Usmle Immuno-1 Flashcards
(149 cards)
2
Q
What comprises the adaptive immune system?
A
Lymphocytes, B and T cells
And
Plasma cells
3
Q
What are the three major APCs?
A
Macrophages (innate immunity)
B-Cells
Dendritic cells (innate immunity)
4
Q
What are 5 important characteristics of the Adaptive immune system?
A
Inducible Specific Has Memory Extensive diversity Self versus non-self discrimination Self limiting
5
Q
What part of the immune response is the alternative pathway?
A
Innate response– Don’t need antibodies to initiate it
6
Q
What IL signal causes differentiation of a pluripotent stem cell into a Lymphoid stem cell?
A
IL-7
7
Q
What are three things a Lymphoid stem cell can become?
A
NK -Cell (and part of the innate immune system)
T-cell
B-cell
8
Q
What happens to a T progenitor cell after it differentiates from a Lymphoid stem cell in the BM?
A
It travels to the thymus and can become a helper T-cell or a cytotoxic T cell
9
Q
What signals are needed to cause differentiation of a Pluripotent stem cell into a Myeloid stem cell?
A
GM-CSF
and
IL3
10
Q
What lineages can arise from a Myeloid stem cell?
A
Granulocyte/Monocyte progenitor Eosinophils Basophils Megakaryoctes Erythroid progenitors
11
Q
What are three cells that can be derived from a Granulocyte/Monocyte progenitor cell?
A
Neutrophils
Dendritic cells
or
Monocytes that can lead to macrophages
12
Q
What signal causes differentiation of a Myeloid stem cell into an Eosinophil?
A
IL-5
13
Q
What signal causes differentiation of a Megakaryocyte (from a myeloid stem cell) into platelets?
A
IL-11
14
Q
What cell types can arise from a Basophil progenitor?
A
Basophils
or
Mast cells
15
Q
What is the major membrane marker for Monocytes and macrophages?
A
CD 14— Horseshoe shaped nucleus
16
Q
What is the function of a follicular dendritic cell?
A
Helps maintain antigen memory by holding immune complexes on its dentrites and constantly poking the immune system
17
Q
What is function of the APC dendritic cells?
A
Capture antigen and present them
18
Q
What are two causes of elevated eosinophil count?
A
Parasitic infection
and
Type 1 hypersensitivity
19
Q
What are the major CD markers seen on B-cells?
A
19, 20 and 21
B7
CD40
MHC II
20
Q
What are the major CD markers seen on T-helper cells?
A
CD 3 and CD4
CD 28
CD40L
21
Q
What are the major CD markers seen on cytotoxic T-cells?
A
CD3
and
CD 8
22
Q
What are the major CD markers are seen on NK cells?
A
CD 16 and CD 56 and Receptors for MHC 1
23
Q
What is an ISOTYPE? (AKA class)
A
Whether the molecule is an IgG, IgM, IgD etc…
24
Q
What determines the isotype of an immunoglobulin?
A
The Constant regions
25
Q
What is the function of the constant region of an IgG/IgM?
A
Determines the biological effects of the Ig after it binds antigen
and
Determines the isotype
26
What region of an immune globulin determines the cells idiotype?
The variable region
27
Antibody molecules can bind how many antigens in the least?
2--they are at least bivalent
28
How many molecules of antigen can a T-cell receptor bind?
Just one....always monovalent
29
What is the T-cell antigen receptor made of?
An alpha and a Beta chain...
Alpha is analogous to...light chain of Ig
Beta is analogous to...heavy chain of Ig
30
What is the only type of molecule a T-cell receptor can bind?
Peptides...these must have been chewed up and presented on an MHC complex first
31
What are the components of a B-cell signal transduction complex that tell the cell It has bound antigen?
Ig-alpha and Ig-beta on either side of the constant region within the cell membrane
and
CD 19, 20 and 21...
32
What is the function of CD 19, 20 and 21 in a B-cell signal transduction complex?
Lowers the threshold for the amount of antigen needed to bind before the cell gives a response.
33
What is the function of the CD3 molecule attached to T-cells?
Acts as the signal transduction complex to tell the cell that something has been bound to the T-cell receptor
34
What enzyme are responsible for the rearranging of segments of B and T cells that give them antibody specificity?
RAG 1 and RAG 2 enzymes that encode RECOMBINASES
35
What is the first part of a T or B cell that gets rearranged when making the variable regions?
The Heavy chain....First the D and J segments come together and intervening segments are removed. Then the V segment joins the already combined D and J segments. This makes the VDJ region, which attaches to the Constant region
36
How does light chain rearrangement differ from heavy chain rearrangement?
It happens AFTER heavy chain has already rearranged.
The constant region here is a Kappa or Lambda Chain.
There are only V and J segments
37
What is the function of Tdt?
It incorporates random nucleotides in between the V and D and D and J segments of heavy chains, leading to increased diversity of the variable region
38
What disease is Tdt often used as a marker for?
ALL
39
What is the concept of allelic exclusion WRT heavy or light chain rearrangement?
The idea that if you get one good rearrangement on your heavy chain from Mom, you shut down gene rearrangement from Dad's chromosome so you don't get more than one specificity per cell
40
What are the only two isotypes seen on naive B or T cells (before they have encountered antigen?)
D or M types
41
What is Omenn Syndrome?
A mild version of SCID---caused by a missense mutation in the RAG gene that does not allow for recombination to occur in B and T cells...Leads to absence of B cells and decreased T cells
42
What is SCID?
Severe combined immunodeficiency...
| Caused by a nonsense mutation in RAG genes that leads to an absence of B and T cells.
43
What is seen in a Pro-B-cell as far as markers?
CD 19, 20 and 21
Tdt...
This is where heavy chain rearrangement occurs
44
What is seen in a Pre-B-cell as far as markers?
CD 19, 20, and 21
Tdt
This is where light chain rearrangement occurs...you can see cytoplasmic Mu chains at this point
45
What markers are seen in an Immature B-cell?
CD 19, 20, 21
and
Surface IgM but no Surface IgD
46
What markers are seen on a naive B-cell?
CD 19, 20, 21
| Surface IgM and IgD....this is the first cell type to leave the bone marrow and enter the periphery
47
What is clonal anergy?
Occurs when a self-reactive B-cell is released into the periphery. When it interacts with a self-antigen it is shut off.
48
What is the site within the Thymus where selection occurs?
In the cortex...this is where T-cells are exposed to MHC molecules
49
What type of T cells are seen in the medulla of the thymus?
Mature T-helper and cytotoxic cells which will eventually exit and circulate in the blood
50
Where are MHC class 1 expressed?
All nucleated cells and the ones from mom and dad are expressed as co-dominant.
51
Where is B2 microglobulin found?
On MHC I molecule and is required for expression of MHC I
52
What are the components of a Class II MHC molecule?
An alpha and a beta chain....antigen binding occurs between the two chains
53
Where are MHC II molecules found?
On all Antigen presenting cells.. co-dominantly expressed again
54
What is positive selection of a T-cell?
```
Ensuring that it can bind MHC...if this doesnt occur the T-cell is not selected for.
If it binds class I it becomes cytotoxic
If it binds class II it becomes a helper
```
55
What is negative selection in the Thymus?
When a T-cell binds MHC either I or II but it binds it with too high an affinity. This might lead to autoimmune response, so it is negatively selected and dies
56
What markers are expressed on pre-thymic T-cells?
Tdt only
57
What markers are expressed on T-cells in the thymic CORTEX?
```
These are pre-T-cells which express
Tdt
CD2
CD3
CD4
CD8
```
58
What markers are expressed on the T-cells seen in the thymic MEDULLA?
CD2
CD3
and
CD4 OR CD8
59
How does antigen enter the Lymph Nodes?
Via afferent lymphatics
60
What is the B-cell rich region of the Lymph Node?
The cortex...this is where follicles are located, and where germinal centers (secondary follicles) are located after antigen exposure.
61
What it the T-cell rich region of the Lymph node?
The paracortex, between the cortex and the medulla of the LN
62
What is found in the medulla of the Lymph Node?
Plasma cells, (differentiated in the germinal center) which will leave via the efferent lymphatics and re-enter circulation
63
What is the region surrounding the splenic artery and what resides there?
This is the PALS, periarteriolar lymphatic sheath. T-cells live here
64
What is the B-cell rich region of the spleen?
The marginal zones, and in follicles within the white pulp which surround the PALS
65
Via what structure to Naive lymphocytes enter the Lymph Nodes?
Via High Endothelial Venules
66
What molecules on lymphocytes allow then to bind to HEVs?
L-selectins...This bind addressins on HEVs allowing them to enter the LNs
67
What is the difference between an antigen and an immunogen?
An immunogen will ALWAYS give you an immune response...antigens will only most of the time
68
What is the epitope, or antigenic determinant?
The specific portion of the Immunogen or Antigen that the immune system is recognizing
69
What is a hapten?
A small antigen that is usually ignored by the immune system until it attaches to another molecule, such as an RBC
70
What are some common drugs that can act as haptens?
Streptomycin
Aspirin
Sulfa drugs
Succinyl Choline
71
What is present on endothelium that allows the binding of Mucin like CAMs on Neutrophils?
E-selectin---interaction seen during the 'rolling' process
72
What is the problem in LAD, leukocyte adhesion deficiency and what is the underlying cause?
Inability of the leukocytes to adhere and migrate into the tissues where infection is occurring.
Caused by absence of CD 18, the common B2 chain of integrins.
(AKA LFA-1 integrin)
73
What are three clinical features of LAD, leukocyte adhesion deficiency?
Omphalitis! Inflammation of the unbilical cord/stump leading to some difficulty in separation after birth.
Chronic bacterial infections with really high white counts
NO pus or abscess formation.
74
What cell type predominantly makes IL-8?
Macrophages
75
What is the main function of IL-8?
Chemotaxic agent to recruit white cells to an infection.
76
What is the major chemotatic molecule of the complement system?
C5a
77
What chemoattractant molecule can be made from the breakdown of membrane phospholipids?
Leukotriene B4 via the lipoxygenase pathway.
78
What is formyl-methionyl peptides?
Molecules released from microorganisms with a formyl group attached. Recognized by the body as foreign and thus acts to attract WBCs
79
What are the three pro-inflammatory molecules
IL1
IL6
TNF-alpha
--- increase fever, increase white cells increase complement
80
What are two molecules that can act as opsonins an increase the phagocytotic capabilities of macrophages?
IgG
and
C3b
81
What is the function of NAPDH Oxidase
Converts O2 to free radicals, superoxide radicals and hydrogen peroxide
82
What is the function of Myeloperoxidase?
Converts hydrogen peroxide to hypochlorite (bleach)
83
What is the main defect in Chronic Granulomatous Disease?**
Absence of NAPDH oxidase, so you do not make superoxide radicals and oxygen radicals...
H2O2 is still made from the normal metabolism of bacteria so myeloperoxidase can convert this to Hypochlorite.
84
Which organisms commonly invade people with Chronic Granulomatous Disease?**
Catalase positive bacteria (esp S. aureus) as these degrade the hydrogen peroxide which in NADPH-oxidase deficient individuals is their only way to kill bacteria.
85
List 5 catalase + bacteria?**
```
S. Aureus
E. coli
Salmonella
Shigella
Pseudomonas
Aspergillus
```
86
What does a positive Nitroblue Tetrazolium test indicate?
It indicates that a patients NADPH oxidase enzyme is working (sample turns blue or purple...)
87
What will be the result of a nitroblue tetrazolium test in a pt with CGD?
Negative.
88
What type of antigens are recognized by MHC I receptors?
Endogenous peptides (for example viral peptides)
89
How does the processing of a peptide antigen occur so it may be attached to an MHC I receptor on a cell surface?
The endogenous peptide enters a proteosome, which shreds it down to 8-10 AA pieces
The pieces go thru the TAP transporter into the ER where they are attached to an MHC I molecule...This leaves the ER and Golgi to the cell surface.
90
What disorder is the following Autoantibody associated with: Antinuclear Antibodies?
SLE
91
What disorder is the following Autoantibody associated with: Anti-dsDNA or anti Smith?
Specific for SLE
92
What disorder is the following Autoantibody associated with: Antihistone?
Drug induced lupus
93
What disorder is the following Autoantibody associated with: Anti-IgG (rheumatoid factor?)
Rheumatoid arthritis
94
What disorder is the following Autoantibody associated with: Anticentromere?
CREST
95
What disorder is the following Autoantibody associated with: Anti-Scl-70?
Scleroderma
96
What disorder is the following Autoantibody associated with: Antimitochondrial?
Primary Bilary Cirrhosis
97
What disorder is the following Autoantibody associated with: Antigliadin?
Celiac disease
98
What disorder is the following Autoantibody associated with: Antiendomysial?
Celiac disease
99
What disorder is the following Autoantibody associated with: Anti-BM?
Goodpasture's
100
What disorder is the following Autoantibody associated with: Antidesmoglein?
Pemphigus Vulgaris
101
What disorder is the following Autoantibody associated with: Antimicrosomal?
Hashimoto's
102
What disorder is the following Autoantibody associated with: Antithyroglobulin?
Hashimoto's
103
What disorder is the following Autoantibody associated with: Anti-Jo1?
Polymyositis or Dermatomyositis
104
What disorder is the following Autoantibody associated with: Anti-SS-A? (Anti Ro)
Sjogrens Syndrome
105
What disorder is the following Autoantibody associated with: Anti-SS B? (Anti-La)
Sjogrens Syndrome
106
What disorder is the following Autoantibody associated with: Anti-U1-RNP?
Mixed connective tissue disease
107
What disorder is the following Autoantibody associated with: Anti-Smooth Muscle?
Autoimmune hepatitis.
108
What disorder is the following Autoantibody associated with: Anti-glutamate Decarboxylase?
DM I
109
What disorder is the following Autoantibody associated with: C-ANCA?
Wegener's granulomatosis
110
What disorder is the following Autoantibody associated with: P-ANCA?
Think vasculitides besides Wegener's.
111
What is the origin of an Autograft?
From self
112
What is the origin of a syngenic graft?
From identical twin or clone (AKA isograft)
113
What is the origin of an Allograft?
From a nonidentical member of the same species
114
What is the origin of a Xenograft?
From a different species
115
Which diseases is associated with the HLA subtype A3?
Hemochromatosis
116
Which diseases is associated with the HLA subtype B27?
```
PAIR
Psoriasis
Ankylosing spondylitis
Inflammatory Bowel disease
Reiter's syndrome
```
117
Which diseases is associated with the HLA subtype B8?
Grave's disease
118
Which diseases is associated with the HLA subtype DR2?
MS
Hay Fever
SLE
Goodpastures
119
Which diseases is associated with the HLA subtype DR3?
DM I
120
Which diseases is associated with the HLA subtype DR4?
RA
| DM I
121
Which diseases is associated with the HLA subtype DR5?
Pernicious anemia
| Hashimoto's thyroiditis
122
Which diseases is associated with the HLA subtype DR7?
Steroid-responsive nephrotic syndrome
123
What is the main defect in Chediak-Higashi disease?
Defect in microtubule functioning and lysosomal emptying of phagocytic cells... Phagocytic granules cannot fuse
124
What are the main clinical features of Chediak-Higashi?
Recurrent pyogenic infections with staph and strep
Partial Albinism******
Peripheral Neuropathy.
125
What is defective in Chronic Mucocutaneous Candidiasis?
Idiopathic dysfunction of T-cells, esp against Candida. Leads to excessive skin and mucous membrane Candidiasis.
126
What is defective in Selective Immunoglobulin Deficiency?
Idiopathic B cell defect in a specific class of immunoglobulins....possibly due to defect in isotype switching.
127
What is the most common selective immunoglobulin deficiency and what are common clinical signs??
IgA deficiency--- leads to sinus and lung infections, with milk allergies and diarrhea.
Anaphylaxis can occur on exposure to IgA blood products.
128
What is the defect in Ataxia Telangiectasia?
Idiopathic B-cell deficiency that leads to defect in DNA repair enzymes associated with decreased IgA and thus increased pulmonary infections.
129
What are the clinical presentations of Ataxia Telangiectasia?
Cerebellar problems, like ataxia
and
Spider angiomas
130
What is the defect in Common Variable Immunodeficiency?
Idiopathic B cell deficiency that leads to a normal number of circulating B-cells but decreased amounts of Plasma cells and decreased Ig.
OCCURS IN TEENAGE ISH Years
131
What are two things Common Variable Immunodeficiency puts you at increased risk of acquiring?
Autoimmune disease
and
Lymphoma
132
What is the main defect in Jobs syndrome?
Defect in IFN-gamma production by T-helper cells leading to decreased activation of neutrophils... (They don't respond to chemotactic stimuli)
133
What are the clinical manifestations of Jobs syndrome?
```
FATED
Facies are course
Abscesses (cold staph abscesses)
Teeth (primary teeth are retained)
IgE is increased (because IFN-gamma downregulates Th2 cytokines and it is absent)
Dermatologic Problems (Eczema)
```
134
What is the main defect in Wiskott Aldrich Syndrome?
Defect in the ability to mount an IgM response to capsular polysaccharides of bacteria, decreased activation of B-cells.
135
What are the main clinical signs and symptoms of Wiskott Aldrich Syndrome?
```
WIPE
Wiskott Aldrich
Infections (pyogenic)
Purpura (thrombocytopenic)
Eczema..
Elevated IgE and IgA...Low IgM
```
136
What is the main defect in HyperIgM syndrome?
Defect in CD 40 ligand on CD4 T-helper cells, leading to the inability to class switch.
137
What are the clinical manifestations of HyperIgM Syndrome?
Severe pyogenic infections in early life.
| High High IgM and low everything else.
138
What is the clinical presentation of a pt with an IL-12 receptor deficiency?
Disseminated mycobacterial infections due to decreased TH1 response.
139
What is the underlying cause of SCID?
A defect in B and T cells leading to the inability to differentiate.
140
What are the clinical presentations of SCID?
Recurrent infections of all kinds, and no rejection of allografts occurs.
141
What are the three different kinds of SCID?
ADA deficiency, AR
Defective IL-2 receptors, X-linked
Failure to synthesize MHC II antigens
142
What is the underlying cause of Thymic aplasia?
Failure of the 3rd pharyngeal pouche to develop...
143
What is the presentation of a DiGeorges patient?
Tetany from hypocalcemia
Recurrent viral and fungal infections from lack of T-cells
Congenital defects in the heart/great vessels
144
What is the underlying cause of Brutons Agammaglobulinemia?
Decreased production of B cells caused by a defect in the BTK (Bruton's tyrosine Kinase) gene. Low levels of all levels of Igs and decreased number of B-cells.
145
What are the clinical features of Brutons agammaglobulinemia?
Bacterial infections after 6 months of age (when maternal IgG declines)
Normal numbers of pro-B cells in marrow
Boys only (X-linked)
146
What type of hypersensitivity reaction is seen in Anaphylaxis?
Type I
147
What type of hypersensitivity reaction is seen in allergic rhinitis?
Type I
148
What type of hypersensitivity reaction is seen in Hemolytic anemia?
Type II
149
What type of hypersensitivity reaction is seen in Pernicious anemia?
Type II
150
What type of hypersensitivity reaction is seen in Idiopathic throbocytopenic Purpura?
Type II
