Immunology Flashcards
1
Q
What is the innate immune response?
A
Provides rapid response and depends on pre-formed and rapidly synthesised components. It has limited specificity (pattern recognition of ‘danger signals’
2
Q
What is the acquired immune response?
A
It depends on clonal selection (expansion of cells or antibodies, selected for antigen specificity”. It is slow (starts in days) and is highly specific to foreign antigens. It provides memory
3
Q
What are the anatomical barriers of the innate immune system, preventing infection? (3)
A
Skin- mechanical barrier
Mucus- traps microbes
Cilia- propulsion on epithelia
4
Q
What are the physiological barriers of the innate immune system? (5)
A
Low pH Secretion of lysozyme Interferons Antimicrobial peptides Complement
5
Q
What triggers the innate immune system? Give examples
A
PAMPs (pathogen associated molecular patterns)
e.g. dsRNA in cytoplasm, bacterial cell wall components
DAMPs (damage associated molecular patterns)
e.g. monosodium urate, high extracellular ATP, reactive oxygen species
6
Q
What recognises PAMPs and DAMPs?
A
Pattern-recognition receptors
7
Q
What are types of extracellular and intracellular PRRs (pattern-recognition receptors)?
A
Extracellular danger signals detected by:
- TLRs (Toll-like receptors)
Intracellular danger signals detected by:
- NLRs (NOD-like receptors)
- RLRs (RIG-I-like receptors)
- AIM2
8
Q
What does the innate immune system do?
A
1) Destroys invading nucleic acid (viruses) in the cytoplasm
2) Activates interleukins (e.g. IL-1b, IL-18), which in turn activate inflammatory pathways
3) Elicits type 1 interferons, for antiviral defence
9
Q
What is an antigen?
A
Molecules that are recognised and bound by antibodies or T-cells
10
Q
What are immunogens?
A
Antigens that can induce an immune response in the host
11
Q
What are antibodies?
A
Proteins (immunoglobulins) found in the blood and body fluids produced in response to antigen and bind specifically to a particular antigen. They are the adaptive component of the humoral (soluble, non-cellular) immune response
12
Q
What are lymphocytes?
A
Mononuclear cells. Subdivided into B lymphocytes and T lymphocytes. Each lymphocyte expresses a single specificity of antigen receptor on their surface to enable recognition of a specific antigen
13
Q
What are naive lymphocytes?
A
Lymphocytes that have never encountered the antigen to which their cell surface receptor is specific for, and thus have never responded to it
14
Q
What are memory lymphocytes?
A
A product of an immune response, ensuring that the specificity of their antigen receptor remains in the pool of lymphocytes in the body, and that an efficient response can be made after re-exposure to the antigen
15
Q
What is active immunity?
A
The induction of an immune response within an individual by the introduction of antigen
16
Q
What is passive immunity?
A
Immunity gained without antigen induction of a response, i.e. by transfer of antibody, immune serum or activated lymphocytes into a naive recipient
17
Q
What is a primary immune response?
A
The response made by naive lymphocytes when they first encounter their specific antigen
18
Q
What is a secondary immune response?
A
The response made by memory lymphocytes when they re-encounter their specific antigen
19
Q
What are T-lymphocytes? How do they recognise antigen? What are their surface markers?
A
Lymphocytes that develop in the thymus
They only recognise processed antigen presented at the cell surface by MHC molecules
Surface markers: CD3 (all T cells), CD4 (a subset of T cells) and CD8 (a different subset of T cells)
20
Q
What are B-lymphocytes? How do they recognise antigen? What are their surface markers?
A
Lymphocytes that develop in the bone marrow
They recognise free antigen in the body fluids or intact antigen directly on cell surfaces.
Surface markers: CD19, CD20 and surface immunoglobulin
21
Q
What is clonal selection?
A
When T and B cells meet their specific antigen they replicate and produce effector memory cells in response, each with the same antigen receptor.
22
Q
What are the effector arms of acquired (adaptive) immunity?
A
Cellular immunity
Humoural immunity
23
Q
What is involved in cellular immunity
A
T lymphocytes
24
Q
What is involved in humoral immunity?
A
B lymphocytes and antibodies
25
What part of an antigen binds to an antibody?
An epitope
26
What are the mechanisms by which an antibody can kill a virus?
1) Binds to virus and prevents attachment to a cell
2) Opsonisation: virus-Ab complex is phagocytosed
3) Complement-mediated lysis of enveloped viruses
4) Antibody-dependent cell-mediated cytotoxicity (ADCC), mediated by natural killer cells
27
What is opsonisation?
Where antigen is coated with 'opsonin' (e.g. antibody) which forms a complex aiding phagocytosis
28
What percentage of cells are lymphocytes out of a) circulating WBCs and b) cells in the lymph
a) 20-40% of circulating WBCS
| b) 99% of cells in the lymph
29
What are the two types of T cell?
Helper T-cell
| Cytotoxic T-cell
30
How long are the phases of primary and secondary immune response?
Primary immune response- Lag phase: 5-6 days (no response) then primary response occurs
Secondary is almost immediate
31
What is a B-cell antigen receptor? What does it bind?
Receptor is a membrane-bound antibody (i.e. a surface immunoglobulin)
Binds intact antigens
32
What is a T cell receptor? What does it bind?
T cell expresses two protein chains (α and β) which together make the T cell antigen receptor
It binds digested ('processed') antigen fragments
33
How does the T cell recognise antigen?
TCR recognises a complex of antigen peptide + HLA (MHC) molecule
34
How does the immune response actually clear a pathogen? (2)
1) Cytotoxic T lymphocytes (CTLs) kill infected cells
| 2) Antibodies bind to pathogens: the complex is destroyed or ingested by cells
35
What are three types of antigen presenting cell?
1) Macrophage
2) Dendritic cell
3) B lymphocyte
36
What are lymphoid organs? What is their function?
Organised tissue in which lymphocytes interact with non-lymphoid cells
They are sites of initiation and maturation of adaptive immune responses
37
What are the primary lymphoid organs? (2)
Thymus
| Bone marrow
38
What are the secondary lymphoid organs?
Lymph nodes
Spleen (white pulp)
Mucosa- associated lymphoid tissue (MALT)
39
What is lymphopoiesis? What is it's major location?
The generation of lymphocytes
| Occurs mainly at primary lymphoid organs (thymus and bone marrow)
40
What happens to thymic output as a person ages?
Declines
41
What are Peyer's patches?
Numerous areas of lymphoid tissue in the wall of the small intestine which are involved in the development of immunity to antigens present there. Contains germinal centres during immune responses
Predominantly B lymphocytes
42
How much lymph is returned to the blood each day?
2-3 litres
43
Where is the B cell zone and T cell zone in the lymph node and what are they called?
B cell zone (lymphoid follicle) around the outside of the node
T cell zone (parafollicular cortex) in the middle of the lymph node
44
What is the function of the spleen?
Filters the blood for antigens
45
The presence of what in the spleen show an ongoing immune response?
Germinal centres
46
What is mucosa-associated lymphoid tissue? Give examples of locations
MALT is a diffuse system of small concentrations of lymphoid tissue found in various mucosal sites of the body
e.g. gastrointestinal tract, thyroid, breast, lung, salivary glands, eye and skin
47
What immune cells are present in the skin?
```
Langerhans cells (dendritic cells of the epidermis)
Intraepidermal lymphocyte
T lymphocytes (in dermis)
Macrophage (in dermis)
Dermal dendritic cell (APC)
```
48
What is the process of extravasation of T cells into lymph nodes?
1) Rolling: L-selectin on naive T cells binds to CD34 on the endothelium (high endothelial venules) forming weak bond allowing it to roll along
2) Activation: Binding to a chemokine causes activation of LFA-1
3) Adhesion: LFA-1 binds to ICAM-1
4) Migration: (transendothelial) naive T cell mirates through the endothelium
49
What lymphatic vessel do activated APCs enter a lymph node through?
Afferent
50
What lymphatic vessel do activated lymphocytes leave the lymph node through?
Efferent
51
What are cluster of differentiation markers used for?
CD markers
Bind to cell surface molecules (antibodies) to discriminate between cells of the haematopoietic system (e.g. B and T cells)
52
What are CD4+ cells?
T helper cells (2/3 of cells)
| Regulatory T cells that secrete cytokines
53
What are CD8+ cells?
Cytotoxic T cells (1/3 of cells)
| Lyse infected cells, secrete cytokines
54
APCs initiate what kind of immune response?
Acquired (adaptive)
55
What is the only type of APC to present to B cells?
Follicular dendritic cells
56
What type of immune response recognises PAMPs and DAMPs using PRRs?
Innate immunity
57
Is the innate immune system enhanced during second exposure?
No
58
Is the acquired immune system enhanced during second exposure?
Yes
59
What is the process of leukocyte extravasation?
1) Rolling: Selectin ligand on leukocytes bind to selectin on endothelium
2) Activation: Chemokines activate integron on leukocytes
3) Adhesion: Integrin bind to integrin ligand on endothelium
4) Migration: PECAM-1 (CD31) binds on leukocyte and endothelium and leukocyte moves through gap between cells in vessel wall
60
What causes neutrophil extravasation?
Release of chemokines (e.g. TNF-α, IL-1) from macrophages
61
What are the two types of neutrophil killing mechanism?
Oxygen-dependent
| Oxygen-independent
62
What are the types of oxygen-independent neutrophil killing mechanism? (4)
Enzymes
Lysozyme
Hydrolytic enzymes
Antimicrobial peptides (defensins)
63
What are the types of oxygen-independent neutrophil killing mechanism? (7)
```
Respiratory burst: toxic metabolites
Superoxide anion
Hydrogen peroxide
Singlet oxygen
Hydroxyl radical
Reactive nitrogen intermediates
Nitric oxide
```
64
What receptors do macrophages express? (6)
```
Mannose receptor
CD11b/CD18
Scavenger receptor
Glycan receptor
CD11c/CD18
LPS receptor (CD14)
```
65
What occurs when bacteria bind to a macrophage?
Release of cytokines
| Engulf and digest bacteria
66
What different type of cytokine are there and what is their function? (5)
```
Interleukins (IL-x): between leukocytes
Interferons (IFN): anti-viral effect
Chemokines: chemotaxis
Growth factors
Cytotoxic tumour necrosis factor (TNF)
```
67
What does IL-1 do?
Alarm cytokine
Fever
Diapedesis
68
What does TNF-α do?
Alarm cytokine
| fever, apoptosis, inflammation
69
What does IL-6 do?
Acute phase proteins
| Liver
70
What does IL-8 do?
Chemotactic for neutrophils
71
What does IL-12 do?
Directs adaptive immunity
| Activates NK cells
72
What is the complement system? Where are the components produced?
A complex series of ∼30 proteins and glycoproteins. When triggered an enzyme cascade system causes cleavage to form complement which causes a rapid amplification of the immune response
73
What are the complement activation pathways that lead to complement activation?
Classical pathway: initiated by Ag-Ab complexes
Alternative pathway: direct activation by pathogen surfaces
Lectin Pathway: Lectins binding to carbohydrates only found on pathogens
ALL CONVERGE AT C3 which leads to →
Common pathway: late phase of complement activation
Ends with formation of: Membrane Attack Complex (MAC)
74
What are the functions of complement? (4)
Lysis
Opsonisation
Activation of inflammatory response
Clearance of immune complexes
75
What is secreted by mast cells?
Histamine
| other inflammatory mediators including cytokine
76
What complement product can activate mast cells?
Anaphylatoxins
77
Summarise a typical inflammatory respose to a localised infection (e.g. glass in skin)
1) Tissue damage leads to the formation of complement products that act as opsonins, anaphylatoxins, and chemotactic agents. Bradykinin and fibrinopeptides induce by endothelial damage mediate vascular changes. Mast cell degranulation causes release of histamine
2) Neutrophils migrate to tissue (diapedesis) in response to chemotactic agents
3) Monocytes and lymphocytes then arrive
78
What occurs in a systemic acute phase response?
Accompanies local inflammatory response after 1-2 days
Fever, increased production of white blood cells, production of "acute phase" proteins in the liver; induced by cytokines
79
Give examples of acute phase proteins (4)
C-reactive protein (CRP)
Mannan-binding lectin (MBL)- opsonin for monocytes
Complement
Fibrinogen
80
What are NK cells? What do they do?
Large granulated cytotoxic lymphocytes
Lyse target cells and secrete IFN-γ
No Ag-specific receptor but express both activating and inhibitory receptors
Has receptors which bind to antibody coated cells (ADCC)
Important in defence against tumour cells and viral infections (especially herpes)
81
Chronic granulomatous disease (CGD) causes a defect in innate immunity. What defect?
Reactive oxygen based killing is defective
82
Leukocyte adhesion deficiency (LAD) causes a defect in innate immunity. What defect?
Lack of migration of neutrophils out of blood vessels
83
Interferon-γ receptor deficiency causes a defect in innate immunity. What defect and what does this cause increased susceptibility in?
Poor macrophage activation
| Increased susceptibility to tuberculosis
84
In cellular immunity what cell kills bacteria?
Phagocytes
85
In cellular immunity what cell kills viruses?
NK cells
86
In humoral immunity what is the response to bacteria?
Complement activation
87
In humoral immunity what is the response to viruses?
Interferons
88
What cell produces antibodies?
B lymphocytes
89
What is the structure of an antibody?
Two heavy chains in the middle (both the same) with a light chain either side (light chains are both the same)
Disulphide bridges form between light and heavy chains
N polypeptide terminal (at even end)
C polypeptide terminal (at uneven end)
Fab portion = V
Fc portion = I
90
Describe the antigen binding site
Made up of 3 hypervariable regions- CDRs (complemenarity determining regions)
91
What forces are involved between antibody and antigen? (4)
Hydrogen bonds
Ionic bonds
Hydrophobic interactions
van der Waals interactions
92
What is antibody affinity?
The strength of the total non-covalent interactions between a single antigen binding site and a single epitope on the antigen
93
What is antibody avidity?
The overall strength of multiple interactions between an antibody with multiple binding sites and a complex antigen with multiple epitopes
94
Is antibody affinity or antibody avidity a better measure of binding capacity in biological systems?
Antibody avidity
95
What is antibody cross-reactivity? Give two examples
Antibody elicited in response to one antigen can sometimes recognise a different antigen of similar structure
e.g. Cowpox vaccination induces antibodies which are able to recognise smallpox
Antibodies made against microbial antigens on common intestinal bacteria may cross-react with carbohydrates on erythrocytes
96
What are the heavy chain and light chain antibody isotypes?
Heavy chain: α, δ, γ, ε, μ
| Light chain: κ, λ
97
What are the antibody allotypes?
The allele of the antibody chain found in the population
98
What are the different antibody classes?
```
IgA
IgG
IgE
IgD
IgM
```
99
How many Ch domains do the different antibody classes have?
```
IgG: 3
IgA: 3
IgM: 4
IgD: 3
IgE: 4
```
100
In antibodies is the chain which decides the class (e.g. γ in IgG) the light chain or the heavy chain?
Heavy chain
101
What is the most abundant immunoglobulin?
IgG
102
How many subclasses of IgG are there? And what are they?
4
| IgG1, IgG2, IgG3 and IgG4
103
What subclasses of IgG are major activators of the complement pathway?
IgG1 and IgG3
104
What is the most abundant IgG subclass?
IgG1 (70%)
105
What antibody can cross the placenta?
IgG
106
What is the second most abundant immunoglobulin?
IgA
107
Does IgG occur on it's own or as multiple bound antibodiea?
As a monomer
108
Does IgA occur on it's own or as multiple bound antibodies?
As a monomer in the blood
| As a dimer in secretions
109
What is the major secretory immunoglobulin?
IgA
110
What antibody is found protecting mucosal surfaces?
IgA
111
What joins two IgA antibodies when they form a dimer?
J chain + secretory component
112
How does IgA cross from the submucosa into the lumen?
1) Released from a plasma cell as a dimer
2) Binds to poly-Ig receptor
3) Endocytosed
4) Enzymatic cleavage
5) Exocytosed into lumen (secreted)
113
Does IgM occur on it's own or as multiple bound antibodies
As a large pentameric molecule
114
Where is IgM found?
Mainly confined to the blood (80%)
115
What is the first immunoglobulin synthesised after exposure to an antigen, providing primary antibody response?
IgM
116
What antibody is efficient at agglutination?
IgM
117
What antibody activates complement?
IgM
118
What antibody is involved in B cell development and activation?
IgD
119
What antibody is produced in response to parasitic infections?
IgE
120
What antibody is produced in allergy?
IgE
121
What antibody cross-links with antigen to cause mast cell degranulation?
IgE
122
What antibodies are found in the blood?
IgG
| IgM
123
What antibody is found in extracellular fluid?
IgG
124
What antibody is found in breast milk?
IgA
125
What antibodies occur as monomers?
IgG
IgD
IgE
IgA
126
What type of epitope do T cells recognise?
Linear epitopes
127
What type of epitope do antibodies recognise?
Structural epitopes
128
What cells prevent repeat infections?
Memory B cells
129
How is a lymphocyte activated?
Interaction between a foreign molecule and specific receptor
130
What is the B cell receptor?
A membrane immunoglobulin molecule associated with a disulphide linked heterodimer of Ig-α and Ig-β
131
How does signal transduction occur in the BCR?
Through the Ig-α/Ig-β heterodimer which interacts with intracellular signalling molecules
132
How many different antibody molecules can be generated?
10,000,000,000
133
How is antigen receptor diversity generated?
Recombination
134
What are the three regions that are rearranged in recombination?
Variable: V
Diversity: D
Joining: J
135
How many VJC regions are there?
V: 65
D: 27
J: 6
136
What VDJ segment do light chains not have?
D
137
What enzyme complex is needed for recombination? What proteins does it contain?
VDJ recombinase
| Rag1 and Rag2
138
What is the process of recombination to produce an antibody heavy chain?
Start with germline DNA
1) Somatic recombination- DJ joined together
2) Somatic recombination- VDJ joined together: Rearranged DNA
3) Transcription- Primary transcript RNA
4) Splicing- mRNA
5) Translation- Formation of heavy chain
139
What is the process of recombination to produce an antibody light chain?
Start with germline DNA
1) Somatic recombination- VJ joined together
2) Transcription- Primary transcript RNA
3) Splicing- mRNA
4) Translation- Polypeptide chain
140
What do naive lymphocytes require to be activated?
```
Antigen
Accessory signal (directly from microbial constituents or from a T-helper cell)
```
141
What antibodies are produced by B cells in thymus-dependent production? What provides the signal? Does it provide memory?
All Ig-classes
Signal: T helper cell
Memory
142
What antibodies are produced by B cells in thymus-independent production? What provides the signal? Does it provide memory?
Only IgM produced
Signal: Microbial constituents
No memory
143
What is the process of B cell activation from a T helper cell?
1) Ag cross-links mIg generating signal= increased expression of MHC II and costimulatory B7
2) Internalisation and presentation of Ag
3) T helper cell recognises Ag and costimulation = activation of T helper cells
4) T helper cell expresses CD40L
5) CD40L interacts with CD40 on B cell = signal 2
6) B7-CD28 (B cell-Th cell) interaction = costimulation for T helper cells
7) B cells expresses cytokine receptors
8) T-cell derived cytokines bind to receptors on B cell
9) B cells enters DNA synthesis and differentiation
144
After collaboration with T helper cell what are the two possible outcomes for B cell?
Plasma cell
| Memory cell
145
What are the proliferation cytokines?
IL-2
IL-4
IL-5
146
What are the differentiation cytokines?
IL-2, IL-4, IL-5
IFN-γ
TGF-β
147
What is an effector B cell?
Plasma cell- produces antibodies
148
What is the process of B cell activation to produce plasma and memory cells?
1) Antigen stimulated B cells migrate into germinal centres- reduce surface Ig expression and undergo rapid cell division and mutation (rearranged V-region genes in dark zone)
2) Migrate to light zone and increase surface Ig expression (called centrocytes)
3) B cells with high-affinity surface Ig interact with follicular dendritic cells and bind antigen
4) B cells with low-affinity surface Ig die by apoptosis
5) Those that pass antigen selection receive a second survival signal from T helper cells and differentiate into memory B cells or plasma cells
149
What MHC class do CD4 co-receptors see antigen on?
MHC class II
150
What MHC class do CD8 co-receptors see antigen on?
MHC class I
151
How do CD8 cells detroy their targets?
Induce apoptosis
152
How do CD4 cells destroy their target?
Recruit effector cells of innate immunity, help activate macrophages
Amplify and help Tc and B cell responses
153
Where are the immature and mature thymocytes located in the thymus?
Immature- cortex
| Mature- Medulla
154
What are the recombination events that occur in production of TCR?
VJ cleavage for α chain
| VDJ cleavage for β chain
155
What DNA regions are used to code for the α chain?
Variable and joining
156
What DNA regions are used to code for the β chain?
Variable, diversity and joining
157
What checks are performed on the αβ chain to ensure if is functional?
Is it functional? (Can it bind MHC? yes)
Is it functional? (Can it bind weakly to MHC? yes)
Is it dangerous/autoreactive? (Can it bind strongly to MHC? no)
158
What is the difference between Th1 and Th2 cells?
Th1 cells produce IFN-γ and IL-2
| Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13
159
What antigen is presented on MHC class I?
Transplantation antigen
160
What MHC class is mainly involved in immune response?
MHC class II
161
What are the four regions on an MHC molecule?
Peptide-binding region
Immunoglobulin-like region
Transmembrane region
Cytoplasmic region
162
What size peptides does MHC class I accommodate?
8-10 amino acids long
163
What size peptides does MHC class II accommodate?
>13 amino acids long
164
What cells express MHC class I
All nucleated cells (although at various levels, may be altered during infection or by cytokines)
165
What cells express MHC class II
Only on professional antigen presenting cells (may be regulated by cytokines)
166
What subunits make up the structure of MHC class I?
α1, α2, α3 and β2-microglobulin
167
What subunits make up the structure of MHC class II?
α1, α2, β1 and β2
168
How many subunits are in the transmembrane region and cytoplasmic region of MHC class I? Which?
One (α3)
169
How many subunits are in the transmembrane region and cytoplasmic region of MHC class II? Which?
Two (α2 and β2)
170
What are the two pathways of antigen presentation?
```
Endogenous antigen in MHC class I is restricted to CD8 T cells
Exogenous antigen in MHC class II is restricted to CD4 T cells
```
171
What is endogenous antigen?
Antigen synthesised in the cytoplasm
172
What is exogenous antigen?
Antigen captured from external environment
173
What type of antigen do MHC class I present and on which cells?
Endogenous on CD8 T cells
174
What type of antigen do MHC class II present and on which cells?
Exogenous on CD4 T cells
175
What is the pathway for endogenous antigen presentation?
Endogenous antigen synthesised in cytoplasm
1) Endogenous antigen is degraded by proteasome
2) Peptide if transported to RER via TAP
3) Class I MHC α chain binds calnexin, then β2 microglobulin. Calnexin dissociates. Calreticulin, tapasin and ERp57 bind. MHC captures peptide, chaperones dissociate
4) Class I MHC-peptide is transported from RER to Golgi complex to plasma membrane
176
What is the pathway for exogenous antigen presentation?
Exogenous antigen captured from external environment
1) Class II MHC α and β bind invariant chain, blocking binding of endogenous antigen
2) MHC complex is routed through Golgi to endocytic pathway compartments
3) Invariant chain is degraded, leaving CLIP fragment
4) Exogenous antigen is taken up, degraded, routed to endocytic pathway compartments
5) HLA-DM mediates exchange of cLIP for antigenic peptide
6) Class II MHC-peptide is transported to plasma membrane
177
To switch to effector cells what do T cells require? (3)
1) Antigen recognition
2) Co-sitmulation
3) Cytokines
178
What MHC pathway presents viral antigen?
Class I and II
179
What area in post-capillary venules do T cells enter the lymph node through?
High-endothelial venules
180
Explain the process of cytotoxic T lymphocyte (CTL)-mediated killing of target cells
1) CTL and target cell interact via MHC class I and form a conjugate
2) CTL rearranges cytoplasm so Golgi stack and granules are towards point of contact with target cell
3) Granules released by exocytosis
4) Dissociation of conjugate
5) CTL recycled and target cell dies by apoptosis
181
What enzymes are stored in cytotoxic granules for apoptosis?
Perforin
Granzymes
Granulysin
182
What does perforin do to induce apoptosis?
Polymerises and forms pores
183
What doe s amacrophage do once activated? (3)
1) Kills phagocytosed microbes
2) Increases expression of MHC molecules and co-stimulators (B7) molecules
3) Secretes cytokines (TNF, IL-1, chemokines, IL-12)
184
What happens if the source of an antigen is not completely eradicated?
Chronic stimulation
| Granuloma formation
185
What is delayed type hypersensitivity?
Th cells encounter certain types of antigens (e.g. poison ivy) and secrete cytokines that induce a localised inflammatory reaction (large influxes of non-specific inflammatory cells- mainly macrophages)
186
What are the two phases of delayed-type hypersensitivity?
Sensitisation phase
| Effector phase
187
What happens in the sensitisation phase of delayed-type sensitivity?
```
Antigen presenting cells present antigen on MHC class II molecule to T cells (generally Th1 cells, occasionally CD8)
T cells then differentiate and proliferate
```
188
What happens in the effector phase of delayed type hypersensitivity?
Second exposure to antigen
Th cells secrete a variety of cytokines and chemokines. They attract and activate macrophages and other non-specific inflammatory cells
189
Give an example of DTH that occurs with Th2 cells and what happens
Eosinophil activation occurs
e.g. Chronic asthma
Chronic allergic rhinitis
190
Give an example of DTH that occurs with Th1 cells and what happens
Macrophage activation
| e.g. Contact dermatitis (tuberculin reaction)
191
Give an example of DTH that occurs with cytotoxic T cells and what happens
Cell or matrix associated antigen
Direct cytotoxicity
e.g. Contact dermatitis
192
What are the subsets of T helper cells and their roles?
Th1: Pro-inflammatory (Boost cellular immune response)
Th2: Pro-allergic
Treg: Anti-inflammatory (Limit the immune response)
Tfh: Pro-antibody
Th17: Pro-inflammatory (Control bacterial and fungal infection)
193
Why is immune regulation required? (2)
1) To avoid excessive lymphocyte activation and tissue damage during normal protective responses to infections
2) To prevent inappropriate reactions against self antigens ("tolerance")
194
Generally, what causes autoimmunity?
Susceptibility genes and environmental triggers
195
What is allergy?
Harmful responses to non-infectious antigens which cause tissue damage and disease
196
What antibody/cells mediates acute anaphylactic shock?
IgE
| Mast cells
197
What cells mediate delayed type hypersensitivity?
T cells (Th1)
198
What is immunological tolerance?
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
199
What does breakdown of self-tolerance result in?
Autoimmunity
200
What is the therapeutic potential of inducing tolerance? (3)
1) Prevent graft rejection
2) Treat autoimmune diseases
3) Treat allergic diseases
201
What is central tolerance?
Where self-reactive T or B cells are destroyed before they enter the circulation
202
What is peripheral tolerance?
Where self-reactive T or B cells are destroyed or controlled if they have entered the circulation
203
What is the mechanism of central tolerance? (3)
1) Apoptosis
2) Change in receptors (B cells)
3) Development of regulatory T lymphocytes (CD4+ T cells only)
204
What is the mechanism of peripheral tolerance? (4)
1) Anergy
2) Apoptosis
3) Ignorance
4) Regulation
205
How does a T cell that develops in the thymus encounter MHC bearing peptides expressed in other parts of the body?
AutoImmune Regulator
AIRE is a transcription factor that allows thymic expression of genes that are expressed in peripheral tissues. This allows thymic expression of genes from other tissues
206
What is AIRE?
Autoimmune regulator- A transcription factor allowing thymic expression of genes expressed in periheral tissues
207
What autoimmune disease results from a mutation in AIRO?
Autoimmune Polyendocrinopathy Syndrome type 1
208
What is anergy in peripheral tolerance?
If a naive T cell see's it's MHC/peptide ligand without costimulatory protein it becomes anergic.
It will be less likely to be stimulated in the future even if co-stimulation is present
209
What is ignorance in peripheral tolerance? Give examples of where this occurs
Where antigen is present in too low a concentration to reach the threshold for T cell receptor triggering. This subthreshold stimulation would lead to apoptosis to cells and antigen are compartmentalised
e.g. eye, brain
210
What is known as the "death ligand" as it induces apoptosis?
Fas ligand
211
What type of T cell are Treg cells?
T helper cells
212
Defective Treg has been observed in what condition?
Multiple sclerosis
213
What are the different types of Treg cell?
1) nTreg (natural
Develop in thymus and reside in peripheral tissue to prevent harmful reactions against self
2) iTreg (inducible)
Develop from mature CD4 T cells exposed to antigen in the periphery
214
What are the effects of Th1 and Th2 cells on macrophage activity?
Th1- activates phagocytes to kill ingested bacteria
| Th2- Inhibits macrophage activation
215
What is the "master regulator" key inflammatory cytokine?
IL-10
216
What is the function of IL-10?
Blocks proinflammatory cytokine synthesis (including TNF, IL-6, IL-8 and IFN-γ)
Downregulates macrophages
217
How does class switching occur under T cell influence? What determines the class?
T cells release a cytokine which causes class switching. The cytokine released depends on the type of T helper cell
218
What is the function of eosinophils and basophils?
They defend against parasites too large to be phagocytosed
219
Summerise, generally, the sequence and timing of events following an infection
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First 12 hours: Innate immunity
Cellular and chemical barriers (e.g. skin), phagocytes, dendritic cells, complement, NK cells, ILCs (Innate Lymphoid Cells)
1 day onwards: Adaptive immunity
B lymphocytes- antibodies
T lymphocytes- T effector cells
Days 0-3: Antigen recognition
Day 7: Lymphocyte activation
Day 11-14: Antigen elimination
Day 16-19: Contraction (homeostasis)
Day 20
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