The Immune Response Flashcards
(79 cards)
1
Q
What are four principles of the immune response?
A
- Immunological recognition
- Immune effector functions
- Immune regulation
- Immunological memory
2
Q
How can an immune response be considered effective?
A
- Response not harm host
- Response present as soon as exposure occurs (birth)
- Rapid response
- Appropriate response for that pathogen
3
Q
What soluble proteins and cells are characteristic of innate immunity?
A
• Complement, cytokine, phagocytes, NK cells
4
Q
Adaptive immunity?
A
• Antibodies, cytokines, lymphocytes
5
Q
What cells can originate from a lymphoid progenitor?
A
- B cells from bone marrow (Memory, Plasma)
- T cells from thymus (CD4, CD8)
- Dendritic Cells
6
Q
What cells can originate from a myeloid progenitor?
A
- Dendritic cells
- Cells with granules
- Macrophages
7
Q
What are some pattern recognition receptors?
A
- TLR
- NOD (nucleotide binding oligomerisation domain)
- RIG-I (retinoic acid inducible gene)
- Collectins
8
Q
What are PAMPs and DAMPs?
A
- PAMPs (pathogen associated molecular patterns)
* DAMPs (danger associated molecular patterns)
9
Q
What is a constitutive soluble factor? What molecules fall in this category?
A
- Present in absence of PAMPs
- Lysozyme
- C-reactive protein
- Mannose Binding Lectin
- Complement Proteins
10
Q
What is a induced soluble factor? What molecules fall in this category?
A
• After PAMP interaction • Cytokines o Affects behaviour of nearby cells • Chemokines o Attracts cells with right receptors o Two receptor groups : CC, CXC (c for cysteine)
11
Q
What are the complement pathways?
A
- Classical pathway (antibody binding)
- Lectin Pathway (mannan binding)
- Alternative Pathway (pathogen surfaces)
12
Q
What does a complement pathway lead to?
A
• All lead to cleavage of C3 protein and more protein production
13
Q
What is the role of the variable region?
A
• Variable region binds to specific antigen
14
Q
What is the role of the constant region?
A
• Constant region can help with activated lymphocytes
15
Q
What is another name for a BCR?
A
• Antibody
16
Q
How do TCRs and BCRs differ?
A
- BCR can interact with antigens/molecules alone
* TCR interacts with peptides presented on MHC
17
Q
How does lymph flow?
A
• extracellular → afferent lymphatic vessel → lymph node → efferent lymphatic vessel → thoracic duct→ venous system (heart) , possibly back to tissue
18
Q
How do B cells and T cells circulate through lymph nodes?
A
- T and B cells circulate through lymph nodes by an artery and vein for entry and exit (Hilum)
- Naïve B or T cells in blood → high endothelial vessels (HEV) → Paracortex and Cortex
19
Q
How are MHC I and MHC II markers different?
A
MHC I Display peptides for CD8 T cells (toxic) Display cytosolic peptides MHC II Display peptides for CD4 T cells (helper) Display endosomal peptides
20
Q
What signals are required for T cell activation?
A
- TCR and MHC binding with antigen
- Co-stimulatory protein ligation
- Cell adhesion proteins and specific cytokine induction
21
Q
What does the third signal facilitate?
A
• TH cell differentiation
22
Q
Which cytokines produce which TH cells? Which TH cells produce which cytokines and what is the result of this?
A
TGFβ (no pathogen, display self-antigens)
T reg
TGFβ, IL-10
Regulation anti-self reponses
IL-6, TGFβ (early in infection)
TH17
IL-6, IL-17
Recruit neutrophils
IL-12 (as infection persists)
TH1
IFNγ, TNF
Activate macrophage, antibodies (IgG), inflammation
IL-4, IL-33
TH2
IL-4, IL-5
Mast cell, eosinophil activation, antibodies (IgE), parasite immunity, allergy
IL-6
TFH
IL-21
Help B cells activate and proliferate
23
Q
Where do activated T cells go?
A
• Leave lymph node and go to site of infection
24
Q
Where do activated B cells go?
A
• Migrate to medulla or germinal centres
25
What can antibody production lead to and which antibodies are involved in the responses?
* Activate complement (IgM, IgG)
* Opsonisation (IgG)
* Block adherence (IgA)
* Toxin neutralisation (IgA, IgG, IgM)
26
What are the main outcomes of immune activation?
* Suppress excessive responses
| * Removal of the infectious agent
27
What are the main differences between innate and adaptive immunity?
Innate Immunity
Recognise shared molecular patterns (danger)
Rapid response
No memory
Antimicrobial chemicals, epithelial cells, phagocytes, NK cells, complement, cytokines
```
Adaptive Immunity
Recognise antigens
Slower response
Memory
Lymphocytes, lymphoid tissue, antibodies, cytokines
```
28
How can the innate immune response be manipulated?
* Use PAMPs, agonists to stimulate PRRS or block PRR action
* Use cytokines to boost induction, shape or suppress immune response
* Interfere with cell trafficking
29
Which receptors on the innate immune system are expressed on the endosomal membrane? What molecules do they recognise?
* TLR3 (dsRNA)
* TLR7 (ssRNA)
* TLR9 (cpGDNA)
30
Which receptors on the innate immune system are expressed on the cell membrane? What molecules do they recognise?
* TLR1, TLR6, TLR2 (peptidoglycan)
* TLR5 (flagellin)
* TLR4 (LPS, HSP)
* Dectin-1 (β-glucan)
* MR (mannose)
31
What kind of cytokines can be produced from activated macrophages? What do they do?
```
• Inflammatory cytokines
o Cause fever
o IL-1 activates vascular endothelium
o TNF instigates cell migration
o IL-6 produces proteins
• Antiviral cytokines
o IFNα
• Stimulatory cytokines
o IL-12 for T cells and NK cells
• Suppressive cytokines
o IL-10
o TGFβ for regulatory cells
```
32
What can direct administration of PRR agonists do?
* Trigger local antiviral cytokine production
| * Boost the immune response
33
What do adjuvants do?
• Boost the immune response using potent and appropriate cytokines and T cell differentiation pathways
34
How can immune responses be suppressed by manipulating innate immunity?
* Blocking over the top immune responses
| * Deviating the immune response (e.g. counter excess TH2 cytokines to cope with allergies)
35
What is septic shock?
• Not a localised infection, LPS in blood
What does LBP do?
• LPS binding protein which binds to LPS and can activate T cells leading to coagulation cascade and production of fibrin
36
How can the septic shock response be prevented?
• By blocking TLR4 and LPS interactions
37
How can innate response cytokines be manipulated to shape the immune response?
* Boost antigen presenting cell activity (promote Th1 response for intracellular pathogens)
* Boost antiviral response (administer interferons)
* Antibodies against inflammatory cytokines (control inflammation)
38
How can the adaptive immune response be manipulated?
* Passive immunisation
* Active immunisation
* Immunotherapy
39
How do passive and active immunisation differ?
* Passive delivers antibodies and doesn’t actually stimulate the system (short lived)
* Active delivers antigens which stimulates a response and is longer lived
40
What are sources of passive antibodies?
• Animals, blood bank serum, recombinant human antibodies
41
What are the pros and cons of active immunity?
```
• Pros
o Long lived
o Humoral and cellular antibodies
o Can target specific tissue
o Induces WT immune response
• Cons
o Takes time to induce
o Results vary depending on age
```
42
What characteristics should vaccines have?
* Safe
* Offer protection
* Cost effective
* Stable
* Easy to administer (e.g. logistics)
* Few side effects
* Aim for herd immunity
43
What needs to be understood to use the active immune response to our advantage?
* How does pathogen cause disease, what is effect of blocking the virulence factors?
* Where should the response be directed?
* What kind of immune response is needed?
44
How can virulence factors be blocked?
• Block adhesisns or receptor binding molecules to stop infection
• Block evasion mechanisms (e.g. prevent capsule formation)
• Neutralise toxins
What determines the outcome of inducing a successful immune response?
• Antigen
45
What can vaccines be made of?
* Live attenuated (loose pathogenicity, not immunogenicity)
* Subunits of purified pathogen
* Killed microorganisms
* VLPs
46
How do live attenuated and killed viruses differ?
```
Live Attenuated
Oral, parenteral
Long lived
Replicate (determines site and quantity. E.g. deliver salmonella vaccine orally)
Labile/sensitive
Reversion to virulence
Multiple antigens present (beneficial)
```
```
Killed or extracted antigen
Parenteral
Shorter (boosters)
No replication (repeated high doses needed)
Stable
A-virulent
Restricted number of antigens
```
47
What should vaccines do to antibodies?
* Mimic or improve their features
* Provide class/isotype switching
* Provide high affinity antibodies
* Induce memory B cells
48
Which antibodies are produced without T cell help?
• IgM
49
What can’t be achieved through BCR and antigen binding alone?
* Wont stimulate B cell proliferation, correct isotype production
* Only IgM made
* Won’t stimulate memory cell production
50
What is needed apart from B cell activation for a vaccine to work? How does it work? What requirements are there?
* T cell activation
* All the 3 signals required
* Induces CD40 (co-stimulatory protein) and cytokine production
* 1. Activated T cells move to B cell area of lymphoid tissue
* 2. Interact with B cells
* 3. CD40L and cytokine interaction induces isotype switching, high affinity antibodies and memory cells
* Vaccine needs epitopes which are also recognised by T cell
51
What epitopes must a vaccine contain?
• Ones also recognised by T cells
52
What do CD4+ T cells do?
* Help B cells (Ab production)
* Make IFNy
* Expand effector CD8+ T cells
* Make signals to promote CD8+ memory
53
What do CD8+ T cells do?
• Lyse infected cells
54
What role can adjuvants have when it comes to vaccine induced CD4 T cells?
• Can mimic PAMPs and up regulate co-stimulatory molecules
55
Where must vaccine induced CD4 T cells go? Why? What does signal 2 require?
* Antigens from vaccine need to access endosomes in antigen presenting cells (APCs) for MHC II presentation
* Signal 2 requires co-stimulatory molecules CD80 and CD86 which are induced by PAMPs/PRRs interactions on APCs
56
Can TH cells swap classes? What does this imply about signal 3?
• No
• Signal 3 very important in influencing differentiation
Where must vaccine induced CD8 T cells go? Why?
• Needs to access cytosol of APC for presentation by MHC I (signal 1)
57
What kind of vaccine works best for vaccine induced CD8 T cells? Why?
• Easier for live attenuated because have natural ability to invade cells
58
How can antigens in a vaccine be delivered to access MHC I markers if non-living?
* Direct delivery to cytosol
* Cross presentation pathway
* 1. Clone antigen to a-virulent viral vector
* 2. Trap in a lipid immune stimulatory complex
* 3. Use VLP
59
What does CD8 activation lead to?
• CD8 should stimulate proliferation, activation and cytotoxic granules
60
What is the structure of the gut?
* Small intestine 3-4 metres human
* Many folds with many villi
* Villi have intestinal epithelial cells (enterocytes) with microvilli (Huge surface area)
* Lots of protein interaction which can stimulate immune system (70-100g a day)
* Peyers Patches
61
What and where are enterocytes?
• Intestinal epithelial cells that line the villi and secrete immune-modulatory cytokines, chemokines and defensins
62
What are Peyers Patches? What happens at them?
• Lymphoid tissue where T and B cell activation is induced
63
What make up villi?
* Enterocytes
* Crypts at base
* Paneth cells
* Goblet Cells
* Laminar propria lymphocytes
* Intraepithelial lymphocyte
64
What do enterocytes secrete?
• Secrete immune-modulatory compounds (cytokines, chemokine, defensins)
65
What are lamina propria lymphocytes?
• Effecter cells
66
What do goblet cells secrete?
• Secrete mucins, lysozymes, lactoferrin (bacteria protection)
67
What are intraepithelial lymphocytes?
• Non-conventional lymphocytes
68
What is the surface area of the small intestine?
• 250 square metres
69
What are the consequences of the structure of the gut?
* Area for breakdown, absorption of water and nutrients
* Vulnerability to adhesion, entry of microbes (need good immune response)
* Innocuous pathogens from food, commensal organism may stimulate inappropriate response (need tolerance to avoid continuous immune activation)
70
What causes continuous immune activation?
• A lack of tolerance, the immune system responds inappropriately to innocuous pathogens
What must the mucosal immune system do?
• Discriminate between harmful and innocuous pathogens
• Eliminate pathogens and remain tolerant towards harmless antigens
71
What are the innate defences of the gut?
* Peristalsis
* Acid
* Mucous layer and glycocalyx (molecular sieve)
* Tight epithelial junctions
* Antimicrobial factors (bile, defensins, lactoferrin, complement etc.)
* Cytokines, chemokines
* Innate immune system cells
72
How does lymphoid tissue differ between the systemic immune system and mucosal immune system?
• In systemic,
o Lymph nodes and spleen are capsulated and antigens only enter and exit via lymphatics
• In mucosal,
o Lymphocytes scattered and organisation varies
o Antigen accessed directly from mucosal tissue
o Down regulation of immune response predominates
o Most lymphocytes and lymphoid tissue in MALT
73
How does antigen access differ for antigens at mucosal surfaces and antigens in blood/tissue?
• Mucosal antigens can be sampled directly from the mucosal lumen (e.g. gut)
74
Where do lymphoid cells in GALT drain?
• To the mesenteric lymph node
75
Where are B cells located in GALT?
• In the follicle associated epithelium
76
Where do lymphocytes from the blood enter GALT?
• Through high endothelial venules
77
What characterises M cells?
* Differentiate from enterocytes
* No microvilli
* No glycocalyx, no mucus secretion
* Controlled antigen uptake (endocytosis)
* Located right over sites of organised lymphoid
* Transport antigen lumen to sub epithelial space
* Don’t express MHC II (sample but can’t activate CD4 T cells)
* Has MHC I
78
Which T cells can interact with M cells?
• CD8 (MH1)
79
In what two ways can antigens access GALT?
* Through M cells and Peyer’s patches
| * Through dendritic cells
