effector functions

A
  1. Release highly toxic granule proteins and free radicals upon activation to kill leading to tissue damage in allergic reactions
  2. Synthesise & release prostaglandins, leukotrienes, and cytokines to amplify the inflammatory response by activating epithelial cells and recruiting leukocytes
141
Q

What is autoimmunity?

A

Immune system has various regulatory control to prevent it from attacking self proteins and cells.
Failure of controls will result in immune attack of host components

142
Q

Central tolerance

A

Destroy self reactive T or B cells before they enter circulation.
Select TCR for binding self MHC - Strong binding to self MHC = neglect.

143
Q

Peripheral tolerance

A

Destroy or control any self-reactive T or B cells which do not enter the circulation.
3 types = Ignorance, anergy, regulation

144
Q

Ignorance tolerance

A

Antigen is present in low concentration - does not reach threshold for T cell receptor triggering

145
Q

Anergy tolerance

A

Naive T cells need costimulatory signals to be activated. And need MHC II
If naive T cells see MHC/peptide ligand without co-stimulatory protein = anergic = less likely stimulated

146
Q

Regulation tolerance

A

Subset of helper T cells - Treg inhibit other T cells by releasing cytokines IL-10 and TGFb
Defective T reg can lead to multiple sclerosis

147
Q

What might trigger a breakdown of self tolerance?

A

Loss of/problem with regulatory cells
Release of sequestered antigen
Modification of self
Molecular mimicry

148
Q

Modification of self - Cirullination

A

Citrulline - amino acid not coded for by DNA.
Arginine converted into citrulline as post translational modification by PAD enzymes = turns self peptide into peptide that is not self - change to structure of peptide
Citrullination may be increase by inflammation

149
Q

Molecular mimicry - rheumatic fever

A

Disease is triggered by infection with streptococcus pyogenes.
Antibodies to strep cell wall antigens may cross react with cardiac muscle. - may have similar structures

150
Q

Antibodies in autoimmune pathology - immune complexes in SLE and vasculitis

A

Auto-antibodies soluble antigens from immune complexes - deposited in tissue - activation of complements and phagocytic cells
Immune complexed depositing in kidney leading to renal failure.

151
Q

T cells in autoimmune pathology

A

Can have direct killing against certain tissues.
Direct killing by CD8 CTL
Self destruction induced by cytokines - TNFa
recruitment and activation of macrophages leading to bystander tissue destruction.
CD4 provide help for antibodies and cytotoxicity

152
Q

TH17 cells in autoimmune

A

Produce IL-17
Implicated in autoimmune disease including spondyloarthropathy, MS and diabetes
Increase inflammatory - produce cytokines invovled in recruitment, migration and activation of immune cells

153
Q

Therapeutic strategies against autoimmunity

A

Anti-inflammatories - NSAID, corticosteroids
T&B cell depletion - anti-CD4, anti-CD20
Therapeutic antibodies - anti-TNF block adhesion
Antigen specific therapies - glatiramer acetate, increases T reg

154
Q

Primary immunodeficiencies

A

Condition resulting from genetic or developmental defect.
Defect present from birth and is mostly inherited.
May not be clinically observed until later in life

155
Q

Secondary immunodeficiencies

A

Originate as a result of malnutrition, cancer, drug treatment or infection.
Most well-known and commonly occurring = AIDS

156
Q

X linked agammaglobinulinaemia

A

Defect in BTK gene
BTK gene encodes Bruton’s tyrosine kinase
Needed for pre-B cell receptor signalling - defect blocks B cell development

157
Q

Diagnosis of X-linked agaamaglobinulinaemia

A

B cells absent/low plasma cells
All Ig absent of very low
T cells normal

158
Q

Selective IgA deficiency

A

Most common - most cases asymptomatic
Some develop infections of respiratory, urogenital or GI tract
Low serum and secretory IgA levels - Increase incidence of allergic disease

159
Q

SCID causes

A

Problems in cytokine signalling - common cytokine receptor γ-chain defect
IL-7 needed for pre-T cell survival - defective T cell development and lack B cell = low antibodies
RAG1/RAG2 defect - no T and B cell

160
Q

Diagnosis of SCID

A

Low lymphocyte count leading to SCID
Low or absent T or B cells
Ig are low
T cell function low proliferation and cytokine production

161
Q

SCID treatment

A 
Isolation to prevent infection 
DO NOT GIVE LIVE VACCINES
IV Ig replacement
Blood products from CMV negative donors
Bone marrow/HSC transplant
gene therapy
162
Q

DiGeorge syndrome

A

Thymic hypoplasia due to deletion in chromosome 22 q11 = failure to develop 3+4th pharyngeal pouches
Can lead to cardiac problems/thyroid problems
Dysmorphic face - cleft palate, low set ears, fish shaped mouth
Hypocalcaemia, cardiac abnormalities

163
Q

Variable immunodeficiency - DiGeorge syndrome

A

Complete DiGeorge - absent thymus

Incomplete DiGeorge - reduced thymus

164
Q

Wiskott Aldrich syndrome

A

X linked
Defect in WASP
WASP = protein involved in actin polymerisation - T cell remodelling cytoskeleton for correct signalling

165
Q

Diagnosis Wiskott Aldrich syndrome

A

Thrombocytopenia, eczema, infections
Progressive immunodeficiency - T cell loss - decrease T cell proliferation
Decrease antibody production

166
Q

Chronic granulomatous

A

Defective oxidative killing of phagocytosed microbes
Mutation in pahogocyte oxidase NADPH - no destruction of phagolysosome
Form granulomas filled with macrophages unable to clear pathogens

167
Q

Chediak higashi syndrome

A

Rare genetic disease
Defect in LYST gene - regulates lysosome traffic
Neutrophils have defective phagocytosis - repetitive, severe infections
Diagnosis - low number of neutrophils and giant granules

MICROBIOLOGY AND IMMUNOLOGY (3 decks)

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