Immunology Flashcards
(162 cards)
1
Q
Which innate immune cells are cytotoxic?
A
Eosinophils, NK cells
2
Q
What are the secondary lymphoid tissues?
A
Lymph nodes, spleen, peyer’s patches
3
Q
What is the structure of an antibody?
A
FC region - defines the isotype
Varible ragion - infinitely different
4
Q
What do TCRs detect?
A
CD8 cells target MHCI bound (cytosolic) peptide
CD4 cells target MHCII bound peptide (endosomal, extracellularly derived, only presentable by pro APCs - B cells, macrophages, dendritic cells)
5
Q
What is the costimulation moleculre needed for naive T cell activation?
A
CD28!
6
Q
What kind of cell can recognise lipid and DNA components as pathogenic?
A
Only abs and BCRs. T cells can’t do this - they can only recognise peptide.
7
Q
What’s the third signal that determines the type of T cell the T cell will become?
A
Cytokines from the APC typically, or the microenvironment activation is occuring.
8
Q
What are the defining cytokines produced by Th1 cells?
A
INF-gamma - stimulate macrophage activation. Intracellular killing. Also make TNF alpha which attract macrophages out of circulation.
9
Q
What are the defining cytokines produced by Th2 cells?
A
IL-4, IL-5, IL-13. Parasite killing.
10
Q
What are the defining cytokines produced by Th17 cells?
A
IL-17, IL-22. Extracellular killing.
11
Q
Apart from Th1 cells, what other T-cells are involved in killing intracellular pathogens?
A
CD8- killer T cells
12
Q
What help signal do Th2 cells provide to B-cells?
A
Cause isotype switching to IgE
13
Q
What T cells are involved in type 1 hypersensitive reactions?
A
Th2
14
Q
What cell types express Fcepsilon receptors?
A
Mast cells and eosinophils
15
Q
What happens once allergen binds to FCe/FCeR complexes?
A
The cross link and mast and eosinophils degranulate
16
Q
What are type 2 hypersensitivity reactions?
A
IgG and IgM mediated - binding to ECM or cell surface antigens and causing inflammation.
17
Q
What is type III hypersensitivity?
A
Immuno complex forming disease - ab targeting soluble antigen. Circulate around, eventually lodge somewhere, attract neutrophils and complement and become inflammed.
18
Q
What is type IV hypersensitivity?
A
T-cell mediated inflammation.
19
Q
Do innate lymphoid cells have T cell receptors? Or B-cell receptors?
A
No, they are activate by cytokines and other mediators produced at their site of residence.
20
Q
What are the two signalling pathways downstream of the 10 toll like receptors present on immune cells?
A
1) NF-kappa B and 2) interferon regulatory factors pathways.
21
Q
Which caspase is activated when intracellular NOD receptors activated?
A
Via the inflammasome, NOD-like receptors activate Caspase 1, which cleaves the precursor for Interleukin-1, causing it to be released.
22
Q
How is gout pro-inflammatory?
A
Urate crystals are recognised by NOD-like receptors, triggering inflammasome activity and IL1 prodcution.
23
Q
What does a C-type lectin receptor do?
A
Innate PAMP receptor - present on immune cells. Important for macs and DCs to detect fungi
24
Q
What do cytosolic RIG like receptors detect? What happens when bound?
A
Intracytosolic viruses. Causes interferon production. Activate the STING pathway.
25
What is the STING pathway?
STimulator of Interferon Genes. Ends up producing interferon alpha. Activated by binding to intracellular PAMP/DAMP receptors. Overactive in interferonopathies.
26
What is that residue that is only on bacterial proteins that leukocytes have receptors for?
N-formylmethionyl. Is also on some mitochondrial proteins, but you know, these are bacteria.
27
Do NK cells have FC recepotrs?
Yes. They can kill antibody bound targets.
28
What cytokines stimulate the proliferation of NK cells?
IL-2 and IL15
29
What cytokines cause NK cells to activate and kill their target cells and secrete IFN-gamma?
IL-12
30
What is the role of the RAG1/2 genes inmaturing lymphocytes?
Responsible recombination to form the unique lymphocyte receptors (TCR and BCR).
31
Are the majority of lymphocytes in the blood B cells? T cells? Or something else?
T cells make up 60-70% of circulating lymphocytes.
32
What constitutes signal two for activation of T cells?
Binding of CD80 (aka, B7, antigen presenting cell side) to CD28 (on the T cell)
33
What cell marker is ubiquitous to all T cells?
CD3
34
Whats unique about the gamma delta T cell receptor compared to alpha beta T cell receptor?
Not requierd to bind MHC to activate. Binds peptides, lipids, and small moleculres.
35
What proportion of T cells are normal CD4+/CD8+ve
60% CD4, 30% CD8, the rest are other types.
36
What are the two membrane boutn Ig isotypes on naive B cells?
IgM and IgD
37
What is the role of the CD21 (aka complement receptor 2) on B-cells?
It binds to antigen bound C3b and increases the chance of B cell activation and longevity on encountering this antigen.
38
What is the role of Ig-beta and Ig-alpha?
Components of the BCR much like CD3 and the delta chains on T cells, required for signal transduction and activation. Ubiquitous to B cells.
39
Which virus uses CD21 (aka complement receptor 2, aka CR2) for cell entry into B cells?
Epstein Barr Virus
40
What is the receptor on B cells used to receive cognate help from helper T cells?
CD40. The ligand on the helper T cell is called (uncreatively) - CD40L (CD40 ligand)
41
What are the immature dendritic cells in in the skin called?
Langerhans cells
42
Follicular dendritic cells accumulate around B cell follicles in lymph nodes and in the spleen. Where do the classical dendritic cells accumulate once bound to antigen?
The T cell zones in lymphoid organs
43
What are the primary lymphoid organs?
The bone marrow and thymus
44
What is the middle bit of the lymph node referred to as?
The mmmmiddle is the mmmmedulla
45
What is the outer (crust) of the lymph node called?
The outer (cccccrust) of the node is called the ccccortex
46
Where are the B cells and where are the T cells in lymph nodes normally?
The be cells are in the outer cortex and the T cells are in the inner medullar. Strikingly.
47
The spleen is like a big lymph node. What is it for?
It's the meeting place of antigens in the blood stream and the lymphocytes.
48
What are all the secondary lymphoid organs?
LNs and spleen, but also cutaneous and mucosal lymphoid systems including the tonsils, peyer patches.
49
What is in the 'follicles' of lymph nodes?
The B cells are in the medullary 'follicles'.
50
What is the difference between a follicle and a germinal centre?
The follicle is the area that a germinal centre (ring of B cells cloning themselves) is situated in.
51
Where do T cells sit in the spleen?
Periarteriolar lymphoid sheaths (around small aterioles)
52
Where do B cells sit in the spleen?
In follicles just distant to the T cells sitting in their periarteriolar sheaths. They are also referred to as the 'white pulp'
53
MHC1 is composed of an alpha chain linked nonvalently to a smaller nonpolymophic protein called beta 2-microglobulin. What genes encode the alpha chain components?
HLA-A/B/C
54
Which part of MHC class I binds to CD8?
alpha 3 subunit of the alpha heavy chain
55
Where are the components of MHC class II encoded?
HLA-D (subregions DP/Q/R)
56
Which domain (alpha 1/2 or beta 1/2) of the MHC class 2 binds to CD4?
The beta 2 subunit.
57
What three cell types present antigen to helper T cells typically?
B cells
Dendritic cells
Macrophages
As they all express MHC class II
58
What is the HLA haplotype?
The combination of HLA-A/B/C and DP/Q/R genes inherited from each parent.
59
Why is so hard to find donor matches?
HLA regions are extremely polymorphic from individual to individual. Best chance of genetically identical HLA haplotype is from identical twin (will be the same) or a sibling - 1 in 4 chance of having the same haplotype.
60
Why is MHC/HLA haplotype important for autimmune diseases an allergy?
Autoreactive or allergen reactive T cells and B cells is only half the story. MHC class II are required to be able to present the autoantigen or allergen to the naive T or B cell to initiate the immune activation in the first place.
61
What produces IL-12?
Dendritic cells primarily
62
What does IL-12 do?
Prodcued by dendritic cells in response to intercepting pathogenci antigen, it matures T helper cells to Thb1 cells, activates NK cells, stimulates the production of infterferon gamma and TNF.
63
Which cytokines are primarily thought of as the antiinflammtory products of T cells?
IL-10 and TGF-beta
64
Are T cell costimulatory B7/CD80/86 receptors constituitively expressed on the surface of antigen presenting cells?
No, they are only expressed after the APC is activated by phagocytosis of a DAMP or PAMP detected through innate receptors. This is important, as it limits the accidental activation of T cells to damage or pathogen related antigens.
65
What is the role of IL-4 produced by Type 2 helper T cells?
Isotype swithcing from B cells to IgE, creates more Th2 cells. Causes Th2 cells to make more IL-5 and IL-13.
66
What two steps of B cell maturation require helper t cells?
Isotype switching and affinty maturation (necessary step for B cell formation)
67
What are the T cells calle that usually provide help to maturing B cells?
T follicular helper cells (Tfh cells). So called because the co-locate with maturing B-cells in the lymph node follicles.
68
Which Ig isotype is actively transported across the placenta to protect the foetus?
IgG
69
What is the half life of circulating IgG?
About 3 weeks.
70
Where do very long lived plasma cells migrate to?
Bone marow from the lymph nodes.
71
What is the late phase (2-24hrs after exposure) type 1 hypersensitivity reaction typically look like?
Allergic rhinitis or bronchial astham. Can last for several days. Is triggered by infiltration of exposed tissue by eosinophils, neutrophils, basophils, monocytes, and CD4 positive T cells.
72
What does IL-13 do?
Enhances IgE production and acts on epithelial cells to stimulate mucous secretion. Produced by Th2 cells.
73
What does IL-5 do?
Attracts, matures, activates and promotes proliferation fo eosinophils
74
The late phase following an immediate type 1 hypersensitivity reaction is caused by cytokines released from mast cells. What they?
TNF alpha, IL-1, IL-4.
75
What are the two major damaging compounds in eosinophils?
Major basic protein and eosinophilic cationic protein.
76
What is the weird pro-inflammatory crystal left behind by eosinophils when they die?
Charcot -Leyden crystals - composied of protein galaectin-10.
77
What is the typical target for autoantibodies in autoimmune thrombocytopoenic purpura?
GpIIb:IIIa integrin (for binding fibrinogen- recall activated platelets)
78
Which cells are largely responsible for antibody dependent cellular cytotoxicity?
NK cells and macrophages. Lysis occurs without phagocytosis.
79
What type of hypersensitivity reaction is a incompatibility transfusion reaction?
Type II antibody mediated
80
What is thought to be the pathophysiology behind reactive arthritis?
Type III immune complex forming hypersensitivity reaction leading to depositiong in joints a local immune reactions at those joints.
81
What is the viral diseas associated with PAN?
Hep B
82
Why do immune complex forming diseases cause pain in the joints?
Becuase synovial fluid, like urine, is formed by forcing fluid through a membrane under pressure. Complexes lodge here and in the kidneys, then cause inflammation
83
What is seen under the microscope in vessel walls occluded by immune complexes that have succumbed to an inflammatory death?
Fibrinoid necosis
84
How can molecules (not proteins) cause a T cell response?
It's thought that the molecule modifies a self protein that then becomes the substrate antigen to allow for T cell activation
85
What is central tolerance?
Refers to toleracne built in from bone marrow and thymus maturation in B and T cells respectively
86
What gene is dysfunctional in patients with autoimmune polyendocrine syndrome?
The AIRE gene. Loss of normal negative selection of T cells in the thymus.
87
What happens to the T cells that don't die during negative selection due to their self antigen recognition?
They are matured into T regulatory cells
88
What is B cell receptor editing?
It is the process of reactivating BCR rearrangement after the initially produced BCR was found to be autoreactive. If receptor editing can't occur, the cell dies via apoptosis.
89
What causes lymphocyte anergy in peripheral regulation?
Binding of B or T cell receptors without costimulatory signals.
90
Where is CTLA-4 expressed, and what does it bind?
CTLA-4 is expressed on T cells. It competes with CD28 for binding B7-1/2 (CD80/86) expressed by APCs and confers inhibitory intracellular signals to naive T cells.
91
What is PD-1, where is expressed, and what does it do?
PD-1 is a receptor that confers inhibitory signals to active an naive T cells. It binds to PD-L1/2 that are expressed by many cells.
92
What are the two membrane proteins expressed in high amounts on the surface of T-regulatory cells?
FOXP3 and CD25 (alpha IL-2 receptor).
93
What peripheral tolerance key protein is mutated in the disease IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked)?
FOXP3
94
What cytokines do T-regulatory cells produce that cause immune inhibtiory functions?
TGF-beta, IL-10
95
Central a peripheral tolerance is mediated by self reactive cell behavioural change (e.g. T regulatory cell formation, BCR receptor editing) or by apoptosis. Both the intrinsic an extrinsic pathways of apoptosis are considered critical for this. What happens in patients with self reactive lymphocytes that don't have functional extrinsic apoptosis proteins Fas/FasL due to mutations?
They develop a disease call autoimmune lymphoproliferative syndreome, where autoreactive T and B cells are able to replicate out of control.
96
What are the immunoprivalaged sites?
Testes, eyes, synovium and brain
97
What happens when the Fc receptor of B cells binds to IgG bound to an antigen?
Anergy. Another way of preventing over activity.
98
How to infections contribute to autoimmunity?
Upregulation of costimulatory molecules on APCs
Increased production of proinflammatory cytokines, leading to increased probability of self-reactive lymphocyte activation
Molecular mimicry leading to accidental autoimmunity
B-cell proliferation as in EBV
99
Why does UV worsen lupus rashes?
It liberates nuclear antigens for ab binding and inflammation
100
In autoimmune diseases, what is epitope spreading?
Autoimmunity to one autoreactive antigen leads to damage to tissue, which releases more self antigen in an inflammatory mileu in a at risk host, possibly driving more autoimmunity.
101
Which ab is most specific to a diagnosis of SLE?
Anti smith and DS-DNA
102
Which ab is associated with diffuse systemic sclerosis?
Topoisomerase 1 (Scl-70)
103
Which ab is associated with limited systemic sclerosis?
Anti-cetromere abs
104
Which ab is associated with systemic sclerosis, renal crisis and malignancy?
RNA pol III
105
What hitidylaminoacyltRNA synthase (Jo1), Mi-2 abs, MDA5 abs and TIF1 gamma abs associated with?
Dermatomyositis variants
106
What does a diffuse nuclear ANA stain indicate?
Binding to chromatin, histones and occasionally DNA. Common in SLE.
107
What does a rim or peripherial nuclear ANA stain indicate?
Abs binding to double stranded DNA and sometimes ot the nuclear envelope.
108
What does a speckled ANA pattern indicate?
Ab binding to non-DNA nuclear constiuents such as Sm antigen, ribnucleoprotein, SSA or SSB. Least specific.
109
What does a nucleolar pattern of ANA stranding indicate?
Represnets antibodies directed at RNA- seenin systemic sclerosis.
110
What is meant by centromeic pattern ANA?
Indicates abs directed at centromeres, as seen in systemic slcerosis with limited skin involvement, but also Sjogrens disease.
111
What is an LE cell?
Lupus erythematosus cell - it referst to any blood leukocyte that has phagocytosed a the denatured nucleus of an injured cell. Old test for diagnosing SLE
112
Which is most common class of lupus nephritis?
Class IV
113
What is the joint involvement like in SLE?
Non-erosive arthritis.
114
What are the coronaries like in patients with SLE?
They get accelerated CAD, not clear why, but maybe due to repeated use of steroids, but possibly also due to aPL abs.
115
Which drugs are classically associated with drug induced SLE?
Anti-TNF, isoniazide, dyralazine, procainamide, d-penicillamine.
116
What is the most common concurrent autoimmune disease with Sjogrens?
Rheumatoid arthritis
117
What are the most abundant cells found to have infiltrated salivary and lacrimal glands of patients with Sjogren's syndrome?
Helper T cells.
118
What cancer to Sjogren's patients develop?
B cell lymphomas. About 5% develop marginal zone B cell lymphomas.
119
Do patients with sjogren's disease get renal glomerula disease?
No. Extremely rare.
120
Do the antibodies seen in the types of systemic sclerosis participate in the pathogenesis of the disease?
Probably not. The fibrotic process is likely driven by autoreactive helper T cells and their production of pro-fibrotic cytokines.
121
What type of lung disease to systemic sclerosis patients with anticentromere abs get?
Pulmonary hypertension. Fibrosis is tyically seen in anti-Scl 70 asscoaited diffuse disease.
122
The term mixed connective tissue disease is used to describe patients with phenotypes which overlap with which other diseases?
SLE, systemic sclerosis and polymyositis.
123
Which ab is classically associated with mixed connective tissue disease?
Anti U1 RNP.
124
What are th direct and indirect pathways of antibody presentation in graft rejection?
Direct - graft APCs present antigen to host lymphocytes.
Indirect - host APCs harvest antigen and present it to host lymphocytes
125
What mediates hyperacute rejection of a graft?
Preformed antibodies specific for antigens on the graft endeothelial cells.
126
What mediates acute cellular rejection (days to weeks) of a transplanted graft?
T cells.
127
What mediates acute antibody-mediated rejection (days to weeks) of a transplanted graft?
Anitboides and complement of course
128
What is thought to drive chronic rejection of grafts?
Activated helper T cells
129
What do calcineurin inhibotrs do?
Calcineurin is needed to activate the transcription factor NFAT (nuclear factor of activated T cells). NFATalows for prodcution of IL2 - needed for T cell survival. Therefore calcineurin inhibitors (e.g. cyclosporin A and tacrolimus) inhibit T cell replication and survival.
130
What is the origina of damage causing cells in GVHD?
Donor T cells
131
What defect do patients have with leukocyte adhesion deficiency type 1?
Beta-2 chain shared by integrins used for leukocyte adhesion.
132
What defect do patients have with leukocyte adhesion deficiency type 2?
sialyl lewis X, the fructose containing ligand for E and P selectins on the endothelium, is absent.
133
What doesn't work in the immunodeficiency syndreom Chediak-Higashi syndrome?
There is defective fusion of phagosomes with lysosome (the LYST protein is dysfunctional) so phagocytosed pathogens and waste material can't be destroyed. Neutrophilia occurs as they neutrophils that are phagocytosing things die. They also get albanism, platelet dysfunction and bleeding, and nervous system dysfunction.
134
What is the most common defect in chronic granulamotaous disease?
X-linked gp91phox defect, and autosomal recessive p47phox and p67phox. Each leads to inability to produce adequate oxidative burst.
135
What is the most common complement deficiency?
C2
136
What is the most serious complement deficiency to have?
C3
137
What causes severe combined immundeficiecny?
usually T cell issue, leading to consequent humoral defciencies.
138
What causes X-link SCID (most common form)?
Mutation in the gamma-chain of cytokine recepotrs. It disables receptors for IL-2/4/7/9/11/15/21.
IL-7 is needed for the survivial of all T-cell precurors.
These pts usuall have little to no T-cells or NK cells, and normal B cell counts with failure to class switch.
139
What causes the most common type of autosomal recessive SCID?
Deficiecny of adenosine deaminase. Leads to accumulation of its target deoxyadenosine and its derivates which are toxic to dividing T cells.
These pts have low T cell counts and low normal B cell counts.
140
Other than adenosine deaminase (the most common cause of autosomal recessive SCID), what other genes can be mutated to give rise to autosomal recessive SCID?
RAG (antigen gene recombination machinary protein) - leads to T and B cell absence.
JAK3 - downstream of the gamma chain on IL recepotrs. Absence or very low number of T cells. Normal number B cells but dysfunctional.
TCR mutations.
141
X-linked agammaglobulinaemia (bruton agammaglobulinaemia) is caused by a mutation where?
Cytoplasmic brutons tyrosine kinase - needed for the BCR light chain rearrangmeent. Maturation is arreseted in the pro-BCL stage when BTK is inhibited, as final BCR formation and movement to the plasma membrane is necessary to provide BCR mediated growth signals to keep the cell alive and proliferating.
142
What causes bare lymphocyte syndrome?
Deficiency in MHCII development because of mutations in transcription factors needed for its production. Leads to only immature lymphocytes being present as they cannot mature through APC MHCII presentation.
143
Mutationsin the X-linked CD40L gene lead to what disease?
Hyper IgM syndrome. CD40L is needed for CD4 helper T cell provided help to B cells (CD40) to enable isotype switching. These patients have no Ig isotypes other than IgM. Though CD40L mutation is the most common cause, it can also be caused by Cd40 mutation, or mutation in downstream signalling systems used by the B cell to isotype switch.
144
Can you give IgA to IgA deficient patients?
No it causes a reaction - the IgA is treated as foreign.
145
What is X-linked lymphoproliferative disease?
Mutation in the SLAM-associated protein, normally required for NK, /T (esp T follicular helper) and B cell activation, leading to difficulty clearing viral infections due to impaired follicle formation and inability to form high affinity abs. Can lead to severe and sometimes fatal EBV.
146
What is defective in Job syndrome?
Th17 cells
147
What is the cause of Wiskott-Aldrich syndrome?
Mutations in the WASP protein - thought necessary for linking the membrane proteins to cytoskeletal proteins. Critical for cell migration and signal transduction. The disease is associate with eczema, progressive loss of T cells, failure to form polysaccharide antigen abs, low IgM, paradoxically high IgA and IgE, B cell lymphomas. Treatment is HSC.
148
How is ataxia telangeiectasis inheritied?
Autosomal recessive
149
What are the clinical features of ataxia telangiectasia?
Abnormal gait, vascular malformations, telangiectesases, neurologic deficits, increased rate of tumours and immundeficiency.
150
What is the underlying defect leading to ataxia telangiectasia?
ATM (ataxia, telangiectasia mutate) - a protein kinase responsible for p53 activation on the recognition of DNA double stranded breaks during the cell cycle. It seems to play a very important role in VDJ recombination, which is maybe why it affects B and T cells as it does.
151
What cells other than T cells are infected by HIV?
DCs and macrophages.
152
CanHIV infect naive T cells?
No, only memory or activated T cells
153
Which receptor(s) does HIV use to enter cells?
CD4, but it needs co-receptors that are chemochine receptors (in particular CCR5 and CXCR4).
154
Why do CD4 T cell numbers drop during HIV infection?
Mainly because of the direct cytopathic effects of the replicating virus
155
What virus is associated with Kaposi sarcoma?
HHV8
156
Apart from HHV8 associated tumours, what other viral associated tumours are HIV pts at risk of?
HPV associated tumours - SCC of the cervis, head and neck, anus. Also associated with B cell lymphomas.
156
What dye is used to see amyloid?
Congo red dye - apple-green birefingence under polarysed light is amyloid
157
What area the 4 types of amyloidosis?
Fibril
AL protein
AA protein
ATTR
158
What type of amyloid protein accumulates due to chronic haemodialysis?
Beta-2 microglobulin
159
What amyloid accumulates in systemic senile amyloidosis?
Transthyrtetin (ATTR)
160
What is the most commonly effected vital organ in amyloidosis of any kind?
The kidney
161
