Immunology Flashcards

1
Q

Why do IgG antibodies against hepatitis C envelope proteins not provide immunity against infection?

A

The envelope proteins have variations in their antigenic structure due to an RNA-dependent RNA polymerase with no proofreading 3’→5’ exonuclease activity (error prone).

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2
Q

What are common features of sarcoidosis?

A

African American younger adults. Cough and dyspnea. Skin lesions, uveitis, Lofgren syndrome. Imaging shows bilateral hilar adenopathy. Elevated angiontensin converting enzyme and hypercalcemia/hypercalciuria (granulomas produce and secrete ACE and vitamin D). Noncaseating granulomas seen on pathology. CD4+ T cells predominate with a high CD4+/CD8+ ratio in bronchoalveolar lavage fluid.

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3
Q

What is etanercept?

A

It is a tumor necrosis factor-alpha inhibitor. It is added to methotrexate to treat moderate-to-severe rheumatoid arthritis in patients who have failed MTX therapy alone. It is a fusion protein linking a soluble TNF-alpha receptor to the Fc component of human IgG. It reduces the activity of TNF-alpha by acting as a decoy receptor. The suffix “-cept” represents a receptor molecule.

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4
Q

How do eosinophils play a role in host defense against parasitic infections?

A

When stimulated by antibodies bound to parasitic organisms, they destroy the parasites via antibody-dependent cell-mediated cytotoxicity (ADCC). This involves degranulation and release of cytotoxic proteins (e.g. major basic protein) and reactive oxygen intermediates. Macrophages, neutrophils and NK cells also use ADCC.
Eosinophils also are involved in late-phase type 1 hypersensitivity reactions and chronic allergic reactions (not helpful for fighting parasites).

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5
Q

What is Chédiak-Higashi syndrome?

A

Autosomal recessive syndrome consisting of immunodeficiency (get recurrent pyogenic infections by strep and staph), albinism, and neurologic defects (e.g. nystagmus, peripheral and cranial neuropathies). Causes by a defect in lysosomal trafficking regulator gene (LYST). This causes microtubule dysfunction in phagosome-lysosome fusion. Also, neutrophils, CD8+ cells and melanocytes fail to release granules.

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6
Q

What cell type is responsible for the intense inflammatory response seen in gout?

A

Neutrophils

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7
Q

What is systemic mastocytosis?

A

Clonal mast cell proliferation due to KIT receptor tyrosine kinase mutations. This causes excessive histamine release due to degranulation of mast cells. Symptoms include syncope, flushing, hypotension, pruritis, urticaria, and abdominal cramps. It may also cause gastric ulceration due to increase acid production.

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8
Q

What are features of leukocyte adhesion deficiency (LAD)?

A

Due to an absence of CD18 antigens, which are necessary for the formation of integrins (needed for leukocyte adhesion to endothelial surfaces). Patients with LAD get recurrent skin and mucosal infections (often due to Staph aureus or gram-negative rods) and periodontal disease. Infection is notable for lack of purulence due to absence or leukocytes in peripheral tissues. Wound healing is also impaired, including late separation (>21 days) of the umbilical cord. Persistent leukocytosis is a common finding due to leukocytes not being able to migrate out of the blood vessels.

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9
Q

What medications cause medication-induced IgE-independent mast cell activation?

A

Opioids, radiocontrast agents, and some antibiotics (e.g. vancomycin). They can induce mast cell degranulation by activation of protein kinase A and PI3 kinase. This results in release of several mediators, including histamine, bradykinin, heparin, and a number of enzymes and chemotactic factors. Common symptoms include diffuse itching and pain, bronchospasm, and localized swelling.

Do not confuse with IgE-mediated degranulation, which can be causes by environmental exposures (e.g. food, stings) and certain medications (e.g. beta-lactam and sulfonamide antibiotics).

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10
Q

What are Langhans giant cells?

A

They are large cells found in granulomatous conditions, such as tuberculosis. They are formed by the fusion of macrophages, and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery

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11
Q

What cytokine is responsible for B-cell antibody class switching?

A

IL-4. It is secreted by Th2 lymphocytes along with IL-5. Both IL-4 and IL-5 help to activate B-cells, by IL-4 is primarily responsible for signaling B-cells to class switch from IgM to IgG, IgA or IgE. IL-4 is also responsible for stimulating differentiation of Th0 (naïve) T-cells into Th2 helpers.

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12
Q

What is tryptase?

A

It is released from mast cells in response to allergic reactions, such as anaphylaxis. Tryptase is relatively specific to mast cells, and elevated serum levels of tryptase are often used to support a clinical diagnosis of anaphylaxis after a patient has been stabilized.

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13
Q

What HLA allele is associated with reactive arthritis following GU infections by Chlamydia trachomatis or bacterial enteritis (e.g. Salmonella, Shigella, Yersinia, Campylobacter, or C. diff)?

A

HLA-B27

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14
Q

What is the mechanism behind sarcoidosis?

A

Cell-mediated immune response driven by TH1 type CD4+ helper T cells, which secrete IL-2 and interferon-𝛾. IL-2 stimulates autocrine proliferation of TH1 cells. INF-𝛾 activates macrophages, promoting granuloma formation.

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15
Q

What tumor is common in myathenia gravis?

A

Thymoma

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16
Q

What is affinity maturation?

A

The process of enhancing the hypervariable region antigen binding affinity that occurs after initial binding of antigen to membrane-bound immunoglobulin on a naïve B lymphocyte and subsequent migration of that B-lymphocyte to a lymph node. Within the germinal center of the lymph node, affinity maturation is accomplished by the process of somatic hypermutation, resulting in new immunoglobulins with similar, better, or worse affinity for antigen; only B cells expressing antibody with enhanced affinity for antigen will be selected for. This process does not occur for T-lymphocyte maturation.

17
Q

What enzyme is inducible and is only present in inflammatory cells in the setting of inflammation (induced by IL-1, TNF-alpha)?

A

COX-2. Celecoxib is a selective inhibitor of COX-2 (safer for patients with a history peptic ulcers).

18
Q

What mnemonic is useful for remembering the interleukins?

A

“Hot T-bone stEAK”
IL-1: fever (hot)
IL-2: stimulates T cells
IL-3: stimulates bone marrow
IL-4: stimulates IgE production (and IgG class switching)
IL-5: stimulates IgA production
IL-6: stimulates aKute phase protein production

19
Q

What is the function of IL-8?

A

Major chemotactic factor for neutrophils. “Clean up on aisle 8.” Neutrophils are recruited by IL-8 to clear infection.

20
Q

What is the function of IL-12?

A

Induces differentiation of T cells into Th1 cells. Activates NK cells.

21
Q

What is the function of interferon-𝛾?

A

Secreted by NK cells and T cells in response to IL-12 from macrophages; stimulates macrophages to kill phagocytosed pathogens. Inhibits differentiation into Th2 cells.

22
Q

What is the function of IL-10?

A

Attenuates inflammatory response. Decreases expression of MHC class II and Th1 cytokines. Inhibits activated macrophages and dendritic cells. Also secreted by regulatory T cells. TGF-β also attenuates the immune response.

23
Q

What is Wiskott-Aldrich syndrome?

A

It is characterized by eczema, recurrent infections, and thrombocytopenia. X-linked recessive. Thrombocytopenia causes petechiae, purpura, hematemesis and epistaxis. There is also a defect in B and T lymphocytes which puts patients at risk for pyogenic infections from encapsulated bacteria (due to lack of humoral response) and opportunistic infections (due to decreased T cell response). Becomes more apparent after maternal antibodies are lost after 6 months of age. Treatment is bone marrow transplantation.

24
Q

What is the preferred method for diagnosing chronic granulomatous disease (CGD)?

A
Dihydrorhodamine (DHR) flow cytometry (assesses the production of superoxide radicals by measuring the conversion of DHR to rhodamine). 
Nitroblue tetrazolium (NBT) testing can also be used.
25
Q

What syndrome are anti-centromere antibodies seen in?

A

Highly specific for CREST syndrome (Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasias)

26
Q

What are 4 factors associated with neutrophil chemotaxis?

A

C5a, LTB4, IL-8, and Kallikrein

27
Q

What cells have CD14 cell surface markers?

A

The monocyte-macrophage cell lineage

28
Q

What type of cell exclusively secretes IL-2?

A

T lymphocytes. It stimulates the growth and differentiation of T cells, B cells, NK cells, and macrophages. If present for a lengthy period, it can even promote Fas-mediate apoptosis.

29
Q

Absence of CD40 ligand on T cells is diagnostic of what immunodeficiency syndrome?

A

Hyper-IgM syndrome. This is because CD40 (binds to CD40L on T cells) on B cells signals class switching.

30
Q

What drug(s) inhibits tumor necrosis factor alpha (TNF-alpha)?

A

Infliximab is a monoclonal antibody to TNF-alpha; etanercept is a recombinant TNF receptor fusion protein that serves as a decoy.