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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
Resident innate immune cells of laminate Propria
Macrophages Dendritic cells
26
What are the cells of the GI immune tissue?
Organised lymphoid structures Intraepithelial lymphocytes Resident innate immune cells of lamina propria
27
What are the receptors uninvolved in activation of immune cells?
Toll like receptors (TLR) NOD like receptors Cytokine receptors Opsonins and their receptors
28
What is an example of cytokine receptor?
IFN Gamma R (bind to their own distinct receptor IL1)
29
What are specific opsonin recognised by?
FcyRs
30
What do Toll-like receptors recognise?
Microbe-derived motifs
31
Who proposed the pathogen recognition theory?
Charlie Janeway JR
32
What do all bugs contain?
Pathogen associated molecular pattern (PAMP)
33
What are some examples of PAMP?
dsRNA, LPS, peptidogylcan, B glucan
34
What do innate immune cells possess?
Pattern recognition receptors (PRR)
35
Where was toll like receptor discovered?
Drosophila important for embryogenesis
36
What happens if toll-like receptor was knocked out before embryogenesis?
Grows legs out of head —> dorsoventral pattern of fly
37
What does Hoffman and Lemaitre show?
When toll receptors are knocked out in adult drosophila - toll mutant flies are susceptible to fungal infections
38
What are not susceptible to to fungal infections?
Wild type flies
39
What do TLR recognise?
Specific patterns in pathogen
40
What do TLR1 and TLR2 recognise?
Bacterial parasites
41
Where are TLR1 and TLR2 located?
Cell membrane
42
What do TLR2 and TLR6 recognise?
Gram positive bacteria and fungi
43
What do TLR4 recognise?
Gram negative bacteria
44
If TLR4 are mutated, what doesn’t the mouse respond to?
Endotoxin
45
Where are receptors located?
Surface of immune cells and enclosed and hidden in the intracellular compartment known as endosomes
46
Where are TLR3, TLR7, TLR8 and TLR9 located?
Endosomes
47
What does TLR3 recognise?
Viral double stranded RNA
48
Where are TLR7 and TLR8 recognise?
Viral single stranded RNA
49
What does TLR9 recognise?
Unmethlyated DNA
50
Where is mammalian DNA methylated?
cpg-motifs
51
Who proposed the danger recognition?
Polly Matzinger
52
What does infections and tissue damage induce?
Stress and release danger associated molecular patterns (DAMPS)
53
What is DAMP recognised as?
Altered self/ non-self
54
What are some examples of DAMPS that can be recognised by immune system as danger signals?
Heat shock proteins Histones Double stranded DNA/RNA
55
What does APC possess?
Danger recognition receptor (DRR)
56
What does activation of DRR promote?
Activation of adaptive immunity
57
What are multiple activators for the inflammations?
NLRP1, NLRP3, NOD1 and NOD2
58
What does the common activation pathway lead to?
caspase 1 protease
59
When caspase 1 protease is activated what does it cleave?
Downstream targets of pro-IL1 B into IL-1B and IL-1B secretion resulting in its secretion
60
Toll like receptors transmit signals through what molecules?
MyD88
61
What does MyD88 activate?
Transcription factor (NF-KB)
62
Why is interleukin 1 (IL1) important?
All bodily cells have receptors to detect IL-1
63
What does IL-1 cause the release of?
Increase in bodily temperature Activation of neutrophil recruitment
64
What are cryopyrin associated periodic syndrome?
Group of rare, inherited and auto inflammatory disease
65
What is the cause of CAPS?
Autosomal dominant mutations of the NLRP3 gene
66
What do the individuals of CAPs develop?
Rashes induced by cold
67
What are the three subtypes of CAPS?
Familial cold autoinflammatory syndrome (FCAS) Muckle-Wells syndrome (MWS) Neonatal-onset Multisystem Inflammatkey DIdease (NOMID)
68
What are the treatments if CAPS?
IL1Beta is IL1Beta receptor blockers
69
What examples of IL1Beta blockers?
Anakinra Canakinumab Rilonacept
70
What do NOD1/2 recognises?
Bacterial amino acids
71
What are NOD1 and NOD2?
Cytosolic sensors
72
Where are the receptors of NOD1/2 driven from?
Microbial peptidogylcan cell wall
73
What are peptidoglycan cell wall made up of?
Lipids and proteins
74
What are 2 proteins from bacterial cell wall that are detected as foreign in immune system?
Muramyl dipeptide D-glutamyl-mesodiaminopimelic acid
75
What is Crohn’s disease?
Auto-inflammatory condition Affects any part of gastrointestinal tract from mouth to anus
76
What is Crohn’s disease caused by?
Combination of environmental and genetic factors Abdominal pain Diarrhoea Fever Weight loss
77
What are the treatment of Crohn’s disease?
Antibiotics Mesalazine ( 5-ASA TNF inhibitors: infliximab and adalimumab
78
What is ulcerative colitis?
Affects colon causes megacolon Inflammation of joint, liver and colon cancer
79
What is the treatment of ulcerative colitis?
Corticosteroid 5-ASA and mesalazine TNF inhibitors: infliximab and adalimumabfor non corticosteroids responders
80
What are NOD1 and NOD2?
Inflammatory bowel disease susceptibility genes
81
Where are NOD 1 and NOD2 genes found through?
Genome wide association studies
82
Where is NOD2 expressed?
Phagocytes and macrophages
83
Where is NOD1 expressed?
Epithelial cells of gut barrier
84
Conventional pathway
Activation of map kinases Go downward and activate ERK, JNK, P38 as well as NF-Kb
85
Inflammasome complex activation
IL1 cleavage by caspase 1
86
Autophagy
Clearance of intracellular infections Elimination of all toxic or unwanted waste in lysosomes
87
What does inflammasome pathway result in?
Release of IL-1 to the extracellular space and activating immune system
88
What does conventional pathway lead to?
Expression of inflammatory genes
89
What are dendritic cells?
Very efficient antigen presenting cells
90
What does damage and infection in mucosa stimulate?
Inflammation
91
What does detection of PAMP from microbes such as bacteria release?
Cytokines (interleukins 1 and 8) and tumour necrosis factor by the resident phagocytes
92
What does the wound bleeding cause?
Wash out foreign bodies and enclose by forming a barrier with the outside world —> blood clot
93
What drives the innate immune responses?
The recognition of danger and inflammation
94
What detects soluble factors IL-1?
Neutrophils from the bloodstream
95
Why are neutrophils important?
Detect and kill phagocytes very efficiently
96
Where are T cells born and what are they
Thymus and naive T cells Localise to the secondary lymph node and wait for the message from dendritic cell to be trained
97
T cells differentiate into TH1 cells in the presence of what?
IL-12 and IL-23
98
What do IL-12 and IL-23 cytokines do?
direct T cells to become TH1 and produce TNF and IFN-Y
99
TH0 can differentiate into TH2 in the presence of what?
IL-4
100
When does TH0 differentiate into TH2?
When a parasite is recognised by mast cells resulting in IL-4 secretion
101
What does TH2 remove?
Parasites from the body
102
What do B cells produce?
Immunoglobulins
103
What factors cause inflammatory conditions in the skin?
Genetic and environmental
104
What is Psoriasis?
Chronic T cell mediated autoimmune condition
105
What are the causes of Psoriasis?
Overproduction of skin cells (keratinocytes) via their stimulation and responses to bacteria/virus and other stressors
106
What are the inhibitors of Psoriasis?
IL-17A [secukinumab] -cosentyx, Novartis IL-23 - selective for IL-23p19: tildrakizumab, guselkimab Unselective (bot IL23 + IL12): ustelinumab TNF alpha inhibitor: certolizumab pegol
107
What is Atopic Dermatitis: Eczema?
Common inflammatory skin disease
108
Who does eczema affect?
20% of children and up to 3% adults
109
What is Eczema characterised by?
Biphasic inflammation
110
USA
E.coli 91-99 1.6 billion
111
Peru
Cholera 91 770 million
112
UK
BSE 90-98 39 billion
113
Asia
SARS 2003 30 billion
114
Tanzania
Cholera 98 36 million
115
India
Plague 95 1.7 billion
116
Malaysia
Nipah 99 625 million
117
Stomach
Lactobacillus Candida Streptococcus H.pylori
118
Proximal Ileum
Streptococcus | Lactobacillus
119
Colon
Bacteroides
120
Clostridium groups
IV and XIV
121
What is predominant in the initial/acute phase of Eczema ?
TH2-biased immune response | IL4, IL12, TSLP and eosinophil
122
What is dominant in chronic phase of Eczema?
TH1/TH0 | IFN gamma, IL-12, IL-5, GM-CSF

Immunology (20 decks)

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