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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

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2
Q

What cells activate the adaptive immune response?

A

Dendritic cells

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3
Q

What does adaptive immunity involve?

A

Humoral response- antibodies
T and B lymphocytes
Slower
Specific to antigen

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4
Q

What do T and B lymphocytes provide?

A

Immunological memory

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5
Q

What are antigens?

A

Proteins/peptides on pathogen surface that are recognised by lymphocytes to initiate an immune response

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6
Q

Name of primary lymphoid organs?

A

Thymus, Red bone marrow

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7
Q

What occurs in primary lymphoid organs?

A

Sites of lymphocyte development and maturation from bone marrow derived stem cells

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8
Q

Where are B and T lymphocytes made?

A

Bone marrow

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9
Q

Where do B cells mature and develop?

A

Bone marrow

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10
Q

Where do T cells mature and develop?

A

Thymus gland

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11
Q

Examples of secondary lymphoid organs?

A

Lymph nodes
Spleen
MALT

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12
Q

What occurs in secondary lymphoid organs?

A

Lymphocytes are activated

Immune response is coordinated

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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

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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

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15
Q

What are the 3 types of T effector cell?

A

Cytotoxic T cell
Helper T cell
Regulatory T cell

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16
Q

What does the regulatory T cell do?

A

Suppresses the immune system

preventing autoimmune responses

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17
Q

What does T helper cell do?

A

Activates other T cells and B plasma cells to produce antibodies

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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

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19
Q

What happens when TCR binds to antigen?

A

Proliferation causing:
Cytotoxicity (killing cells)
Helping other immune cells
Regulation (turning off immunity)

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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

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21
Q

Why are BCRs and TCRs different?

A

Each bind to a specific antigen

Therefore each cell responds to a certain pathogen

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22
Q

How are different BCRs and TCRs made?

A

Chopped into segments

Stuck back together

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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
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24
Q

Name of process of creating new TCRs?

A 
VDJ recombination (somatic recombination)
Gene rearrangement
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25
Q

Alpha chain of TCR

A

54 V segments
61 J segments
1 C segment

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26
Q

Beta chain of TCR

A

67 V segments
2 D segments
14 J segments
2 C segments

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27
Q

Structure of BCR

A 
Heterodimeric receptors 
2 chains
Light and heavy chains
held by disulphide bonds 
Variable region (top bit)
Constant region (bottom bit)
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28
Q

How are new BCRs made?

A

Nucleotides can be added/removed to make them more specific to antigen
Somatic recombination- done in bone marrow

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29
Q

What are the differences between BCRs and TCRs?

A

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

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30
Q

What are the 3 signals T cells need to be activated?

A
  1. TCR binding to antigen presented by MHC on APC
  2. Costimulation (B7 molecules)
  3. Cytokines (IL-4/10/12/23)
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31
Q

2 main types of T cell

A

T helper cell

Cytotoxic T cell

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32
Q

co-receptor of cytotoxic T cell?

A

CD8

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33
Q

What kind of APCs do cytotoxic T CD8 cells bind to?

A

MHC I

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34
Q

Function of cytotoxic T cell

A

Kills virally infected cells directly

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35
Q

co -receptor on T helper cell?

A

CD4

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36
Q

What kind of APCs do T helper CD4 cells bind to?

A

MHC II (professional)

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37
Q

Function of T helper cell

A

releases cytokines

activates other T cells and B plasma cells to make antibodies

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38
Q

What are human leukocyte antigens (HLA)

A

Group of proteins that are encoded by the MHC gene

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39
Q

What HLAs do MHC class I code for?

A

A,B,C

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40
Q

What HLAs do MHC class II code for?

A

DP, DR, DQ

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41
Q

What are epitopes?

A

When large protein antigens are digested into small peptides

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42
Q

Where are epitopes bound to in a HLA encoded by a MHC gene?

A

Antigen binding groove- on MHC

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43
Q

Where are MHC class I found?

A

All nucleated cells

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44
Q

How many amino acids can antigen binding groove of MHC I hold?

A

8-10

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45
Q

Where are MHC II found?

A

On professional APCS

e.g macrophages and dendritic cells

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46
Q

how many amino acids does antigen binding groove of MHC II hold?

A

at least 13

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47
Q

What are MHC genes like and why?

A

Highly polymorphic
To protect from population from infection
Have a broad specificity meaning they can bind to many types of antigens

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48
Q

Apart from HLAs that MHC genes code for what do other proteins do that the MHC gene codes for?

A

Processes antigen

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49
Q

What does the p arm (short arm) of MHC gene on chromosome 6 code for?

A

Many HLAs

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50
Q

How does an APC MHC I present antigens onto its surface?

A
  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
  7. Activates CD8 cytotoxic T cells
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51
Q

How do cytotoxic cells kill cells expressing MHC I foreign antigen?

A

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

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52
Q

How does cytotoxic T cell kill cells? (4 steps)

A
  1. Conjugate formation
  2. Membrane attack
  3. T cell detaches from target cell
  4. Target cell killed by apoptosis
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53
Q

What is conjugate formation?

A
  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
Q

What is membrane attack by cytotoxic cells?

A

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
Q

How does Fas-Fas ligand induce apoptosis?

A 
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
Q

How is antigen presented in APC MHC II?

A
  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
Q

What 3 things do professional APCs do?

A
  1. Express MHC II
  2. costimulatory molecules
  3. cytokines
58
Q

How is expression of professional APCs increased?

A

Cytokines

e.g IFN-Gamma

59
Q

How does a professional APC become mature?

A 
increased production
1. Costimulatory molecules
2. Cytokines
3. MHC II
in order to activate T cell when APC binds to it
60
Q

Can dendritic cells also present antigens on MHC I?

A

yes- by cross presentation

61
Q

Costimulation

A

B7 molecules on APC
activate CD28 on T cells
Enhances binding of APC and T cell

62
Q

When APC releases cytokines when binding to T cell which cytokines can these be?

A 
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
Q

What does it mean if different cytokines can be released from APC?

A

different T helper cell subtypes are made

64
Q

IL-12 generates T helper subtype…

65
Q

IL-4 generates T helper subtype…

66
Q

IL-6/21 generates T helper subtype…

67
Q

IL-23/6/TGF-Beta generates T helper subtype…

68
Q

TGF-beta generates…

69
Q

Function of IL-12

A

Activates macrophages

70
Q

Function of IL-4

A

Activate eosinophils, mast cells and macrophages

71
Q

Function of IL-6/21

A

Enhances neutrophil response

72
Q

Function of IL-23/6/TGF-Beta

A

Activates and matures B cells

73
Q

Function of T-regulatory cells

A

Suppresses T effector cells

74
Q

Activated T cell gives survival signal back to APC by?

A

CD40-CD40 ligand

75
Q

How do T cells recirculate the blood?

A 
Develop in thymus
enter the bloodstream
enter secondary lymphoid organs
enter lymphoid tissue
return to blood stream via lymphatics
76
Q

What are naive T cells?

A

Mature recirculating T cells that haven’t encountered their specific antigen on an APC

77
Q

How can a naive T cell be activated in an immune response?

A

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
Q

What happens when T cell recognises specific antigen on dendritic APC?

A

T cell migrates to lymphoid organs
T cell undergoes proliferation and differentiation
(effector T cells and memory cells)

79
Q

What happens once T cell has recognised antigen and has differentiated?

A

T cell exits lymphatics via efferent lymphatic vessel into bloodstream

80
Q

How is a T cell immune response induced?

A

Naive T cell meets dendritic APC in a secondary lymphoid organ which has antigens specific to the T cell

81
Q

What must dendritic cells do once they have picked up the antigens?

A

Travel to lymphoid organs where it’s T cells are found to activate these T cells

82
Q

Free antigens

A

bacteria/viruses travel through lymphatics to lymphoid organs
They are taken up by APCs there

83
Q

What regulates T cell entry into secondary lymphoid organs?

A

Chemokines

84
Q

What happens once T cell has encountered antigen on dendritic APC?

A

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
Q

What does lymphocyte entry into secondary lymphoid organs depend on?

A

Chemokines and adhesion molecules

86
Q

In secondary lymphoid organs what initiates T cell responses?

A

Activated dendritic cells

87
Q

What picks up antigens in the bloodstream?

A

APCs in the spleen

88
Q

Where must antignes be taken to?

A

Lymphoid tissue- LN/Spleen/MALT/tonsils

89
Q

What happens to pathogens in skin wound?

A

Transported in lymph and trapped in lymph nodes

90
Q

What happens to pathogens infecting mucosal surfaces?

A

Transported across mucosa into lymphoid tissue e/g peyer’s patches in small intestine

91
Q

Development of immature dendritic cell into a mature one

A

They express high levels of MHC II complexes
and co-stimulatory molecules
can release cytokines to activate CD4/CD8 T cells

92
Q

How do immature dendritic cells become activated?

A

Via their TLRs (PPRs)
Tissue damage
cytokines produced in inflammatory response

93
Q

What happens once dendritic cells are activated?

A

Migrate to Lymph node

express co-stimulatory molecules needed to activate naive T cell

94
Q

What do mature dendritic cells do in lymphoid tissue?

A

APCs- present specific antigen to naive T cell

Activates other T cells to divide- reenter circulation

95
Q

How are macrophages induced in lymphoid tissue?

A

Via their PPRs
They express co-stimulatory molecules
and act as APCs

96
Q

Where in the lymph node are dendritic cells found?

A

Paracortex of lymph node

97
Q

What are the strongest activators of naive T cells?

A

Mature dendritic cells

98
Q

Where are macrophages found in the lymph node?

A

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
Q

Where are b cells mainly found in the lymph node?

100
Q

What induces immature dendritic cells to migrate to lymphoid organs and mature?

A

PRRs (TLR) signalling and chemokines

enhances antigen processing

101
Q

What are resting macrophages like?

A

Few/no MCH II molecules on their surface and dont express B7 N (co-stimulatory molecules)

102
Q

How do macrophages become activated to show MHC II on surface and B7?

A

PPRs on surface

103
Q

Macrophages don’t initiate T cell immunity so what do they do?

A

They express co-stimulatory molecules to expand primary/secondary responses already initiated by dendritic cells
Maintain function of effector/memory T cells

104
Q

What MHC class do B cells present on their surface?

105
Q

What does B cell do once it has represented antigen and become APC?

A

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
Q

How do B cells use their surface antiboides (BCRs) to present antigens on its surface

A

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
Q

Summary of adaptive immunity

A

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
Q

How does dendritic cell activate adaptive immunity?

A

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
Q

IL-12

IFN-Gamma

A 
Activates macrophages
Activates B cells- and class switching
110
Q

IL-4

A

Made by T helper 2
activates mast cells, eosinophils
activates B cells- class switching

111
Q

TGF-Beta

IL-6

A

Made by T helper 17

secrete IL-17= recruits more leukocytes to infected sites

112
Q

TGF-Beta cytokine

A

Made by Regulatory T cell

Inhibit mature dendritic cell to enter lymph node

113
Q

IL-6

A

Produced by Tfh- activates B cells, class switching and proliferation

114
Q

What survival signal does APC give back to T cell?

115
Q

During costimulation (2nd step) what happens?

A

B7 molecules on APC activate CD28 ON T cells
This enhances interaction between TCR and APC
Costimulation- boosts strength of activation signal

116
Q

When APC releases cytokine IL-2 when binding to T cell what does IL-2 do?

A

By autocrine signalling- enhances proliferation of T cell

117
Q

How are cytotoxic T cells stimulated?

A

By IL-2 released by T helper cells

118
Q

What do cytotoxic T cells kill?

A

Kill the cell expressing MHC I antigen

119
Q

What happens once progenitor T cell is made from progenitor lymphoid cell in bone marrow?

A

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
Q

3 signals that T cell receives from APC need to be activated

A
  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
Q

How are cytotoxic T cells stimulated?

A

When T cell binds to MHC I APC
T helper cell releases cytokines IL-2
IL-2 stimulates proliferation of cytotoxic T cells

122
Q

Humoral vs cell mediated immunity

A

Humoral= extracellular- B cells- soluble factors- acute phase, complement, antibodies (made by plasma cells)
cell mediated= intracellular- T cells (APCs)- helper and cytotoxic

123
Q

How is a CD4+ T helper cell activated?

A

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
Q

How is a CD8+ Cytotoxic T cell activated?

A

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
Q

What is an inflammasome?

A

multiprotein intracellular complex that detects pathogenic microorganisms
Activates pro-inflammatory cytokines interleukin

126
Q

What are inflammasomes activated by?

A

NOD-like receptors

127
Q

What antibody is found in the lungs?

128
Q

Which antibody is mainly in secondary immune response?

129
Q

Which cytokine causes IFN-Gamma to be made in T cell?

130
Q

function of t helper 1 cells

A

involved in the cell-mediated response and delayed (type IV) hypersensitivity
secrete IFN-gamma, IL-2, IL-3

131
Q

function of t helper 2 cells

A

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
Q

Role of IgM

A

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.

Immunology (7 decks)

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