Immunology Flashcards
What is the difference between first-degree and second-degree immune organs?
First-degree: where immune cells develop (i.e., bone marrow and the thymus)
Second-degree: where immune cells are assisted (spleen, lymph nodes, tonsils, Peyer patches)
True or false: lymph nodes typically have more afferent vessels than efferent vessels.
True.
What is the main role of the lymph node medulla?
To communicate with the efferent lymphatic; medullae are typically T cells, B cells, and macrophages
Which part of the lymph node is likely to be impaired or underdeveloped in children with DiGeorge?
The paracortex
The superficial inguinal lymph nodes drain everything below the umbilicus with a few exceptions: ________________.
the testes, ovaries, and uterus drain into the para-aortic lymph nodes; the posterior calf and dorsolateral foot drain into the popliteal lymph nodes
T cells and B cells reside in which parts of the spleen?
T cells: periarteriolar lymphatic sheath
B cells: germinal centers
Where do macrophages catch encapsulated bacteria in the spleen?
In the marginal zone between the red pulp (RBCs) and white pulp (T cells and B cells, depending on the kind of white pulp)
What mechanism leads to immune vulnerability in post-splenectomy patients?
Decreased production of IgM –from decreased germinal centers –results in decreased complement activation, and complement activation is needed to kill encapsulated organisms.
What labs and histologic exams might you see in someone without a spleen?
Target RBCs
Lymph- and thrombocytosis (because they are normally sequestered in the spleen in a healthy person)
Howell-Jolly bodies (bits of DNA in RBCs normally removed by macrophages in the spleen)
Thymomas are associated with what two disorders?
Myasthenia gravis (no idea why) and superior vena cava syndrome
C-reactive protein is produced in response to _________. What does it do?
IL-6; it binds to dying cells –both human and bacterial – and stimulates the complement cascade to help get rid of cellular debris
One more time: which is MHC II, HLA-B or HLA-DR?
HLA-DR (“Two letters”)
True or false: MHC I is present on all cells.
False. It is not present on RBCs.
Which HLA types are associated with lupus?
D2 and D3 (“2 and 3 for S-L-E”)
Describe the maturation of T cells.
1) Bone marrow
2) Thymus cortex; CD4 and CD8 positive (positive selection: making sure it fits MHC)
3) Thymus medulla; CD4 or CD8 positive (negative selection: making sure it doesn’t recognize self-antigen)
4) Lymph node paracortex
Tonic expression of ___________ near M cells allows for development of Treg. Addition of __________ stimulates development of Th17.
TGF-beta; IL-6
IL-_____ down regulates Th1.
10 (produced by Treg)
Expression of the ________ gene is crucial during negative selection.
AIRE (because this causes thymic expression of proteins found throughout the body, thus ensuring that developing T cells can see all of the self-antigens)
Which interleukin stimulates development of Th2?
IL-4
Again, which interleukin stimulates Th1?
IL-12 (“twelve men to convict one prisoner”)
IL-12 is released by macrophages.
Describe the positive feedback between T cells and macrophages.
Macrophages secrete IL-12 which activates Th1 cells, and then Th1 cells secrete IFN-gamma which activates macrophages.
______________ kill cells with perforins and granzymes.
CD8+ T cells and NK cells
Which receptors do Tregs possess?
CD3, CD4, CD25, and FOXP3
(You already know the first two because they’re helper T cells, and you can use these mnemonics to recall the last two: 2x5 = 10, and Tregs secrete IL-10; and you need to be “cool as a fox” to help calm down your immune response.)
Diabetes in a male infant accompanied with dermatitis might be signs of _______________.
IPEX
Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked
A defect in the FOXP3 receptor that would normally allow Tregs to calm the body down.
The heavy chain contributes to ______________ and the light chain contribures to _______________.
the Fc and Fab regions; the Fab region
Why should you remember the Cs when it comes to the Fc region?
Complement binding
Constant
Carbohydrate side chain
Carboxy terminus
True or false: naive B cells express only IgD.
False. They express both IgM and IgD.
The complement-fixing antibodies include _______.
IgG and IgM
IgA circulates as __________.
monomers; it gets dimerized during transcytosis
Antigens lacking ___________ cannot be presented on MHC.
peptide exterior (that is, if they only have lipopolysaccharide such as Gram-negative bacteria, then APCs cannot present that in MHC)
What two receptor interactions are needed for T-cell activation?
MHC-II + antigen – CD4
CD80/86 (aka B7) – CD28
What two receptor interactions are needed for B-cell activation?
MHC-II + antigen –CD4
CD40 –CD40L
Five lab values with increase in response to acute inflammation and two will decrease. List them.
Increase:
- CRP
- Fibrinogen
- Ferritin
- Hepcidin
- Serum amyloid A
Decrease:
- Albumin
- Transferrin
Which complement cytokines can cause anaphylaxis?
C3a, C4a, and C5a
AAA can cause anaphylaxis.
What proteins form the membrane attack complex?
C5b –C9b
Which complement protein attracts neutrophils?
C5b
What is the alternative complement pathway?
C3 can spontaneously lyse on bacterial surfaces (that is, without mannose-binding lectin or C1)
Trace the classical complement pathway.
Antigen-antibody complexes activate C1.
C1 cleaves C2 and C4.
C4b2b (aka C3 convertase) cleaves C3.
C4b2b3b (aka C5 convertase) cleaves C5, activating the MAC.
How is the alternative pathway different?
C3bBb acts as C3 convertase, and C3bBb3b –yes, two 3bs –acts as C5 convertase.
ACE inhibitors are contraindicated in those with what complement disorder?
C1 esterase deficiency (characterized by angioedema of the face)
GPI anchors what receptor?
Decay-accelerating factor, also called CD55
Again, what is the “Hot T Bone stEAK” mnemonic?
IL-1: fever IL-2: T cell proliferation IL-3: bone marrow stimulant IL-4: igE production IL-5: igA production IL-6: aKute phase proteins (stimulating CRP)
In addition to causing fever, what does IL-1 do?
It promotes expression of adhesion molecules.
IL-12 stimulates Th1 cells and __________.
NK cells
Going off your jury mnemonic for IL-12, think of TWELVE jurors sentencing ONE man because he’s a NATURAL-born KILLER.
What does TNF-alpha do?
It causes vascular leaking, WBC recruitment, granuloma formation, and cachexia.
(“Trickling Nodular Fatigue Attractor”)
Interferon-gamma inhibits the production of which lymphocyte?
Th2 cells (because interferon-gamma is secreted by Th1 cells)
Which T cell type secretes IL-4, IL-5, and IL-10?
Th2
It secretes these to aid in granuloma formation and tamping down of the immune response.
What pathway is inhibited in the X-linked immune disorder that presents with a negative methylene blue test?
O2 -> O2–• (NADPH oxidase)
O2–• -> H2O2 (superoxide dismutase)
H2O2 -> HCLO• (myeloperoxidase)
Interferon alpha and beta primarily work to ______________.
prime uninfected cells to avoid spreading infection by down-regulating protein production
Which receptor is specific to Treg?
CD25 (“25 regulations are too many”)
All antigen-presenting cells have what two receptors?
MHC II and B7 (aka CD80/86)
What receptor is specific to hematopoietic stem cells?
CD34
True or false: T cells are not needed to activate macrophages.
True. When macrophages bind a PAMP – such as through their receptor CD14 –they become activated without any other signals.
What does the “attenuated” part of live attenuated virus mean?
That the toxicity has been removed.
Which vaccines are inactivated?
Rabies
Influenza (injection)
Polio (Salk)
Hepatitis A
(“RIP Always”)
Explain the immune response that usually occurs with live and inactivated vaccines.
Live: cellular and humoral
Inactivated: humoral
Describe the cellular mechanism behind type I hypersensitivity reactions.
IgE on mast cells and basophils bind and cross link antigen. This activates these cells and causes them to release histamine. Delayed inflammation arises from production of leukotrienes.
Why do immune complexes cause damage?
They activate complement which attracts neutrophils (C5a). Neutrophils release cytotoxic enzymes.
What is the Arthus reaction?
Injecting antigen into someone who has already developed antibody to that antigen leads a local immune complex lump that can lead to necrosis.
There are two kinds of type IV hypersensitivity reactions: __________________.
CD8-mediated (in which T cells do the killing) and CD4-mediated (in which T cells activate macrophages that do the killing)
What is a common cause of hyperacute anaphylaxis to blood transfusions?
Giving IgA-containing blood to individuals who are deficient in IgA
Note: this is a type I hypersensitivity reaction.
True or false: hyperacute blood reactions are antibody-mediated.
False. Hyperacute reactions (those within minutes) are IgE-mediated and thus considered type I reactions. Antibody-mediated blood reactions present 1-6 hours after transfusion.
There can be two kinds of type II hypersensitivity reactions to blood products: ________________.
hemolytic (in which antibodies are directed against RBCs) and nonhemolytic (in which antibodies are directed against WBCs)
What causes acute lung reactions to blood products?
Donor anti-WBC antibodies attack in the lungs or attack pulmonary endothelium, leading to ARDS
What antibody is commonly seen in type 1 diabetics?
Anti-glutamic acid decarboxylase
Drug-induced lupus presents with anti-___________ antibodies.
histone
Antibodies are needed to eliminate what virus?
Enterovirus and polio virus (hence, boys with Bruton’s will get polio if given live, Sabin polio vaccines)
Which immune deficiencies are associated with autoimmune disease?
IgA deficiency and Wiskott-Aldrich syndrome
_______________ is a defect in B-cell differentiation.
CVID (hence the normal levels of B cells and T cells and defective Ig/plasma cells)
Which immune deficiency disorder presents with Th1 malfunctions?
Selective IL-12 receptor mutations
What causes chronic mucocutaneous Candidiasis?
Selective defects in response to Candida antigens; otherwise normal
What genetic inheritance pattern does the most common SCID disorder have?
XLR (being IL-2 receptor mutations)
Note: ADA deficiency is AR.
Those with SCID will have decreased levels of __________.
serum TRECs
The neurocutaneous disorder that presents with selective immunodeficiency has low levels of ______________.
IgA, IgG, and IgE
The run-in describes ataxia-telangiectasia which is caused by defects in DNA rearrangement.
Those with CD-40L deficiency have high levels of ________ and are at increased risk of _______________.
IgM; pneumonia, Cryptosporidium, and CMV
What causes Wiskott-Aldrich syndrome?
Defects in actin skeletons that prevent leukocyte cytoskeletal rearrangement and cause failure to show MHC
Remember: WA is XLR
When would you worry about delayed umbilical cord?
Typically 30 days
Which immune deficiency syndrome presents with enlarged granules in the cytosol?
Chédiak-Higashi
In addition to having a negative tetrazolium blue test, those with defects in NADPH oxidase will have negative _______________.
dihydrorhodamine tests (i.e., decreased green fluorescence in flow cytometry)
Hyperacute graft rejections are type _________ hypersensitivity reactions.
II (meaning they have to have preformed antibodies to the transplant)
Histologically, what will you see in acute transplant rejections?
Dense CD8+ infiltrate in vessels of organs leading to vasculitis
What type of hypersensitivity reaction is chronic transplant rejection?
II and IV
That is, antibodies and CD4+ T cells develop after transplantation.
What histologic pattern is common in chronic organ transplant rejection?
Obliterative fibrosis (of lungs, kidneys, and liver–the last of which can show disappearing bile duct syndrome)
Which two organ transplantations most often lead to graft-versus-host disease?
Liver (rich in lymphocytes) and bone marrow (really rich in lymphocytes, hehe)
Cyclosporine inhibits _____________ which decreases IL-2 transcription.
calcineurin (by binding cyclophilin)
Cyclosporine : cyclophilin = tacroliums : ________________.
FKBP
“TACOs with Fish, Kale, Beef, and Pico”
Which immunosuppressive medications are neurotoxic?
Tacrolimus and cyclosporine
IL-2R stimulates what intracellular mediator?
mTOR (which is inhibited by sirolimus)
Stimulation of ____________ leads to the activation of calcineurin which then ______________.
TCR (CD4 and CD3); dephosphorylates NFAT, allowing it to transcribe IL-2
Sirolimus is often used in what organ transplants?
Kidneys, because sirolimus is not nephrotoxic
“SiRolimus allows the kidneys to SuRvive.”
Which drug acts “upstream” in the sirolimus pathway?
Basiliximab and daclizumab –both are IL-2R antagonists
Remember Basil Chang on the pogo stick.
Corticosteroids work by inhibiting _____________.
NF-kB
Azathioprine ultimately inhibits which enzyme?
PRPP amidotransferase (which is needed in purine synthesis)
________________ reversibly binds to IMP dehydrogenase.
Mycophenolate mofetil
____________ is associated with invasive CMV infections.
Mycophenolate mofetil
What’s the difference between filgrastim and sargramostim?
filGraSTIM activates G-CSF.
sarGraMoSTIM activates GM-CSF.
What does oprelvekin do?
It stimulates platelet development.
What disorders is rituximab used in?
Rituximab is an antibody against CD20 and is thus used in any disorder in which B cells are causing a problem: NHL, RA, ITP, and CLL of B-cell origin.
Which antibody targets HER2/neu?
Trastuzumab (“tras2zumab”)
Which cancers are treated with cetuximab?
Colorectal cancers
Note: cetuximab targets EGFR.
Etanercept has a similar effect to which antibodies?
Infliximab and adalimumab
Etanercept is a decoy TNF-alpha receptor. (“It interCEPTs TNf-alpha.”)
Eculizumab can treat which condition?
Paroxysmal nocturnal hematuria
Eculizumab is an antibody to C5.
(Think: eCulizumab.)
Ustekinumab targets what receptor and is used in which conditions?
It targets IL-12 and is used for psoriasis.
Think of USbEKastan with psoriasis all over it. Also, Th1 cells are important mediators of psoriasis.
Denosumab mimics what endogenous molecule?
Osteoprotegerin
High-risk infants with RSV can be given _______________.
palivizumab
For LIV VIruZ
