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Immunology and inflammation > IMI1: The components of the immune system and introduction to innate immunity > Flashcards

IMI1: The components of the immune system and introduction to innate immunity Flashcards

1
Q

What are the effects of X-linked serve combined immunodeficiency (SCID)

A

Born without a functional immune system

No: T cells & NK cells and non-functional B-cells

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2
Q

Which types of cells are lymphoid?

A

T cells, B cells and NK cells

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3
Q

Which type of cells are myeloid cells?

A

monocytes (precursors to macrophages), mast cells, dendritic cells, neutrophils, basophils and eosinophils

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4
Q

T or F only B cells are mediators of immune memory? Explain your answer

A

False: Both B and T cells mediate memory, they are produced at the same time as effector cells

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5
Q

Can you survive long without T cells?

A

No you would die in infancy

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6
Q

What are NK cells?

A

Large cytotoxic lymphocytes that patrol the blood for virally-infected or damaged cells, which hey are able to recognise despite lacking variable receptors

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7
Q

Which types of microorganisms can cause disease?

A
  • viruses
  • bacteria
  • fungi
  • commensal micro-organisms (if they become out of control or leave natural environment)
  • parasites
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8
Q

How does SCID come about?

A

one single mutation in a chain that makes part of a cytokine receptor complex (γC)

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9
Q

What are cytokines?

A

small polypeptides that are used as messengers in the immune system. Several cytokines utilise common cytokine receptor γ-chains (γC) and, through these receptors, control essential immune responses that use both common and distinct checkpoints

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10
Q

What does commensal bacteria mean?

A

good bacteria

including viruses, fungi and archaea

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11
Q

Individuals who develop allergies are thought to..?

A

Have less diverse microbiomes

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12
Q

How much smaller are viruses then bacteria?

A

10x

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13
Q

How many m^2 of skin is there on average on a human body?

A

2

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14
Q

How many m^2 of mucus membrane is there on average on a human body?

A

400

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15
Q

Describe the mechanical and chemical defence of the skin

A

M: Longitudinal flow of air or fluid
C: fatty acid, B-defensins, lamellar bodies, cathelicidin

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16
Q

Describe the mechanical and chemical defence of the gut

A

M: Longitudinal flow of air or fluid
C: Low pH, Enzyme (pepsin), a-defensins (cryptdins), Reglll (lecticidins), Cathelicidin

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17
Q

Describe the mechanical and chemical defence of the lungs

A

M: Movement of mucus by cilia
C: Pulmonary surfactant and Cathelicidin

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18
Q

Describe the mechanical and chemical defence of the eye/nose/oral cavity

A

M: Tears and nasal cilia
C: Enzymes in tears and saliva (lysozyme) and histatins, B-defensins

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19
Q

What is the mechanical protection common to all barriers?

A

Epithelial cells joined by tight junctions

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20
Q

What chemical barrier do skin, gut and lungs have in common?

A

Cathelicidin

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21
Q

Which barriers have B-defensins as part of the chemical mechanisms?

A

Skin

Eyes/nose/oral cavity

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22
Q

Which barriers have a-defensins as part of the chemical mechanisms?

A

Gut

Lungs

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23
Q

What is the common microbiological barrier for skin, gut, lungs and eyes/nose/oral cavity?

A

The normal microbiota which competes with pathogenic ones

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24
Q

What is the second line of defence against a pathogen

A

innate immune response

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25
Q

State the typical features of innate immune response

A

Broad-acting (lacking specificity)

fast-acting and can last for days

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26
Q

Why is the adaptive immune response of only deployed is completely necessary?

A

It involves an array of new cells and proteins and thus costs much metabolic energy to the body which could be used otherwise in other physiological functions.

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27
Q

Name the organs of the immune system

A
  • Adenoids
  • Tonsils
  • Thymus
  • Bronchial-associated lymphoid tissue (BALT)
  • Axillary lymph nodes
  • Bone marrow
  • Lymph nodes
  • Lymphatic vessels
  • Appendix
  • Spleen
  • Peyer’s patch
  • Inguinal lymph nodes
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28
Q

What are adenoids?

A

A pair of mucosa-associated lymphoid organs located inside the nose

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29
Q

Describe the tonsils

A

Large group of lymphoid cells that are located on each side of the larynx

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30
Q

What matures in the thymus?

A

T-cells

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31
Q

What is bronchial-associated lymphoid tissue?

A

lymphoid cells and tissues of the respiratory tract found in bronchi – not usually found in adult humans but it can be found in kids.

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32
Q

Where are axillary lymph nodes located?

A

arm pit

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33
Q

What happens in the bone marrow?

A

Platelets, white and red blood cells are formed

B cells are developed

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34
Q

What occurs in the lymph nodes?

A

Secondary lymphoid tissue found where lymphatic vessels converge and where antigens are presented to lymphocytes

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35
Q

What is the function of the spleen?

A

secondary lymphoid organ where immune responses to blood-borne pathogens are initiated. It is responsible for the removal of old and damaged red blood cells, for holding some extra blood and recycling iron. It is located on the left behind the stomach (upper left side of the peritoneum).

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36
Q

How is Peyer’s Patch involved in the immune system?

A

part of the gut-associated lymphoid tissue (GALT) and a site where an adaptive immune response can start; located in the small intestine, particularly the ileum.

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37
Q

Inguinal lymph nodes are located where?

A

Groin

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38
Q

Describe the appendix and where it is found

A

Secondary lymphoid tissue found at the beginning of the colon

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39
Q

What are lymphatic vessels?

A

Akin to blood vessels but they transport lymph instead of blood

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40
Q

What are the first cells pathogens come into contact with if they break through the physical barriers?

A

Macrophages

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41
Q

What do macrophages recruit?

A

Neutrophils

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42
Q

What type of cells are neutrophils?

A

the most abundent type of leukocytes

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43
Q

What are macrophages capable of?

A

recognising pathogens as well as old and damaged cells, and engulf them in a process known as phagocytosis.

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44
Q

What do PAMPs stand for?

A

Pathogen-associated molecular patterns

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45
Q

What do DAMPs stand for?

A

Danger-associated molecular patterns

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46
Q

What are PAMPs?

A

structural features on pathogens, that are essential to their survival and serve as markers to immune cells

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47
Q

What are DAMPs?

A

structural features on damaged cells, that are essential to their survival and serve as markers to immune cells

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48
Q

APC cells stands for?

A

Antigen presenting cell

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49
Q

What are the two types of responses by APC cells?

A

1) Self: No immune response

2) Non-self response: Immune response mounted

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50
Q

When an APC cell comes into contact with a non-self-cell what happens?

A

Signal 1 occurs
- MHC + antigen
No immune response results

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51
Q

When an APC cell comes into contact with a non-self-cell what happens?

A 
Signal 1 (MHC + Antigen)
Signal 2 (CD80/CD86)
Activation of immune response
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52
Q

What does MHC stand for?

A

Major histocompatibility molecules

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53
Q

What do recognition of PAMPs by PRRs lead to?

A

The activation of Signal 2 (CD80/CD86)

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54
Q

What do PRRs stand for?

A

Pattern Recognition Receptors

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55
Q

What was the first PRR discovered?

A

Toll-Like receptor (TLR4)

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56
Q

What do PRRs control in invertebrates?

A

The innate arm of the immune system and they can also modulate the adaptive immune response

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57
Q

What may PAMPs include?

A 
Flagellin
sugar or lipid structures (not found in vertebrates)
nucleic acids (single or double stranded RNA)
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58
Q

Where are PAMPs found?

A

Present in forms and/or locations that are not usually found in healthy vetebrates

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59
Q

What are PAMPs thought to be involved in?

A

signalling cascades that recognise DAMPs, when these are released from necrotic cells

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60
Q

What types of structures can PRRs recognise?

A

Bacteria
Virus
Parasites
Yeast

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61
Q

How many signals are needed for a CD4 T cell response to be triggered?

A

At least two: antigen bound to MHC and the CD80/CD86

62
Q

What types of PAMP are present on bacteria?

A
  • Lipoteichoic acid (LTA)
  • Peptidoglycan (PGN)
  • Lipoproteins
  • DNA
  • Flagellin
  • Lipopolyssacharide (LPS)
63
Q

What types of PAMP are present on viruses?

A

Coat protein
Nucleic acid (ssRNA, dsRNA)
DNA

64
Q

What type of PAMP are present on parasites?

A

Glycosylphosphatidylinis (GPI) anchor proteins

65
Q

What type of PAMP are present on Yeast?

A

Zymosan (B-glucan)

66
Q

What is one of the biggest differences between the adaptive and innate immune response?

A

The innate immune system can identify the threat and phagocytose or induce its death (e.g. via apoptosis) it even before the adaptive immune system is aware of it

67
Q

What is a benefit of the fast acting innate immune response?

A

it will engage different PRRs and this will lead cells such as macrophages, dendritic cells (DCs) and innate lymphoid cells (ILKs) to induce the secretion of different cytokines

68
Q

What if the benefit of the innate immune response inducing the secretion of particular cytokines?

A

It will determine which immune cells will be called into action (through differentiation processes) to execute the adaptive response

69
Q

Once a dendritic cell has secreted a helper T cell cytokine, what will happen?

A

there will be a relay of signalling involving other cytokines:

  • The DC will secrete a cytokine that tells the T-cell which cytokines to secrete
  • the T cell will secrete cytokines that tell B cells and cytotoxic effector cells which one of them is required and how they should go about fighting the present danger
70
Q

Are innate immune cells able to act differently for different types of pathogens?

A
  • Innate immune cells express several different innate receptors, capable of recognising different types of pathogens
71
Q

Where else can the expression of innate receptors be found (other than innate immune cells)?

A
  • Keratinocytes
  • Epithelial cells
  • B&T cells
72
Q

Where can innate immune receptors be found?

A

not just the cell surface but also the internal cell membranes e.g. endosomal system & insoluble parts of the cytosol

73
Q

What are innate receptors called?

A

PRR (pattern recognition recptors)

74
Q

What are the 5 main classes of SIGNALLING PRRs?

A
  • Toll-like receptors (TLR)
  • Nucleotide-binding oligomerisation domain-like receptors (NLRs)
  • C-type lectin receptors (CTLRs)
  • RIG-I like receptors (RLR)
  • Cytoplasmic DNA sensors (CDSs)
75
Q

What are the two main groups of PRRs?

A

Those that initiate signalling cascades within a cell and those that do not

76
Q

What are 6 types of pattern recognition receptors that do not lead to signalling, but instead trigger phagocytosis?

A
  • Mannose receptor (CD206)
  • Scavenger receptors A and B (SR-A and SR-B)
  • Macrophage receptors with collagenous structure
  • Lipopolysaccharide (LPS) receptor (CD14)
  • Complement receptor 3&4 (CD11b/CD18)
  • Dectin-1
77
Q

List the different type of immune responses there can be

A
  • Direct killing by lysis
  • Pathogen made more attractive to phagocytosis (opsonization)
  • Direct phagocytosis by membrane bound PRR
  • Increase of phagocytic cell function
  • Increase in the levels of antimicrobial molecules
  • Induction of cytokines and chemokines
  • Differentiation of effector cells
78
Q

What 2 types of PRRs are there?

A
  • soluble

- cell-associated

79
Q

Explain the soluble PRR mechanism

A

1) Binding of microorganisms by soluble PRR molecules
2) Enhancement of phagocytosis of PRR-bound PAMPs
3) Proteolytic cascade resulting in lysis of microorganism

80
Q

Explain the cell-associated PRR mechanism

A

1) Phagocytosis of PAMP associated microorganism
2) Activation of immune cell encountering PAMP
3) Release of ‘cytokines’ to amplify response

81
Q

What releases danger signals?

A

tissue damaged that induces necrosis

82
Q

What are danger signals also known as?

A

alarmins or DAMPs

83
Q

How do necrotic cells get recognised by the immune system if they don’t have non-self molecules?

A

Cell membranes become leaky and thus molecules that are not usually exposed become exposed

84
Q

Describe the pathway following a severe injury?

A

DAMPs expressed leading to necrosis, which releases DAMPs into cytosol. Soluble and cell-associated PRRs recognise DAMPs leading to an immune response

85
Q

Describe the pathway following a mild injury?

A

DAMPs expressed leading to regulated cell death, DAMPs not released and instead apoptosis is carried out. DAMPs remain hidden: recognition and phagocytosis of apoptotic cells by macrophage, meaning the immune system remains quiescent

86
Q

How many different types of innate receptors are there? Where are they expressed? What is the benefit of this?

A

> 100
Each cell type expresses just a few types
Helps the cell to understand where the infection is located and what type of infection it is (cytoplasm, organelles, extracellular, intracellular, bacterial, viral, fungal)

87
Q

What is cellular heterogeneity?

A

Individual effector cells of a certain functional immune cell type can express different combinations of PRRs

88
Q

What is the benefit of cellular heterogeneity?

A

It increases the cell’s ability to identify non-self cells

89
Q

What do macrophages express?

A

Other phagocytic receptors such as complement receptors and scavenger receptors

90
Q

What do complement receptors and scavenger receptors do?

A

Dismissal of the pathogen but unlike PRRs such as TLRs, they do not signal further downstream

91
Q

How do you increase effector functions?

A

Cellular conversation such as phagocytic receptors

92
Q

What does increasing effector function mean?

A

increasing macrophages’ ability to phagocytose or produce antimicrobial proteins and it leads to the production of soluble messenger proteins, most notably cytokines.

93
Q

PRR activation can induce differentiation of what cells?

A

Dendritic cells, allowing them to acquire more specialised functions

94
Q

How many cytosolic molecules can sense PAMPs and DAMPs?

A

Roughly 23

95
Q

What PRR Families are there?

A 
TLRs
RLRs
NLRs
PKR
DAI, AIM2 and cGAS
96
Q

Describe TLRs

A

They can be found on the cell surface or in endosomes and signal intracellularly via the TIR domains. They can sense: triacyl lipopeptides (TLR 1/2); diacyl lipopeptides, lipoteichoic acid (TLR2/6); lipoproteins; peptidoglycan; lipoarabinomannan, porins, envelope glycoproteins; GPI-mucin; phospholipomannan; zymosan, β-Glycan (TLR2); dsRNA (TLR3); LPS, envelope glycoproteins, glycoinositolphospholipids, Mannan, HSP70 (TLR4); Flagellin (TLR5); ssRNA (TLR7,8); CpG DNA (TLR9).

97
Q

Why are there different PRR families?

A

They are either membrane associated or soluble receptors responsible for sensing PAMPs and DAMPs.

98
Q

Describe RLRs

A

reside in the cytoplasm and have helicase domains (present in proteins that function to unwind nucleic acids). They are involved in transducing caspase recruitment domain (CARD)-dependent signalling after being activated by: dsRNA (short), 5 -triphosphate RNA (RIG-I) or dsRNA (long) (MDA5)

99
Q

Describe NLRs

A

which are also cytoplasmic, have a central NOD domain and a c-terminal LRR that recognises: Diaminopimelic acid (NOD1); MDP (NOD2 and NALP1); ATP and uric acid crystals (NALP3) They too signal via CARD domains

100
Q

Describe PKR

A

Is a dsRNA-activated kinase and an IFN-stimulated gene. Its activation by dsRNA, or 5 -triphosphate RNA leads to the inhibition of mRNA translation.

101
Q

What are DAI, AIM2 and cGAS activated by?

A

(non-self) DNA

102
Q

When are cytokines released?

A

Released by immune cells after an encounter with PAMPs or DAMPs

103
Q

Name some different types of cytokines

A 
>40 types of interleukins (ILs)
chemotactic chemokines
antiviral interferons (IFNs)
104
Q

Can cytokines act in an autocrine, paracrine or endocrine manner?

105
Q

What does pleiotropic mean?

A

Many different functions

106
Q

What can chemokines lead to?

A

Phagocytosis

Leading to cell migration

107
Q

What can cytokines activate and what does this activate in turn?

A

Dendritic cells>cell differentiation
Macrophages>cell activation
Endothelium>cell contraction, cytokine secretion

108
Q

Upon infection, pro-inflammatory cytokines are induced.. Which ones?

A

IL-1B, IL-6, IL-12, CXCL8 and TNF-a

109
Q

Why is inflammation needed to resolve the infection?

A

It causes local redness and swelling, less blood flow and vascular permeability that allows the exit from blood of neutrophils and other leukocytes and induce the proliferation of natural killer cells

110
Q

At the site of infection, what do macrophages secrete?

A 
Inflammatory cytokines
IL-1B
TNF-a
IL-6
CXCL8
IL-12
111
Q

What does IL-8B and TNF-a do?

A

Induces blood vessels to become more permeable, enabling effector cells and fluid containing soluble effector molecules to enter the infected tissue

112
Q

What does IL-6 do?

A

Induces fat and muscle cells to metabolise, make heat and raise the temperature in the infected tissue

113
Q

What does CXCL8 do?

A

Recruits neutrophils from the blood and guides them to the infected tissue

114
Q

What does IL-12 do?

A

Recruits and activates natural killer (NK) cells that in turn secrete cytokines that strengthen the macrophages’ response to infection

115
Q

Why are cytokines needed?

A

PRRs are not sufficiently specific to determine the adaptive immune response needed to counteract a pathogen that has managed to defeat the innate arm of the immune system

116
Q

How exactly do cytokines determine the nature of the adaptive immune response?

A

During the priming phase of the adaptive immune response: because they lead to the production of specific cytokines and chemokines: in doing so, they recruit specific sets of immune cells and determine the sort of adaptive immune response best suited to deal with the invader

117
Q

Each member of the TLR can detect different types of _____

118
Q

What does TLR5 recognise?

119
Q

Bacterial genome contain what that is recognised by TLR9, once the genome has been degraded in the lysosome?

A

Methylated CpG oligonucleotide motifs

120
Q

What are TLRs composed of?

A

multiple leucine-rich repeats

121
Q

What do TLRs do in the endosome?

A

Survey fragments of pathogen taken up by endocytosis

122
Q

TLR2 dimers with what to recognise what?

A

TLR6

diacyllipopeptides

123
Q

TLR1 dimers with what to recognise what?

A

TLR2

triacyllipopetide

124
Q

What does TLR4 recognise?

A

Lipopolysaccharide (LPS) - component of gram negative bacteria

125
Q

Where is TLR3 and TLR7 located?

A

Endocytic vesical

126
Q

What does TLR3 recognise?

A

Double stander RNA

127
Q

What does TLR7 recognise?

A

Single stranded RNA

128
Q

When a TLR is activated what happens?

A

It sends a signal to the nucleus where it activates transcription factors thus causing particular genes to be transcribed

129
Q

What two classes of receptors can detect pathogens in the cytosol and signal their presence to the immune system?

A
  • Nucleotide oligomerisation domain (NOD) (NOD2 is an example) -> causes mRNA to be transcribed
  • RNA helicase domain & 2x caspase recruitment domains (RIG-I is an example) -> recognises dsRNA (common in lifecycle of virus) -> causes type 1 interference to be produced
130
Q

Which TLRs work on the plasma membrane?

A 
TLR4/4
TLR2/1
TLR2/6
TLR5/5
TLR11/11
TLR12/12
131
Q

Which TLRs work in endosomes/lysosomes?

A 
TLR4/4
TLR3/3
TLR7/7
TLR8/8
TLR9/9
132
Q

How many mammalian TLRs are there?

133
Q

What do both human and Drosophila share?

A

Toll/IL-1 receptor (TIR) domain

134
Q

TRL-4 and co-receptor (MD-2) bind to what?

A

LPS (also bacterial endotoxin) which is a major component of gram-negative bacteria’s outer membrane

135
Q

TLR-4 is highly immunogenic and is one of the big culprits in _____?

A

Septic shock

136
Q

The formation of stable TLR-4/MD-2 provides an opportunity for the two _______ to come into close proximity and interact

A

TIR domains

137
Q

What is LBP and what is its role?

A

LPS-binding protein: LPS is not accessible on the surface of the bacteria but is extracted with the help of LBP, a serum factor called LPS-binding protein, and dispersed into the blood stream by complement

138
Q

The LPS is then transferred by LBP to _____ and presented to _____ a receptor complex

A

CD14

TLR-4/MD-2

139
Q

What TIR domains of the adapter proteins do TIR domains come into contact with and interact with?

A

MyD88/MAL

TRIF/TRAM

140
Q

What adapters do most TLR receptors interact with?

141
Q

Which TLR doesn’t interact with MyD88?

A

TLR-3

It interacts with TRIF

142
Q

What does interaction of TLR with adapters lead to?

A

Activation of the kinase IKK, which phosphorylates IκB, an inhibitor of NF-κB. When IκB is phosphorylated it gets targeted for degradation thereby releasing NFκB. NF-κB, a key transcription factor that regulates inflammation, is now free to be transcriptionally active.

143
Q

TLRs lead to the activation of?

A

Other transcription factors such as IRFs, which also help provide specificity.

144
Q

What are the results of interaction of downstream signalling molecules of TLRs with DNA in the nucleus?

A

Transcription of: cytokine, chemokines, antimicrobials, interferons a&b

145
Q

Specifically describe CLR

A
  • Trans membrane proteins localized at the plasmamembrane
  • Recognize glycans from the wall of fungi and some bacteria
  • Activate kinase syk and CARD9/MALT1/Bcl-10 adaptor complex

Dectin-1/CLEC7A recognises B-1/3-glucans of the cell wall of various fungi species

146
Q

Specifically describe NLR

A
  • Cytoplasmic sensors
  • multiple subfamilies: 1) NLPRs recognise bacterial, viral, parasitic and fungal PAMPs 2) AIM2 detects viral and bacterial DNA
  • Form multiprotein signalling complexes known as inflammasomes
  • Activates caspase-1-mediated processing and activation of pro-interleukins IL-1B and IL-18

NOD1 & NOD2 recognise peptidoglycan

147
Q

Specifically describe TLR

A
  • Transmembrane proteins localised either at the plasma membrane or in endosomes
  • Broad range of specificities recognising proteins, nucleic acids, glycans etc
  • Activate MAP kinase, NFkB and IRF

TLR4 recognises lipopolysaccharide (LPS)

148
Q

Specifically describe RLR

A
  • Cytoplasmic sensors of viral RNA
  • Signal via the mitochondrial adaptor protein MAVS
  • Trigger antiviral responses including the production of type I interferon

RIG-I and MDA5

149
Q

What WB cells are involved in the innate immune system

A

Phagocytes
Macrophages
Neutrophils
Dendritic cells

150
Q

What WB cells are involved in specific defence?

A

lymphocytes
antibodies
memory cells

151
Q

The PAMP/DAMP-PRR interaction leads to the production of ___?

A

cytokines which in turn activate the adaptive immune response

Immunology and inflammation (11 decks)

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