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Pharmacology > Immune System > Flashcards

Immune System Flashcards

1
Q

What is the immune system?

A

All cells dedicated to defence

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2
Q

What is immunogen?

A

Molecule that stimulates the immune system to produce a response

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3
Q

What is an antigen?

A

Part of the immunogen that reacts with immune effector cells or soluble antibodies

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4
Q

What is an epitope?

A

Part of antigen that reacts with immune effector cells or soluble antibodies

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5
Q

What is a pathogen?

A

Any organism with potential to cause disease

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6
Q

What are the 4 main types of pathogens?

A

Bacteria
Viruses
Fungi
Parasites

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7
Q

Where do you get white blood cells?

A

Haematopoiesis

Bone marrow

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8
Q

What are the primary lymphoid organs?

A

Bone marrow

Thymus

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9
Q

What are the secondary lymphoid organs?

A 
Spleen
Adenoids
Tonsils 
Appendix
Lymph nodes
Peyer's Patches
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10
Q

Describe bone marrow

A

B cells originate + mature here

T cells originate in it BUT leave at immature stage

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11
Q

Describe thymus

A

Located above heart

Immature T cells migrate here

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12
Q

What happens to T cells as they mature in thymus?

A

Move from cortex to medulla

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13
Q

What are secondary lymphoid tissues?

A

Sites where mature lymphocytes are activated to respond to invading pathogens

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14
Q

Where do lymphatic vessels originate?

A

In connective tissues, where they collect plasma fluid

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15
Q

What is the plasma fluid called?

A

Lymph

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16
Q

How is lymph returned?

A

To blood vessels via thoracic duct

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17
Q

What happens to arriving lymphocytes in lymph nodes?

A

Segregate in different areas of the lymph nodes

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18
Q

What happens during infection at lymph nodes?

A

Pathogens are drained in lymph nodes from afferent lymphatic vessels, where they are trapped by dendritic cells + macrophages

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19
Q

What happens when B + T cells meet pathogen?

A

Activated

Undergo clonal expansion + differentiation

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20
Q

What happens to lymph nodes as lymphocyte numbers increase?

A

Lymph node increases in size

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21
Q

What is MALT?

A

Mucosa Associated Lymphoid Tissue

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22
Q

What does MALT include?

A 
Nasopharyngeal lymphatic tissues (tonsils + adenoids)
Bronchus associated (Peyer's patches + appendix) 
Isolated follicles in intestinal mucosa
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23
Q

What are 2 types of immunity?

A

Innate

Adaptive

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24
Q

Describe innate immunity

A 
Rapid response
No memory
Fixed
Limited specificity 
Constant during response
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25
Q

Describe adaptive immunity

A 
Slow response (days to weeks)
Memory
Variable 
Highly specific
Improve during response
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26
Q

What are the cells of innate immunity?

A

Neutrophils
Eosinophil
Basophil
Monocyte

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27
Q

What are the cells of adaptive immunity?

A

B cell

T cell

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28
Q

What are the cells of both innate + adaptive immunity?

A

Macrophages - dendritic cell

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29
Q

What are the immediate innate immune responses?

A

Barriers
Antimicrobial peptides
Complement system

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30
Q

What are the mechanical barriers?

A

Epithelial cells joined by tight junctions
Longitudinal flow of air or fluid
Movement of mucus by cilia

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31
Q

What are the chemical barriers?

A

Fatty acids
Low pH
Enzymes (pepsin)
Salivary enzymes (isozyme)

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32
Q

What are the microbial barriers?

A

Normal flora

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33
Q

What are the anti-microbial peptides for fungi?

A

Defensins
Cathelicidins
Histatins

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34
Q

What are the anti-microbial peptides for bacteria?

A

Defensins
Cathelicidins
Histatins
Lectins

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35
Q

What are the anti-microbial peptides for viruses?

A

Defensins

Histatins

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36
Q

What is the complement system?

A

Group of 30 serum + membrane proteins
Act in sequence
Have initial activation = highly regulates enzymatic cascade

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37
Q

What is role of complement system?

A

Some activated proteins bind covalently to bacteria opsoning them
Bacteria are phagocytosed by cells with complement receptors

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38
Q

Describe classical pathway of complement system

A

Both antibody dependent/independent

C4b opsonin

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39
Q

Describe alternative pathway of complement system

A

C3b opsonin
C3a/C5a pro-inflammatory
MAC complex

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40
Q

Describe complement inactivation

A

EGTA
Complement inhibitors
56 degrees heating
Important role in transplant rejection

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41
Q

What are some other roles of complement system

A

Recruit phagocytes to the site + regulate inflammatory response
Some products activate B cells
Terminal components generate MAC = lysis of pathogens

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42
Q

What are the main phagocytic cells in phagocytosis?

A

Neutrophils + mononuclear phagocytes

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43
Q

What are the stages of phagocytosis?

A

Recognition + attachment
Engulfment
Killing + degradation

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44
Q

What happens in recognition + attachment in phagocytosis?

A

Opsonin receptors:
Microbe coated in opsonin proteins
Phagocytes express high affinity for
C3b breakdown product of complement + Cd4

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45
Q

What are major opsonins?

A

IgG

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46
Q

What happens in engulfment in phagocytosis?

A

After bound to phagocyte receptors
Plasma membrane forms vesicle that encloses particle
Phagosome fuses with lysosomal granule

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47
Q

What happens in killing + degradation in phagocytosis?

A

Lysosomal enzymes
OR
Reactive O species or reactive N species

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48
Q

What are cytokines secreted by?

A

Cells that stimulate or inhibit activity

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49
Q

How many cytokines is there?

A

20

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50
Q

What are cytokines produced by?

A

Mediators + regulators of innate immunity
Mediators + regulators of adaptive immunity
Stimulators of haematopoiesis

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51
Q

What are mediators + regulators of innate immunity?

A

Produced by mononuclear phagocytes

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52
Q

What are mediators + regulators of adaptive immunity?

A

Produced by T lymphocytes

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53
Q

What are stimulators of haematopoiesis?

A

Produced by bone marrow stromal cells

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54
Q

What are features of inflammation?

A

Vasodilation
Increased vascular permeability
Leukocyte migration

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55
Q

What do bacterial LPS activate?

A

Toll like receptors in macrophages

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56
Q

What happens in signal transduction of TLR4 vs bacteria?

A

TLR4 expressed in macrophages detect bacteria
Bind to receptor to stimulate signal transduction pathway
Activate NF-kB + transcription of genes encoding for pro-inflammatory cytokines

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57
Q

What happens in signal transduction of TLR7 vs ssRNA?

A

TLR7 detects ssRNA + signal to activate IRF7
= produces IFN-alpha + IFN-beta
IFN-alpha + IFN-beta have anti-viral properties

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58
Q

What are NK cells activated by?

A

Cytokines IFN-alpha + IFN-beta

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59
Q

What do NK cells do?

A

Kill cells infected by viruses

60
Q

What can NK cells produce?

61
Q

Describe what happens with NK cells

A

IFN bind to receptors expressed by NK cells, activating them
NK cells proliferate + differentiate in effector NK cells
Effector NK cells kill virus-infected cells by inducing apoptosis

62
Q

Describe what happens for bacteria

A

Immediate innate immune response = all 3
Induced innate response = TLR1, 2, 4, 5, 9
Phagocytosis
Cytokines production + inflammation

63
Q

Describe what happens for viruses

A 
Immediate innate response = all 3
Induced innate response = TLR3, 7, 8, 9
Interferons Type I (alpha + beta)
NK cells
Cytokines production + inflammation
64
Q

Describe the structure of an antibody

A 
Y-like shape
4 polypeptide chain structure
2 identical heavy chains
2 identical light chains
Held together by covalent + non-covalent bonds
Each chain = variable + constant region
65
Q

What do antigen-binding site in antibody molecule consist of?

A

Vh + Vl

And are part of Fab

66
Q

How many antigens can one Ig bind?

67
Q

What do Ch regions interact with?

A

Effector cells + complement

Part of Fc region

68
Q

What are the 5 classes of antibodies?

A 
IgG
IgM
IgD
IgA
IgE
69
Q

What are the antibodies that have 3Ch domains?

70
Q

What are the antibodies that have 4Ch domains?

71
Q

How many types of L chains are there?

72
Q

How many types of H chains are there?

73
Q

What do Ig class determine?

A

Type of heavy chain

74
Q

What are the Ig in BCR form?

A

All occur as monomers

75
Q

What are Ig in soluble secreted form (antibodies)?

A

IgD, IgE + IgG = monomers
IgA = dimers
IgM = pentamers

76
Q

Describe antibody-antigen interaction

A

V regions are specific for given Ab

Concentrated region of variability

77
Q

What are the hypervariable regions?

A

3 in Vh

3 in Vl

78
Q

What does the pairing of heavy + light chain bring?

A

6 hypervariable loops together, which create hypervariable surface = forms Ag binding site

79
Q

What are the 6 hypervariable regions called?

A

Complementary-determining regions (CDRs)

80
Q

What is the difference between different CDRs?

A

Different Abs create both specificity + diversity of antigen binding sites

81
Q

What are the antibody-anti-bacterial specific function?

A

Neutralisation
Opsonisation
Complement activation

82
Q

What happens in antibody-anti-viral specific immunity?

A

Antibodies neutralise free virus = no entry = stop spread
Opsonise to increase phagocytosis
Activate complement = lysis

83
Q

What are the functions of Abs?

A 
Neutralisation bacteria, virus + allergens 
Activation of complement
Opsonisation 
Inflammation 
Activation of effector cells
84
Q

Describe IgM

A

Secreted as pentameric molecule
1st Ab to be produced
Primary response
Defence of tissues + prevention of septicaemia

85
Q

Describe IgG

A

Secondary response
Defence of tissues + prevention of septicaemia
Protection of foetus during pregnancy

86
Q

Describe IgA

A

Prevention of septicaemia
Protects surfaces of mucosal epithelium
Present in maternal milk

87
Q

Describe IgA

A

Defence against parasite infections

Important in allergies

88
Q

Describe immunoglobulin

A

Treatment for primary + acquired immune deficiencies

Neutralise toxins

89
Q

Describe monoclonal antibodies

eg. immunosuppressive

A

Prevent transplant rejection
Treat autoimmune disease
Reduce immune response
Produced in mice

90
Q

Describe depleting monoclonal Abs - mechanism of action

A

Monoclonal IgG Abs bind to target cells, which have Fc receptors
Target cells killed by phagocytosis or ADCC

91
Q

Describe nondepleting monoclonal Abs - mechanism of action

A

Block function of target proteins without killing cell that bears it

92
Q

What is the problems with humanisation of monoclonal Abs?

A

Human may develop Ab response against non-human Ab
= interferes with therapeutic action
= leads to allergic reactions

93
Q

What is solution to problems with humanisation of monoclonal Abs?

A

Make Abs not recognised as foreign by human immune system

94
Q

Describe chimeric Abs

Solution

A

V regions from mouse are spliced onto human Ab constant regions

95
Q

Describe humanised Abs

Solution

A

Murine hypervariable regions are spliced into a human Ab

96
Q

Describe fully human Abs

Solution

A

Entirely derived from human sequences + produced from cell lines

97
Q

Describe the stages of B cell lymphocyte development

A

Generation of BCR
Negative selection
Migration + final maturation of B cells
B cells activation + Ab production

98
Q

Describe activation of B cells production

A

Mature B cells eaten by secondary lymphoid tissue
Absence of specific antigen, B cell leaves lymph node + recirculates
Naïve B cells encounter antigens in secondary lymphoid tissue

99
Q

Describe how B cells work

A

Generation in bone marrow
Negative selection in bone marrow
Migration of B cells through circulatory system to lymphoid organs + B cell activation
Ab secretion + memory cells in bone marrow + lymphoid tissues

100
Q

What happens after B cells encounter antigens in secondary lymphoid tissues?

A

B cells further activated by T cells
Some activated B cells proliferate
= PRIMARY RESPONSE

101
Q

What do other B cells do?

A

Migrate in a secondary lymphoid follicle
= mature more slowly
= form plasma cells

102
Q

What happens as primary immune response subsides?

A

B cells develop into memory cells

103
Q

What happens at secondary encounter of pathogen?

A

Memory cells rapidly activate + develop stronger Ab response

104
Q

Describe T cell receptor structure (TCR)

A

2 polypeptide chains = alpha + beta
Constant + variable regions
Each V chain = 3 CDRs

105
Q

What do T cells receptors also include?

A

Proteins of CD3 complex = signal transduction

106
Q

Describe MHC class I

A

Made of transmembrane heavy chain (alpha) = 3 extracellular domains + 1 transmembrane domain

107
Q

What does MHC I bind to?

A

TCR of CD8 T cells

108
Q

Describe MHC class II

A

Mainly expressed on antigen presenting cells

Made of 2 chains (alpha + beta), each with transmembrane region + 2 extracellular domains

109
Q

What does MHC II bind to?

A

TCR of CD4 T cells

110
Q

What do T cells use TCR to recognise?

A

Short peptide fragments bound to MHC

111
Q

What are 2 types of MHC?

A

Class I

Class II

112
Q

Describe endogenous antigen presentation to CD8 T cells

A

Proteins made from pathogens in cytoplasm
Class I
Proteins processed to peptides before binding MHC

113
Q

What do all nucleated cells have?

A

MHC class I molecules

114
Q

Describe exogenous antigen presentation to CD4 T cells

A

Exogenous antigens internalised
Class II
Proteins processed to peptides

115
Q

Describe T cell development

Same as B cell development

A

Bone marrow
Rearrange receptor genes
Express pre-T receptor
Elimination of self-reactive T cells

116
Q

Where do T cells undergo development?

117
Q

What is different from T cell development to B cell development?

A

Alternative lineages

118
Q

Describe how T cells work

A

T cell precursor rearranges T cell receptor genes in thymus
Immature T cells recognise self MHC receive signals for survival
Those interact with self antigen = removed
Mature T cells encounter foreign antigens in peripheral lymphoid organs + activated
Activated T cells proliferate + eliminate infection

119
Q

Describe positive selection

A

Selects T cells with TCR able to bind to molecules

120
Q

When does positive selection occur?

A

When TCR of double-positive T cells recognise MHC molecules expressed on cortical epithelial cells

121
Q

What do double-positively selected cells do?

A

Move to medulla + mature to single positive cells

122
Q

Describe negative selection

A

Remove cells with TCR binding tightly to self peptides

123
Q

When does negative selection occur?

A

When TCR of CD4 or CD8 T cells recognise MHC molecules expressed on dendritic cells/macrophages with high affinity
= these cells undergo apoptosis

124
Q

What do dendritic cells present?

A

Variety of self peptides with MHC I + II of T cells

125
Q

What are T cells with moderate binding to MHC self peptides allowed to do?

126
Q

What can selected T cells do?

A

TCR capable of binding self MHC
Depleted of dangerous self-reactive T cells
Exit thymus as mature, single positive T cells

127
Q

What do activated T cells acquire?

A

Effector functions in secondary lymphoid tissues

128
Q

What do CD8 T cells acquire?

A

Cytotoxic activity

129
Q

What do CD4 T cells function by?

A

Secrete cytokines

130
Q

What happens once TCR have acquired effector functions?

A

No longer require co-stimulation

131
Q

What happens once TCR change location?

A

No longer enter lymph nodes

Enter tissues via activated endothelia at sites of infection + inflammation

132
Q

What are the 2 ways to activates CD8 T cells?

A

Infected cell presenting MHC I

Help from CD4 T cells (through release of cytokines)

133
Q

What are the 2 mechanisms that induce apoptosis?

A

Secretion of cytotoxic granules

Fas ligand on T cells interacts with Fas on target

134
Q

What happens in secretion of cytotoxic granules?

Apoptosis inducing mechanism

A

Perforin polymerises in membrane

Granzymes enter cell

135
Q

What happens in Fas ligand on T cells interacts with Fas on target?
Apoptosis inducing mechanism

A

Secrete IFN-gamma as NK cells
Inhibits viral replication
upregulates MHC I expression + antigen presentation
Increases macrophage phagocytosis of dead cells

136
Q

What are the type of specific CD4 T helper responses?

A

TH1 = active against intracellular pathogens
TH2 = extracellular pathogens
TH17 = extracellular pathogens
Tfh + Treg = regulatory functions

137
Q

Describe what happens with TH1

A

Release cytokines to activate macrophages
= increase intracellular killing of pathogens
HELP macrophages

138
Q

Describe what happens with TH2

A

Release cytokines, support Ab production
= activate mast cells + eosinophils
HELP B cells

139
Q

Describe what happens with TH17

A

Induced early in infection
Release cytokines to amplify neutrophilic responses
HELP neutrophils

140
Q

Describe what happens with Tfh

A

Present in lymph nodes
Stimulate IgM production during primary response
Support isotype switch during secondary response

141
Q

Describe what happens with Treg

A

Inhibit antigen presentation to T cells

= block their activation

142
Q

What do cytotoxic T cells do against viruses?

A

Recognise viral peptide + MHC I

Kill virus infected cells

143
Q

What do cytokines with anti-viral activity do against viruses?

A

eg. IFN-gamma

Induce resistance to virus

144
Q

How do th1cells protect against intracellular bacteria?

A

Activate mainly macrophages

145
Q

How do th1cells protect against extracellular bacteria?

A

Activate mainly neutrophils

Pharmacology (40 decks)

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