Adaptive Immunity Flashcards
1
Q
When does adaptive immunity come in to place
A
Infection overcomes innate defence mechanisms
so pathogen continues to replicate and antigen accumulates
2
Q
What cells activate the adaptive immune response?
A
Dendritic cells
3
Q
What does adaptive immunity involve?
A
Humoral response- antibodies
T and B lymphocytes
Slower
Specific to antigen
4
Q
What do T and B lymphocytes provide?
A
Immunological memory
5
Q
What are antigens?
A
Proteins/peptides on pathogen surface that are recognised by lymphocytes to initiate an immune response
6
Q
Name of primary lymphoid organs?
A
Thymus, Red bone marrow
7
Q
What occurs in primary lymphoid organs?
A
Sites of lymphocyte development and maturation from bone marrow derived stem cells
8
Q
Where are B and T lymphocytes made?
A
Bone marrow
9
Q
Where do B cells mature and develop?
A
Bone marrow
10
Q
Where do T cells mature and develop?
A
Thymus gland
11
Q
Examples of secondary lymphoid organs?
A
Lymph nodes
Spleen
MALT
12
Q
What occurs in secondary lymphoid organs?
A
Lymphocytes are activated
Immune response is coordinated
13
Q
What happens during development and maturation of B cells in bone marrow?
A
Express receptor- BCR (antibody) that binds to antigen
Plasma cells produce antibodies
14
Q
What happens during development and maturation of T cells in the thymus gland?
A
Express a T cell receptor(TCR)- binds to antigen on APC
15
Q
What are the 3 types of T effector cell?
A
Cytotoxic T cell
Helper T cell
Regulatory T cell
16
Q
What does the regulatory T cell do?
A
Suppresses the immune system
preventing autoimmune responses
17
Q
What does T helper cell do?
A
Activates other T cells and B plasma cells to produce antibodies
18
Q
What happens when BCR binds to antigen?
A
Phagocytosis of pathogen
Phagolysosome destroys pathogen
Antigens are loaded onto MHC II in phagolysosome
Antigens are presented onto surface
B cell APC MHC II
B cell becomes activated by T helper cell- costimulation (CD40), Cytokines (IL-4,IL-10,IFN-Gamma) Induce class switching
19
Q
What happens when TCR binds to antigen?
A
Proliferation causing:
Cytotoxicity (killing cells)
Helping other immune cells
Regulation (turning off immunity)
20
Q
Advantage of secondary immune response?
A
Triggers a quicker secondary response when same pathogen re-infects
Correct, specific antibodies produced in a shorter time before symptoms arrive
21
Q
Why are BCRs and TCRs different?
A
Each bind to a specific antigen
Therefore each cell responds to a certain pathogen
22
Q
How are different BCRs and TCRs made?
A
Chopped into segments
Stuck back together
23
Q
Structure of TCR
A
Heterodimeric 2 chains- alpha and beta held together by disulphide bonds C= Constant region J= Junctional - join things together V= Variable region D= Diversity- only found in Beta chain
24
Q
Name of process of creating new TCRs?
A
VDJ recombination (somatic recombination) Gene rearrangement
25
Alpha chain of TCR
54 V segments
61 J segments
1 C segment
26
Beta chain of TCR
67 V segments
2 D segments
14 J segments
2 C segments
27
Structure of BCR
```
Heterodimeric receptors
2 chains
Light and heavy chains
held by disulphide bonds
Variable region (top bit)
Constant region (bottom bit)
```
28
How are new BCRs made?
Nucleotides can be added/removed to make them more specific to antigen
Somatic recombination- done in bone marrow
29
What are the differences between BCRs and TCRs?
BCRs- bind directly to antigen even if they are still attached to pathogen
TCRs- binds to antigens present on surface of APCs
So TCRs must bind to APC e.g macrophages/dendritic cells
30
What are the 3 signals T cells need to be activated?
1. TCR binding to antigen presented by MHC on APC
2. Costimulation (B7 molecules)
3. Cytokines (IL-4/10/12/23)
31
2 main types of T cell
T helper cell
| Cytotoxic T cell
32
co-receptor of cytotoxic T cell?
CD8
33
What kind of APCs do cytotoxic T CD8 cells bind to?
MHC I
34
Function of cytotoxic T cell
Kills virally infected cells directly
35
co -receptor on T helper cell?
CD4
36
What kind of APCs do T helper CD4 cells bind to?
MHC II (professional)
37
Function of T helper cell
releases cytokines
| activates other T cells and B plasma cells to make antibodies
38
What are human leukocyte antigens (HLA)
Group of proteins that are encoded by the MHC gene
39
What HLAs do MHC class I code for?
A,B,C
40
What HLAs do MHC class II code for?
DP, DR, DQ
41
What are epitopes?
When large protein antigens are digested into small peptides
42
Where are epitopes bound to in a HLA encoded by a MHC gene?
Antigen binding groove- on MHC
43
Where are MHC class I found?
All nucleated cells
44
How many amino acids can antigen binding groove of MHC I hold?
8-10
45
Where are MHC II found?
On professional APCS
| e.g macrophages and dendritic cells
46
how many amino acids does antigen binding groove of MHC II hold?
at least 13
47
What are MHC genes like and why?
Highly polymorphic
To protect from population from infection
Have a broad specificity meaning they can bind to many types of antigens
48
Apart from HLAs that MHC genes code for what do other proteins do that the MHC gene codes for?
Processes antigen
49
What does the p arm (short arm) of MHC gene on chromosome 6 code for?
Many HLAs
50
How does an APC MHC I present antigens onto its surface?
1. Body cell is infected by virus
2. virus enters cell
3. Virus is degraded and broken down by proteosome
4. Antigens are retained and loaded onto MHC I in the endoplasmic reticulum
5. Antigens are on antigen binding groove of MHC I
6. Antigens are presented onto cell membrane
6. Activates CD8 cytotoxic T cells
51
How do cytotoxic cells kill cells expressing MHC I foreign antigen?
Release perforin- punctures holes in cell membrane
| Surface of cytotoxic T cell has fas ligand= induces apoptosis of infected cell when FADD binds to it
52
How does cytotoxic T cell kill cells? (4 steps)
1. Conjugate formation
2. Membrane attack
3. T cell detaches from target cell
4. Target cell killed by apoptosis
53
What is conjugate formation?
1. TCR binds to antigen on APC MHC I
2. Adhesion molecules such as LFA-1 on T cell
3. LFA-1 binds to ICAM on target cell
4. if antigen is recognised- LFA-1 binds tighter to ICAM on target cell
54
What is membrane attack by cytotoxic cells?
Granules in cytotoxic cells release perforin and granzymes
Perforins puncture holes in cell membrane of target cell
Granzymes enter target cell= DNA fragmentation and apoptosis
55
How does Fas-Fas ligand induce apoptosis?
```
Fas is found on T cells
Fas is found on target cell
Fas-Fas interaction= activates FADD
activates pro-caspase 8
induces pro caspase 3
caspase 3 activated
apoptosis
```
56
How is antigen presented in APC MHC II?
1. APC phagocytoses pathogen by phagocytosis
2. Pathogen chopped up by phagolysosomes
3. Antigens are loaded onto MHC II in the phagolysosome
4. Activates CD4 T helper cells
57
What 3 things do professional APCs do?
1. Express MHC II
2. costimulatory molecules
3. cytokines
58
How is expression of professional APCs increased?
Cytokines
| e.g IFN-Gamma
59
How does a professional APC become mature?
```
increased production
1. Costimulatory molecules
2. Cytokines
3. MHC II
in order to activate T cell when APC binds to it
```
60
Can dendritic cells also present antigens on MHC I?
yes- by cross presentation
61
Costimulation
B7 molecules on APC
activate CD28 on T cells
Enhances binding of APC and T cell
62
When APC releases cytokines when binding to T cell which cytokines can these be?
```
IL-2,IL-4 with IL-5,IL-10
OR
IL-6,IL-21
IL-2
IFN-gamma, IL-4, IL-17 or IL-10
```
63
What does it mean if different cytokines can be released from APC?
different T helper cell subtypes are made
64
IL-12 generates T helper subtype...
Th-1
65
IL-4 generates T helper subtype...
Th-2
66
IL-6/21 generates T helper subtype...
Th17
67
IL-23/6/TGF-Beta generates T helper subtype...
TfH
68
TGF-beta generates...
T-reg
69
Function of IL-12
Activates macrophages
70
Function of IL-4
Activate eosinophils, mast cells and macrophages
71
Function of IL-6/21
Enhances neutrophil response
72
Function of IL-23/6/TGF-Beta
Activates and matures B cells
73
Function of T-regulatory cells
Suppresses T effector cells
74
Activated T cell gives survival signal back to APC by?
CD40-CD40 ligand
75
How do T cells recirculate the blood?
```
Develop in thymus
enter the bloodstream
enter secondary lymphoid organs
enter lymphoid tissue
return to blood stream via lymphatics
```
76
What are naive T cells?
Mature recirculating T cells that haven't encountered their specific antigen on an APC
77
How can a naive T cell be activated in an immune response?
Meet it's specific antigen
Present on APC
T cell proliferates and differentiates into effector T cells (t helper and cytotoxic t cells)
These effect the host cell (not pathogen)
78
What happens when T cell recognises specific antigen on dendritic APC?
T cell migrates to lymphoid organs
T cell undergoes proliferation and differentiation
(effector T cells and memory cells)
79
What happens once T cell has recognised antigen and has differentiated?
T cell exits lymphatics via efferent lymphatic vessel into bloodstream
80
How is a T cell immune response induced?
Naive T cell meets dendritic APC in a secondary lymphoid organ which has antigens specific to the T cell
81
What must dendritic cells do once they have picked up the antigens?
Travel to lymphoid organs where it's T cells are found to activate these T cells
82
Free antigens
bacteria/viruses travel through lymphatics to lymphoid organs
They are taken up by APCs there
83
What regulates T cell entry into secondary lymphoid organs?
Chemokines
84
What happens once T cell has encountered antigen on dendritic APC?
T cell loses ability to exit lymph node
T cell is activated- proliferates and differentiates into T effector cells
After several days T effector cells gain rceeptors to allow them to exit LN
85
What does lymphocyte entry into secondary lymphoid organs depend on?
Chemokines and adhesion molecules
86
In secondary lymphoid organs what initiates T cell responses?
Activated dendritic cells
87
What picks up antigens in the bloodstream?
APCs in the spleen
88
Where must antignes be taken to?
Lymphoid tissue- LN/Spleen/MALT/tonsils
89
What happens to pathogens in skin wound?
Transported in lymph and trapped in lymph nodes
90
What happens to pathogens infecting mucosal surfaces?
Transported across mucosa into lymphoid tissue e/g peyer's patches in small intestine
91
Development of immature dendritic cell into a mature one
They express high levels of MHC II complexes
and co-stimulatory molecules
can release cytokines to activate CD4/CD8 T cells
92
How do immature dendritic cells become activated?
Via their TLRs (PPRs)
Tissue damage
cytokines produced in inflammatory response
93
What happens once dendritic cells are activated?
Migrate to Lymph node
| express co-stimulatory molecules needed to activate naive T cell
94
What do mature dendritic cells do in lymphoid tissue?
APCs- present specific antigen to naive T cell
| Activates other T cells to divide- reenter circulation
95
How are macrophages induced in lymphoid tissue?
Via their PPRs
They express co-stimulatory molecules
and act as APCs
96
Where in the lymph node are dendritic cells found?
Paracortex of lymph node
97
What are the strongest activators of naive T cells?
Mature dendritic cells
98
Where are macrophages found in the lymph node?
Distributed but mainly in marginal sinus where afferent lymph collects before going deeper into lymphoid tissue
and in medullary sinuses before passing into efferent lymphatics into the blood
In medullary cords too
99
Where are b cells mainly found in the lymph node?
Follicles
100
What induces immature dendritic cells to migrate to lymphoid organs and mature?
PRRs (TLR) signalling and chemokines
| enhances antigen processing
101
What are resting macrophages like?
Few/no MCH II molecules on their surface and dont express B7 N (co-stimulatory molecules)
102
How do macrophages become activated to show MHC II on surface and B7?
PPRs on surface
103
Macrophages don't initiate T cell immunity so what do they do?
They express co-stimulatory molecules to expand primary/secondary responses already initiated by dendritic cells
Maintain function of effector/memory T cells
104
What MHC class do B cells present on their surface?
MHC II
105
What does B cell do once it has represented antigen and become APC?
T helper stimulates B cell by binding to it Antigen binds to BCR
Signal created for gene expression= pathogen engulfed in by phagocytosis via vesicles= APC (MHC II)
Causes T helper CD4 to bind to B cell APC
Co-stimulation by T helper cell via CD40
Cytokines released by T helper cell= cause proliferation of B cell to produce B plasma cells
cytokines IL-4, IL-10, IFN-gamma= induce class switching= isotypes
106
How do B cells use their surface antiboides (BCRs) to present antigens on its surface
BCRs allow antigen to bind directly to it
B cell endocytoses antigen
Antigen in vesicles bind to MHC II molecules
Vesicles transported to cell surface where MHC II can be recognised by T cell
107
Summary of adaptive immunity
Naive T cell comes into contact with mature dendritic APC in secondary lymphoid organ= T cell is activated
T cells continuously recirculate through lymphoid organs and blood to ensure antigen through body can be targeted by T cells
T cell migrating to lymphoid tissue is guided by chemokines
Adhesion molecules= allow T cells to migrate into T cell zone of lymphoid organs to meet APC dendritic cell
108
How does dendritic cell activate adaptive immunity?
TNF-alpha released by macrophages in innate response can activate migration of dendritic cell to lymph node for adaptive immunity
Dendritic cell has CCR7 (chemokine receptor on its surface) and LN has CCL21 chemokine
These 2 are attracted to each other so DC flows into LN
Dendritic APC cell enters lymph node via afferent vessel
Activates naive T cells- to become T helper(Th1/2/17)/killer/memory cells (in paracortex)
109
IL-12
| IFN-Gamma
```
Activates macrophages
Activates B cells- and class switching
```
110
IL-4
Made by T helper 2
activates mast cells, eosinophils
activates B cells- class switching
111
TGF-Beta
| IL-6
Made by T helper 17
| secrete IL-17= recruits more leukocytes to infected sites
112
TGF-Beta cytokine
Made by Regulatory T cell
| Inhibit mature dendritic cell to enter lymph node
113
IL-6
Produced by Tfh- activates B cells, class switching and proliferation
114
What survival signal does APC give back to T cell?
CD40
115
During costimulation (2nd step) what happens?
B7 molecules on APC activate CD28 ON T cells
This enhances interaction between TCR and APC
Costimulation- boosts strength of activation signal
116
When APC releases cytokine IL-2 when binding to T cell what does IL-2 do?
By autocrine signalling- enhances proliferation of T cell
117
How are cytotoxic T cells stimulated?
By IL-2 released by T helper cells
118
What do cytotoxic T cells kill?
Kill the cell expressing MHC I antigen
119
What happens once progenitor T cell is made from progenitor lymphoid cell in bone marrow?
Pro T cell migrates to thymus
pro T cell develops into naive T cell by somatic recombination= obtains a unique TCR (binds to specific antigen)
In lymph node naive T cell will meet its antigen first time on dendritic/macrophage APC
Naive T cell proliferates and differentiates into cytotoxic/helper T cell
120
3 signals that T cell receives from APC need to be activated
1. Binding of T cell to MHC
2. Costimulation(B7 activate CD28 on T cell)
3. Cytokines (IL-4,IL-10,IL-12,IL-23)
121
How are cytotoxic T cells stimulated?
When T cell binds to MHC I APC
T helper cell releases cytokines IL-2
IL-2 stimulates proliferation of cytotoxic T cells
122
Humoral vs cell mediated immunity
Humoral= extracellular- B cells- soluble factors- acute phase, complement, antibodies (made by plasma cells)
cell mediated= intracellular- T cells (APCs)- helper and cytotoxic
123
How is a CD4+ T helper cell activated?
Naive CD4+ T helper cell made in thymus
In secondary lymphoid organs:
T cell CD4+ coreceptor binds to MHC II APC of a non-infected phagocyte (macrophage/dendritic cell) by phagocytosis: pathogen chopped up by phagolysosomes, Antigens are loaded onto MHC II in phagolysosome
Activates CD4+ T helper cells
124
How is a CD8+ Cytotoxic T cell activated?
Naive mature CD8+ T cell made in thymus
In secondary lymphoid organs:
naive CD8+ T cell co receptor binds with MHC I APC of an infected phagocyte (e.g dendritic cell)
Dendritic cell presents antigens via cross presentation:
Virus is chopped up by proteasome
Antigens are loaded onto MHC I in ER or ER Makes viral proteins which are assembled onto surface
Activates CD8+ Cytotoxic T cells
125
What is an inflammasome?
multiprotein intracellular complex that detects pathogenic microorganisms
Activates pro-inflammatory cytokines interleukin
126
What are inflammasomes activated by?
NOD-like receptors
127
What antibody is found in the lungs?
IgD
128
Which antibody is mainly in secondary immune response?
IgG
129
Which cytokine causes IFN-Gamma to be made in T cell?
IL-12
130
function of t helper 1 cells
involved in the cell-mediated response and delayed (type IV) hypersensitivity
secrete IFN-gamma, IL-2, IL-3
131
function of t helper 2 cells
involved in mediating humoral (antibody) immunity
e.g. stimulating production of IgE in asthma
secrete IL-4, IL-5, IL-6, IL-10, IL-13 (Induce class switching of antibody)
132
Role of IgM
pentamer antibody that is raised with acute infections. It is the first antibody to be generated after exposure to an antigen
IgM easily binds to complement C1, triggering the classical pathway
This allows the opsonisation of foreign antigens.
