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Immune System Flashcards

1
Q

What is the immune system?

A

All cells dedicated to defence

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2
Q

What is immunogen?

A

Molecule that stimulates the immune system to produce a response

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3
Q

What is an antigen?

A

Part of the immunogen that reacts with immune effector cells or soluble antibodies

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4
Q

What is an epitope?

A

Part of antigen that reacts with immune effector cells or soluble antibodies

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5
Q

What is a pathogen?

A

Any organism with potential to cause disease

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6
Q

What are the 4 main types of pathogens?

A

Bacteria
Viruses
Fungi
Parasites

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7
Q

Where do you get white blood cells?

A

Haematopoiesis

Bone marrow

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8
Q

What are the primary lymphoid organs?

A

Bone marrow

Thymus

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9
Q

What are the secondary lymphoid organs?

A 
Spleen
Adenoids
Tonsils 
Appendix
Lymph nodes
Peyer's Patches
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10
Q

Describe bone marrow

A

B cells originate + mature here

T cells originate in it BUT leave at immature stage

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11
Q

Describe thymus

A

Located above heart

Immature T cells migrate here

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12
Q

What happens to T cells as they mature in thymus?

A

Move from cortex to medulla

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13
Q

What are secondary lymphoid tissues?

A

Sites where mature lymphocytes are activated to respond to invading pathogens

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14
Q

Where do lymphatic vessels originate?

A

In connective tissues, where they collect plasma fluid

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15
Q

What is the plasma fluid called?

A

Lymph

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16
Q

How is lymph returned?

A

To blood vessels via thoracic duct

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17
Q

What happens to arriving lymphocytes in lymph nodes?

A

Segregate in different areas of the lymph nodes

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18
Q

What happens during infection at lymph nodes?

A

Pathogens are drained in lymph nodes from afferent lymphatic vessels, where they are trapped by dendritic cells + macrophages

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19
Q

What happens when B + T cells meet pathogen?

A

Activated

Undergo clonal expansion + differentiation

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20
Q

What happens to lymph nodes as lymphocyte numbers increase?

A

Lymph node increases in size

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21
Q

What is MALT?

A

Mucosa Associated Lymphoid Tissue

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22
Q

What does MALT include?

A 
Nasopharyngeal lymphatic tissues (tonsils + adenoids)
Bronchus associated (Peyer's patches + appendix) 
Isolated follicles in intestinal mucosa
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23
Q

What are 2 types of immunity?

A

Innate

Adaptive

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24
Q

Describe innate immunity

A 
Rapid response
No memory
Fixed
Limited specificity 
Constant during response
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25
Describe adaptive immunity
``` Slow response (days to weeks) Memory Variable Highly specific Improve during response ```
26
What are the cells of innate immunity?
Neutrophils Eosinophil Basophil Monocyte
27
What are the cells of adaptive immunity?
B cell | T cell
28
What are the cells of both innate + adaptive immunity?
Macrophages - dendritic cell
29
What are the immediate innate immune responses?
Barriers Antimicrobial peptides Complement system
30
What are the mechanical barriers?
Epithelial cells joined by tight junctions Longitudinal flow of air or fluid Movement of mucus by cilia
31
What are the chemical barriers?
Fatty acids Low pH Enzymes (pepsin) Salivary enzymes (isozyme)
32
What are the microbial barriers?
Normal flora
33
What are the anti-microbial peptides for fungi?
Defensins Cathelicidins Histatins
34
What are the anti-microbial peptides for bacteria?
Defensins Cathelicidins Histatins Lectins
35
What are the anti-microbial peptides for viruses?
Defensins | Histatins
36
What is the complement system?
Group of 30 serum + membrane proteins Act in sequence Have initial activation = highly regulates enzymatic cascade
37
What is role of complement system?
Some activated proteins bind covalently to bacteria opsoning them Bacteria are phagocytosed by cells with complement receptors
38
Describe classical pathway of complement system
Both antibody dependent/independent | C4b opsonin
39
Describe alternative pathway of complement system
C3b opsonin C3a/C5a pro-inflammatory MAC complex
40
Describe complement inactivation
EGTA Complement inhibitors 56 degrees heating Important role in transplant rejection
41
What are some other roles of complement system
Recruit phagocytes to the site + regulate inflammatory response Some products activate B cells Terminal components generate MAC = lysis of pathogens
42
What are the main phagocytic cells in phagocytosis?
Neutrophils + mononuclear phagocytes
43
What are the stages of phagocytosis?
Recognition + attachment Engulfment Killing + degradation
44
What happens in recognition + attachment in phagocytosis?
Opsonin receptors: Microbe coated in opsonin proteins Phagocytes express high affinity for C3b breakdown product of complement + Cd4
45
What are major opsonins?
IgG
46
What happens in engulfment in phagocytosis?
After bound to phagocyte receptors Plasma membrane forms vesicle that encloses particle Phagosome fuses with lysosomal granule
47
What happens in killing + degradation in phagocytosis?
Lysosomal enzymes OR Reactive O species or reactive N species
48
What are cytokines secreted by?
Cells that stimulate or inhibit activity
49
How many cytokines is there?
20
50
What are cytokines produced by?
Mediators + regulators of innate immunity Mediators + regulators of adaptive immunity Stimulators of haematopoiesis
51
What are mediators + regulators of innate immunity?
Produced by mononuclear phagocytes
52
What are mediators + regulators of adaptive immunity?
Produced by T lymphocytes
53
What are stimulators of haematopoiesis?
Produced by bone marrow stromal cells
54
What are features of inflammation?
Vasodilation Increased vascular permeability Leukocyte migration
55
What do bacterial LPS activate?
Toll like receptors in macrophages
56
What happens in signal transduction of TLR4 vs bacteria?
TLR4 expressed in macrophages detect bacteria Bind to receptor to stimulate signal transduction pathway Activate NF-kB + transcription of genes encoding for pro-inflammatory cytokines
57
What happens in signal transduction of TLR7 vs ssRNA?
TLR7 detects ssRNA + signal to activate IRF7 = produces IFN-alpha + IFN-beta IFN-alpha + IFN-beta have anti-viral properties
58
What are NK cells activated by?
Cytokines IFN-alpha + IFN-beta
59
What do NK cells do?
Kill cells infected by viruses
60
What can NK cells produce?
INF-gamma
61
Describe what happens with NK cells
IFN bind to receptors expressed by NK cells, activating them NK cells proliferate + differentiate in effector NK cells Effector NK cells kill virus-infected cells by inducing apoptosis
62
Describe what happens for bacteria
Immediate innate immune response = all 3 Induced innate response = TLR1, 2, 4, 5, 9 Phagocytosis Cytokines production + inflammation
63
Describe what happens for viruses
``` Immediate innate response = all 3 Induced innate response = TLR3, 7, 8, 9 Interferons Type I (alpha + beta) NK cells Cytokines production + inflammation ```
64
Describe the structure of an antibody
``` Y-like shape 4 polypeptide chain structure 2 identical heavy chains 2 identical light chains Held together by covalent + non-covalent bonds Each chain = variable + constant region ```
65
What do antigen-binding site in antibody molecule consist of?
Vh + Vl | And are part of Fab
66
How many antigens can one Ig bind?
2
67
What do Ch regions interact with?
Effector cells + complement | Part of Fc region
68
What are the 5 classes of antibodies?
``` IgG IgM IgD IgA IgE ```
69
What are the antibodies that have 3Ch domains?
IgD IgA IgG
70
What are the antibodies that have 4Ch domains?
IgE | IgM
71
How many types of L chains are there?
2
72
How many types of H chains are there?
5
73
What do Ig class determine?
Type of heavy chain
74
What are the Ig in BCR form?
All occur as monomers
75
What are Ig in soluble secreted form (antibodies)?
IgD, IgE + IgG = monomers IgA = dimers IgM = pentamers
76
Describe antibody-antigen interaction
V regions are specific for given Ab | Concentrated region of variability
77
What are the hypervariable regions?
3 in Vh | 3 in Vl
78
What does the pairing of heavy + light chain bring?
6 hypervariable loops together, which create hypervariable surface = forms Ag binding site
79
What are the 6 hypervariable regions called?
Complementary-determining regions (CDRs)
80
What is the difference between different CDRs?
Different Abs create both specificity + diversity of antigen binding sites
81
What are the antibody-anti-bacterial specific function?
Neutralisation Opsonisation Complement activation
82
What happens in antibody-anti-viral specific immunity?
Antibodies neutralise free virus = no entry = stop spread Opsonise to increase phagocytosis Activate complement = lysis
83
What are the functions of Abs?
``` Neutralisation bacteria, virus + allergens Activation of complement Opsonisation Inflammation Activation of effector cells ```
84
Describe IgM
Secreted as pentameric molecule 1st Ab to be produced Primary response Defence of tissues + prevention of septicaemia
85
Describe IgG
Secondary response Defence of tissues + prevention of septicaemia Protection of foetus during pregnancy
86
Describe IgA
Prevention of septicaemia Protects surfaces of mucosal epithelium Present in maternal milk
87
Describe IgA
Defence against parasite infections | Important in allergies
88
Describe immunoglobulin
Treatment for primary + acquired immune deficiencies | Neutralise toxins
89
Describe monoclonal antibodies | eg. immunosuppressive
Prevent transplant rejection Treat autoimmune disease Reduce immune response Produced in mice
90
Describe depleting monoclonal Abs - mechanism of action
Monoclonal IgG Abs bind to target cells, which have Fc receptors Target cells killed by phagocytosis or ADCC
91
Describe nondepleting monoclonal Abs - mechanism of action
Block function of target proteins without killing cell that bears it
92
What is the problems with humanisation of monoclonal Abs?
Human may develop Ab response against non-human Ab = interferes with therapeutic action = leads to allergic reactions
93
What is solution to problems with humanisation of monoclonal Abs?
Make Abs not recognised as foreign by human immune system
94
Describe chimeric Abs | Solution
V regions from mouse are spliced onto human Ab constant regions
95
Describe humanised Abs | Solution
Murine hypervariable regions are spliced into a human Ab
96
Describe fully human Abs | Solution
Entirely derived from human sequences + produced from cell lines
97
Describe the stages of B cell lymphocyte development
Generation of BCR Negative selection Migration + final maturation of B cells B cells activation + Ab production
98
Describe activation of B cells production
Mature B cells eaten by secondary lymphoid tissue Absence of specific antigen, B cell leaves lymph node + recirculates Naïve B cells encounter antigens in secondary lymphoid tissue
99
Describe how B cells work
Generation in bone marrow Negative selection in bone marrow Migration of B cells through circulatory system to lymphoid organs + B cell activation Ab secretion + memory cells in bone marrow + lymphoid tissues
100
What happens after B cells encounter antigens in secondary lymphoid tissues?
B cells further activated by T cells Some activated B cells proliferate = PRIMARY RESPONSE
101
What do other B cells do?
Migrate in a secondary lymphoid follicle = mature more slowly = form plasma cells
102
What happens as primary immune response subsides?
B cells develop into memory cells
103
What happens at secondary encounter of pathogen?
Memory cells rapidly activate + develop stronger Ab response
104
Describe T cell receptor structure (TCR)
2 polypeptide chains = alpha + beta Constant + variable regions Each V chain = 3 CDRs
105
What do T cells receptors also include?
Proteins of CD3 complex = signal transduction
106
Describe MHC class I
Made of transmembrane heavy chain (alpha) = 3 extracellular domains + 1 transmembrane domain
107
What does MHC I bind to?
TCR of CD8 T cells
108
Describe MHC class II
Mainly expressed on antigen presenting cells | Made of 2 chains (alpha + beta), each with transmembrane region + 2 extracellular domains
109
What does MHC II bind to?
TCR of CD4 T cells
110
What do T cells use TCR to recognise?
Short peptide fragments bound to MHC
111
What are 2 types of MHC?
Class I | Class II
112
Describe endogenous antigen presentation to CD8 T cells
Proteins made from pathogens in cytoplasm Class I Proteins processed to peptides before binding MHC
113
What do all nucleated cells have?
MHC class I molecules
114
Describe exogenous antigen presentation to CD4 T cells
Exogenous antigens internalised Class II Proteins processed to peptides
115
Describe T cell development | Same as B cell development
Bone marrow Rearrange receptor genes Express pre-T receptor Elimination of self-reactive T cells
116
Where do T cells undergo development?
Thymus
117
What is different from T cell development to B cell development?
Alternative lineages
118
Describe how T cells work
T cell precursor rearranges T cell receptor genes in thymus Immature T cells recognise self MHC receive signals for survival Those interact with self antigen = removed Mature T cells encounter foreign antigens in peripheral lymphoid organs + activated Activated T cells proliferate + eliminate infection
119
Describe positive selection
Selects T cells with TCR able to bind to molecules
120
When does positive selection occur?
When TCR of double-positive T cells recognise MHC molecules expressed on cortical epithelial cells
121
What do double-positively selected cells do?
Move to medulla + mature to single positive cells
122
Describe negative selection
Remove cells with TCR binding tightly to self peptides
123
When does negative selection occur?
When TCR of CD4 or CD8 T cells recognise MHC molecules expressed on dendritic cells/macrophages with high affinity = these cells undergo apoptosis
124
What do dendritic cells present?
Variety of self peptides with MHC I + II of T cells
125
What are T cells with moderate binding to MHC self peptides allowed to do?
Survive
126
What can selected T cells do?
TCR capable of binding self MHC Depleted of dangerous self-reactive T cells Exit thymus as mature, single positive T cells
127
What do activated T cells acquire?
Effector functions in secondary lymphoid tissues
128
What do CD8 T cells acquire?
Cytotoxic activity
129
What do CD4 T cells function by?
Secrete cytokines
130
What happens once TCR have acquired effector functions?
No longer require co-stimulation
131
What happens once TCR change location?
No longer enter lymph nodes | Enter tissues via activated endothelia at sites of infection + inflammation
132
What are the 2 ways to activates CD8 T cells?
Infected cell presenting MHC I | Help from CD4 T cells (through release of cytokines)
133
What are the 2 mechanisms that induce apoptosis?
Secretion of cytotoxic granules | Fas ligand on T cells interacts with Fas on target
134
What happens in secretion of cytotoxic granules? | Apoptosis inducing mechanism
Perforin polymerises in membrane | Granzymes enter cell
135
What happens in Fas ligand on T cells interacts with Fas on target? Apoptosis inducing mechanism
Secrete IFN-gamma as NK cells Inhibits viral replication upregulates MHC I expression + antigen presentation Increases macrophage phagocytosis of dead cells
136
What are the type of specific CD4 T helper responses?
TH1 = active against intracellular pathogens TH2 = extracellular pathogens TH17 = extracellular pathogens Tfh + Treg = regulatory functions
137
Describe what happens with TH1
Release cytokines to activate macrophages = increase intracellular killing of pathogens HELP macrophages
138
Describe what happens with TH2
Release cytokines, support Ab production = activate mast cells + eosinophils HELP B cells
139
Describe what happens with TH17
Induced early in infection Release cytokines to amplify neutrophilic responses HELP neutrophils
140
Describe what happens with Tfh
Present in lymph nodes Stimulate IgM production during primary response Support isotype switch during secondary response
141
Describe what happens with Treg
Inhibit antigen presentation to T cells | = block their activation
142
What do cytotoxic T cells do against viruses?
Recognise viral peptide + MHC I | Kill virus infected cells
143
What do cytokines with anti-viral activity do against viruses?
eg. IFN-gamma | Induce resistance to virus
144
How do th1cells protect against intracellular bacteria?
Activate mainly macrophages
145
How do th1cells protect against extracellular bacteria?
Activate mainly neutrophils

Pharmacology (40 decks)

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