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Immunology > Mucosal Immunity And Infection > Flashcards

Mucosal Immunity And Infection Flashcards

1
Q

Respiratory

A

Influenza, common cold agents, measles

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2
Q

Genitoutinary

A

Sexually transmitted agents

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3
Q

Alimentary Tract (gut)

A

Campylobacter, cholera, salmonella

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4
Q

Skin

A

Streptococci, percutaneous (vector borne diseases e.g. arbovirus)

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5
Q

Eye

A

C.trachomatis

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6
Q

Transplacental

A

Cytomegalovirus

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7
Q

What is the importance of GI tract?

A

Protective against pathogens Largest interval organ exposed to external antigens (400m2) Unique because it contains trillions of microorganisms

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8
Q

What are the properties and function of GI tract?

A

Mucosal battier Absorptive surface Regulation to balance immune response to foreign antigen Fostering symbiotic commensalism microbiota Maintain go balance tolerance to benign antigens Maintain balanced immune response to pathogenic organism

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9
Q

What is the GIT structure?

A

Stars in the mouth and is continuous towards the anus

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10
Q

What are the components of the innate immunity?

A

Intestinal epithelial cells Antimicrobrial peptide Toll-like receptors and NOD like receptors Intestinal microbiome Innate Immune cells

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11
Q

What secretory IEC maintain barrier function?

A

Enteroendocrine cells Goblet cells Paneth cells

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12
Q

What do Goblet cells and paneth cells secrete?

A

Mucins

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13
Q

What does mucins do?

A

Give viscosity to the intestinal lumen

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14
Q

What does secretory IEC produce?

A

Antimicrobrial proteins

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15
Q

What does AMP establish?

A

Physical and biochemical barrier to microbial contact with the barrier and underlying immune cells

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16
Q

What are the extracellular components of IEC barrier?

A

Mucins Antimicrobrial peptides Cytokines

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17
Q

What are examples of Antimicrobial peptides?

A

Destroy bacterial cell wall Alpha and beta defensins Cateclidins

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18
Q

What are some examples of cytokines?

A

IL1, IL4, IL6, IL13. TNF

Microbial adhesive proteins

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19
Q

What cytokines mount pro-inflammatory response?

A

IL-1, IL-6,IL-13 and TNF

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20
Q

What cytokine induce differentiation of naive helper T cells?

A

IL-4

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21
Q

What do intraepithelial cells do?

A

Act as barrier separating immune cells from microbial world

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22
Q

How are innate immune responses achieved?

A

Phagocytes

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23
Q

What are organised lymphoid structures?

A

Payers patches Isolated lymphoid follicles Mesentetic lymph nodes

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24
Q

Intraepithelial lymphocytes

A

The secretory immunoglobulin A producing plasma B cell

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25
Q

Resident innate immune cells of laminate Propria

A

Macrophages Dendritic cells

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26
Q

What are the cells of the GI immune tissue?

A

Organised lymphoid structures Intraepithelial lymphocytes Resident innate immune cells of lamina propria

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27
Q

What are the receptors uninvolved in activation of immune cells?

A

Toll like receptors (TLR) NOD like receptors Cytokine receptors Opsonins and their receptors

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28
Q

What is an example of cytokine receptor?

A

IFN Gamma R (bind to their own distinct receptor IL1)

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29
Q

What are specific opsonin recognised by?

A

FcyRs

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30
Q

What do Toll-like receptors recognise?

A

Microbe-derived motifs

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31
Q

Who proposed the pathogen recognition theory?

A

Charlie Janeway JR

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32
Q

What do all bugs contain?

A

Pathogen associated molecular pattern (PAMP)

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33
Q

What are some examples of PAMP?

A

dsRNA, LPS, peptidogylcan, B glucan

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34
Q

What do innate immune cells possess?

A

Pattern recognition receptors (PRR)

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35
Q

Where was toll like receptor discovered?

A

Drosophila important for embryogenesis

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36
Q

What happens if toll-like receptor was knocked out before embryogenesis?

A

Grows legs out of head —> dorsoventral pattern of fly

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37
Q

What does Hoffman and Lemaitre show?

A

When toll receptors are knocked out in adult drosophila - toll mutant flies are susceptible to fungal infections

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38
Q

What are not susceptible to to fungal infections?

A

Wild type flies

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39
Q

What do TLR recognise?

A

Specific patterns in pathogen

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40
Q

What do TLR1 and TLR2 recognise?

A

Bacterial parasites

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41
Q

Where are TLR1 and TLR2 located?

A

Cell membrane

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42
Q

What do TLR2 and TLR6 recognise?

A

Gram positive bacteria and fungi

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43
Q

What do TLR4 recognise?

A

Gram negative bacteria

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44
Q

If TLR4 are mutated, what doesn’t the mouse respond to?

A

Endotoxin

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45
Q

Where are receptors located?

A

Surface of immune cells and enclosed and hidden in the intracellular compartment known as endosomes

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46
Q

Where are TLR3, TLR7, TLR8 and TLR9 located?

A

Endosomes

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47
Q

What does TLR3 recognise?

A

Viral double stranded RNA

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48
Q

Where are TLR7 and TLR8 recognise?

A

Viral single stranded RNA

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49
Q

What does TLR9 recognise?

A

Unmethlyated DNA

50
Q

Where is mammalian DNA methylated?

A

cpg-motifs

51
Q

Who proposed the danger recognition?

A

Polly Matzinger

52
Q

What does infections and tissue damage induce?

A

Stress and release danger associated molecular patterns (DAMPS)

53
Q

What is DAMP recognised as?

A

Altered self/ non-self

54
Q

What are some examples of DAMPS that can be recognised by immune system as danger signals?

A

Heat shock proteins Histones Double stranded DNA/RNA

55
Q

What does APC possess?

A

Danger recognition receptor (DRR)

56
Q

What does activation of DRR promote?

A

Activation of adaptive immunity

57
Q

What are multiple activators for the inflammations?

A

NLRP1, NLRP3, NOD1 and NOD2

58
Q

What does the common activation pathway lead to?

A

caspase 1 protease

59
Q

When caspase 1 protease is activated what does it cleave?

A

Downstream targets of pro-IL1 B into IL-1B and IL-1B secretion resulting in its secretion

60
Q

Toll like receptors transmit signals through what molecules?

A

MyD88

61
Q

What does MyD88 activate?

A

Transcription factor (NF-KB)

62
Q

Why is interleukin 1 (IL1) important?

A

All bodily cells have receptors to detect IL-1

63
Q

What does IL-1 cause the release of?

A

Increase in bodily temperature Activation of neutrophil recruitment

64
Q

What are cryopyrin associated periodic syndrome?

A

Group of rare, inherited and auto inflammatory disease

65
Q

What is the cause of CAPS?

A

Autosomal dominant mutations of the NLRP3 gene

66
Q

What do the individuals of CAPs develop?

A

Rashes induced by cold

67
Q

What are the three subtypes of CAPS?

A

Familial cold autoinflammatory syndrome (FCAS) Muckle-Wells syndrome (MWS) Neonatal-onset Multisystem Inflammatkey DIdease (NOMID)

68
Q

What are the treatments if CAPS?

A

IL1Beta is IL1Beta receptor blockers

69
Q

What examples of IL1Beta blockers?

A

Anakinra Canakinumab Rilonacept

70
Q

What do NOD1/2 recognises?

A

Bacterial amino acids

71
Q

What are NOD1 and NOD2?

A

Cytosolic sensors

72
Q

Where are the receptors of NOD1/2 driven from?

A

Microbial peptidogylcan cell wall

73
Q

What are peptidoglycan cell wall made up of?

A

Lipids and proteins

74
Q

What are 2 proteins from bacterial cell wall that are detected as foreign in immune system?

A

Muramyl dipeptide D-glutamyl-mesodiaminopimelic acid

75
Q

What is Crohn’s disease?

A

Auto-inflammatory condition Affects any part of gastrointestinal tract from mouth to anus

76
Q

What is Crohn’s disease caused by?

A

Combination of environmental and genetic factors Abdominal pain Diarrhoea Fever Weight loss

77
Q

What are the treatment of Crohn’s disease?

A

Antibiotics Mesalazine ( 5-ASA TNF inhibitors: infliximab and adalimumab

78
Q

What is ulcerative colitis?

A

Affects colon causes megacolon Inflammation of joint, liver and colon cancer

79
Q

What is the treatment of ulcerative colitis?

A

Corticosteroid 5-ASA and mesalazine TNF inhibitors: infliximab and adalimumabfor non corticosteroids responders

80
Q

What are NOD1 and NOD2?

A

Inflammatory bowel disease susceptibility genes

81
Q

Where are NOD 1 and NOD2 genes found through?

A

Genome wide association studies

82
Q

Where is NOD2 expressed?

A

Phagocytes and macrophages

83
Q

Where is NOD1 expressed?

A

Epithelial cells of gut barrier

84
Q

Conventional pathway

A

Activation of map kinases Go downward and activate ERK, JNK, P38 as well as NF-Kb

85
Q

Inflammasome complex activation

A

IL1 cleavage by caspase 1

86
Q

Autophagy

A

Clearance of intracellular infections Elimination of all toxic or unwanted waste in lysosomes

87
Q

What does inflammasome pathway result in?

A

Release of IL-1 to the extracellular space and activating immune system

88
Q

What does conventional pathway lead to?

A

Expression of inflammatory genes

89
Q

What are dendritic cells?

A

Very efficient antigen presenting cells

90
Q

What does damage and infection in mucosa stimulate?

A

Inflammation

91
Q

What does detection of PAMP from microbes such as bacteria release?

A

Cytokines (interleukins 1 and 8) and tumour necrosis factor by the resident phagocytes

92
Q

What does the wound bleeding cause?

A

Wash out foreign bodies and enclose by forming a barrier with the outside world —> blood clot

93
Q

What drives the innate immune responses?

A

The recognition of danger and inflammation

94
Q

What detects soluble factors IL-1?

A

Neutrophils from the bloodstream

95
Q

Why are neutrophils important?

A

Detect and kill phagocytes very efficiently

96
Q

Where are T cells born and what are they

A

Thymus and naive T cells Localise to the secondary lymph node and wait for the message from dendritic cell to be trained

97
Q

T cells differentiate into TH1 cells in the presence of what?

A

IL-12 and IL-23

98
Q

What do IL-12 and IL-23 cytokines do?

A

direct T cells to become TH1 and produce TNF and IFN-Y

99
Q

TH0 can differentiate into TH2 in the presence of what?

A

IL-4

100
Q

When does TH0 differentiate into TH2?

A

When a parasite is recognised by mast cells resulting in IL-4 secretion

101
Q

What does TH2 remove?

A

Parasites from the body

102
Q

What do B cells produce?

A

Immunoglobulins

103
Q

What factors cause inflammatory conditions in the skin?

A

Genetic and environmental

104
Q

What is Psoriasis?

A

Chronic T cell mediated autoimmune condition

105
Q

What are the causes of Psoriasis?

A

Overproduction of skin cells (keratinocytes) via their stimulation and responses to bacteria/virus and other stressors

106
Q

What are the inhibitors of Psoriasis?

A

IL-17A [secukinumab] -cosentyx, Novartis IL-23 - selective for IL-23p19: tildrakizumab, guselkimab Unselective (bot IL23 + IL12): ustelinumab TNF alpha inhibitor: certolizumab pegol

107
Q

What is Atopic Dermatitis: Eczema?

A

Common inflammatory skin disease

108
Q

Who does eczema affect?

A

20% of children and up to 3% adults

109
Q

What is Eczema characterised by?

A

Biphasic inflammation

110
Q

USA

A

E.coli
91-99
1.6 billion

111
Q

Peru

A

Cholera
91
770 million

112
Q

UK

A

BSE
90-98
39 billion

113
Q

Asia

A

SARS
2003
30 billion

114
Q

Tanzania

A

Cholera
98
36 million

115
Q

India

A

Plague
95
1.7 billion

116
Q

Malaysia

A

Nipah
99
625 million

117
Q

Stomach

A

Lactobacillus
Candida
Streptococcus
H.pylori

118
Q

Proximal Ileum

A

Streptococcus

Lactobacillus

119
Q

Colon

A

Bacteroides

120
Q

Clostridium groups

A

IV and XIV

121
Q

What is predominant in the initial/acute phase of Eczema ?

A

TH2-biased immune response

IL4, IL12, TSLP and eosinophil

122
Q

What is dominant in chronic phase of Eczema?

A

TH1/TH0

IFN gamma, IL-12, IL-5, GM-CSF

Immunology (20 decks)

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