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MBChB Year 3 > Week 0 - Immune Intro > Flashcards

Week 0 - Immune Intro Flashcards

1
Q

What are the 2 soluble factors in the innate immunity?

A
  1. Antibacterial factors

2. Complement system

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2
Q

What is the cellular factor of the innate immunity?

A

Scavenger Phagocytes

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3
Q

What is a lysozyme?

A

Enzyme present at mucosal surfaces that breaks down the gram positive cell wall

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4
Q

What does lactoferrin do (protein found at mucosal surfaces)?

A
  • Chelates iron & reduces soluble iron in the GI/respiratory tract
  • Inhibits growth of bacteria
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5
Q

What are the 3 pathways in the complement system of innate immunity?

A
  1. Classical Pathway
  2. MB-Lectin Pathway
  3. Alternative Pathway
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6
Q

Describe the classical pathway of the complement system?

A

Antigen : Antibody complexes

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7
Q

Describe the MB-Lectin Pathway of the complement system?

A

Lectin binding to pathogen surfaces

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8
Q

Describe the Alternative pathway of the complement system?

A

Activated through pathogen surfaces

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9
Q

What 3 things does complement activation do?

A
  1. Recruit inflammatory cells
  2. Opsonization of pathogens
  3. Killing of pathogens
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10
Q

What does MB-Lectin stand for?

A

Mannose-binding lectin

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11
Q

What are the 2 key roles of macrophages?

A
  1. Clearance of micro-organisms

2. Summon help (releasing cytokines)

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12
Q

What is the difference between monocytes and macrophages?

A
  • Monocyte= blood

- Macrophages= tissue

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13
Q

Describe phagocytosis?

A
  • Specialises in destruction of pathogens

- Removes harmless debris

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14
Q

Describe antigen presentation?

A

Processes engulfed particles, travels to draining lymph nodes & presents to T cells in MHC II

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15
Q

What 3 things are pattern recognition receptors able to do?

A
  1. Recognise molecules found in micro-organisms
  2. Recognise extracellular & intracellular threats
  3. Respond to bacteria, fungi and yeasts
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16
Q

Why is the immune system not enough at times?

A
  1. Highly pathogenic bacteria

2. Structural failure

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17
Q

What % of neutrophils are in white blood cells?

A

50-70%

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18
Q

Neutrophils provide a _____ response to infection?

A

Rapid

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19
Q

What are the 4 factors of neutrophils?

A
  1. Chemotaxis
  2. Phagocytic
  3. Degranulation
  4. Die locally
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20
Q

Describe neutrophil chemotaxis?

A

Migrate towards bacterial products (LPS), chemokines & “danger signals” (complement components)

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21
Q

Describe neutrophil phagocytosis?

A

Ingest & destroy pathogens using proteases, reactive oxygen species, lysozyme etc.

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22
Q

Describe neutrophil degranulation?

A

Release toxic granules extracellularly

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23
Q

Describe how neutrophils die locally?

A

By producing characteristic pus

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24
Q

Eosinophils have a pathological role in _____?

A

Allergy

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25
What are the 3 factors of eosinophils?
1. Chemotaxis 2. Degranulation 3. Cytokine production
26
Describe eosinophil degranulation?
Release toxic substances onto surface of parasites e.g. Major Basic Protein, Eosinophil Cationic Protein, Eosinophil Peroxidase
27
What does eosinophils classically respond to?
Parasites
28
What is the difference between basophils and mast cells?
- Basophils= blood | - Mast cells= tissues
29
What are basophils/mast cells important in?
Allergy
30
What are the 2 factors of Basophils/Mast cells?
1. Degranulation | 2. Cytokine release
31
Describe Basophil/Mast cell degranulation?
Rapid release pre-formed granules containing cytokines & mediators
32
What is the typical reaction caused by basophils/mast cell degranulation?
Histamine Wheal & Flare reaction
33
What are the 3 factors of dendritic cells?
1. Phagocytosis 2. Migration 3. Antigen presentation
34
Describe dendritic cell phagocytosis?
- Not specialised in destruction of pathogens | - Functions mainly as antigen presenting cells
35
Describe dendritic cell migration?
- In tissues constantly sampling environment | - When activated will travel to draining lymph nodes
36
Describe dendritic cell antigen presentation?
Presents to CD4 T cells & can initiate an adaptive immune response
37
What are the 2 types of adaptive immunity?
1. Humoral | 2. Cellular
38
What is the humoral adaptive immunity mediated by?
B cells
39
What does the B cells do in humoral adaptive immunity?
Release antibodies (immunoglobulins) which targets extracellular pathogens ie. bacteria
40
What 2 things mediate the cellular adaptive immunity?
1. CD4 T cells | 2. CD8 T cells
41
What do the CD4 T cells in the cellular adaptive immunity do?
- Directs B cells & CD8 T cells | - Cytokine secretion
42
What are CD4 T cells also known as?
"Helper" T cells
43
What are DC8 T cells also known as?
"Killer" or "Cytotoxic" T cells
44
Describe the 2 regions on an antibody?
- Fab region: antigen binding | - Fc region: binds to Fc receptors on phagocytes & activates complement
45
What are the 3 functions of antibodies?
1. Opsonise for phagocytosis 2. Activate complement for lysis 3. Neutralise toxins & pathogen binding sites
46
Describe IgM?
- Main antibody of primary immune response - Low affinity - Activates Complement
47
Describe IgG?
- Main antibody of secondary immune response - Higher affinity as part of secondary response - Activates Complement, binds Fcg receptor on phagocytes (opsonsises) - Crosses placenta
48
Describe IgA?
- Present in secretions & lines epithelial surfaces | - Neutralises by blocking binding of pathogens
49
Describe IgE?
- High affinity binding to Mast cells through Fc receptor | - Role in allergy
50
The antibody isotopes differ in ______?
Fc regions
51
Describe the primary B cell response?
- 5-10 days - Smaller peak - IgM>IgG
52
Describe the secondary B cell response?
- 1-3 days - Larger peak - Increase in IgG & sometimes IgA / IgE
53
List the 5 things that T cells can encourage in the immune system response?
1. Clonal expansion of specific B cells 2. Progression to antibody secreting cells (plasma cells) 3. Progression to memory B cells 4. Isotype switching to IgG, IgA & IgE 5. Affinity Maturation
54
Where are B cells developed?
Bone marrow
55
How do B cells die?
If B cell receptor binds strongly to “self” antigen in bone marrow it dies by apoptosis
56
Where are T cells developed?
Bone marrow and migrate to thymus
57
How do T cells die?
If T cell receptor binds strongly to “self” antigen in thymus it dies by apoptosis
58
T cells only see antigen in context of ____?
MHC
59
Describe Class I MHC?
- Presents to CD8 T Cells - Found on all nucleated cells - Presents intra-cellular antigen
60
Describe Class II MHC?
- Presents to CD4 T Cells - Presents extra-cellular derived antigen (phagocytosed) - Found on Antigen Presenting Cells
61
List 3 antigen presenting cells?
1. Dendritic cells 2. Macrophages 3. B cells
62
What are the 2 primary organs of the adaptive immune system?
1. Thymus | 2. Bone marrow
63
What are the 3 secondary organs of the adaptive immune system?
1. Lymph nodes 2. Spleen 3. Mucosal Associated Lymphoid Tissue of GI Tract (MALT) & Bronchial Tract (BALT)
64
What is the function of the spleen?
Filters blood of senescent cells & | blood borne pathogens
65
List the 4 functions of the adaptive immune system?
1. Provides specific antibodies to innate immune system, enhancing pathogen clearance 2. Provides cytokines to innate immune system to upregulate activity 3. Finishes off clearing pathogens 4. Develops memory to prevent future infection
66
List the 5 immune cells in the secondary immune response?
1. Memory B cells 2. Memory T cells 3. Memory lymphocytes 4. Preformed antigen specific IgA 5. Preformed high affinity IgG
67
Describe the role of memory lymphocytes in the secondary immune response?
Have lower threshold for activation & actively patrol sites of previous pathogen entry
68
What happens to B cells in an immune response?
Enters lymphoid follicle to form germinal centre & undergo affinity maturation
69
What is the classification framework called for the adaptive immune system?
Coombes and Gell Classification
70
Describe type I hypersensitivity response?
- Immediate, atopic - IgE mediated bound to mast cells - Increase in severity with repeated challenge
71
Describe type II hypersensitivity response?
- Cytotoxic, antibody dependent - IgM or IgG bound to cell/matrix antigen - Uncommon cause of allergy
72
Describe type III hypersensitivity response?
- Immune complex - IgM or IgG bound to soluble antigen - Aggregate in small blood vessels
73
Describe type IV hypersensitivity response?
- Mediated by action of lymphocytes infiltrating area | - T cells (CD4+ & CD8+)
74
What is type I hypersensitivity responsible for?
Most allergies
75
List the 6 stages of type I hypersensitivity/ an allergic response?
1. Sensitisation 2. Mast cells primed with IgE 3. Re-exposure to antigen 4. Antigen binds to IgE associated with mast cells 5. Mast cells degranulate 6. Pro-imflammatory process stimulates and amplifies future responses
76
List 6 things that mast cells release when degranulating in an allergic response?
1. Toxins (i.e. histamine) 2. Tryptase 3. Pro-inflammatory cytokines 4. Chemokines 5. Prostaglandins 6. Leukotrienes
77
What 2 things does the early phase tissue effects in type I hypersensitivity result in?
1. Smooth muscle contraction | 2. Increased vascular permeability
78
What 2 things does the late phase tissue effects in type I hypersensitive result in?
1. Sustained smooth muscle contraction/ hypertrophy | 2. Tissue remodelling
79
What is anaphylaxis?
Severe, systemic type I hypersensitivity
80
Describe anaphylaxis?
- Widespread mast cell degranulation caused by systemic exposure to antigen - Vascular permeability is principle immediate danger: ie. Soft tissue swelling threatening airway, loss of circulatory volume causing shock
81
What is type II hypersensitivity a common cause of?
Autoimmune disease
82
List the 3 stages of type II hypersensitivity?
1. Sensitisation 2. Opsonisation of cells 3. Cytotoxicity: Complement activation, inflammation, tissue destruction
83
What can happen in some cases of type II hypersensitivity?
Direct biological activation with antigen (i.e. receptor activation, impaired enzyme action)
84
What 2 things is type III hypersensitivity a cause of?
1. Autoimmune disease | 2. Drug allergy
85
What 3 things can happen due to type III hypersensitivity aggregating in small blood vessels?
1. Direct occlusion 2. Complement activation 3. Perivascular inflammation
86
What is type IV hypersensitivity also known as?
Delayed type hypersensitivity
87
Give an example of type IV hypersensitivity?
Dermatitis
88
What is the exception for autoimmune disease?
Autoimmune diseases which fit into a single category of hypersensitivity
89
What is the definition of an autoimmune disease?
Harmful inflammatory response directed against ‘self’ tissue by the adaptive immune response
90
Describe type I diabetes?
Selective, autoimmune destruction of the pancreatic β-cells
91
What type of hypersensitive is type I diabetes?
Often mix of Type II & Type IV
92
What precedes symptoms of type I diabetes?
Inflammation of the Islets of Langerhans
93
Describe Myasthenia Gravis?
Syndrome of fatigable muscle weakness (limbs, respiratory, head & neck)
94
What is Myasthenia Gravis caused by?
IgG against acetylcholine receptor which therefore prevents signal transduction
95
List 5 examples of systemic autoimmune disease?
1. Rheumatoid arthritis 2. Systemic lupus erythematosus 3. Inflammatory bowel disease 4. Connective tissue disease 5. Systemic vasculitis
96
List the signs and symptoms of rheumatoid arthritis?
- Pulmonary nodules & fibrosis - Pericarditis & valvular inflammation - Small vessel vasculitis - Soft tissue nodules - Skin inflammation - Weight loss, anaemia
97
Describe the pathophysiology of rheumatoid factor?
- IgM & IgA directed against IgG Fc region | - Forms large immune complexes
98
Where are the large immune complexes in rheumatoid factor located?
- High conc in synovial fluid | - Also found in other tissues
99
Describe the pathophysiology of rheumatoid arthritis?
- Inflammation = release of PAD from inflammatory cells - Further chemoatraction of inflammatory cells into synovium - Osteoclast activation & joint destruction - Fibroblast activation & synovial hyperplasia
100
What is common in rheumatoid arthritis?
Anti-citrullinated protein/ peptide antibodies
101
What does PAD do?
Alters variety of proteins by converting alanine --> citrulline
102
What 3 inflammatory cells are sent into the synovium during rheumatoid arthritis?
1. Macrophages 2. Neutrophils 3. Lymphocytes
103
What are the 3 means of treatment for autoimmune diseases?
1. Steroids 2. Inhibitors of metabolism 3. Inhibitors of T-cell function
104
What are biologic therapies?
Therapeutic agents synthesised biologically rather than chemically
105
What is the nature of biologic agent Infliximab & what is its target?
- NATURE: monoclonal antibody | - TARGET: soluble cytokine
106
What is the nature of biologic agent Etanercept & what is its target?
- NATURE: soluble receptor | - TARGET: soluble cytokine
107
What is the nature of biologic agent Rituximab & what is its target?
- NATURE: monoclonal antibody | - TARGET: surface marker
108
List 3 examples of biologic therapies?
1. Infliximab 2. Etanercept 3. Rituximab
109
What are the 3 benefits of biologic therapies for treating rheumatoid arthritis?
1. Reduces joint swelling & pain 2. Decreases systemic inflammation 3. Delays & prevents appearance of erosions & bone deformity
110
What is the risk of biologic therapies for treating rheumatoid arthritis?
Increased risk of infection especially TB
111
What can biologic therapeutics turn off in the during the inflammatory reaction in rheumatoid arthritis?
TNF-alpha
112
List the 3 environmental factors which can lead to autoimmune diseases?
1. Infection 2. Geographical factors 3. Modifiable personal risk factors
113
Give 2 examples of how infection can be a factor for autoimmune disease?
1. Molecular mimicry | 2. Tissue damage exposing self-antigens
114
Give an example of a geographical factor which can lead to autoimmune disease?
Vit D deficiency
115
Give an example of a modifiable personal risk factor which could lead to autoimmune disease?
Smoking
116
What autoimmune disease is a deficiency in Vit D associated with?
Multiple Sclerosis
117
How is smoking associated with rheumatoid arthritis?
Smoking is associated with conversion of alanine to citrulline
118
What are the 2 different types of autoimmune diseases?
1. Organ specific | 2. Systemic

MBChB Year 3 (15 decks)

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