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JMP Y2S1 > Week 32- Immune function: Deficiency > Flashcards

Week 32- Immune function: Deficiency Flashcards

1
Q

What are the 2 main arms of the immune system?

A

Adaptive and innate

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2
Q

How fast, specific and ability of memory is in the innate immune response?

A
  1. Rapid response
  2. Broad response
  3. No memory
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3
Q

What is the speed, specificity and memory of the adaptive immune response?

A
  1. Slow response
  2. Specific response
  3. Long-term memory
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4
Q

What are the key components in the innate immune system?

A 
Neutrophil
Eosinophil
Basophil
Macrophage
Mast cells
NK cell
Complement
Dendrites --> presents antigens to the adaptive immune system
etc
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5
Q

What are key components of the adaptive immune system?

A 
CD4+ T cells
CD8+ T cells
B cells
Memory B cells
etc
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6
Q

What are the two arms of both the adaptive and innate immune systems?

A

Cell-mediated immunity —> mediated by cells eg macrophages or cytotoxic T cells
Humeral immunity —> molecules found in extracellular fluid eg complement proteins, antimicrobial proteins, antibodies

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7
Q

Is complement part of the innate or adaptive immune pathway?

A

Part of the innate –> but can also work with the adaptive immune response if required

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8
Q

What are the three activation pathways of complement?

A
  1. Classical —> antibody binding to the pathogen
    1. Lectin —> activated by lectin binding to mannose molecules on pathogen surface
    2. Alternative —> binding of complement to pathogen in absence of antibody.
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9
Q

What is the three core actions of complement?

A
  1. Recruitment and activation of immune cells
    1. Opsonisation (coats) of pathogen —> promotes internalisation immune cells
    2. Killing pathogens directly through lysis (membrane attack complex)
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10
Q

What are antibodies produced by and by which arm/response?

A

B cells —> via humeral adaptive response

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11
Q

What is the region in which B cell antibodies bind?

A

Epitope (single specific region on an antigen)

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12
Q

What are the 6 mechanisms antibodies drive clearance and containment of pathogens?

A
  1. Agglutination: Clump pathogen together, limitingspread
  2. Opsonisation: Binds to pathogen and recognised by phagocytosis receptors on white cells, increasesinternalisation
  3. Neutralisation: Prevents binding of pathogen tohost cells or interferes with toxin activity
  4. ComplementActivation: Activation of the classicalpathway
  5. Inflammation: Activates immune cells in presenceof pathogen
  6. Antibody‐Dependent CellMedicated Cytotoxicity(ADCC):
    Initiates killing of pathogen by immunecells
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13
Q

What are some examples humeral immunity mediators?

A

Component –> in innate

Antibodies –> in adaptive

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14
Q

What are the overall functions of the Humeral immunity?

A

Limits pathogen proliferation and spread
Promotes pathogen recognition by immune cells
Activate inflammation
Induce direct killing of pathogens

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15
Q

Where do all white blood cells originate?

A

Common progenitor cell in the bone marrow –> hematopoietic stem cell

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16
Q

What are some examples of myeloid cells and their roles?

A
  1. Macrophages –> Phagocytosis, bactericidal mechanisms, antigen presentation
  2. Dendritic cell –> Antigen uptake in peripheral sites, antigen presentation
  3. Neutrophil –> Phagocytosis, bactericidal mechanisms
  4. Eosinophil –> killing antibody coated parasites
  5. Basophil –>Promotes allergic response, anti-parasite immunity
  6. Mast cell –> release granules containing histamine and active agents
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17
Q

Main role of macrophages and which immune system are they a member?

A

A key member of the innate immune system:

  1. Phagocytosis
    • Recognition of pathogen results in internalisation andkilling (enhanced by complement activation)
  2. MediatorProduction / Release
    • Toxic mediators that kill pathogen directly (e.g. nitric oxide
    • Cytokines that activate and recruit immune cells (e.g.chemokines
  3. Antigen Presentation
    • Process pathogen and activate antigen‐specific T cells
  4. WoundRepair
    • Repair tissue damage during the resolution ofinflammation
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18
Q

What dictates the activation method and role of macrophages in the immune response?

A

The environmental cues —> help tailor to pathogen / inflammation

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19
Q

What is the classical activation of macrophages induced by and what is their response?

A

Induced by inflammatory cytokines (TNF(alpha)/ IFN(gamma)

Response –> killing of pathogen via phagocytosis and release of toxic molecules eg nitric oxide

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20
Q

What is the alternate activation of macrophages induced by and what is their response?

A

Induced by Type-2 cytokines (eg IL-4)

Response –> activate wound repair and resolution of inflammation

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21
Q

What is the Anti-inflammatory activation of macrophages induced by and what is their response?

A

Induced by regulatory T-cells (eg IL-10)

Response –> supresses inflammation and protects tissue from damage

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22
Q

What is the role of granulocytes?

A

produce inflammatory molecules, which arereleased from intracellular vesicles (granules)

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23
Q

What are the main granulocytes?

A

Neutrophils
Eosinophils
Basophils

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24
Q

What is the most common white blood cell in the body?

A

Neutrophils

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25
Q

What are neutrophils activated by?

A

Rapidly enter tissue during infection, in response toactivating cytokines and chemokines (e.g. IL‐8)

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26
Q

How do neutrophils kill pathogens?

A

Phagocytosis and toxic molecule release (reactive oxygen species ROS)

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27
Q

How do neutrophils contain pathogens?

A

Deploying extracellular traps (NETS)

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28
Q

How does neutrophils recruit other immune cells?

A

Generate cytokines

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29
Q

What proportion of white cells are eosinophils?

A

1-3% in blood

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30
Q

What is the role of eosinophils?

A

Kill multicellular pathogens (helminths worms) via toxic mediators

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31
Q

When can eosinophils be inappropriately activated?

A

In allergic disease and cause tissue damage eg asthma

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32
Q

How common are basophils in the blood?

A

Rare —> (0.5-1%) of white cells

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33
Q

What is the role of basophils?

A
  1. Secrete anticoagulants (heparin) to limit clotting in hypersensitivity reactions
    1. Release histamine to dilate vessels to recruit immune cells to area of injury
    2. Involved in allergic reactions as well
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34
Q

Where are mast cells present and why?

A

In tissues only —> circulate as immature progenitors and mature upon tissue entry.

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35
Q

What tissues are mast cells mainly present?

A

In most tissues but mainly at sites of pathogen entry:
Skin
Lungs
GIT

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36
Q

What is the roles of mast cells?

A
  1. Release histamine for blood vessel dilation
    1. Release cytokines, chemokines, growth factors in response to activation
    2. Best known for roles in anaphylaxis and allergic reaction (through its functions in histamine induced blood vessel dilation)
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37
Q

How are mast cells activated and what happens when they are?

A
  1. Binding of antigen to IgE antibody on mast cell surface:
    When activated —>
    • Rapid degranulation
    • Release of mediators
      2. Recognition of pathogen surface receptors:
    • Cytokine release
    • Chemokine release
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38
Q

What are NK cells and what immune system are they apart?

A

Major cytotoxic cells —> part of the innate immune system

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39
Q

What do NK cells kill?

A

Other cells —> infected or tumour

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40
Q

What determines what cells NK cells kill?

A
  1. If they cannot recognise MHC-I (normally present on all cells)
    1. The MHC-I is missing in abnormal cells (tumour, virus infected, transplanted cells
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41
Q

How do NK cells kill other cells?

A

Release of cytotoxic molecules (eg perforin, granzyme) to induce cell apoptosis

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42
Q

How do Innate Lymphoid cells (ILCs) develop and how are they different?

A

Bridge innate and adaptive immune cells:

  • Develop from lymphoid pathway (similar to T and B cells)
  • BUT they do not express adaptive receptors (TCR or BCR)
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43
Q

What are the subtypes of Innate Lymphoid cells (ILCs)?

A

Different subtypes activated depending on pathogen

  • Type 1 —> intracellular bacteria or virus
  • Type 2 —> multicellular parasites
  • Type 3 —> extracellular bacteria
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44
Q

What is the role of the Innate Lymphoid cells (ILCs)?

A

Support activation of the adaptive immune system

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45
Q

What is the main role of T lymphocytes?

A

T-cells are key in the adaptive immune response

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46
Q

How does T cells do their job?

A
  1. Each T-cell has a different T cell receptor (TCR) on their surface (1 type per cell) —> this receptor recognises an antigen bound by MHC.
    1. Once activated—> rapidly proliferate to create a clonal pool of antigen specific cells
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47
Q

Where do T cells arise and develop?

A
  1. Arise from immature progenitors

2. Develop in the Thymus

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48
Q

What is the reason for the Selection process of T-cells in the thymus?

A

Ensure that when they bind antigen + MHC they do not cause an auto-immunity response against self antigens

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49
Q

What is the TCR?

A

T Cell receptor

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50
Q

How is the TCR generated/rearranged?

A

TCR gene locus contains cassettes that are randomly combined to generate a wide range of TCRs
Each different TCR can potentially recognise a different antigen

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51
Q

Briefly describe the selection process T cells must undergo in the Thymus?

A
  1. Lymphocyte progenitor enters thethymus from bone marrow
    1. TCRrearrangement occurs in “double negative (DN)” (CD4‐CD8‐) progenitors
    2. Positive selection: T cells with a surfaceTCR that binds MHC survive —>RemovesTcells that cannot interact with MHC
    3. Negative selection: T cells activated byMHC+self‐antigen are removed “Central tolerance” –removes self-reactive cells that may cause autoimmune reaction
  2. Naïve Tcells exit thymus and circulate inperiphery
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52
Q

What happens when a Naïve T cell recognise a MHC + antigen?

A

They are activated causing a rapid clonal expansion to generate a pool of antigen specific T cells

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53
Q

After activated T-cell rapidly form clonal colonies what happens?

A

Migrate to peripheral tissue —> for effector function as well as generation of memory cells to protect against repeat exposure.

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54
Q

What are the 4 main subsets of T cells?

A

T Helper (TH) cells
Cytotoxic T cells
Memory T cells
Suppressor/Regulatory T cells (Tregs)

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55
Q

What is the roles of T Helper (TH) cells?

A
  • Express CD4+
  • Activated by antigen on MHC-II
  • Go on to activate antigen specific B cells, cytotoxic T cells and Macrophages
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56
Q

What are the different functions of the T helper cell subsets?

A 
Type 1 (TH1) --> intracellular pathogens and autoimmunity
Type 2 (TH2) --> extracellular pathogens (eg parasites) allergy and asthma
Type 17 (TH17 --> extracellular bacteria and autoimmunity
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57
Q

What is the roles of Cytotoxic T cells (CTLs)?

A
  • Express CD8+
  • Activated by antigen on MHC-I
  • Directly kill infected and tumour cells
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58
Q

What is the roles of Memory T cells?

A
  • Persist long term after infection (CD4+ or CD8+) long term immune memory
  • Rapidly proliferate upon re-exposure to antigen
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59
Q

What is the roles of Suppressor/Regulatory T cells (Tregs)?

A
  • Limit immune responses to prevent auto-immunity and inflammatory disease
    • Release cytokines to inhibit immune activation
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60
Q

What immune system are B cells apart?

A

Humeral Adaptive immune system

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61
Q

Where are B cells produced?

A

Bone marrow

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62
Q

What kind of receptors are on B cells?

A

Unique B cell receptors (BCR)

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63
Q

What are the functions of B cells?

A
  1. Antigen presentation —> B cells internalise pathogen using their antigen specific BCR—> antigen is processed and presented to T- helper cells
  2. Antibody production —> when activated by T-helper cells
  3. Immune memory —> long term antibody producing cells survive
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64
Q

What chains are TCR and BCR made from?

A 
TCR = alpha and beta chains
BCR = Heavy and light chains (2 of each)
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65
Q

What are the steps in B cell development?

A
  1. Initiated in the bone marrow
  2. Positive selection:
    • Heavy chain rearrangement surface expression needed for survival
    • Light chain rearrangement —> functional surface BCR needed for survival
  3. Negative selection
    • Self reactive B cells are removed to prevent autoimmunity
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66
Q

What 2 events are needed for B cell activation?

A
  1. BCR binding to antigen —> antigen internalised for presentation on MHC-II
    1. T-Helper support —> TCR binding to MHC-II + antigen on B cell
67
Q

What happens when Antigen specific activation occurs (TCR on MHC-II+antigen on B cell)?

A
  1. B-cell proliferation
  2. Differentiation and antibody class switching
  3. Antibody release —> alternate RNA processing removes transmembrane portion for secretion
68
Q

What does prolonged antigen exposure result in?

A
  1. Somatic hypermutation—> addition of mutagens within the immunoglobulin gene variable region
  2. Affinity maturation—>B cells making antibodies with higher affinity binding to antigen are favoured —> hence these antibodies with high affinity are more prevalent.
69
Q

Role of IgM?

A

Primary antibody in early response

70
Q

Role of IgD?

A

Co-expressed on cell surface with IgM prior to B-cell activation —> post activation is in secreted form

71
Q

Role of IgG?

A

Enhanced phagocytosis, neutralises toxins, in highest concentration in blood

72
Q

Role of IgA?

A

Secreted into mucous and saliva as a dimer

73
Q

Role of IgE?

A

Parasite response and allergy.

74
Q

What is the MHC?

A

Major Histocompatibility Complex

75
Q

What does the MHC do/allow?

A

—> display antigen on the cell surface for activation of the adaptive immune cells
Allows recognition of infected and abnormal cells

76
Q

What is the HLA Gene locus?

A

Human Leukocyte Antigen locus —> encodes the MHC genes
Each individual has multiple MHC-I and MHC-II genes with parents giving separate sets —> giving broad allele diversity in the population

77
Q

Why is MHC compatibility important for transplant?

A

Non compatible tissue will contain different MHC alleles —> this is recognised by NK cells which kill donor cells/tissue.

78
Q

What is the differences between the MHC-I and MHC-II?

A

MHC-I —>
1. expressed by all cells except RBC
2. Displays antigens from the cytoplasm (recognises abnormal protein production)
3. Recognised by CD8+ cytotoxic cells
MHC-II —>
1. expressed by antigen presenting cells (dendritic, B and macrophages)
2. Displays antigens from extracellular space (outside pathogens)
3. Recognised by CD4+ helper T-cells

79
Q

What results in the activation of the adaptive immune response?

A

Failure of the innate immune response to clear the infection

80
Q

What type of immunity does T cells vs B cells give?

A

T cells –> adaptive cellular

B cells –> adaptive humeral (antibodies)

81
Q

What happens with repeat encounters with a pathogen and the adaptive immune system?

A

Enhanced responses

Less collateral tissue damage

82
Q

What is the primary presenting cell?

A

Dendritic cells

83
Q

How does dendritic cells function to induce adaptive immunity?

A
  1. Collect antigen in peripheral tissues
    1. Pathogens are digested and portions (antigens) are displayed on the cell surface in MHC molecules
    2. Migrate to lymph nodes
    3. Antigen +MHC is recognised by naïve T cells that are reactive to that specific antigen (signal 1)
    4. Dendritic cells also produce cytokines to activate these antigen specific T cells and promotes their proliferation (signal 2)
84
Q

What is the two major vaccination strategies and how do they work?

A

Passive immunisation –> transfer of preformed antibodies to the at-risk individual
Active immunisation –> Stimulation of the individuals immune system to induce antibody production

85
Q

What is Thrombocytopenic purpura and what mediates it?

A

Reduction in circulating blood platelets –> due to factors such as immune mediated thrombocytopenic purpura (ITP)

86
Q

What happens in Immune Thrombocytopenic Purpura?

A

Autoimmune disease with antibodies against several platelet surface structures

87
Q

What happens when there is an incompatibility of an antigen on transfused cells?

A

Acute haemolytic transfusion reaction –> this can also be non immune mediated

88
Q

What is the immune strategy for extracellular bacteria?

A

MAINLY –> Innate immune system via phagocytosis (macrophages, neutrophils)

89
Q

What is an issue with encapsulated bacteria and the immune response?

A

They have a polysaccharide capsule that helps them resist uptake

90
Q

How does the immune system have to then deal with encapsulated bacteria?

A

Too counter them antibodies from adaptive B cells can bind

—>activate complement and promote phagocytosis

91
Q

How is intracellular bacteria dealt with by the immune system?

A
  1. The pathogen proteins are processed into MHC-II on cell surface
  2. T-Helper (TH1) recognises bacterial pathogen is present
92
Q

How is intracellular bacteria infected immune cells dealt with vs non immune cells?

A

Immune —> eg macrophage —> its activated to kill bacteria

Non-immune—> apoptosis is induced to kill bacteria and the cell

93
Q

What is a way virus infections try to evade that adaptive immunity?

A

Downregulate surface MHC-I expression

94
Q

What is some mechanisms of the innate immune system to deal with virus infections?

A
  1. Type 1 interferon (IFN) release can protect target cells from initial virus infection
    1. NK cells kill cells with low MHC-1 expression –> which is a virus mechanism to evade the adaptive immune response
95
Q

What is the adaptive immune response to virus?

A
  1. B cells produce virus specific antibodies

2. CD8+ cytotoxic T cells (CTLs) recognise viral antigens presented in surface MHC-I and kills these cells.

96
Q

What is the immune response to parasites?

A
  1. Initial tissue damage is responded to by neutrophils and macrophages but they often fail to remove parasite
  2. Pathogen specific CD4+ T-helper 2 (TH2) activated by APCs and trigger immune activation
  3. Mast cell activation —> release soluble factors to damage worm and recruit immune cells
  4. Eosinophils activation —> release toxic mediators to damage pathogen
  5. B cells activated —> produce pathogen specific antibodies to helminth
97
Q

What is selective IgA deficiency?

A
  1. Most common primary genetic immunodeficiency (GENETIC)
    1. Characterised by a B-cell defect that leads to low IgA antibody,
    2. Normal B and T numbers
98
Q

What is the symptoms of a selective IgA deficiency?

A
  1. Mostly asymptomatic (85-90%) —> can lead to recurrent infection of mucosal tissue (resp, GI, urogenital tract)
    1. In severe cases may generate autoantibodies to IgA —> causes severe reactions to blood transfusion
99
Q

What is severe combined immunodeficiency (SCID)?

A
  1. Severe genetic T and B cel development defect
    1. No adaptive immunity —> no T cells or antibodies
    2. Characterised by very low T cells in blood (those there are non functioning), low antibody levels
    3. Mothers antibodies provide some early protection
100
Q

What is some symptoms of severe combined immunodeficiency (SCID)?

A
  • Severe, repeated infections in first 6 months
  • Poor growth
  • Chronic diarrhoea
  • Early death (1-2 years) –> if untreated
101
Q

How is severe combined immunodeficiency treated?

A
  • Infection management (antibiotics, antivirals, antifungals)
  • Isolation
  • Enzyme replacement
  • Antibody infusions
  • Bone marrow transplantation –> from matched donor without mutation
102
Q

What are some ways cancer is related to immunodeficiency?

A
  • Blood cancer —> uncontrolled proliferation on immune cells may affect immune cell function and/or production
  • Chemotherapy and radiation therapy—> interferes with proliferation and can result in neutropenia (low neutrophils)
103
Q

What are some examples of Cancer induced immunodeficiencies –> blood disorders?

A

Leukaemia –> blood cells or bone marrow
Lymphoma –> lymphocytes
Myeloma –> plasma cells

104
Q

How does cancer therapies (chemotherapy and radiation) cause immunodeficiencies?

A

Suppress cellular proliferation –> to limit tumour growth
Immune cells production is interfered with
Neutropenia results –> impaired innate immune system, reduced phagocytosis –> increased infection risk

105
Q

How to some pathogens cause immunodeficiency?

A
  • Evolved to suppress the immune response

- Can directly infect immune cells to interfere with their function and cause a loss of immune cells

106
Q

How do secondary infections occur?

A
  1. Primary viral infection suppresses immune system:

2. Secondary infection commonly bacterial is able to manifest

107
Q

How does a primary viral infection impair the immune system to increase likelihood of secondary infection?

A

Reduces the physical barrier
Reduces mucosal clearance
Impaired immune cell function

108
Q

What is HIV?

A

Human immunodeficiency virus

109
Q

How does HIV suppress the immune system?

A
  1. Directly infects CD4+ T cells
  2. Impairs T helper cells –> reduced immune cell activation
    Leads to Increases rates of opportunistic infection
110
Q

How does anti-inflammatory drugs like corticosteroid suppress inflammation?

A
  • Reduced cytokines
  • Reduced immune mediators
  • Reduced immune cell recruitment
  • Increased immune cell apoptosis
111
Q

What can happen more readily with this impaired inflammation?

A

Impaired pathogen response –> increased infections

112
Q

Why does transplantation lead to related immunodeficiency?

A

Requires immunosuppressive drug treatment to prevent organ rejection

113
Q

What would happen if a transplant patient did not take their immunosuppressive drugs?

A

CD8+ CTL and NK cells recognise donor tissue as non-self and will induce apoptosis

114
Q

What is the roles of the spleen?

A

Clearance of blood-borne bacteria
Removal of ages platelets/RBC’s
Adaptive immune development (particularly memory B cells (antibody responses))

115
Q

When is a splenectomy indicated?

A

Trauma
Cancer
Blood disease –> eg idiopathic thrombocytopenic purpura

116
Q

What happens post splenectomy (Immune related issue)?

A

Increased susceptibility to bacterial infections –> can lead to sepsis

117
Q

What are some considerations usually post splenectomy?

A

Vaccinations –> limit bacterial infections
Antibiotics –> prophylactic daily in children –> also immediately upon symptoms of infection
Travel advice –> limit travel away from regions of known infection eg malaria

118
Q

What is immunodeficiency?

A

Immune responses are compromised or absent

119
Q

What is the result of impairment in innate vs adaptive immunity?

A

Innate –> rapid microorganism expansion –> illness –> death
Adaptive –> pathogen persistence and chronic infection

120
Q

What is primary vs secondary immune deficiency?

A

Primary (10%)—> genetic cause –> often present at birth or early life
Secondary (90%) —> environmental factors –> appears later in life

121
Q

What are some causes of immunodeficiency?

A 
Genetically determined
Cancer-induced
Infection induced
Drug induced
Transplant related
122
Q

How does IgG levels in foetal stage and newborns change and compare?

A

Increases till birth (passive transfer of maternal IgG)

Drops off from birth and hits very low levels at 6-12 months

123
Q

What is significance of recurrent infections and immunodeficiency?

A

Recurrent infections may indicate an underlying immunodeficiency

124
Q

What are some key warning signs of immunodeficiency?

A 
Ear infections
Sinus infections
Pneumonias
Abscesses
Thrush/Fungal infections
Family history of immunodeficiency
125
Q

What do many chemotherapy drugs target?

A 
Uncontrolled proliferation (cell division) of cancer cells
--> leading cancer cells to cell death (cytotoxicity) by apoptosis
126
Q

Why can broad targeting chemotherapy drugs be used?

A

Tumour cells go through the cell cycle more frequently and are more sensitive than normal cells to interference with DNA synthesis and mitosis

127
Q

What are the main tissue types apart from tumours which are susceptible to chemotherapy?

A 
Rapidly dividing cell types:
GIT lining --> vomiting 
Hair --> alopecia
Skin --> wound healing
Bone marrow
128
Q

What can make treating tumour/cancers difficult?

A

The cancer can be a series of “environment” with populations of cells at different stages of the cell cycle. Cell division blocking treatments will leave the G0 cancer without effect. To account for the different environments commonly multiple drugs are used

129
Q

What type of anti neoplastic agent is an “alkylating agents”?

A

Chemotherapy

130
Q

What kind of treatment is chemotherapy?

A

Cytotoxic therapy

131
Q

How do Alkylating agents (e.g. cyclophosphamide) function?

A
  1. Chemical groups form covalent bonds with DNA
    1. These groups cause intra and inter-chain cross linking
    2. These cross links interferes with transcription and DNA replication
    3. Cell arrests in S phase (G2 block) and undergoes apoptosis/cell death.
132
Q

How is cyclophosphamide activated?

A

It is a pro-drug –> delivered in an Inactive form –> metabolised in the liver by cytochrome P450 –> active form

133
Q

What cell type does cyclophosphamide have the greatest effect on?

A

Lymphocytes –> leads to immunosuppression

134
Q

What nucleotides are purines?

A

A, G

135
Q

What nucleotides are pyrimidines?

A

C, T, U

136
Q

How do antimetabolites pyrimidine antagonists e.g. 5’ fluorouracil work?

A
  1. Targets S phase
    1. “Fake” precursors to nucleotide inhibits thymidylate synthetase and stops pyrimidine synthesis
    2. Blocks DNA synthesis
    3. Cells apoptosis
    4. Purine antagonists work in much the same mechanism
137
Q

How does antimetabolites folic acid antagonists (Eg methotrexate) work?

A
  1. Competitively inhibits the enzyme dihydrofolate reductive
    1. Inhibiting conversion of folic acid to folinic acid
    2. Inhibits DNA and RNA synthesis
138
Q

What is the drive for targeted therapies like Monoclonal antibodies and Kinase inhibitors for cancer treatment?

A

Targeted treatments don’t have such wide spreading and subjectively nasty side effects as cytotoxic treatments

139
Q

How do monoclonal antibodies (e.g. cetuximab) help treat cancer?

A
  • Recombinant antibodies bind to the epidermal growth factor EGFR
  • Causes reduced proliferation and induces apoptosis in cells that over express EGFR (cancer)
140
Q

How do Kinase inhibitors (e.g. Erlotinib) work?

A
  1. Inhibits ATP binding to kinase active site, by reversible inhibiting EGFR tyrosine kinase
    1. Useful for cancers with EGFR mutation –> cancer needs this to be affective
141
Q

What is the mechanism for the cancer immunotherapy Pembrolizumab?

A

Inhibitor of programmed cell death protein (PD-1)

  • -> this blocks PD-1 receptor on T cells and PD-L1 ligand on cancer cells
  • -> this connection is normally required alongside MHC docking –> Pembrolizumab blocks the PD-1 docking and activates the T cell
  • -> cytotoxic T cells drive anti-cancer immunity
142
Q

How does the hormonal antineoplastic drugs “oestrogen receptor modulators eg tamoxifen work?

A
  • Completes with oestrogen for receptor sites on breast tissue
  • Inhibits tumour growth through this anti oestrogen effect
143
Q

How does the hormonal neoplastic drugs “Aromatase inhibitors” eg letrozol work?

A
  • Reversible inhibits aromatase
  • Aromatase is responsible for conversion of androgens to oestrogen
  • Therefore reduces oestrogen production and negatively impacts cancers dependant on oestrogen interaction
144
Q

What affects bone marrow during cancer treatment?

A

Chemotherapy –> bone marrow suppression –> usually neutropenia

145
Q

What can be done to limit affect on the bone marrow during chemotherapy?

A

Bonus drugs to stimulate bone marrow production to maintain immune function
E.g. –> pegylated G-CSF –> prevents neutropenia –> stimulates granulocyte production

146
Q

What does Haematopoiesis have to do with WBCs?

A

It is the differentiation process by which all blood cells are formed

147
Q

Where does haematopoiesis occur in adults?

A

Mainly bone marrow

–> can occur in low amounts in the liver, thymus and spleen

148
Q

What is the main differences between the innate vs adaptive immune system?

A

Innate –> fast –> non specific –> no memory

Adaptive –> slower –> specific –> memory

149
Q

What are some common situations where patients can become immunosuppressed?

A 
Malnutrition 
Diabetes
Kidney failure
Age --> reduces T cell function
Pregnancy 
Post infection/current infection
Cancer/chemotherapy
150
Q

What are clinical signs of immunosuppression?

A

Frequent reoccurring infections
Frequent opportunistic infection
Blood disorders –> low platelets or anaemia
Delayed growth and development
Autoimmune disorders –> lupus, arthritis, type 1 diabetes

151
Q

How is bone marrow normally sampled?

A

The biopsy is done using a small needle inserted into thebone. Thebone marrowtissue is removed and then sent to a lab and checked under a microscope.

152
Q

What is iatrogenic harm?

A

iatrogenic ailments are those where doctors, drugs, diagnostics, hospitals, and other medical institutions act as “pathogens” or “sickening agents.

153
Q

How can iatrogenic harm it impact the suitability of a patients inclusion into a clinical trial?

A

When the trial could do more harm than good to the patient

154
Q

What is prevalence?

A

Number of cases of adiseasethat are present in a particular population at a given time

155
Q

What is incidence?

A

The rate of new cases of disease –> how many new cases were recorded over a certain time

156
Q

What is morbidity?

A

Another term for illness –> patients can have several morbidities at once

157
Q

What is mortality?

A

Mortality is a term for death –> mortality rates are the number of deaths due to disease divided by the total population

158
Q

What is sensitivity?

A

The ability of a test to correctly identify those with disease (high true positive rate)

159
Q

What is specificity?

A

The ability of thetestto correctly identify those without the disease (true negative rate).

160
Q

What is positive predictive value?

A

It is the probability that the subjects with a positive screening test truly have the disease

161
Q

What is Negative predictive value?

A

It is the probability that the subjects with a negative screening test truly don’t have the disease

162
Q

Broadly what is selection bias?

A

Selection biasis thebiasintroduced by theselectionof individuals, groups or data for analysis in such a way that proper randomization is not achieved, thereby ensuring that the sample obtained is not representative of the population intended to be analysed.

163
Q

Broadly what is measurement error?

A

The difference between a measured quantity and its true value –> can be caused by naturally occurring errors (expected error) and systemic errors (mis calibration) which should be avoided.

JMP Y2S1 (24 decks)

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