Adaptive Immunity 1 + 2 Flashcards
(96 cards)
1
Q
What does “humoral” mean
A
Anything produced by cells e.g. antibodies
2
Q
What 2 groups of responses does adaptive immunity consist of?
A
Cell-mediated responses and antibody (humoral) responses
3
Q
Which cells drive cell-mediated immunity the adaptive response?
A
T cells
4
Q
Which cells drive humoral immunity in the adaptive response?
A
B cells
5
Q
What does “immunological memory” refer to?
A
Each pathogen is “remembered” by a signature T cell and/or B cell receptor
6
Q
Describe the kinetics of adaptive immunity
A
Arises following innate immunity. Usually 4-7 days following infection.
7
Q
What are the stages in adaptive immunity?
A
- Infection
- Transport of antigen to lymphoid organs
- Recognition by naive B and T cells
- Clonal expansion and differentiation to effector cells
- Removal of infectious agent
8
Q
What are the 3 main receptors in adaptive immunity?
A
T cell receptor (TCR)
B cell receptor (immnunoglobulins - Ig)
Major histocompatibility complex (MHC proteins)
9
Q
What is the difference between innate and adaptive receptors?
A
Innate receptors e.g. TLRs do not have the potential to rearrange and change shape to recognise different antigens Adaptive receptors (TCR, Ig, MHC) can rearrange their structure depending on gene expression of each protein subunit
10
Q
Where do T cells originate?
A
Bone marrow
11
Q
Where do T cells mature?
A
Thymus
12
Q
What does the T cell repertoire refer to?
A
The diversity in T cell receptors - can respond to numerous antigens
13
Q
What is the purpose of ‘thymus eduction’?
A
Ensures T cells only respond to foreign pathogens and not ‘self peptides’
14
Q
What is the role of T helper cells (CD4+)?
A
Help support other immune cells fight threats
15
Q
What is the role of cytotoxic T cells (CD8+)?
A
Destroy our own cells which have become infected (usually virus-related)
16
Q
What is the role of regulatory T cells (Tregs)?
A
Regulate or suppress other cells in the immune system
Balance homeostasis between pro and anti inflammatory responses
17
Q
What is the role of the CD8 receptor (in CD8+ T cells)?
A
CD8 is a co-receptor that binds to MHC I
18
Q
What is the role of the CD4 receptor (in CD4+ T cells)?
A
CD4 is a co-receptor that binds to MHC II
19
Q
What is the role of the CD3 receptor?
A
CD3 is a co-receptor involved in activation of both CD4+ and CD8+ T cells
20
Q
What are the 2 classes of T cell receptor?
A
Alpha and beta chains (CD4+, CD8+)
A small proportion express gamma and delta chains instead (CD4-, CD8-)
21
Q
What is VDJ recombination?
A
Multiple genes code for each of the 2 chains of T Cell receptors (alpha chain and beta chain)
22
Q
What are the 2 regions in the chains of the T cell receptor?
A
Constant region - does not change in structure
Variable region - protrudes from the membrane, helps receptor bind to antigen
23
Q
What are the 3 gene segments that encode the variable regions in the chains of T cell receptors?
A
V (variable) - both alpha and beta chains
D (diversity) - beta chain only
J (joining) - both alpha and beta chains
24
Q
What is the name of the process that results in gene re-arrangement, and which enzymes drive the process?
A
Somatic recombination
RAG (recombinase) enzymes
25
What does somatic recombination lead to in T cell receptors?
Different receptor structures that can recognise different antigens i.e. different antigen binding sites
26
How many different combinations of receptors are possible in T cell receptor VDJ recombination?
100 billion
27
What happens during thymic education?
Pre-thymic T cells enter the thymus
T cells interact with cortical epithelial cells in the thymus
There are 2 types of selection: positive selection and negative selection
Positive selection - no recognition = apoptosis
Negative selection - recognition of self-antigen = apoptosis
28
Describe the process of T cell emigration
Positively and negatively selected CD4/CD8+ T cells with rearranged T cell receptors leave the thymus and circulate in the blood/lymphatics
Some reside in lymph nodes
These T cells are educated but still 'naive' until they interact with AP cells
29
Describe T cell activation by dendritic cells
Immature dendritic cells take up an process antigen in the epidermis
Once DCs have taken up antigen, they migrate to lymph nodes and mature en route
Mature DCs have co-stimulatory activity and can prime naive T cells
30
Describe the process of 'priming' naive T cells
3 signals are required for activation and determining the fate of T cells:
1. MHC-TCR interaction
2. Co-stimulatory molecules interaction (CD80/CD86 and CD40 on DC; CD40L and CD28 on T cell)
3. Cytokines - this signal dictates what T helper cell the naive T cell will become
31
What are the 3 signals required for activation and determining the fate of T cells?
1. MHC-TCR interaction: activation of T cells
2. Co-stimulatory molecules interaction (CD80/CD86 and CD40 on DC; CD40L and CD28 on T cell): survival and clonal expansion of T cells
3. Cytokines: differentiation into subsets of effector T cells
32
What does the 3rd signal during priming result in in CD8+ T cells?
Effector function e.g. production of enzymes for degradation
33
In priming, signal one without signal 2 is known as what?
Anergy
34
What are the subsets of CD4+ helper T cells?
TH1 = macrophage
TH2 = allergic repsonses/plasma cell generation
TH17= epithelium and underlying tissue cell types
TFH = important for B cell antibody generation
Treg cells = control/dampen the immune response
35
Interferon-gamma is produced by TH1 cells. What is the purpose of interferon-gamma?
Instructs immune cells such as macrophages and cytotoxic T cells to destroy infected cells
36
What is the role of TH2 cells?
Support humoral responses and allergic reactions. Source of interleukin 4,5 and 6 (IL-4, IL-5 and IL-6), which instruct B cells to produce antibodies
37
What is the role of TH17 cells?
Supporting innate immune responses
Enhances clearance of extracellular bacteria and fungi
Produces IL-17 and IL-22
38
What is the role of TFH cells?
T follicular helper cells are found in secondary lymphoid organs
Work with B cells for antibody production
39
What is the role of TH1 cells?
Main role in supporting macrophage function
| Source of interferon-gamma
40
What is the purpose of Treg cells?
Function in immune suppression
Release inhibitory cytokines (IL-10)
Inhibit T cell activation and DC activation
41
What is the role of CD8+ cells?
Activation arises from interaction between MHCI and TCR
Induce host cells to undergo apoptosis
Produces enzymes such as granzyme and perforin
Perforin targets apoptotic signalling pathways
42
What do perforins and granzymes do? (produced by CD8 cells)
Perforin form pores in the plasma membrane
| Granzymes enter the cell and break down proteins, lysing the cell
43
Where do B cells mature?
In the bone marrow
44
Where are B cells found in large numbers
B cells circulate in the blood and the lymph and are found in large numbers in the lymphoid organs
45
How do B cells recognise antigens?
Through the B cell receptor (BCR), which is the actual antibody (IgM or IgD)
46
What does diversity in the BCR enable B cells to do?
Diversity in the BCR = potential to respond to numerous antigens
47
What do B cells change into once activated?
Plasma cells - "antibody factories"
48
What are the 5 types of immunoglobulins produced by B cells?
IgG, IgE, IgD, IgM, IgA
| IgM and IgD are BCRs
49
Which class of antibody is the first to be secreted after an antigen is encountered?
IgM
50
Which class of antibody is found primarily in glandular secretions such as mucus, tears, saliva and semen?
IgA
51
Which is the most prominent antibody in the human body?
IgG
52
Which class of antibody is capable of binding multiple antigens?
IgM
53
Describe the structure of the B cell receptor (BCR)
Variable and constant regions
| Made up of light and heavy chains
54
What are the 3 main functions for antibodies in the human body?
1. Neutralisation
2. Opsonisation
3. Initiation of complement
55
What is the primary goal of antibodies in the human body?
Primary goal is to prevent microbial activity and aid removal of threat from host
56
What is 'neutralisation'?
Coats the outside of the pathogen, prevents it from having an effect in human body
57
What is 'opsonisation'?
Coating the pathogen to induce phagocytosis
Antibody dependent cellular cytotoxicity arises from opsonisation
Mast cell degranulation (allergy)
58
What does ADCC stand for?
Antibody-dependent cellular cytotoxicity
59
Which complement pathway is initiated via antibodies?
Classical pathway
60
Where do B cells originate?
In the bone marrow
| Also mature in the bone marrow
61
What are the developmental stages of B cells defined by?
Rearrangements of the immunoglobulin heavy and light chains
62
Describe the process of VDJ recombination in generating BCR diversity
Heavy chain involves rearrangements of V, D and J genes (similar to beta chain in TCR)
Light chain involves rearrangements of V and J genes (similar to alpha chain in TCR)
63
What is the main receptor expressed on immature B cells?
IgM
64
Which receptors are expressed on the surface of mature B cells?
IgM and IgD
65
Which process ensures that there is no reactivity against self antigens in B cells, and how does this differ from T cells?
B cells undergo negative selection in the bone marrow
Macrophages engulf and remove self-reacting B cells
T cells undergo negative AND positive selection
66
Where does B cell activation occur?
Predominantly in the lymph nodes, but some naive B cells can be activated in the periphery
67
What are the two types of B cell activation?
1. Thymus dependent activation: antigens which require T cell help
2. Thymus independent activation: antigens which do not require T cell help
68
What does activation of B cells result in?
Generation of plasma cells
69
What are plasma cells known as?
Antibody factories
70
Describe thymus dependent activation
Antigens require T cell help
Co-receptor binding involves (CD40 on B cell to CD40L on T cell)
Cytokine signals released from T helper cell to induce proliferation
Generates pool of plasma cells
Generates memory B cells
Plasma cells initially produce IgM before undergoing class switching
71
Describe thymus independent activation
Antigens do not require T cell help
Certain antigens e.g. bacterial LPS can activate B cells directly
Response is weaker than thymus dependent activation
Does not lead to generation of memory B cells - no long term immunity
72
Describe the process of 'class switching' in B cells
```
Activation leads to class switching
IgM response = first response
IgM response is weak; cells class switch to IgG (or IgA or IgE)
Occurs by gene rearrangement BUT antigen binding site remains the same
Repeated exposure to antigen causes affinity maturation
```
73
What does 'affinity maturation' mean?
The antibody has increasing affinity for antigen (stronger response)
74
Define 'affinity' in B cells
Strength of binding of single antibody to antigen
75
Define 'avidity' in B cells
Ability of antibodies to form complexes
76
Which antibodies have a high affinity but low avidity for their antigen targets?
IgG, IgA and IgE
77
Which antibody has a high avidity but low affinity for their antigen targets?
IgM
78
Which antibody is decavalent?
IgM -> high avidity for antigen targets
79
Which antibody is involved in allergy?
IgE
80
Which antibody has the highest opsonisation and neutralisation activities?
IgG
81
Describe 'cross talk' between B and T cells
In lymphoid organs, cross talk between B and T cells leads to generation of both 'arms' of the immune response:
- Humoral immunity
- Cellular immunity
82
What is somatic hypermutation?
The response of an immune cell to external stimuli from an antigen e.g. class switching in B cells
83
Which cells are important in the process of vaccinations against a specific antigen?
B cells and T cells
84
Which classes of B cells are important in generating an immune response?
In the primary immune response, IgM acts early
B cells undergo class switching
IgG response follows
85
What do memory T and B cells enable in the immune response?
Enable a faster immune response upon subsequent exposure to the antigen
86
Describe the basic principle of vaccination
Antigen exposure leads to immunological memory
IgM acts early in the primary immune response. B cells undergo class switching and IgG response follows
The presence of memory B and T cells means that upon subsequent exposure, the immune system can respond much faster
Presence of cells that are primed to produce a more effective (IgG rather than IgM) response immediately
Secondary much more rapid and specific due to presence of memory cells
87
What is immunological tolerance?
A state of immune unresponsiveness to a particular antigen
2 main types:
1) Central tolerance - in the primary lymphoid organs (thymus and bone marrow)
2) Peripheral tolerance - occurs outwit the primary lymphoid organs
88
Describe the basis for central tolerance in T cells
Tolerance occurs due to selection
Occurs in the thymus
2 types of selection for T cells: negative and positive selection
This process leads to elimination of >90% of T cells
89
Describe the basis for central tolerance in B cells
Tolerance occurs due to selection
Negative selection occurs in B cells - B cells that bind strongly to self antigen are eliminated
For B cells, occurs in the bone marrow
90
What can happen if tolerance mechanisms are dysfunctional?
Autoimmunity
| Allergies
91
Describe peripheral tolerance in T cells
Not all self reactive T cells are eliminated
Peripheral tolerance prevents activation of self-reactive T cells
Signal 1 but no signal 2 = anergy
Signal 1 and 2 but no signal 3 = deletion by apoptosis
Treg cells can also directly block activity by binding antigen
92
Describe peripheral tolerance in T cells
Occurs in secondary lymphoid organs
Self reactive B cells require help from self reactive T cells
Since most self-reactive T cells are eliminated, self-reactive B cells do not receive T cell help and therefore become anergic
93
What does 'breach of tolerance' mean?
Self reactive T cells and B cells are not eliminated through selection mechanisms, and are activated. These cells produce an immune response against self antigens or commensal organisms
Breach of tolerance drives many autoimmune diseases
94
What does immunological tolerance ensure?
That the immune system does not attack self antigens
95
What is the purpose of central and peripheral tolerance checkpoints?
Prevent autoimmunity
96
What does breach of tolerance lead to?
Reactivity against self antigens
