Immunology 1 Flashcards
1
Q
The key regulatory cells are all T cells with which CD marker?
A
CD4+
2
Q
Th17 cells produce which interleukin?
A
IL-17
3
Q
Cytotoxic T cells have which CD marker?
A
CD8+
4
Q
Allergic people and animals have a reduced number of which cells?
A
Allergen-specific Treg cells. This permits the inappropriate activation of allergen-specific Th2 cells and B cells and therefore the production of allergen-specific IgE antibody.
5
Q
What are the four distinct levels of the skin barrier?
A
- The microbiome
- The chemical barrier
- The physical barrier
- The immunological barrier
6
Q
Where are beta- defensins and cathelicidins derived from and what is their role in skin barrier function?
A
They are derived from keratinocytes and immune cells and may directly mediate microbial killing in addition to acting as leucocyte chemoattractants and immunomodulators.
7
Q
What needs to be absent for a NK cell to recognise and destroy a target?
A
MHC Class I. The NK cell expresses an inhibitory receptor that binds to class I on normal tissue cells and prevents cytotoxicity from occurring.
8
Q
What are:
PAMPs
MAMPs
DAMPs?
A
Pathogen associated molecular patterns
Micro-organism associated molecular patterns
Damage associated molecular patterns
9
Q
What do PAMPs/MAMPs/DAMPs bind to on dendritic cells?
A
Pattern recognition receptors (Toll-like receptors)
10
Q
What is T cell plasticity?
A
T cell lineage differentiation is not absolute and that it is possible for one type of mature effector to transform into another (e.g. Th1 to Treg) at a particular stage of an immune response.
11
Q
Which cytokines do group 1 innate lymphoid cells produce and which cells to they stimulate/promote?
A
- Group 1 ILCs (ILC1 cells and NK cells) produce IFN-gamma and stimulate Th1 immunity
12
Q
What modifications are made to the vascular endothelium at the site of antigen exposure?
A
- Transformation of vascular endothelial cells into larger cuboidal cells to increase turbulence and leukocyte-endothelial interaction
- Increased expression of E-selectin, ICAM-1, VCAM-1
13
Q
Which cells do the below chemokines recruit?
IL-8 (CXCL8)
Monocyte chemotactic proteins
Eotaxins (CCL11, CCL24 and CCL26)
A
IL-8 (CXCL8) - neutrophils
Monocyte chemotactic proteins - primarily monocytes
Eotaxins (CCL11, CCL24 and CCL26) - eosinophils
14
Q
Which mechanisms allow the hair follicle to be a site of immune privilege? Name three (for boards)
A
- Reduction of intraepithelial CD4+ and CD8+ T cells
- Dominance of Treg cells producing IL-10 and TGF-beta
- Expression of FAS ligand within the follicle to delete FAS expressing (potentially autoreactive) T cells
- Downregulation of MHC 1 / 2 expression
- Expression of inhibitory signals (CD200, non-classic MHC class I, etc.)
- Expression of natural immunosuppressants (POMC, a-MSH, TGF-beta, IL-10, IDO, etc.)
- Absent Langerhans cells and presence of functionally altered DC
- Altered trafficking of cells (no direct access to lymphatics in hair bulb, special extracellular matrix)
15
Q
Sebaceous glands produce cytokines that stimulate which cells in particular?
A
Th17 cells - involved in defence against bacteria.
16
Q
In the sensitisation phase of type 1 hypersensitivity reaction, which cells are stimulated in the lymphoid tissue by dendritic cells?
A
Th2 regulated expansion of B cells producing allergen-specific IgE
17
Q
In the sensitisation phase of a type 1 hypersensitivity reaction, Igs are bound to the FceR1 on which cells?
A
Circulating basophils and tissue mast cells
18
Q
What are the clinical consequences of mast cell degranulation?
A
Vascular dilation - tissue oedema and
Bronchoconstriction
Local neurological effects - pruritus
19
Q
The late phase of a type 1 hypersensitivity response involves the influx of which cells?
A
Eosinophils and macrophages
20
Q
Which three pathways can mediate a type 2 (cytotoxic) hypersensitivity?
A
- activation of complement following binding of antibody to target cell with formation of the terminal membrane attack complex and osmotic lysis of the target
- phagocytosis of the antibody opsonized target by a macrophage bearing Fc and C3b receptors
- antibody-dependent cell-mediated cytotoxicity (ADCC) performed by a Natural Killer (NK) cells
21
Q
What is the most common clinical example of a type 2 hypersensitivity reaction?
A
A blood transfusion reaction
The same immunological events underlie IMHA and IMTP
22
Q
How does damage occur during a type 3, antigen-excess, hypersensitivity reaction?
A
Small Ag-Ab complexes lodge in vessel walls. Inflammation occurs within the vessel wall and endothelial damage may lead to local thrombosis and tissue ischaemia.
23
Q
Which T helper cells are involved in a type 4 hypersensitivity reaction?
A
Th1
24
Q
What are the primary lymphoid organs?
A
Thymus and bone marrow
25
Which four mechanisms mediate central tolerance?
1. receptor editing
2. clonal deletion
3. anergy
4. development of natural Treg cells
26
Which four mechanisms mediate peripheral tolerance?
1. ignorance
2. anergy
3. deletion
4. development of inducible regulatory T and B cells
27
Why does the accumulation of dead cells in chronic inflammation help stimulate autoimmunity?
By providing self Ag alongside inflammatory cytokines
28
What are cryptic epitopes?
Hidden parts of protein molecules (due to physical structure, stereochemical alteration or immune privilege). These can be released/exposed by trauma leading to autoimmunity.
29
What is molecular mimicry?
Identical sequences of amino acids shared between pathogen and self - the pathogen stimulates an immune response that is then directed at self.
30
Which complement component, C3a or C3b, is a chemoattractant for neutrophils and activates mast cells?
C3a
31
Which complement component, C3a or C3b, opsonises bacteria and promotes phagocytosis, activates the membrane attack complex and 'punches' holes in some bacterial membranes?
C3b
32
Which complement component attracts eosinophils?
C5a
33
In response to mechanical injury, keratinocytes release which cytokine that in turn causes the release of ICAM-1, VCAM-1, E-selectin and other cytokines which attract T-cells?
IL-1
34
IL-18 is produced by which cells? It acts on Th1 and NK cells inducing their proliferation and production of cytokines such as IFN-gamma.
Keratinocytes
Langerhans cells
Monocytes
35
Which T cells produce IL-2?
Activated Th1 cells
36
Which T cells produce IL-4 and IL-13?
Activated Th2 cells = both
| NK cells, mast cells and basophils = IL-4
37
IL-4 stimulates naive T cells to differentiate into what?
Th2 cells
38
Which cells produce IL-5?
Activated Th2 cells
Mast cells
Eosinophils
39
Does IL-5 acts on B or T cells?
B cells - to proliferate and produce IgA
40
Thymic stromal lymphopoetin produced by _________ elicits the differentiation of naive T cells to ____ cells via _______ cells.
Keratinocytes
Th2
Dendritic
41
Keratinocytes enhance the production of Th2 cytokines from Th2 cells by producing which IL?
IL-33
42
Are CD4 cells typically found in greater numbers in the dermis or epidermis?
Are CD8 cells typically found in greater numbers in the dermis or epidermis?
CD4 cells predominate in the dermis.
| CD8 cells predominate in the epidermis.
43
CD4 cells interact with which MHC?
MHC2 - present extracellular proteins
44
CD8 cells interact with which MHC?
MHC1 - present intracellular proteins
45
What is Prausnitz-Kunstner testing?
Test serum from a hypersensitive individual is injected intradermally into a normal subject; the normal subject is challenged 24–48 hours later with the antigen suspected of causing the immediate hypersensitivity reaction in the hypersensitive individual.
AKA passive transfer test
46
Fill in the blanks:
During sensitisation, ___, ____, and ____are released from inflamed or injured epithelial cells inducing type 2 innate lymphoid cells (ILC2) to produce ____ and ____.
During sensitisation, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP) are released from inflamed or injured epithelial cells, inducing type 2 innate lymphoid cells (ILC2) to produce IL-5 and IL-13
47
During sensitisation, antigen presenting cells (APCs) direct the immune response towards helper T cell (Th)2 with production of which cytokines?
IL-4 and IL-13
48
What is likely to be the major source of histamine and 5-hydroxytryptamine in equine Culicoides hypersensitivity, the Culicoides saliva or the mast cell?
The mast cell
5-HT is responsible for the pain caused by bites and stings from several arthropod species including bees and wasps, yet it has so far not been demonstrated in the saliva of Culicoides.
It is not known whether Culicoides saliva contains histamine.
49
Second signals are required for T cells to be activated.
| ICAM-1 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
LFA-1 (leukocyte function-associated antigen)
50
Second signals are required for T cells to be activated.
| LFA-3 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
CD2 (also called leukocyte function-associated antigen [LFA] 2)
51
Second signals are required for T cells to be activated.
| B7-1 on nucleated and antigen-presenting cells interacts with which adhesion molecule on cytotoxic and helper T cells?
CD28
52
Production of TSLP by primary canine keratinocytes is induced by stimulation with ligands for which TLRs?
TLR-3 and TLR-4
53
IL-10 can downregulate immune responses or mediate which type of inflammation?
Th2
54
Which is most heat stable, IgG or IgE?
IgG
55
The innate immune system comprises of epithelial barriers and their associated secretions, polyreactive antibodies, the alternate pathway of complement and which white blood cells?
Granulocytes, macrophages, natural killer cells and innate lymphoid cells
56
True or false; The adaptive immune system is specific, slower acting, but more potent than the innate response.
True
57
Which key cell links innate and adaptive immunity?
The dendritic cell
58
Dendritic cells sample antigen, and internalize and process it, leading to presentation of antigen-derived peptides associated with which molecules?
Class I or II molecules of the major histocompatibility complex (MHC)
59
Dendritic cells transport sampled antigen to regional lymphoid tissue where they present MHC-peptide to naïve CD4+ T lymphocytes; directing their differentiation to different subsets of CD4+ T cell or activating ____________
CD8+ cytotoxic T cells
60
Adaptive immunity essentially involves achieving a balance between the function of different regulatory lymphocyte subsets and the cytokines that they produce. The key regulatory cells are all ________
CD4+ T cells
61
T helper (Th) 1 cells produce the signature cytokine _________ and mediate cell-mediated immunity involving the activation of cytotoxic T cells, NK cells and phagocytic cells
Interferon (IFN)-gamma
62
Th2 cells, producing IL-4, ___, ___, ___ and IL-13, are involved in providing co-stimulation to B lymphocytes leading to antibody production (humoral immunity).
IL-5, IL-6, IL-9
63
A dendritic cell can have how many encounters per hour with T cells in a lymph node?
~500 per hour
64
A Th1 response leads to cell-mediated/cytotoxic responses against viruses or intracellular pathogens. What does a Th2 response do?
Helps antibody responses against extracellular pathogens - stimulates B cells via IL-4, IL-5, IL-9 and IL-13 to become plasma cells that produce antibodies against extracellular pathogens
65
Which types of Ig and white blood cells have been found in apocrine (sweat) glandular secretions?
IgA
| Plasma cells expressing IgA or IgG
66
Dendritic cells may be identified by their constitutive expression of class II MHC molecules and via other lineage-specific molecules such as ____ and ____
CD1 or CD11
67
Epidermal Langerhans cells may also express IgE bound to the low affinity IgE receptor _____, and this expression may be important in perpetuating hypersensitivity responses to allergens that penetrate the epidermis
CD23
68
Which cytokines do group 2 innate lymphoid cells produce and which cells to they stimulate/promote?
Group 2 ILCs (ILC2 cells) produce IL-4 and IL-13, IL-5 and IL-9 and promote Th2 immunity
69
Which cytokines do group 3 innate lymphoid cells produce and which cells to they stimulate/promote?
Group 3 ILCs (ILC3 cells and lymphoid tissue inducer cells) produce IL-17, IL-22 and TNF and promote Th17 immunity and inflammation.
70
What role does CD40 have on T and B cells?
It is a surface molecule expressed on both cells that interacts to provide the second signal in T cell activation of B cells
71
Vascular adhesion molecules e.g. E-selectin, ICAM-1, VCAM-1 selectively interact with ligands that are expressed by the antigen-specific lymphocytes; give an example
Cutaneous lymphocyte antigen; CLA
72
Immune responses driven by Th17 cells (e.g. to extracellular bacteria) involve recruitment of __________ into infected tissue
Neutrophils
73
In normal animals, CD4+ T cells that also express ___ are regarded as ‘natural suppressors’ (Treg) and work to inhibit the action of effector cells by direct
physical interaction with their targets
CD25
74
Where are resident, normal, tissue macrophages found in the skin?
Most commonly in the superficial dermis, around blood vessels
75
Which TLRs recognise bacterial lipids?
TLR 1, 2, 4 and 6 recognise bacterial lipids
76
Which TLRs recongise viral RNA?
TLR 3, 7 and 8 recognise viral RNA
77
Which TLRs recognise bacterial DNA?
TLR 9 recognises bacterial DNA and double-stranded DNA viruses
78
Which TLRs recognise bacterial or parasite proteins?
TLR 5 and 10 recognise bacterial or parasite proteins
79
CD28 is a co-stimulatory molecule on T cells that binds to which ligands on antigen presenting cells for activation?
CD80 (B7-1) and CD86 (B7-2)
80
CTLA-4 and PD-1 are expressed by activated T cells - stimulation of these molecules has what effect?
Inhibition
81
Name bacterial ligands that interact with TLRs
```
Lipoglycans e.g. lipopolysaccharide, a component of the Gram -ve bacterial outer membrane
Peptidoglycans and lipoteichoic acid (Gram +ve)
Bacterial flagellin (protein)
Nucleic acids (RNA or DNA)
```
82
Name viral ligands that interact with TLRs
```
Coat protein
Nucleic acids (RNA or DNA)
```
83
Name fungal ligands hat interact with TLRs
Beta-glucans from the cell wall e.g. zymosan
84
What are the three types of signal required for APCs to activate T cells?
1. MHC bound antigen binds to CD4 or CD8
2. CD28 on T cell binds to CD80/86 on the APC
3. Cytokines from the APC determine which type of Th cell it becomes
85
Which type of bacteria can the membrane attack complex insert into?
Gram -ve
It forms pores that allow entry of damaging molecules that lead to osmotic lysis e.g. lysozyme
86
In the classical complement pathway, C1 binds to what?
Antibody (tail AKA Fc region)
87
In the alternative complement pathway, what binds directly to the bacteria?
C3 complex (antibody is not required)
88
In normal human skin, which cell is the main source of AMPs?
Keratinocytes
89
Synthesis of AMPs primarily occurs in the stratum granulosum; AMPs are then packaged into _________ and transported to the stratum corneum
Lamellar bodies
90
Other than keratinocytes, which other cells are important sources of AMPs?
Sebocytes, mast cells and neutrophils
91
AMPs are positively charged to aid interaction with negatively charged bacterial cell membranes; how do they cause cell lysis?
1. They attach to, align with, and then insert into the microbial phospholipid bilayer
2. Associate with the lipid headgroups of the phospholipid bilayer causing transmembrane ‘pores’ that disrupt and destabilize the bacterial cell membrane
92
What are three potent inducers of cathelicidin expression?
Infection
Cutaneous injury
Vitamin D3
93
Cathelicidin may help repair skin wounds by inducing keratinocyte migration via transactivation of _________
Epidermal growth factor receptor
94
Cathelicidin has many immunological functions including recruitment of which cells to sites of injury and infection?
Neutrophils
T cells
Mast cells
Monocytes
95
Do cathelicidins promote angiogenesis?
Yes
96
Have recombinant canine beta-defensins been shown to be as effective against MRSP as they are against MSSP?
Yes
97
Are beta-defensins, as well as cathelicidins, involved in wound repair?
Yes – they increase keratinocyte migration and proliferation
98
Step 1 of diapedesis = lymphocyte rolling.
Lymphocyte rolling initiates the contact between lymphocyte and the endothelium. It is mediated by repeated bind-release events between which molecule and their ligands?
Selectins
99
During rolling, chemokines displayed on the endothelial cell can interact with chemokine receptors on the lymphocyte surface. This interaction activates adhesion molecules on the leukocyte of which family?
Integrins
100
VCAM-1 on the vessel wall interacts with which leukocyte adhesion molecule during diapedesis?
VLA-4 (very late antigen-4 also α4β1 integrin)
Mac-1/CD11b/CD18 also reported in M+K
101
What is the role of high endothelial venules (HEV)?
They protrude into the flowing blood, causing local turbulence and increases contact with circulating leukocytes
102
The process of phagocytosis begins with the binding of ________ (i.e. complement or antibody) and/or specific molecules on the pathogen surface (called pathogen-associated molecular patterns [PAMPs]) to cell surface receptors on the phagocyte. This causes receptor clustering and triggers phagocytosis.
Opsonins
103
Following triggering of phagocytosis, the cell membrane extends around the target, eventually enveloping it and pinching-off to form a discreet _______. This vesicle can mature and acidify through fusion with late endosomes and lysosomes to form a __________, in which degradation of the contents can occur via the action of lysosomal hydrolases.
Phagosome
Phagolysosome
104
ICAM-1 on the vessel wall interacts with which leukocyte adhesion molecule?
LFA-1 (leukocyte function-associated antigen, AKA CD11a/CD18)
105
Which cytokines help drive the formation and maturation of phagosomes?
TNF-alpha and IFN-gamma
106
Which receptors are particularly important for the recognition and phagocytosis of opsonised microbes?
- Complement receptors and Fc receptors
| - TLRs, scavenger receptors and lectins also important
107
When does the late phase of type I hypersensitivity reactions occur?
4-24 hours after exposure
108
Which factors can influence whether deposition of circulating immune complexes will occur in a particular vascular bed e.g. type III hypersensitivity reactions?
* Size of the complex
* Nature of the antigen
* Nature of the antibody
* Presence of increased vascular permeability with exposure of basement membrane permitting access for the complexes
* Presence of high blood pressure and turbulent blood flow that marginalizes complexes to the vascular periphery.
109
How long does cellular recruitment take in delayed type IV hypersensitivity reactions? Give a common clinical example in the skin
24-48 hours
Contact allergy
110
True or false; serum ANA may be present in up to 10% of normal animals, and are commonly found in animals with a wide range of chronic inflammatory, infectious or neoplastic diseases
True
111
Which part of the hair follicle is an important source of beta defensins and cathelicidins?
Infundibulum
112
Which is the most immunologically active part of the hair follicle?
Infundibulum
113
The hair follicle bulge is currently considered to be an immune privilege site exhibiting significantly decreased expression of __________ by keratinocytes, reduced numbers of CD1a+ and MHC class II+ Langerhans cells, ____ and ____ T cells, macrophages and mast cells.
```
MHC class I
CD4+ and CD8+ T cells
```
114
Which cytokines are associated with induction of a tolerance reponse?
IL-10
| TGF-beta
115
Which immunosuppressive molecules are expressed at immune privileged sites of the hair follicle?
```
MIF (macrophage migration inhibitor factor)
POMC
alpha-MSH
TGF-beta
IL10
IDO (a tryptophan-catabolizing enzyme)
```
116
The infundibulum recruits Langerhans cells in response to stress via which chemokines?
CCL20 and CCL2
117
Which TLRs are extracellular?
TLR1, TLR2, TLR4, TLR5, TLR6, and TLR10 are surface-expressed
118
Which TLRs are intracellular?
TLR3, TLR7, TLR8, and TLR9 are intracellular
119
Mast cell granule based mediator tryptase is an important chemoattractant for which inflammatory cells?
Neutrophils
120
Occurring some minutes after the initial degranulation event, mast cells will commence synthesis of which lipid derived mediators?
Prostaglandins
Leukotrienes
Thromboxanes
121
Hours after initial degranulation, mast cells produce which cytokines?
```
TNF- alpha
IL-4
IL-5
IL-6
IL-13
```
122
Which molecules interact during the rolling phase of diapedesis?
Endothelial: E- and P- selectin
Leukocyte: PSGL1 (P-selectin glycoprotein ligand)
123
Which molecules interact during the adhesion phase of diapedesis?
Endothelial: ICAM-1, VCAM-1
Leukocyte: LFA-1 VLA-4 (integrins)
124
Which molecules interact during the crawling phase of diapedesis?
Endothelial: ICAM-1
Leukocyte: MAC-1
125
Which molecules interact during the paracellular migration phase of diapedesis?
Endothelial: ICAM-2, PECAM-1
Leukocyte: LFA-1
126
Which cytokines activate macrophages for phagocytosis?
IFN-gamma and TNF-alpha
127
What is a neutrophil extracellular trap (NET)?
Neutrophils have been shown to cast out their DNA in response to infectious stimuli as a type of cell death. When the cell bursts open, this material unfolds into a fibrous structure occupying a volume that is several fold bigger than that of the cell it originated from. Coated in antimicrobial peptides and antibacterial enzymes, this material provides ongoing bacterial killing in both time and space.
128
What is the anti-viral action of interferon?
Interferons prevent replication of viruses, by directly interfering with their ability to replicate within an infected cell. They also act as signalling molecules.
129
Viruses: which TLRs recognise:
Double-stranded RNA
Single-stranded RNA
Double-stranded CpG-rich DNA
TLR-3 recognizes double-stranded RNA (dsRNA)
TLR-7 and TLR-8 single-stranded RNA (ssRNA)
TLR-9 double stranded CpG-rich DNA
130
CCL5, also known as RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted), is a chemoattractant for which cells?
T cells, eosinophils and basophils
131
Macrophage migration inhibition factor (MIF) is an immunoregulatory cytokine that through interactions with its receptor _____, recruits and activates macrophages at inflammatory loci.
CD74
132
The most important source of macrophage migration inhibition factor is ____ cells
Th2
133
What are the three main components of the JAK/STAT signaling pathway?
tyrosine kinase-associated receptor, JAK, and STAT (Signal transducer and activator of transcription)
134
What are the four types of JAK and where are they expressed?
JAK1, JAK2, and Tyk2 = ubiquitous
| JAK3 = principally in hematopoietic cells
135
How is the JAK/STAT pathway activated?
1. Binding of cytokines to their receptors activates JAKs (two JAKs per receptor)
2. The activated JAK activates and phosphorylates its main substrate STAT.
3. Phosphorylated STAT dimerizes with other members of STAT family and is translocated into the nucleus where it binds to DNA sequences
4. Activates or inhibits the transcription of the target genes, including the cytokine signal transduction inhibitor family (negative feedback loop to turn off the JAK/STAT signaling pathway)
136
The third major function of CD8+ T cell destruction of infected cells is via Fas/FasL interactions. Activated CD8+ T cells express FasL on the cell surface, which binds to its receptor, Fas, on the surface of the target cell. What does this cause?
This binding causes the Fas molecules on the surface of the target cell to trimerise, which pulls together signalling molecules. These signalling molecules result in the activation of the caspase cascade, which also results in apoptosis of the target cell.
137
The C-type lectin, langerin (CD207), is expressed on the surface of Langerhans cells. Internalization of langerin mediates the formation of what?
Birbeck’s granules (BGs)
138
Have Birbeck's granules been found in Langerhans cells in dogs and cats?
In cats but not in dogs
139
When follicular keratinocytes are damaged by bacteria, viruses etc., they upregulate pro-inflammatory cytokines such ad IL-1, TNF-alpha which leads to expression of which membrane protein?
MHC I
Become capable of interaction with CD8 T cells
Hair cycle shuts down (anagen becomes catagen)
140
Where do you find central, resident and effector T memory cells?
1. Central memory T cells circulate in blood and traffic through lymphoid tissues
2. Effector memory T cells enter and patrol peripheral tissues, including skin
3. Tissue-resident memory T cells provide local surveillance and are retained in tissues
141
Th1 cells produce which cytokines?
IL-2
IFN-gamma
TNF-alpha
GM-CSF
142
IL-12 and IFN-gamma stimulate which type of Th cells?
Th1
143
IL-2 and IL-4 stimulate which type of Th cells?
Th2
144
Which T cells produce IL-31 in dogs?
Th cells (likely Th2)
