Chapter 6 Flashcards
Epithelial barriers as part of the innate immunity consists of _ and functions to _.
- skin, GI tract, respiratory tract
- Provides mechanical barriers to the entry of microbes
- provide antimicrobial molecules like defensins
- lymphocytes located in the epithelia combat microbes
Which phagocytic cells circulate in blood?
monocytes and neutrophils
Where are dendritic cells located?
In epithelia, lymphoid organs, and most tissues
What are the functions of DC?
- capture protein antigens and display peptides for recognition by T lymphocytes
- Stimulates the secretion of cytokines and mediators that play critical roles inflammation and anti-viral defense
NK cells are early protection against many viruses as well as which category of bacterias?
Intracellular bacteria
which activation pathways of the complement system is involved in innate immunity? In adaptive immunity?
alternative and lectin pathways are in innate immunity.
Classical pathway is in adaptive immunity
What do pattern recognition receptors bind to?
- microbial components that are shared among related microbes
- Damage-associated molecular patterns - injured or necrotic cells
Where are pattern recognition receptors located?
In ALL cellular compartments where microbes may be present
What kind of microbes do Pattern recognition receptors recognize?
Extracellular. Endosomal receptors detects ingested micorbes and cytosolic receptors detect microbes in the cytoplasm
Explain the downstream signaling pathway of Toll-like Receptors (TLRs)
THere’s about 10 different 10 TLRs each recognize a different set of microbial molecules, but they all signal a common pathway that leads to the activation of transcription factors. Once bound, signaling pathway leads to activation of transcription factors NF-kB which stimulates synthesis and secretion of cytokines and expression of adhesion molecules (critical for recruitment and activation of leukocytes). Interferon regulatory factor (IRFs) stimulates production antiviral cytokines (type I interferons)
what is an inflammasome and what are it’s components?
Inflammasome is a protein complex that recognizes products of dead cells and some microbes and induces the secretion of biologically active IL-1. The inflammasome consists of a sensor protein (a leucine-rich protein called NLRP3), an adapter, and enzyme caspase 1.
What part of the cell are NOD receptors located?
In the cytosol.
Which of these receptors are classified as innate immune receptors? A. TLRs B. NLRs C. CLRs D. RLRs E. All of them F. None of them G. A only
E. All of them. TLR = toll like receptor NLR = NOD-like receptor CLR = C-type lectin receptor RLR = RIG-like receptor for viral nucleic acids
Cells of the innate immune system are able to recognize these microbial components that are shared among related microbes and are often essential for infectivity and thus cannot be mutated to allow the microbes to evade defense mechanism.
PAMP (Pathogen - associated molecular patterns)
NOD-like receptors are cytosolic receptors that are able to recognize a wide variety of substances such as 1, 2, and 3. Some NLR signals via 4 which is a cytosolic multiprotein complex which activates caspase 1 tha tcleaves a precursor form of the cytokiene IL-1 to generate active form. IL1 then recruits leukocytes and induces fever.
- Products of necrotic cells (uric acid and released ATP)
- Ion disturbances (e.g. loss of K)
- some microbial products
- inflammasome
Autoinflammatory syndrome, a periodic fever syndrome is a result of gain of function mutation in 1. Can be treated with 2.
- NLR’s
2. IL-1 antagonist
Aside from recognizing microbes, what other pathological conditions also uses the NLR-inflammasome pathway?
- Gout
- obesity-associated type 2 diabetes
- Atherosclerosis
On what cells are C-type lectin receptors located and what do they mainly detect?
Plasma membrane of macrophages and dendritic cells. Detects fungal glycans and elicits inflammatory reactions.
What part of the cell are RIG-like receptors located and what do they stimulate?
They are located in cytoplasm of infected cells and stimulates production of antiviral cytokines
In reaction of the innate immunity, antiviral defense is mediated by mainly what cytokine?
Type 1 interferons
Humoral and Cell-mediated are two types of adaptive immunity. For each, state what it protects against and what the main mediator is.
Humoral: protects against EC microbes and their toxins. Mediated by B-lyphocytes and Ig
Cell-mediated provides defense against IC microbes and is mediated by T lymphocytes
In lyphocyte diversity, explain what is meant by clonal selection
Lymphocytes specific for a large number of antigens exist before exposure to antigen and when an ag enters, it selectively activates the ag-specific cells. this specific selection is clonal selection.
how is ag receptor diversity accomplished?
somatic recombination of the genes that encode the receptor proteins.
During somatic recombination of lymphocytes, gene segment recombine in random sets and variations. What enzymes is this recombination mediated by?
RAG1 and RAG 2. inherited defects in these enzymes result in failure to generate mature lymphocytes
Analysis of antigen receptor gene rearrangement is a valuble assay for detecing tumors derived from lymphocytes. Explain how?
Because T and B cells and its clonal progeny have a unique DNA rearrangement (hence unique antigen receptor) it is possible to distinguish polyclonal (nonneoplastic) lymphocytes proliferation from monoclonal (neoplastic) lymphoid tumors.
95% of TCR is a heterodimer made up of what subunits?
alpha and beta polypeptide chains
TCR consisting of what subunits is able to recognize antigen presented by MHC on the surface of APC?
TCR made up up of alpha and beta subunits. this is what is meant by MHC restriction. it ensures that T cells sees only cell-assistance from MHC proteins.
A small population of T cells are 1 TCR and they recognize _ 2_.
- Gamma delta TCR
2. peptides, lipids, small molecules, without assistance.
Which class of TCR does not need MHC to recognize microbial peptides?
gamma delta
where are gamma delta TCR mainly found?
aggregates at epithelial surface (e.g. skin, GI, urogenital tract)
which subset of T cells express a limited diversity of TCR that which recognizes glycolipids that are displayed by MHC-like molecule CD1?
NK-T cells.
Which cluster of differentiation (CD) on APC binds to what CD on T cells, binding of which is the second signal in the CD4+ T cells and MHC interaction?
CD80/86 on APC and CD28 on T cells. this interaction is forms the 2nd signal.
which CD and proteins are invariant in all T cells and often used as markers to identifiy T cells in the lab?
CD3 and zeta proteins
In the BCR complex, which Ig are membrane bound?
IgM and IgD
Analogous to the CD3 and zeta on TCR, what proteins are seen on BCR that are similarly invariant?
Ig-alpha (CD79a) and Ig-beta (CD79b) proteins.
What receptors on BCR is able to recognize complement products generated during innate immune response to microbes?
CR2 aka CD21
On BCR, to what does EBV bind to gain entry into cell?
CR2
Which cluster of differentiation located on BCR receives signal from helper T cells via what ligand?
CD40 ( on BCR) binds CD40L on T helper.
Which cell is most important APC for initiating T cells response?
Dendritic cell
where are follicular dendritic cells found and are their functions?
Germinal centers of lymphoid follicles in the spleen and lymph nodes. traps ag bound to antibodies or complement proteins. Present antigens to B cells and select the highest affinity B cells.
CD16, a surface receptor for IgG, is a surface marker for what cell?
NK cells
What cells are able to lyse IgG-coated target cells (antibody-dependent cell mediated cytotoxicity (ADCC))?
NK cells
On what cells are CD56 found?
Nk cells
NK cells are regulated such that normal cells are not recognized for destruction. As such, _ receptors recognize surface molecules that are induced by various kinds of stress.
NKG2D
What cytokines does NK cells secrete that which activates macrophages to destroy ingested microbes?
IFN-y
What are innate lymphoid cells (ILCs) and what are their functions?
They are a population of lymphocytes that lack TCR but produce cytokines similar to T cells. Functions involved in early defense against infections, recognize and eliminate stressed cells and provide cytokines that influence the differentiation of T lymphocytes.
NK cells are regulated by many cytokines. Namely, IL-1 and IL-15 are involved in 1, while IL-12 is involved in _ 2_.
- stimulates proliferative cells
2. activates killing and secretion of INF-y
HLA genes are located on which chromosome?
6
MHC I are composed of which HLA subclasses and on which cells are they expressed?
HLA-A; HLA-B; HLA-C. Found on all nucleated cells and platelets.
MHC class I display what kind of microbes?
Intracellular microbial proteins. e.g. proteins from viral and tumor antigens inside the cytoplasm of cells.
MHC class II are mainly expressed on which cells and what HLA subclasses are they mainly?
Expressed mainly on macrophages, B cells, and dendritic cells. Encoded by HLA-D region with subclass: HLA-DP; HLA-DQ; HLA-DR
what are the cytokines involved in innate immune system?
TNF, IL1, IL2, Type I IFN, IFN-y, and chemokines
What are the cytokines involved in adaptive immune system?
IL2, IL4, IL5, IL 17, and IFN-y
which cytokines are involved in stimulating hemotopoiesis?
GM-CSF and IL-7
Cytokine antagonists are good form of therapy for many autoimmune disease. Which antagonists has a dramatic responses to rheumatoid arthritis?
TNF
During T cell activation and elimination of intracelllar microbes, earliest response of CD4 is to secrete 1 and high affinity receptors for 1. 1 is a growth factor that which via autocrine signaling acts on the T cell to activate it’s proliferation.
IL-2
Aside from action of IL2, Helper T cells are also mediated by 1. When CD4 recognize antigens being displayed by macrophages or B cells, these T cells express 1, which engages CD40 on APC and activates these cells.
- CD40L
The classical macrophage activation is a result of combined actions of 1 and 2.
- CD40
2. IFN-y
TH2 produces 1 which stimulates B cells to differentiate into IgE, and 2 which activates eosinophils.
- IL-4
2. IL-5
What activates macrophages via the alternative pathway?
TH2
what is the function of IL-17?
Recruit neutrophils and monocytes to destroy extracellular bacteria and fungi
_ is an imbalance between the effector mechanisms of immune responses and the control mechanism that limit responses.
Hypersensitivity
In Type I hypersensitivity, the injury is caused by effects of what cells?
TH2 cells, IgE, mast cells and leukocytes
In type I hypersensitivity, what do allergens bind to that which stimulate degranulation of mast cells?
IgE antibody on surface of mast cells.
What are the immediate reactions of type I hypersensitivity?
Occurs within minutes after exposure and subsides in a few hours.
- Vasodilation
- Vascular leakage
- Smooth muscle spasm or glandular secretion (depending on location)
What are some examples of late-phase reaction of type I hypersensitivity?
- Allergic rhinitis
- Bronchial asthma
How long does it take for late-phase reaction to take effect, and what are the mediators?
- 2-24 hours and can last for several days.
- Mediators: eosinophils, neutrophils, and basophils, monocytes and CD4 T cells.
Mast cells are the major mediators of type I hypersensitivity. What are some factors that can activate it?
- IgE bound to it’s surface and activation after antigen exposure
- Complement C5a and C3a
- Chemokines (IL8)
- Drugs
- adenosine
- mellitin (bee venom)
- physical stimuli (heat, cold, sunlight)
what are the major action of histamine?
- intense smooth muscle contraction
- increased vascular permeability
- increased mucus secretion
What does it mean when mast cells are sensitized?
IgE-coated mast cells, such that it becomes sensitive to subsequent encounter with specific antigen and all hell breaks loose.
Explain the process involved in type I hypersensitivity. What cells and cytokines are involved in each step?
- Exposure to allergen like pollen
- Allergen is recognized by dendritic cells who presents it to naive CD4 T cells and differentiates to CD4 TH2 cells who then presents the allergen to B cells. TH2 cell produces cytokines: IL4 which stimulates class switching of B cells to IgE and promotes development of more TH2 cells; IL5 activates eosinophils; and IL13 enhances IgE production and acts on epithelial cells to stimulate mucus secretion
- B cells undergoes class switching to produce IgE.
- IgE binds to FceRI on mast cells.
- Upon repeat exposure to that allergen it binds to IgE which is sitting on mast cell and the mast cells are activated and mediators are released.
- Mediators like vasoactive amines, lipid mediators and cytokines, of the mast cells then causes the hypersensitivity reactions.
Once mast cells are activated in the immediate reaction of type I hypersensitivity, what three actions are ensued by the mast cells?
- degranulation (histamine, protease released) (immediate response)
- Membrane phospholipids are activated to produce arachidonic acid and PAF (immediate response)
- Secrete cytokines and chemokines (involved in late phase reaction)
What are some contents of of the preformed mast cells?
- Vasocative amines: histamine which causes intense smooth muscle contraction, increased vascular permeability, and increased mucus secretion
- Enzymes: neutral proteases (chymase, tryptase) and several acid hydrolyses which causes tissue damage, acts on precursor proteins to: generate kinin and activate compounds of complement (e.g C3a.
- Proteoglycans: heparin: anticoagulant, and chondroitin sulfate
What are the lipid mediators of mast cells and how are they formed?
- Reaction in the mast cell membrane leads to activation of phospholipase A2 which converts membrane phospholipids to arachidonic acid and converts leukotrienes and prostaglandins.
- Leukotrienes C4 and D4 are the most potent vasoactive and spasmogenic agents known
- Prostaglandin D2 - causes intense bronchospasm and increased mucus secretion
- Platelet-activating factor (PAF) - causes platelet aggregation, release of histamine, bronchospasm, increased vascular permeability, and vasodilation
What are the cytokines of Mast cells and what effects do they have?
- TNF, IL1 and chemokines - promote leukocyte recruitment (late phase) - inflammation, epithelial cell damage,
- IL-4: amlifies the TH2 response
What is the mediator of late-phase reaction of type I hypersensitivity?
Eosinophils via proteolytic enzymes, major basic proteins, and eosinophil cationic protein
Atophy has been attributed as a genetic cause of allergies. What is atophy and what are its consequences?
Atophy - increased propensity to develop immediate hypersensitivity reactions. Have higher serum IgE levels and more IL4- produceing TH2 cells are present.
As a genetic cause of allergies, studies of patients with asthma shows linkage to polymorphism in what chromosome?
Chromosome 5 - genes encoding cytokines
what are the mediators of Non-atopic allergy, allergies that are triggered by like temperture and exercise?
Does not involve TH2 cells or IgE. Thought to be due to mast cells that are abnormally sensitive to activation
what specific category of hypersensitivity do these belong to:
- Anaphylaxis caused by drugs, bee sting, food
- Bronchial asthma
- allergies rhitis, sinusitis
- food allergies
Immediate hypersensitivity
What are some signs of systemic anaphylaxis?
- vascular shock, ,widespread edema, difficulty breathing.
- within minutes of exposure: itching, hives, erythema
- contraction of respiratory bronchoioles and respiratory distress
- laryngeal edema leading to hoarseness
- vomitting, abd cramps, diarrhea, laryngeal obstruction
What class of hypersensitivity do these belong to:
- autoimmune hemolytic anemia
- autoimmune thrombocytopenic purpura
- pemphigus valgaris
- vasculitis caused by ANCA
- Goodpasture syndrome
- Acute ehrumatic fever
- Myasthenia gravis
- Graves disease
- Insulin-resistance diabetes
- pernicious anemia
Type II
In type II hypersensitivity one way of cell damage is via opsinization and phagocytosis. Explain how and what is being opsinized and what causes the lysis of cell? Give examples
Cells are opsonized IgG or IgM and are recognized by phagocytes Fc receptors. this activates complement system via classical pathway. MAC complex is formed. Cells are lysed via ADCC (antibody-dependent cellular cytotoxicity). lysis without phagocytosis.
Examples: transfusion reaction (mismatched donor); hemolytic disease of newborn (erythroblastosis fetalis); autoimmune hemolytic anemia, agranulocytosis, thrombocytopenia; certain drug reaction like hapten.
In some forms of glomerulonephritis, vascular rejection in organ grafts, an example of type 1 hypersensitivity occurs how?
Type II. Occurs via Inflammation. Ab deposits on the fixed tissues of the basement membrane glomerulus. Deposited Ab activates complements, recruits polymorphonuclear leukocytes, monocytes and anaphylotoxin (C3a, C5a) which increase vascular permeability. Leukocytes produces substances like proteases that digests basement membrane, collagen, elastin, and cartilage and ROS.
Type II hypersensitivity as seen in graves disease and myasthenia gravis, explain the mechanism via how damage occurs.
Cellular destruction. Ab directed against cell surface receptors which impairs function without causing cell injury or inflammation as seen in myasthenia gravis. In Graves disease, ab against thyroid stimulating hormone receptor on thryoid epithelial cells stimulates cells leading to hyperthyroidism.
What is the general mode via how Type III hypersensitivity work?
Ag-Ab complexes (ag can be endogenous or exogenous) are deposited on specific sites, producing tissue damage mainly by eliciting inflammation at sites of the deposition, typically vessel walls (vasculitis), kidney (glomerulonephritis), joints (arthritis)
Acute serum sickness is a protype of systemic immune complex disease seen in what type of hypersensitivity?
Type III
Explain the pathogenesis of Acute serum sickness and some clinical signs. what organs are at risk? What can be monitored as disease activity?
- Formation of immune complex. protein ab triggers immune response and ab is formed typically a week after injection of protein. the Ab-Ag complex circulates in blood
- Deposition of immune complex in various tissues. Medium sized complex is more fatal.
- Inflammation and tissue injury: about 10 days after administration. signs include fever, urticaria, joint pains, lymph nodes enlargement and proteinuria appear. Organs where blood is filtered at high pressure to form other fluilds like urine, synovial fluid. Complements are detected at site of injury and C3 can be monitored for disease activity.
Explain the general mode of injury as seen in type IV hypersensitivity.
Caused by inflammation resulting from cytokines produced by CD4 T cells and cell killing by CD8 T cells.
Delayed type hypersensitivity (DTH) TB test is a prototype example of what specific type of hypersensitivity?
CD4 T cell-mediated Type IV hypersensitivity
Systemic lupus erythematosus; poststretocococal glomerulonephritis, polyartheritis nodosa (hep B viral ag), reactive arthritis (bacterial ag), serum sickness, and arthus reaction (foreign protein ag) are all examples of what kind of hypersensitivity?
immune complex-mediated disease of Type III hypersensitivity
Rheumatoid arthritis, MS, type I diabetes, IBD, psoriassis, and contact sensitivty are all examples of what kind of hypersensitivity?
T-cell mediated diseases of Type IV hypersensitivity
In mechnism of type IV hypersensitivity, explain the CD4 T cell-mediated inflammation stage of how CD4 T cell is activated.
Naive CD4 recognize peptides displayed by DC and secrete IL2 which stimulate proliferation of antigen-response T cells. Antigen-response T cells differentiates into either Th1 or Th17 based on cytokines produced by the APC.
As per mechanism of Type IV hypersensitivity, explain the responses of differentiated effector cell in causing CD4 T cell-mediated inflammation.
Repeat exposure to antigen leads to TH1 secreting cytokines IFNy which activates macrophages. These macrophages then has enhanced ability to phagocytose and kill, express more class II MHC molecules, secrete TNF, IL1 and chemokines leading to inflammation, and produces more IL-2 leading to amplification of TH1 response. Additionally, activated TH17 secrete IL17, IL22 and others–works to recruit neutrophils and mono, produce IL21 which amplifies TH17.
In a tuberculous infection, explain time frame of presentation, and morphological changes seen.
- colonizes lungs and others
- infiltrate is dominated by macrophages after 2-3 weeks
- sustained activation leads to macrophages that undergo a morphologic transformation into epithelioid cells which are large epithelium-like cells with abundant cytoplasm. this microscopic aggregation of the epitheliod cells, usually surrounded by lymphocytes is called granuloma (granulomatous inflammation
what are some examples of CD8 mediated type IV hypersensitivity
Type 1 diabetes
graft rejection after organ transplantaion
-certain tumors
Which of the following are T cell mediated disease: A. Type I DM B. MS C. Rheumatoid arthritis D. scleroderma E. Sjogren syndrome. F. All of the above G. None of the above
F. All of the above.
With regards to central tolerance, what is the difference between how B cells do it and how T cells do it?
T cells: NEgative selection or deletion where immature lymphocytes encounter antigens in the thymus and die by apoptosis or become T regs.
B cells: Many reactivate the machinery of antigen receptor gene rearrangement and express new antigen receptors called receptor editing.
Anergy is a mode of self tolerance as seen in which kind of tolerance?
Peripheral tolerance
Explain how anergy works.
Lymphocytes that recognize self antigens are rendered functionally unresponsive and occurs two possible ways: 1. when ag is presented to T cells by APC in periphery gets no or weak costimulator molecule expression
2. B cells encounter self antigen in peripheral tissues, and in the absence of specific helper T cells, the B cells become unable to respond to subsequent antigenic stimulation
Acceptance of fetus inside the mother’s uterus is deemed possible via a peripheral tolerance mechanism mediated by _
T reg cells, which works to prevent immune reactions against self antigens normally. Defects of T regs leads to recurrent spontaneous abortions
Explain what is meant by immune-privilaged sites and give some examples of such sites.
A protective mechanism for sites where antigens are hidden from the immune system and do not communicate with blood or lymph due to the fear that if antigens of these tissues are released can lead to prolonged tissue inflammation and injury that will can damage that sensitive site. Example Testis, eye, brain.
It is understood that many autoimmune diseases have associations with certain subtype of HLA alleles. Of the following, which disease has the strongest association of the HLA alleles as etiology of the disease? A. Rheumatoid arthritis B. Type I diabetes C. MS D. SLE E. Ankylosing spondylitis F. Celia disease
E. Ankylosing spondylitis. (allele B27) which has a odds ratio of 100-200 All the other ones listed most have odds of 1-10 with the exception of DM which could have up to 35.
Autoimmune disease mediated by infection is fairly common. What are two mechanisms of how infection plays a role in development of autoimmune disease?
- Induction of costimulators on APC. The microbial antigen provides the costimulation thats needed to activate the immune cells.
- Molecular mimicry. The microbe has antigen that looks a lot like the self antigen. For example, in rheumatic heart disease some streptococcal antigens look a lot like cardiac antigens.
1 antibodies are always seen in SLE, but is not diagnostic of the disease. However, detection of 2 antigens which are antibodies to _3_are virtually diagnostic of SLE.
- Antinuclear antibodies (ANA)
- Smith (Sm) antigen
- double strand DNA
Detection of what antibody is a good diagnostic feature of Sjogren syndrome, with 70-95% of cases?
Ro/SS-A
La//SS-B
In 30-40% of patients with lupus _ 1_antibodies are found. These antibodies may cause a false-positive test result (VDRL) for syphilis. These antibodies can interfere with clotting tests which is preferred to as lupus anticoagulant and produce a hypercoagulable state.
- Antiphospholipid Antibodies
While the etiology of SLE is not fully understood, it is believed to have both environmental and genetic involvement. Explain what genetic factors are involved in SLE.
- Specific alleles of the HLA-DQ locus have been linked to the production of anti-double stranded DNA, anti-Sm, and anti-phospholipid antibodies
- Some lupus patients have inherited deficiencies of early complement components and has impaired circulating immune complexes.
What are some environmental factors attributable to development of Lupus?
- exposure UV light
- Gender bias
- Drugs (hydralazine, procainamide, D penicillamine
- Microbiome
Morphologically, how does lupus present in blood vessels? In joints?
- Blood vessels: acute necrotizing vasculitis involving capillaries, small arteries and arterioles
- Joints: non-erosive synovitis with little deformity (opposite of rheumatoid arthritis)
How does SLE present in the Kidney? which one is the most common pattern seen in the kidney?
50% of SLE patients have renal involvement with glomerular deposits of immune complex. There are 6 patterns of glomerular disease:
- Minimal mesangial lupus nephritis (class I): see on EM only –
- Mesangial proliferative lupus nephritis (class II)
- Focal lupus nephritis (class III):
Explain how SLE presents on skin.
Butterly rash on face seen in 50% of cases. Similar rash on extremities and trunk. Exposure to sun makes it worse. On immunoflouresence: deposition of immunoglobulin and complement along the dermal epidermal junction is pretty clear and but not diagnostic since it can also appear in uninvolved skin and in disease like scleroderma and dermatomyositis.
Explain how SLE presents on cardiac tissue and other serosal tissues.
Can present in acute or chronic forms. In the acute form can be seen on mesothelial surfaces where it’s covered with fibrinous exudate. In chronic form, ti can become thickened, opaque and coated with shaggy fibrous tissue and lead to partial or total obliteration of the serosal cavity.
-pleural and pericardial effusion can present.
_ is form of nonbacterial endocarditis that is seen in association with SLE.
Valvular endocarditis aka Libman-sachs.
A 23 year old woman presents with hematuria, and proteinuria and some red cell casts. She states that she has been in and out of the hospital for the past months due to several severe infections due to her immunosuppressive drugs that she takes for her medical condition. On PE you find rashes over her cheeks and glabella which developed after being in outside for several hours at a ball game. She states that she normally avoids the sun, but her friend gave her these free tickets. What is the most likely diagnosis?
Systemic Lupus Erythematosus
How does chronic discoid lupus erythematosus present?
- primarily skin manifestations; rarely systemic.
- -skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border
- usualy face and scalp, but can occur anywhere
How does subacute cutaneous lupus erythematosus present?
- presents with predominant skin involvement
- distinguished from chronic discoid LE by: skin rash tends to be widespread, superficial and nonscarring. the lesions are not raised as you’d see in discoid lupus.
Drug-induced Lupus affects multiple organs, but involvement in what organs is very uncommon?
renal and CNS
what causes sjogren syndrome?
Immunological mediated destruction of the lacrimal and salivary glands leading to lymphocyte infriltration and eventual fibrosis.
a 56 year old diabetic patient presents complaining that lately her visions has gotten worse that it has become blurrier than usual and sometimes burns and itches. She also states that she it has become harder to eat solid food and has been on mostly liquid diet. Upon Pe you notice, cracks and fissures in the mouth, dryness of her buccal mucosa and nasal mucosa. Upon palpation you notice that her parotid gland is slightly enlarged. On urinalysis you find uricosuria, and phosphaturia and urine is slightly more acidodic than normal. You decide to do a biopsy of her cracked lips. what histological findings are you most likely to see?
Woman has Sjogren syndrome. Under the microscope you’ll find intense lymphocytic response in the tissues that are involved with a dominant B cell clone with some mixture of polyclonal T cells.
A 55 year old female presents complaining of hypomotility and respiratory difficulty and states that at times her heart “feels funny and irregular”. Upon PE you notice that her fingers are abnormally thickened. On urinalysis, you find mild proteinuria and other physical findings are suggestive of malignant hypertension. Upon further work up you come up with a diagnosis and you explain to the patient the findings of her fingers is due to _
Raynaud’s phenomenon. patient has scleroderma. Raynaud’s phenomenon is characterizd by episodic vasoconstriction of the arteries and arterioles of the exremities.
what morphological findings are likely in scleroderma?
Widespread damage to small blood vessels, progressive interstial perivascular fibrosis in the skin and then affects multiple organs. Myocardial fibrosis leading to arrhythmias or cardiac failure.
what clinical characteristics are seen in scleroderma ?
- chronic inflammation due to autoimmunity
- widespread damage to small blood vessels
- progressive interstitial and perivascular fibrosis in the skin (early) and multiple organs (GI, kidneys, heart, muscles, and lungs)
- Majority progress with death from renal failure, cardiac failure, pulmonary insufficiency, or malabsorption
- Raynaud phenomenon
- striking cutaneous changes
- Dysphagia –> hypomotility
- respiraotry difficulty
- myocardial fibrosis –> arrhythmias or cardiac failure
A patient presents with calcinosis, raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. what is the most likely diagnosis?
CREST syndrome. a limited version of scleroderma.
_ is a disease with clinical features that are a mixture of the features of SLE, systemic sclerosis, and polymyositis.
Mixed connective tissue disease.
Mixed connective tissue disease is not a distinct entity, but it is associated with some serious complication. Namely _
pulmonary hypertension, interstitial lung disease, and renal disease.
Enlargement and fibrosis of salivary and lacrimal glands is know as 1 syndrome. Along with Redel thyroiditis, idiopathic retroperitoneal fibrosis, and inflammatory pseudotumors of the orbit, lungs, and kidney, this disease is due to tissue infiltration by 2 antibody-producing plasma cells and lymphocytes.
- Miklics syndrome
2. IgG4
A 40 year old man with a history of autoimmune pancreatitis presents with storiform fibrosis and obliterative phlebitis. In laboratory findings you expect to find increased serum levels of _.
IgG4. These findings are suggestive of IgG4 related disease.
In organ graft rejection mechanism, which pathway (direct or indirect) donorAPC in the graft recognizes host MHC?
Direct pathway. In the indirect pathway, recipient’s APC recognizes graft cells.
during recognition of alloantigens in organ grafts, which pathway direct or indirect, damage is mediated CD8 T cells?
Direct pathway. Indirect pathway tissue damage and rejection is mediated by Ig.
A patient presents to ER with renal failure. You find out that patient has gotten a kidney transplant about a month ago, and you assume that the patient’s kidney is being rejected by the body. in such acute rejection, you presume that the signs and symptoms (increased vascular permeability and local accumulation of mononuclear cells) produced by this acute rejection is mediated by cytokines secreted by activated _ cells.
CD4 T cells.
Compared to acute cellular rejection which mainly affects the allografted the organs, chronic rejection lymphocytes react against allogantigens in _
vessel wall.
Hyperacute rejection is 1 mediated reactions, and is due to 2
- antibody mediated reaction
2. occurs when preformed antidonor antibodies are present int he circulation of the recipient.
what kind of recipients are at risk of hyperacute rejection?
- previous transplant
- prior blood transfusion
- multiparous women
In acute anti-body mediated rejection, what is the initial target of the antibodies?
graft vasculature.
what are some ways to increase graft survival?
- HLA matching (good idea for kidney, not so much for liver, heart, and lung transplant)
- immunosuppressive therapy
- T and B cell depleting antibodies
- pooled IVIg
- plasmapharesis in severe cases.
While immunosuppression works to increase graft survival, however, it reactivate some dormant bacterias and viruses. one such virus is polyoma virus which infects what specifically?
renal tubules.
With immunosuppression to increase graft survival, what disease are patients at risk of due to infections?
EBV-induced lymphomas
HPV-induced squamous cell carcinoma
Kaposi sarcoma (HHV8)
explain the basic mechanism in graft-vs-host-disease (GVHD)
immunologically competent cells or their precursors are transplanted into immunologically crippled recipients and the transferred cells recognize alloantigens in the host and attacks the host tissue.
how soon does acute GVHD take onset? and what does it affect mainly?
within days to weeks affects mainly immune system, skin, liver, and intestine
what are some consequences of chronic GVHD?
- extensive cutaneous injury
- chronic liver disease
- damage to GI tract may cause esophageal strictures
- immune system is devastated within involution of the thymus and depletion of lymphocytes in the lymph nodes
- autoimmunity
A six-year old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases?
A. DiGeorge Syndrome B. Severe Combined Immunodeficiency C. Hyper-IgM Syndrome D. Wiskott-Aldrich Syndrome E. Bruton's Agammaglobulinemia
B. SCID
Severe Combined Immunodeficiency (SCID) can be caused by various genetic defects, however, the most common autosomal recessive cause is a deficiency in adenosine deaminase (ADA).
A 3-year-old Cuban-American male has a history of recurrent Pseudomonas and Candida infections. Laboratory analysis reveals no electrolyte abnormalities. Examination of his serum shows decreased levels of IgG and CT scan reveals the absence of a thymus. The child likely has:
A. Severe combined immunodeficiency syndrome
B. X-linked agammaglobinemia
C. DiGeorge syndrome
D. Isolated IgA deficiency
E. Common variable immunodeficiency
A. SCID
Recurrent infections with fungal and bacterial pathogens are likely the result of defective T and B cell immunity. Severe combined immunodeficiency syndrome (SCID) is the only disorder of both B and T cell lineages present among the answer choices. It also results in the absence of a thymic shadow.
A 2-year-old Caucasian male presents with recurrent diaper rash and oral thrush. He has also experienced recurrent episodes of otitis media from repeat Streptoccous pneumoniae. What disease is the child suffering from?
A. X-linked agammaglobulinemia B. Isolated IgA deficiency C. Severe combined immunodeficiency D. DiGeorge syndrome E. MHC class II deficiency
A. SCID.
The patient has difficulty in his immune response to both fungal (Candida) and bacterial (S. pneumonia) infections. This reflects a deficiency in both cell-mediated (T-cell) immunity and humoral (B-cell) immunity. Therefore, combined immunodeficiency is the most likely cause of this patient’s symptoms.
A 30-year-old Caucasian male is brought to the emergency room for recurrent diarrhea. He has had multiple upper respiratory infections since birth and does not take any medications at home. It is determined that Giardia lamblia is responsible for the recurrent diarrhea. The physician performs a serum analysis and finds normal levels of mature B lymphocytes. What other finding on serum analysis predisposes the patient to recurrent diarrheal infections?
A. Deficiency in CD8+ T cells B. Deficiency in neutrophils C. Deficiency in IgA D. Deficiency in NK cells E. Deficiency in IgG
C. Deficiency in IgA
The patient has common variable immunodeficiency disorder (CVID), which leads hypoagammaglobulinemia. Specifically, the patient has a deficiency in IgA, therefore he has an increased susceptibility to Giardia infection.
A 7-year-old boy presents to your office with facial eczema. He has a history of multiple, recurrent infections, including multiple episodes of pneumonia that lasted several weeks and otitis media. Laboratory measurements of serum immunoglobulins showed increased IgE and IgA but decreased IgM. Which of the following additional abonormalities would you expect to observe in this patient?
A. Thrombocytopenia B. Leukopenia C. Anemia D. Pancreatic insufficiency E. NADPH oxidase deficiency
A. Thrombocytopenia
The patient in the question stem is suffering from Wiskott-Aldrich syndrome, a congenital immunodeficiency. Wiskott-Aldrich syndrome presents with the classic triad of “TIE”: (1) thrombocytopenic purpura (2) infections (3) eczema.
Which of the following patient presentations seen in a pediatric immunology clinic is most consistent with a diagnosis of Bruton’s agammaglobulinemia?
A. A 15-month-old girl who has had repeated otitis media, pneumonia, and progressive clumsiness since beginning to walk in the past three months
B. A 10-month-old boy who has had recurrent viral infections as well as hypocalcemia during neonatal period
C. A 4-year-old girl who has had repeated oral candidasis in the past nine months
D. A 9-month-old boy who has had recurrent otitis media and pneumococcal pneumonia in the past three months
E. A 7-month-old boy who has had recurrent pneumococcal pneumonia, eczema, and easy bruising in the past four months
D. A 9-month old boy who has had recurrent otitis media and pneumococcal pneumonia in the past three months.
Bruton’s agammaglobulinemia is an X-linked defect characterized clinically by recurrent sinopulmonary bacterial infections occurring beginning around 6 months of life, when maternally-derived IgG levels wane.
You are seeing a 4-year-old boy in clinic who is presenting with concern for a primary immune deficiency. He has an unremarkable birth history, but since the age of 6 months he has had recurrent otitis media, bacterial pneumonia, as well as two episodes of sinusitis, and four episodes of conjunctivitis. He has a maternal uncle who died from sepsis secondary to H. influenza pneumonia. If you drew blood work for diagnostic testing, which of the following would you expect to find? A. Abnormally low number of B cells B. Abnormally low number of T cells C. Abnormally high number of B cells D. Abnormally high number of T cells E. Elevated immunoglobulin levels
A. Abnormally low number of B cells
This patient has X-linked (Bruton’s) agammaglobulinemia, which results in an abnormally low number of B cells.
A 7-month-old Caucasian male presents with recurrent sinusitis and pharyngitis. The parents say that the child has had these symptoms multiple times in the past couple of months and a throat swab sample reveals the presence of Streptoccocus pneumoniae. Upon workup for immunodeficiency it is noted that serum levels of immunoglobulins are extremely low but T-cell levels are normal. Which of the following molecules is present on the cells that this patient lacks? Topic Review Topic
- CD4
- CD8
- CD3
- CD19
- NKG2D
D. CD19
The lack of immunoglobulins and the recurrent bacterial infections indicate a deficiency in B cell-mediated immunity. CD19 is an important cell-surface receptor present on B-cells.
While playing in the woods with friends, a 14-year-old African-American male is bitten by an insect. Minutes later he notices swelling and redness at the site of the insect bite. Which substance has directly led to the wheal formation?
- IFN-gamma
- Histamine
- IL-22
- Arachidonic acid
- IL-4
- Histamine
A 32-year-old female presents with a three month history of oral ulcerations and blisters throughout her body. When the physician examined the skin, she noted that when the skin was rubbed it sloughed off and formed blisters within a few minutes. A skin biopsy was performed and analyzed via immunofluorescence using anti-IgG antibodies. Which of the following antibodies is also involved or found in a similar type of hypersensitivity reaction as in the case mentioned?
- IgE against the proteins in apitoxin
- Anti-glomerular basement membrane
- Anti-dsDNA
- IgE against pollen
- Anti-Smith
- Anti-glomerular basement membrane
The female in the clinical vignette has pemphigus vulgaris which is a type II hypersensitivity reaction caused by antibodies against desmosomes, specifically the protein desmoglein 3. Anti-glomerular basement membrane antibodies cause Goodpasture’s syndrome which is a type II hypersensitivity reaction.
A 32-year-old pregnant woman (para 2) presents to the clinic for a routine ultrasound; The fetus has become anemic and levels of unconjugated bilirubin have increased dramatically. Which type of hypersensitivity reaction has occurred and what is mediating the disease state?
- Type I hypersensitivity; antibody-mediated opsonization
- Type II hypersensitivity; antibody-mediated opsonization
- Type II hypersensivity; cell killing via cytotoxic T cells
- Type III hypersensitivity; cell killing via cytotoxic T cells
- Type IV hypersensitivity; cell killing via NK cells
- Type II Hypersensitivity; antibody-mediated opsonization
The clinical presentation and ultrasound is consistent with hydrops fetalis, an example of a type II hypersensitivity reaction, in which antibodies bind to antigens on a cell’s surface leading to phagocytosis or lysis. Note the presence of edema in the ultrasound image.
A 28-year-old female suffering from a urinary tract infection is given trimethoprim-sulfamethoxazole (TMP-SMX) by her physician. As a result of the medication, she begins to experience itchiness and joint pain. Laboratory and histologic analysis reveals vasculitis and antibody complexes deposited near the basement membrane of the glomerulus. What other serological finding is expected with this presentation?
- Decreased levels of IgE
- Increased levels of IgE
- Decreased neutrophil count
- Increased serum levels of complement protein C3
- Lowered serum levels of complement protein C3
- Lowered serum levels of complement protein C3
The patient presents with serum sickness as a result of an immune reaction to the TMP-SMX she was prescribed for her urinary tract infection. Serum sickness is the result of immune complex deposition in various tissues of the body which activate/consume C3 and result in decreased serum levels of C3.
A 30-year-old Caucasian male presents with hemoptysis and uremia. Blood tests show the presence of anti-basement membrane antibodies specific for collagen located in glomerular and pulmonary basement membranes. The patient undergoes plasmaphoresis to help reduce the amount of anti-basement membrane antibodies. Which of the following diseases is of the same hypersensitivity category as this disease?
- Myasthenia gravis
- Systemic lupus erythematosus
- A PPD test
- Seasonal allergies
- Poison ivy rash
- Myasthenia gravis
The disease the above patient presents with is Goodpasture’s syndrome (anti-glomerular basement membrane disease), a type II hypersensitivity reaction (antibodies are generated that bind to an aspect of collagen IV molecules located in the basement membrane of glomeruli and alveoli). Myasthenia gravis is also a type II hypersensitivity reaction.
While hunting, a 45-year-old Caucasian male is stung by a bee. He begins to feel unwell and is taken to the hospital. Upon arrival, it is noted that the patient is hypotensive with a blood pressure of 60/40 mmHg. Furthermore, the patient is tachycardic and edematous. What is responsible for this patient’s presentation? Topic Review Topic
- Free IgE binding to the antigen
- IgE on mast cell surfaces binding to the antigen
- IgE activation of complement
- Complexes of IgE binding to the antigen
- IgE on eosinophils binding to the antigen
- IgE on mast cell surfaces binding to the antigen
The patient is experiencing systemic anaphylaxis from the bee sting. The direct effect in a sensitized individual antigen challenge is cross-linking of IgE antibodies on the surface of mast cells, resulting in the systemic activation and degranulation of mast cells.
A 5-year-old African American female has experienced recurrent respiratory infections. To determine how well her cell-mediated immunity is performing, a Candida skin injection is administered. After 48 hours, there is no evidence of induration at the injection site. Of the following cell types, which one would have mediated the reaction?
- Plasma cells
- Basophils
- T-cells
- Mast cells
- Fibroblasts
- T-cells
As most people have been previously exposed to Candida, Candida skin injection is a good test for examining delayed-type hypersensitivity and T-cell-mediated cellular immunity.
You are working in the emergency room of a children’s hospital when a 4-year-old girl is brought in by ambulance due to “difficulty breathing.” The patient had been eating lunch on a school field trip when she suddenly complained of abdominal pain. Shortly thereafter, she was noted to have swelling of the lips, a rapidly developing red rash and difficulty breathing. In the ambulance her blood pressure was persistently 80/50 mmHg despite intramuscular epinephrine. In the course of stabilization and work up of the patient, you note an elevated tryptase level. What is the mechanism behind this elevated tryptase level? Topic Review Topic
- IgG production by plasma cells
- IgM mediated complement activation
- Cross-linking of IgE on mast cells
- Antibody-antigen immune complexes
- Cross-linking of IgG on mast cells
- Cross-linking of IgE on mast cells
This patient has an anaphylaxis reaction to something she ate. Anaphylaxis is mediated by antigen cross-linking of IgE on mast cells leading to activation and the release of several molecules, including tryptase.
A 3-month-old is referred to a pediatric immunologist by his pediatrician for further workup of recurrent sinopulmonary infections which have not abated despite adequate treatment. During the course of the workup, a lymph node biopsy is obtained which is demonstrated in Figure A. Based on these findings, the immunologist decides to pursue a further workup and obtains immunoglobulin levels. Which of the following immunoglobulin profiles is most likely to be observed in this patient?
- Increased IgE; Decreased IgG, IgM
- Decreased IgE, IgM, IgA, IgG
- Increased IgE, IgA; Decreased IgM
- Increased IgE
- Increased IgM; Decreased IgG, IgA, IgE
- Increased IgM; Decreased IgG, IgA, IgE
Increased IgM and decreased IgG, IgA, and IgE is characteristic of hyper-IgM syndrome, which causes severe pyogenic infections and lymphoid hyperplasia (Figure A) in the first months of life.
A 3-year-old boy presents to the pediatrics clinic for follow-up. He has a history of severe pyogenic infections since birth. Further workup revealed a condition caused by a defect in CD40 ligand expressed on helper T cells. This congenital immunodeficiency has resulted in an inability to class switch and a poor specific antibody response to immunizations. One would expect the following on laboratory workup?
- Increased IgE
- Decreased IgA
- Decreased Interferon gamma
- Increased IgE and IgA; and decreased IgM
- Increased IgM; decreased IgG, IgA, and IgE
- Increased IgM; decreased IgG, and IgE
Hyper-IgM syndrome is caused by a defective CD40L on helper T cells resulting in an inability to class switch. Patients have an immunodeficiency characterized by high levels of IgM with a deficiency of IgA, IgG, and IgE, as well as a poor specific antibody response to immunization.
A 32-year-old Caucasian female required a kidney transplant 3 years ago. She presents with elevated creatinine levels (2.6 mg/dl) and an elevated blood pressure (160/90 mmHg). A biopsy is taken of the transplanted kidney. Following histological findings, a diagnosis of chronic graft rejection is made. Which of the following is NOT a likely finding?
- Interstitial fibrosis
- Glomerular destruction
- Tubular atrophy
- Graft arteriosclerosis
- Glomerular crescents
- Glomerular crescents
Chronic graft rejection of a transplanted kidney typically manifests with hypertension and elevated creatinine. Upon renal biopsy, fibrosis in the interstitium, glomerular and tubular atrophy, and arteriosclerosis are often seen.
A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms?
- Donor T-cells
- Recipient T-cells
- Donor B-cells
- Recipient B-cells
- Recipient antibodies
- Donor T-cells
The patient in the question is suffering from graft-versus-host disease (GVHD) following liver transplantation. In GVHD there is donor T-cell-mediated attack of recipient tissues.
Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation?
- Donor T-cells
- Recipient T-cells
- Preformed recipient antibodies
- Donor antibodies
- Deposition of antibody immune complexes
- Recipient T cells
The patient presents with acute rejection of her transplanted organ. This process contains elements of Type II and IV hypersensitivity reactions mediated by recipient T lymphocytes and antibodies which are NOT preformed.
A 45-year-old female is undergoing renal transplantation for management of chronic renal failure secondary to glomerulonephritis. The transplant surgeon placed the donor kidney in the recipient and anastamosed the donor renal artery to the recipient’s external iliac artery as well as the donor ureter to the recipient’s bladder. After removing the clamps on the external iliac artery, the recipient’s blood is allowed to perfuse the transplanted kidney. Within 3 minutes, the surgeon notes that the kidney does not appear to be sufficiently perfused. Upon further investigation, an inflammatory reaction is noted that led to clotting off of the donor renal artery, preventing blood flow to the transplanted organ. Which of the following best describes the pathophysiology of this complication?
- Type I hypersensitivity reaction
- Type II hypersensitivity reaction
- Type III hypersensitivity reaction
- Type IV hypersensitivity reaction
- Graft-versus-host disease
- Type II hypersensitivity reaction
This patient is suffering from hyperacute rejection of the transplanted organ, occurring within minutes after the transplantation. Hyperacute rejection is a type II hypersensitivity reaction caused by preformed antidonor antibodies in the transplant recipient.
A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney?
- Sloughing of proximal tubular epithelial cells
- Lymphocytic infiltrate of the tubules and interstitium
- Drug precipitation in the renal tubules
- Granular immunofluorescence around the glomerular basement membrane
- Crescent formation in Bowman’s space
- Lymphocytic infiltrate of the tubules and interstitium
Cell-mediated, acute allograft rejection occurs when cytotoxic T lymphocytes react against foreign MHCs. It is marked histologically by lymphocytic infiltrate of the tubules and interstitium.
The usual presentation of infants with SCID appears as _
- prominent thrus (oral candidiasis)
- extensive diaper rash
- failure to thrive
- some infants delveop GVDH rash
- extremely susceptible to recurrent infections with c. albicans, p. jiroveci, CMV and others
X-linked agammaglobulinemia is due to _
Failure of B-cells precursors (pro B cells and pre B cells) to devleop into mature B cells.
In laboratory findings, your 6 month old patients shows normal T cells, however, plasma cells are absent, serum levels of all classes of Ig are depressed with virtually no B cells in circulation. 1. This patient is mostly like susceptible to what bacterias?
- what is the diagnosis?
- what is a possible treatment?
- Opportunistic bacterias of the respiraotry tract: Haemophilus influenzae, strep, staph
viruses in bloodstream or mucosa : enteroviruses, echovirus, poliovirus, coxsackievirus
- GI: giardia lambia - X-linked agammaglobulinemia
- replacement therapy with immunoglobulins
What is the embryonic cause of DiGeorge syndrome?
Failure of development of the third and fourth pharyngeal pouches.
A 24-year-old woman with a history of allergic rhinitis is involved in an automobile accident and sustains a splenic laceration. She undergoes abdominal surgery and is then transfused with four units of blood of the appropriate ABO and Rh type. As the transfusion progresses, she becomes rapidly hypotensive and develops airway edema, consistent with anaphylaxis. Which of the following pre-existing conditions best accounts for these symptoms?
(A) AIDS (B) C1 esterase inhibitor deficiency (C) DiGeorge syndrome (D) Selective IgA deficiency (E) Wiskott-Aldrich syndrome
The correct answer is D. Patients with selective IgA deficiency may have circulating antibodies to IgA. Fatal anaphylaxis may ensue if they are transfused with blood products with serum containing IgA, although many patients with selective IgA deficiency are asymptomatic and never diagnosed. Symptomatic patients may have recurrent sinopulmonary infections and diarrhea, as well as an increased incidence of autoimmune and allergic diseases.
A patient with loss of T cell meidated immunity has poor defense against certain fungal and viral infections. Patient also has frequent tetany due to hypocalcemia. On ECHO, it is noted that patient also has some defects of the heart and great vessels. The patient also some obvious abnormal appearance of mouth, ears and facies. This syndrome is considered a component of what other syndrome?
The finding describes DiGeorge syndrome. DiGeorge syndrome is a component of 22q11 deletion syndrome.
What is the cause of hyper-IgM syndrome?
Due to defect in ability of helper T cells to deliver activating signals to B cells and macrophages. As a result pt makes IgM antibodies but can’t produce IgG, IgA, and IgE antibodies.
Pt is being treated for a recurrent pneumococci infection (a pyogenic virus). On labs you find that patient is thrombocytopenic and neutropenic, and elevated IgM, however depressed IgG, IgA and IgE. Patient also requires a blood transfusion due to his hemolytic anemia acting up. what is the likely diagnosis?
Hyper-IgM syndrome
A mother brings her 10-year-old girl to the pediatrician for a routine visit. During the visit, the girl comments that recently she has been having difficulty with her balance and has been falling more than usual. She also complains of a rash on her face that has not resolved despite trying multiple over-the-counter treatments (Figure A). The pediatrician is concerned and pursues a full workup during which the patient’s alpha-fetoprotein (AFP) level is found to be elevated. Which of the following is the most likely cause of this patient’s symptoms? Topic Review Topic
FIGURES: A
- Defect in cellular transport
- Defect in cell surface receptor
- Defect in actin cytoskeleton function
- Defect in microtubule function
- Defect in DNA repair
- Defect in DNA repair
This patient is presenting with ataxia-telangiectasia characterized by cerebellar defects, telangiectasias, and IgA deficiency. It is caused by a defect in cellular DNA repair enzymes.
In patients with common variable immunodeficiency, would you expect to have normal, elevated, diminished, or NO B cells?
Normal or near normal number of B cells. (as opposed to X linked agammaglobulinemia
A white 24 year old woman presents to the ER with severe lung infection and complains of frequent watery bowel movement. You culture pt’s stool and is positive to giarda lambia. Upon checking labs, you notice that patient is severely anemic and tells you that she’s on treatment for Lupus. You make note that this patient should not be transfused with blood containing _.
IgA. Patient has Isolated IgA deficiency and transfusion of IgA can lead to severe anaphylactic reaction because the IgA behaves as foreign to the body.
How does Wiskott-Aldrich syndrome present?
- X linked
- Thrombocytopenia, eczema, and recurrent infection
TO remember: Wiskott- Aldrich Syndrome = W-A-S Triad
W- Weeping skin lesions- eczema
A- Absent platelets- thrombocytopenia - leading to petichiae
S- Severe immunodeficiency…… (low IgM and high IgA & IgE levels)
How does Ataxia-telangiectasis present?
- Autosomal recessive
- abnormal gait (ataxia) vascular malformation (telangiectasis) neurologic deficits, increased incidence of tumors and immunodeficiency.
What glycoproteins do HIV virus use to bind to host CD4 cells?
GP120 and gp41
what is the major capsid protein on HIV virus?
p24
ELISA test detects what protein to diagnose HIV infection?
p24
what cells do HIV virus infects first?
T cells, DC, and macrophages (all have CD4)
What host chemokine receptors does HIV virus use to preferentially infect cells of monocyte/macrophages linage (M tropic)?
CCR5, main used by R5 strain of the virus
X4 strain of HIV virus uses what chemokine receptor to infect T cells (T tropic)
CXCR4
Why is HIV unable to infect naive T cells?
Naive T cells contains an active form of the enzyme APOEBC3G which causes mutation in the HIV genome thus making the HIV unable to infect.
HIV is pretty darn resilient once it has gained entry into a host such that it can degrade APOEBC3G via what viral protein?
Vif
HIV1 can infect and multiply in termianlly differentiated non-dividing macrophages via use of what viral gene?
vpr
90% of acute HIV infections is predominantly of what strain?
M-tropic
Patients with AIDS can’t mount antibody responses to newly encountered antigens, why?
HIV causes polyclonal activation of B cells leading to germinal center B cell hyperplasia, bone marrow plasmacytosis, and hypergammaglobulinemia and produces circulating immune complexes. Essentially diminishes the B cell’s ability to recognize new things.
what are the signs/symptoms of acute retrovial syndrome and what is the time frame of it’s onset and resolution?
Sore throat, myalgias, fever, weight loss, fatigue, rash, cervical adenopathy, diarrhea, and vomitting. Typically occurs 3-6 weeks after infection and resolves within 2-4 weeks.
What are some ways, HIV evades immune detection?
- destroys CD4 T cells that are critical for effective immunity
- antigenic variation
- down modulation of class I MHC molecules on infected cells
Amyloidosis is caused by:
A. Extracellular deposits of fibrillar proteins
B. Intracellular deposits of fibrillar proteins.
C. Extracellular deposit of collagen
D. Intracellular deposit of collagen
A. Extracellular deposits of fibrillar proteins.
Amyloidosis secondary to chronic inflammatory disorder typically involves what organs/tissues?
- kidney
- liver
- spleen
- lymph nodes
- adrenals
- thyroid
Amyloidosis associated with plasma cell proliferation typically involves what organ/tissue?
- heart
- GI Tract
- Respiratory tract
- Peripheral nerves
- Skin
- Tongue
How is Amyloidosis diagnosis usually confirmed?
Tissue biopsy with congo red stain for amyloid
