DD/BL - Unit 3
What does the KOH smear look like for tinea versicolor?
"spaghetti and meatballs"
Describe the morphology of BL
'Starry sky' pattern at lower power.
What is the appearance of the skin in a PXE patient?
'plucked chicken' appearance.
Which of the UV categories (A, B, C) is the main cause of sunburn and vitamin D3 formation? Which is associated with the incidence of melanoma? Which penetrates skin more?
D3: UV- B Melanoma: UV-A, and UV-B More penetration; UVA (longer wavelength)
What is a major concern for patient health in APML? What test is administered for this?
DIC Disseminated Intravascular Coagulation. Fibrinogen: Will be low cos body using it all up in DIC
List skin defenses against ultraviolet radiation.
DNA repair Apoptosis of cells with DNA damage Defense against ROS: peroxidases, catalases, SOD, Glutathione reductase, hioredoxin reductase Melanin - shields keratinocytes.
What are ultraviolet radiation effects on the skin?
Damage to DNA/RNA, Lipids, Proteins Pro-inflammatory Immunosuppressive Induction of innate defenses Induction of Apoptosis Vitamin D synthesis
What is UVR's role in immunosuppression?
Decreases Langherans Cell populations (DC of the skin) Induces Inhibitory cytokines: IL-10, Th2 activity Tolerance Induction: NKT and Treg cells induce tolerance in the T-cells that are present.
What is the classification system for topical corticosteroids?
Defined as categories 1-7 based on potency 1 = Superpotent 7 = Low Potency
What is the most common genetic mutation in CLL?
Deletion of 13q14
Contrast acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in regards to demographics of affected patients, and prognosis.
Demographics: ALL: Rare, 75% of cases are in children under 6 (mostly in the young) AML: Extremely rare, Avg age at diagnosis = 65 (mostly in the elderly) Prognosis ALL: • Children; ~95% remission, 80% cured • Adults: ~70% remission, 50% cured AML: • Worse prognosis. Mean survival ranges from less than a year to just over 10 years. • 60% remission after chemo.
List and describe major cell types involved in anti-viral responses
Dendritic Cells - presenting viral peptide to T-cells NK Cells - containing infection until CTLs can mount specific attack and clear. B-cells - Ab recognize virions, even at surface of infection T-cells - recognize Kill and clear virus infected cells
What is a Langheran cell?
Dendritic cells of the skin and mucosa. They are APC.
What is the difference between stasis dermatitis and cellulitis?
Dermatitis affects the dermis AND epidermis. Cellulitis only affects dermis (So lesions are not as on the surface) Dermatitis: Due to venous insufficiency/edema Cellulitis: Due to infection. Dermatitis - papules, thin plaques with SCALE (scale=epidermis affected, very surface) Also: dermatitis - more itchy. Cellulitis - more pain.
What is a benign tumor of fibroblast origin? What is the diagnostic sign we discussed? How are they treated?
Dermatofibroma Diagnostic: Pinching the sides, looking for the 'dimple sign' where the tumor depresses into the skin a bit. Treatment: Surgical excision.
DIAGNOSE: Purple eyelids, looks like eye shadow, erythema/dryness/fissuring on hands, erythematous widespread area over shoulders, upper back, and upper chest in a V.
Dermatomyositis - Skin findings include purple, heliotrope rash on eyelids, shawl sign on upper torso, erythema/dryness/fissuring or palms, cuticle changes, erythema on dorsal hands over joints (Gottron's papules) i. Important because can be associated with pulmonary fibrosis and GI CANCER, especially in women with rapid onset of severe symptoms
What is the infectious agent in Tinea cases?
Dermatophytes
What are the food sources for: Dermatophytes Candida Yeast involved in Tinea Versicolor
Dermatophytes: Keratin Candida: Sugars, glucose Yeast involved in Tinea Versicolor: Follicular lipids
What is a subtype of Seborrheic keratosis that Morgan Freeman has on his face?
Dermatosis Papulosa Nigra
What type of junction protein connects basal keratinocytes to each other?
Desmosomes.
What is leukoerythroblastosis?
Destruction or crowding out of hematopoietic tissues in the bone marrow by a space-occupying lesion. Results in immature granulocytes, dacrocytes, and nucleated RBC in peripheral blood.
Describe the mechanism behind the observed lymphopenia in Di George syndrome
Di George - failure to develop 3rd and 4th pharyngeal pouch = failure to develop the thymus = failure of T-cells to mature => low number of circulating lymphocytes overall.
Discuss transplantation therapy in immunodeficiency diseases (specifically DiGeorge and SCID). Include a consideration of possible complications.
DiGeorge - Transplant of fetal thymic stroma has proven useful SCID - Marrow transplant works 50% of the time, but graft-versus-host is an issue.
What increases the risk of infection via candida?
Diabetes Corticosteroids Broad-spectrum antibiotics Occlusion
What are the risk factors for gout?
Diet: meat, seafood, fructose (fruit sugar) inc uric acid Alcohol: Esp beer, inc risk Obesity: body makes more uric acid, kidneys secrete less Rx: thiazide diuretics and low dose aspirin (among others) Family History Sex: Men > women Recent Surgery or trauma
What is secondary myelodysplasia and what can cause it?
Different syndrome that mimics MDS. - Certain drugs, including many chemotherapeutic drugs - Deficiencies of vitamin B12, folic acid, or certain essential elements - Viral infection - Toxin exposure, especially heavy metals such as arsenic
What is the most common non-Hodgkins lymphoma?
Diffuse Large B-Cell Lymphoma
Which lymphoma is characteristic of a complete effacement of lymph node architecture?
Diffuse large B-cell lymphoma
Describe direct and indirect cell damage in viral infection and give examples
Direct: The virus itself, in its replication and egress, harms the cell directly Indirect: Viral genome integration causes inflammation and hose immune response.
What is Myasthenia Gravis? What is its mechanism?
Disease of progressive muscle weakness. Immunopathologic Ab against Acetylcholine receptor (AChR). Ab gather, bind AChR, activate complement which causes overall destruction of the euro-muscluar junction. T-cell selection process hindered due to AIRE disfunction. Anti-self T-cells escape selection process.
What is the most common physical location of stasis dermatitis?
Distal lower extremities, medial side.
Describe antigenic drift and shift and how they affect Influenza A and B
Drift: Gradual Amino Acid changes in hemagglutinin or neuraminidase. These variations exist for a few years before being replaced. Shift: Introduction of novel hemagglutinin or neuraminidase into human flu. Usually from another species (birds, swine..)
What is a mineral oil prep?
Drop a little mineral oil on infected skin, scrape skin into mineral oil, place on slide for analysis.
What is the clinical presentation of stasis dermatitis?
Dryness Itching Allergic contact dermatitis (owing to topical antibiotics) Irritant Dermatitis due to wound exudates
Why do many LYMPHOMAS contain genomic translocations?
Due to the process (VDJ) by which B-cells and T-cells attain mature Immunoglobulin and TCRs. There is ALREADY translocation and rearrangement occurring to produce these VDJ genetic combinations. Malignancy, in part, is instigated by derangement of this process.
What is this: Often described as having a "fried-egg" appearance, they typically have a dome-shaped central brown papular component surrounded by a flatter zone of light brown or tan pigmentation
Dysplastic Nevi
Match the congenitally defective protein with the type of Epidermolysis Bullosa: Collagen VII Laminin-5 Keratin filaments 5 and 14 Dystrophic Epidermolysis Bullosa Junctional Epidermolysis Bullosa Epidermolysis Bullosa Simplex
Dystrophic Epidermolysis Bullosa - Collagen VII Junctional Epidermolysis Bullosa - Laminin-5 Epidermolysis Bullosa Simplex - Keratin filaments 5 and 14
Why are cases of allergic contact dermatitis more prevalent in the US than the EU?
EU has tighter regulations on nickel and fragrance content overall.
What are the two common ways a pathogen can get across an epithelial layer?
Either around the cells or through em Can go between lateral membranes of cells or infect the epithelial cells themselves, which may result in the passage of the pathogen to the other side.
Who is most susceptible to cellulitis?
Elderly, children, anyone immune compromised.
Describe basic methods for studying viruses
Electron microscopy Animal models Sequence analysis Cell culture Serology other molecular techniques
Describe typical stages in pathogenesis of an infectious disease.
Encounter Entry Spread Multiplication Damage Outcome
If eosinophils can kill worms, why do M2 macrophages try to wall them off?
Eosinophils can not kill some worms. in these cases M2 act to wall off the invader.
Why can eosinophils kill worms and neutrophils can't?
Eosinophils contain Major Basic Protein which is cytotoxic to helminths, neutrophils do not have this.
What is known as the 'socks and jocks' fungi?
Epidermophyton. Mostly affects groin and feet.
What virus is present in a large amount of endemic BL?
Epstein Barr virus
List three viruses known to have oncogenic roles in some cases of lymphoma.
Epstein-Barr - implicated in Hodgkin's Lymphoma & Burkitt's Lymphoma Human T-Cell Leukemia Virus 1 (HTLV-1) - Implicated in adult T-cell leukemia/lymphoma Kaposi sarcoma herpesvirus/Human herpesvirus 8 (KSHV/HHV-8) - implicated in primary effusion lymphoma
DIAGNOSE: Large painful nodules on knees, lower legs, shins .
Erythema Mendoza
What is the medial term for a scab?
Eschar
MPN: A patient has digital ischemia with paresthesias but no thrombosis noted in the splenic, mesenteric or portal veins. What MPN disorder does this signify?
Essential Thrombocythemia
MPN: A patient has normal cell counts in the peripheral blood but large, irregular megakaryocytes in the marrow. What MPN disorder does this signify?
Essential Thrombocythemia
What is an exanthematous eruption?
Exanthem = rash Exanthematous eruption = rash all over the body.
Where on the body are specialized apocrine glands located?
Eyelids - Moll's glands Breasts - Lactation glands Ears - Cerumen glands (ear wax)
True or False Hydrophilic topical medications penetrate the skin more readily than hydrophobic topical medications.
FALSE
True or False You can administer live vaccines to immunodeficient patients
FALSE
True or False In viruses, transmission is only possible when patient is experiencing symptoms
FALSE
True or False The nerves that sense pruritus and pain in the dermis are the same nerves.
FALSE
True or False Type IV immunopathology involves antibodies
FALSE
True or False You can easily see viruses with a light microscope
FALSE
True or False Wheat is the only grain that makes gluten
FALSE Also in barley and rye.
True or False The INITIAL ssRNA in 'ss(+)RNA with DNA intermediate' can ITSELF be translated.
FALSE Only the (+) RNA produced via the DNA intermediate.
Out of all skin cancer, what is the relative incidence of BCC?
BCC accounts for 3 out of 4 skin cancers.
What can generate a false positive for a TB test?
BCG vaccine. Immunization administered in many countries.
What is BCL2? What is its normal function in a lymph node follicle? What is its activity in FL?
BCL2 (gene and protein): Suppresses apoptosis Normal Follicle: BCL2 activity is LOW to allow for programmed cell death, B-cell selection process. Mutation in FL: BCL2 activity is HIGH which allows cells to avoid/suppress apoptosis -> inc proliferate.
Compare and contrast CLL and SLL
BOTH are considered the same underlying disease, but with different appearances. Small Lymphocytic lymphoma Extra medullary (non-marrow, is lymphoma) sites of disease predominate. Chronic Lymphocytic Leukemia. Affects B-Cell lymphocytes causing uncontrolled proliferation. Affects mainly blood and marrow. Sustained high WBC (lymphocyte) levels in peripheral blood for 3+ months.
What type of vaccine is the Varicella vaccine? What risk does this carry? What type of vaccine is the Zoster vaccine?
BOTH are same vaccine: Live attenuated Varicella (varivax) Can cause disease in the pregnant or immunocompromised BUT Zostavax = 14X more potent than Varivax.
Compare and contrast leukemia and Myeloid tumors
BOTH: Diseases primarily involving the marrow (original transformation/mutation occurs in marrow) Myeloid Tumor : Presents as a solid mass. Leukemia: Presents as high numbers of abnormal WBC in the blood stream. Not a solid mass. (pic)
Compare and contrast leukemia and lymphoma. What is the primary factor that differentiates theses diseases?
BOTH: Disorders of hematopoietic cells. Lymphoma: An abnormality involving only lymphocytes and precursors Leukemia: Can involve myeloid AND Lymphoid cells. Primary differentiating factor: DISEASE PRIMARILY INVOLVES MARROW (leukemia) DISEASE PRIMARILY INVOLVES peripheral LYMPH ORGANS (lymphoma)
Are Chron Disease and Ulcerative colitis genetic or environmental in origin?
BOTH: There are 163 identified loci that area affiliated with increased IBD risk BUT studies in monozygotic (identical twins) show that the diseases are not simply genetic (CD = ~30% concordance, UC = ~ 15% concordance) and that other factors (environmental, 'luck') may be at play.
What is the most common gene mutation in melanoma and what drug is used to treat this? What is its basic mechanism?
BRAF gene function: Promote cell growth and proliferation BRAF gene mutation in melanoma Cause INCREASED BRAF activity Rx: Vemurafenib: It is a BRAF inhibitor.
What is cellulitis?
Bacterial infection of the skin (usually dermis and subcutaneous fat) that typically affects the extremities. Usually caused by injury/fissure to skin.
Which cells are the stem cells of the epidermis?
Basal Keratinocytes.
Describe the Baltimore pathway of classifying viruses.
Based on HOW the Virus goes about making mRNA in the host cell (Characteristics of its hijack of host cell mRNA machinery)
Explain the basic principles for the WHO Classification of lymphomas.
Based on morphology, immunophenotype, genetic findings, location, and age.
What are the clonal cytogenetic findings in MDS?
Basically complex karyotypes involving chromosomes 5, 7, and 8. - Complex karyotypes including monosomy 7, deletion 7q, monosomy 5, or deletion 5q; often seen in t-MDS, but also seen in de novo MDS - Deletion 5q as an isolated cytogenetic abnormality; seen with a specific type of MDS - Trisomy 8; and many others
Discuss how autoimmunity can result from environmental exposure to tissues that cross-react with human organs.
Basically exposure to anything that closely resembles self-tissue, and cross reacts with T-cell immunity, can activate an immune response against the self. Examples have been those working with pig brain or with fresh cadaver brain -> cross reacts and causes self-immune reactions. Activated T-cells can then cross the blood brain barrier and attack the brain itself (myelin etc)
What are the morphological findings in the marrow for MDS?
Basically neutrophils and megakaryocytes with less nucleic lobes than expected and low to no visible granules in neutrophils. - Dyserythropoiesis - Increased ring sideroblasts - Dysgranulopoiesis - Hypolobation of neutrophils. Hypo granularity - Dysmegakaryopoiesis - Megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryocytes often of small size
What granulocyte is increased in number in Chronic Myeloid Leukemia?
Basophils.
What gene fusion is associated with CML? What chromosomal translocation is this associated with?
Bcr-Abl1 The philadelphia chromosome t(9;22)
Why do you not use aspirin as an antipyretic for children under 12 for fevers of viral origin?
Because it causes a derangement in liver metabolism that results in near-fatal encephalitis.
If TB skin tests are indeed TB antigen, why does the body not use this as an opportunity to immunize to it, thereby ruining the accuracy of all further TB skin tests?
Because the effector phase is much more reactive than the immunization phase. It takes far less antigen to trigger the effector phase than the immunization phase. TB skin tests use a very small amount of TB antigen, so as to test the memory cell response, not to immunize.
What is the normal function of BCL1/Cyclin D1?
Binds to and activates CDK4/CDK6 in the cell cycle -> phosphorylation/DEactivation of Rb -> Cell cycle allowed to progress. So more Cyclin D1 = more cell division.
Describe X-linked hyperIgM Syndrome. (Where in lymphocyte development/maturation is the issue? What is the result?)
Block in the IgM -to- IgG switch mechanism. Mutation in B-Cell surface receptor (CD40) that allows for the class switching action of Tfh cells. No class switching results. High IgM with low IgG and IgA
Describe Common Variable Immunodeficiency (CVID). (Where in lymphocyte development/maturation is the issue? What is the result)
Block in the ability of B-Cells to produce specific antibody (become functioning plasma cells). IgG is low. Innate and adaptive immunity affected. Recurrent bacterial infection.
Describe X-linked (Bruton's) Agammaglobulinemia. (Where in lymphocyte development/maturation is the issue? What is the result?)
Block in the development between the pre-B and the mature B-cell. Low B-Cell count with normal T-cell count. No antibody made. Chronic bacterial infections manifesting as pneumonia and diarrhea.
Describe DiGeorge Syndrome (in relation to lymphocyte development issues). (Where in lymphocyte development/maturation is the issue? What is the result?)
Block in the embryonic development of thymic stroma (necessary area for T-cell development). Absent T-cells with normal B-cells.
What are the expected finings in the blood and marrow for ACUTE Leukemias?
Blood: - Immature WBC (blasts) Marrow: - Overabundance of Immature WBC (Blasts) - Cytopenias of many other cell types.
What are pathogenicity and virulence?
Both are considered to be inherent properties of microbes. Pathogenicity - Ability of microbe to cause disease Virulence - the degree of pathogenicity Way to think about it: An organism is defined as being pathogenic (or not), and depending upon conditions, may exhibit different levels of virulence.
Describe the Breslow depth and Clark's level used in staging of melanoma.
Breslow: The physical measurement (in mm) of the tumor from tip to base. < 1mm = great prognosis > 4mm = poor prognosis (5-year survival = 50%) Clark: Describes which layers of skin have been penetrated by the tumor. Lvl 1: Stays in the epidermis Lvl 2: Begun to invade upper dermis Lvl 3: Involves most of the upper dermis Lvl 4: Reached the lower dermis Lvl 5: Invaded to the Subcutis.
The primary skin lesions of pemphigus vulgaris are fluid filled, raised lesions greater than 1cm in diameter, What is the descriptive term for this?
Bulla
Which lymphoma is characteristic of Deeply basophilic cytoplasm with visible lipid vacuoles?
Burkitt's Lymphoma
True or False If a cell is susceptible to a virus, but not permissive, it can still replicate the viral genome, though it may not be infectious.
FALSE Susceptibility - Host cell has functioning receptor (Attachment and Entry OK). This cell may or may not be permissive Permissive - Host cell has capacity to replicate viruses. (Expression, replication, assembly OK) This cell may not be susceptible A host cell MUST be BOTH susceptible and permissive in oder to uptake and reproduce a virus.
True or False Microbes always multiply faster in the human body than in lab culture
FALSE The growth rate of microbes in the host (in vivo) may be much slower than their maximal growth rate in laboratory cultures (in vitro).
True or False Gouty arthritis is diagnosed, in part, by measuring serum uric acid levels.
FALSE Assessment of the synovial fluid is the diagnostic key.
True or False CML is a type of MDS
FALSE CML is a type of MPN.
True or False BOTH cellulitis and Stasis dermatitis are treated with oral antibiotics
FALSE Cellulitis, as it is caused by bacteria entering via breaches in the skin barrier, is treated with antibiotics. Stasis Dermatitis, caused by blood flow issues, is not.
True or False Mechanical joint issues respond to corticosteroids
FALSE Corticosteroids are only used for inflammatory joint disorders.
True or False In DiGeorge syndrome T-cells precursors are mutated
FALSE DiGeorge is an issue in the development of the thymic STROMA, not of the T-cells themselves.
True or False SPF greater than 15 does not actually impart any more of a protective effect.
FALSE FDA says SPF>15 is not necessary. This is NOT TRUE. Higher SPF levels do help according to the Derm world.
True or False Both gout and pesudogout usually initially affect the metatarsal phalangeal joint of the great toe.
FALSE Gout does, pseudo gout does not. Pseudo gout usually initially attacks a large joint, like the knee.
True or False BOTH collagen and ground substance are primarily renewed in times of injury
FALSE Ground substance is constantly being destroyed and renewed. Collagen generally renews in times of injury.
True or False Impetigo and Cellulitis are both very superficial infections
FALSE Impetigo is more superficial, when these same infectious bacteria infect deeper it is cellulitis.
True or False Ringworm involves worms
FALSE It is a fungal infection. (tinea)
True or False Blasts are increased in CML
FALSE It is chronic, cells are mature but abnormal. Only in acute do you see the blast count increase.
True or False Collagen is synthesized and assembled within the cytosol of the fibroblast
FALSE It is synthesized in the cytosol but is assembled extracellularly.
True or False Atopic eczema is associated with higher levels of IgA in the blood.
FALSE Its associated with higher levels of IgE
True or False Lymphoma involves only lymphoid cell and leukemia involves only myeloid cells
FALSE Lymphoma ONLY includes Lymphoid cells. Leukemia can be EITHER lymphoid or myeloid.
True or False BOTH MDS and MPN have effective hematopoiesis.
FALSE MDS does NOT. MPN does.
True or False Osteoarthritis and RA both usually involve the wrist and the distal interphalangeal joints
FALSE RA involves the wrists and does NOT involve the DIP OA does NOT involve the wrist and DOES involve the DIP
True or False The epidermis and dermis both contain blood vessels
FALSE The epidermis does NOT. The dermis does.
True or False Atopic dermatitis present initially as a erythematous area that eventually starts to itch
FALSE The itch comes before any visible rash in atopic dermatitis.
True or False Apocrine sweat glands produce a milky, viscid, carbohydrate-rich secretion that smells strongly. This is why we have body odor.
FALSE The secretion of all sweat glands is odorless. Bacterial activity (breaks down the sweat into odiferous acids) is the case of odor.
List five factors affecting prognosis in ALL.
- Age: worse prognosis for (<1 year) and (>10 years) - WBC: worse if elevated at time of diagnosis. - Slow/poor response to therapy: worse prognosis if either of these occurs - Number of chromosomes: good if >50 but <66 bad if <46 chromosomes - B versus T lineage: T-ALL worse than B-ALL
True or False Candida are not found normally in the human body
FALSE They are found in the GI of 80% of all individuals. Also In the nasal pharynx, on the skin.
True or False In X-linked hyperIgM Syndrome, no antibodies are made
FALSE They are made, they are nearly all IgM.
True or False The phases of hair growth on the scalp (anagen, telogen, catagen) occur in a regular cyclic pattern.
FALSE They occur randomly and in random order.
True or False Increased osteoarthritis seen in the lower extremities of obese patients is directly due to an increased load on the joint.
FALSE This is a potential cause but the actual cause is still unclear. Metabolic processes are also a potential factor.
True or False Aspirin, at any dose, acts to activate URAT1 thereby increasing the risk of gout.
FALSE Turns out high-dose aspirin is a URAT1 INHIBITOR, thereby increasing the excretion of uric acid. Go figure.
True or False UVA is required to make vitamin D in the body. UVB does not facilitate this reaction.
FALSE UVB + Skin = Vitamin D (inactive, must go through liver -> kidneys to be active) UVA is not involved in vitamin D synthesis.
True or False To fully treat lice you need only administer anti-lice shampoo, creams to the infected area.
FALSE You MUST physically remove the Nits (usually fine tooth comb) to rid the body of the infestation.
True or False If you biopsy cellulitis you will commonly see the infectious agent
FALSE You have to send some sample to culture. You will rarely see the bacteria in biopsy.
True or False In performing a KOH prep you can take the skin sample from anywhere in the infected lesion.
FALSE You must take it from the leading edge of the growing lesion. This is where the fungi are most active.
True or False Just as with CLL/SLL, follicular lymphoma has a higher male:female disease ratio.
FALSE male=female in follicular lymphoma.
True or False BOTH Eccrine and Apocrine glands empty directly onto the surface of the skin
FALSE only the eccrine glands do. Apocrine empty into the hair follicle.
True or False Certain diagnostic procedures can distinguish whether a primary or recurrent infection
FALSE Cant distinguish
True or False Congenital CMV syndrome can be contracted while in utero, while passing through the birth canal, or by drinking breast milk
FALSE Congenital CMV, and its accompanying symptoms, can only be acquired in utero.
True or False Shingles is transmissible when its resurgence is asymptomatic
FALSE Herpes Zoster (shingles) is the only herpesvirus that has visible lesions with every reactivation. VZV only transmissible via lesions.
True or False Host cells contain their own, endogenous RNA-dependent RNA polymerase that does not act on viral genomes.
FALSE Host cells don't contain RNA-dependent RNA polymerase at all. This is why they are good drug targets - our cells don't have them.
True or False The term infection is indicative of microbial invasion into the body that causes an inflammatory or immune response
FALSE Infection just means that a microbe has entered into a relationship with the human body. It may or may not cause disease.
True or False Viruses, like bacterium, grow in an exponential manner
FALSE They grow in bursts as they are replicated in a cell then released.
True or False Natural Infection with VZV (intentionally exposing children to other VZV infected children) carries no real risk.
FALSE While children infected with VZV experience much less severe symptoms than adults, in all cases there is a risk for Cellulitis, Pneumonia, Necrotizing Infections, or Encephalitis. The Vaccine is said to be safer for this reason.
True or False Most acute leukemias arise as a result of unintentional exposure to benzene.
FALSE Actually MOST acute leukemias occur in the apparent absence of risk factors.
True or False The cause for dark versus light skin is based on the number of functional melanocytes in the skin.
FALSE It is due to a combination of the type of melanin produced and the location/size of the the melanocyte of the melanosomes. Dark skin: Melanosomes: larger and closer to the surface. Eumelanin Light Skin: Melanosomes: smaller, closer to the base. Pheomelanin
True or False Burkitt's lymphoma tests positive for BCL2
FALSE It tests negative
True or False Ab do not bind or recognize virally infected cells
FALSE Once the virus is in the cell, its proteoglycans are on the surface of the cell. Ab can bind these and trigger other responses.
True or False Rheumatoid arthritis (RA) and SLE usually present in larger joints of the body
FALSE They usually present in smaller joints and in a symmetrical manner. Axial arthropathies usually present in larger joints.
True or False UVA mainly affects keratinocytes and UVB mainly affects melanocytes and fibroblasts.
FALSE UVA penetrates deeper thereby acting on all the epidermis/dermis and can penetrate to the CT and the fibroblasts. UVB does not penetrate as deep and acts on the keratinocytes, melanocytes and Langerhans cells.
True or False Fitzpatrick skin type V individuals experience less immunosuppression from UVR than Fitzpatrick skin type I
FALSE UVR's immunosuppressive effects do not things on skin color.
True or False RA usually presents in the elderly
FALSE Usually presents at a younger age.
True or False An invading worm in the body is attacked by complement and is lysed by the MAC, that or they are engulfed by neutrophils and digested.
FALSE to both They are impervious to complement-lysis and neutrophils can not digest them.
CD10 and CD6 are markers expressed by germinal B-cells (B-cells active in the follicle of lymph nodes). What are the relative levels present in Follicular Lymphoma and Mantle cell Lymphoma?
FL: Positive test (cos involves proliferation of germinal center cells) MCL: Negative test (cos mantle cells, not germinal cells, are proliferating)
List three molecular markers currently used to predict prognosis in AML-NOS patients, and know which of these "trumps" the other two as a driving prognostic factor.
FLT3 ITD - TRUMP. Positivity for internal tandem duplications (ITDs) in the FLT3 gene are a NEGATIVE prognostic factor for AML, NOS NPM1 - Positivity for a mutation of the nucleophosmin-1 gene is a positive prognostic factor in AML, NOS (but only if it is negative for the FLT3 ITD). CEBPA - Positivity for a mutation of the CEBPA gene is a positive prognostic factor in AML, NOS (but only if it is negative for the FLT3 ITD).
DIAGNOSE: Fever of Unknown Origin. (FUO) 54 year Caucasian Female with 10 day history of malaise, fatigue, fever with night sweats, shortness of breath, blood in the urine and cough. Darker colored spots on palms and in nails.
FUO Infective Endocarditis Splinter hemorrhages in nails Janeway lesions (acute, +) Osler nodes (subacute, -) Roth spots Usually pre-existing valvular dysfunction For boards know Strep. viridans from teeth
What factor is considered in the 'entry' of an infectious disease? What are examples of active and passive entry?
Factor: How the agent enters the host, mechanism. Active entry: Microbe invades on its own Passive entry: Injection, bites, transfusion, organ transplantation, etc.
What are the two types of melanin and what pigment do they produce?
- Eumelanin: black to brown pigment - Pheomelanin: yellow to red-brown pigment
What are the signs and symptoms exhibited by patients with acute leukemia? Explain the reasons for these findings.
Fatigue, malaise, dyspnea - Loss of RBC Easy Bruisability, weight loss - Loss of platelets Bone pain, abdominal pain - Neuro symptoms -
What month traditionally has peak flu activity?
Feb, by a lot.
What cell is the source for a keloid scar?
Fibroblast, but it is not a hyperplasia of fibroblasts but rather an overproduction of collagen 1 and 3.
What is the function of filaggrin and where is it found in the skin?
Filaggrin - acts to cross link keratin in the formation of the cornified envelope. ALSO its break down product forms Natural Moisturizing Factor (NMF) which binds H2O and keeps skin moist while limiting water loss though the epidermis.
What is the mechanism behind atopic dermatitis?
Filaggrin defect (70% of patients) causes extremely dry skin
What is a drug used to treat androgenic alopecia in MEN?
Finasteride (Propecia) - selective inhibitor of 5-α-reductase. Blocks conversion of testosterone to DHT.
What is a morphological factor used in APML diagnosis
Finding of promyelocytes with auer rods.
What is an FTU?
Fingertip unit. 1 FTU is the amount of ointment dispensed from a 5 mm diameter nozzle that is applied to the distal third of the index finger, from the crease under the distal interphalangeal joint to the fingertip.
Differentiate between a first-set and second-set graft rejection. What does this characteristic prove?
First set: The first time a graft from strain A is placed onto strain B, due to inherent similarity of MHCs (5-10%) forming reaction. longer response 10-20 days. Second set: Second time a graft from strain A is placed onto strain B, Faster response because this is now a reaction of memory t-cells generated during first set exposure. This proves that graft rejection is immune mediated.
What is the incubation time for influenza? and for AIDS?
Flu: 1-2 days AIDS: 1-10 years
What is the best vehicle for hair bearing regions: Creams, Gels, or Foams?
Foams
What are the current treatment modalities for Varicella?
For uncomplicated Varicella (i.e. reg Chickenpox) NO treatment as the disease is self limiting. Acyclovir - can accelerate VZV resolution if administered in first 48-72 hours of infection. Varizig - VZV immune globulin. Reduces severity if given in first 4 days.
What is the difference between a frank and opportunistic pathogen?
Frank - Cause disease in normal hosts Opportunistic - Cause disease only in the immuno compromised.
Which nervous tissue feature in the dermis is responsible for pruritus? Where is this feature located?
Free nerve endings near the dermoepidermal junction.
What is a dermatophyte?
Fungi that require keratin for growth. (skin eaters)
What are auer rods and what is their clinical significance?
Fuzed granules in the cytoplasm of abnormal myeoblasts.
What are tripe palms usually associated with?
GI issues, or cancer.
What common disease, prevalent in hospitals, does not respond to EtOH based hand sanitizers?
C.Diff
What is the primary cellular marker we need to know in testing for hematopoietic stem cells and their immediate downstream products?
CD 34
What are the markers used in the diagnosis of AML?
CD34, CD117, myeloperoxidase are the ones to know.
What are Chronic Frustrated Immune Responses?
CFIR: Any time the immune system is trying to get rid of a foreign antigen that it can't eliminate or encapsulate, it will remain chronically active and the tissues in which it takes place will become a metaphoric battlefield, as ravaged and scarred as the real thing. Not necessarily 'Auto-immune' as that implies the involvement of Antibodies, which don't necessarily have to play a part.
What are Classical Hodgkin and non-hodgkin lymphoma?
CHL - A lymphoma that derives from a very specific form of B-cell called a Hodgkin-Reed-Sternberg (HRS) cell. (Or RS cell for short) NHL - All lymphomas derived from mature B-cells, T-cells, and NK cells that do NOT involve RS cells
Why is the presence of CD5 in CLL/SLL and mantle cell lymphoma an odd occurrence and a diagnostic factor?
CLL/SLL and MCL are both diseases involving B-cell proliferation. CD5 is a T-cell marker, not a B-cell. B-Cells in CLL/SLL and MCL are strange for expressing it.
MPN: A patient has small, round Megakaryocytes with round nuclei in the marrow. What MPN disorders can this signify?
CML
Explain the clinical manifestations of primary infection and reactivation for CMV
CMV Primary:
What are the discussed examples of congenital and acquired Collagen and Elastic fiber abnormalities?
COLLAGEN: Acquired: Scurvy Congenital: Ehlers-Danlos syndrome ELASTIC FIBERS: Acquired: Solar Elastosis Congenital: Pseudoxanthoma Elasticum (PXE)
What are the common symptoms of PV?
Can be asymptomatic BUT most commonly associated with pruritus, especially after getting skin wet.
What is the common clinical presentation for someone with candidiasis?
Can present in a variety of ways and in a variety of places. Mucous membranes: white, non scaly (creamy) substance. Skin: Redness, itching, discomfort, can be accompanied by white substance.
List skin diseases (skin cancer, photodermatoses) caused by ultraviolet radiation.
Cancers: Melanoma Basal Cell Carcinoma Squamous Cell Carcinoma Photodermatoses: Solar Urticaria (hives) PMLE Actinic Prurigo (sunlight-induced, pruritic, papular or nodular skin eruption) Xeroderma Pigmentosum Chemical photosensitivity: drug induced, porphyria Photoaggrevated Dermatoses: Psoriasis, Atopic Dermatitis
What is the most common candida found in human infections?
Candida albicans
Discuss the pathogenesis of Celiac disease, and the relative role played by antibody and T cells.
Celiac: Body forms ANTIBODY against the gut smooth muscle (endomysium). SPECIFICALLY against transglutaminase 2 (TG2) which causes immune attack TG2 (in some people) can bind giladin from gut with strong affinity, and not release. This forms a 'foreign+self' hybrid antigen that an APC will present to a T-cell. But still this does NOT account for symptoms on its own. TG2/Giladin hybrid taken up by an APC in Peyer Patches of GI -> Presented to T-helper cells on MHC II (HLA-DQ2 or 8 allele) -> T-helper reacts to this HLA-DQ2/8-TG2/Giladin combination -> Tfh cell activates B-cells that are against TG2 -> Antibody against TG2/endomyesium produced -> Chronic inflammation.
Describe Basal Cell Carcinoma (BCC) Cell of origin Benign or Malignant Clinical appearance Link to other cancer
Cell of origin: Basal cell of epidermis B/m: Mostly benign, rarely metastasize Appearance: flat, firm, pale areas or as small, raised, pink or red, translucent, shiny, waxy areas that may bleed after minor injury. Link: Within 5 yrs of BCC diagnosis, 35-50% of patients have another form of skin cancer.
Pat has a chronic bilateral lower extremity rash with worsening erythema, swelling, warmth and tenderness in the left leg over the past week. What is the most likely diagnosis? Allergic Contact Dermatitis Cellulitis Erysipelas Rosacea Stasis Dermatitis
Cellulitis: Key words = swelling, warmth, tenderness,
What two syndromes does Varicella Zoster Virus cause?
Chickenpox Shingles
List the etiologies of hematologic malignancies?
Chromosomal translocations Viruses Inherited immunodeficiencies Inherited genomic instability Ionizing radiation exposure DNA-damaging chemotherapy
What are the two major Inflammatory Bowel Diseases that we discussed?
Chron Ulcerative Colitis
What is the most common leukemia in the western world?
Chronic Lymphocytic Leukemia ~30% of all leukemia.
What are the causes of stasis dermatitis?
Chronic venous insufficiency of the lower extremities associated with lower extremity edema. Lack of blood flow (blood is static)
Are persistent and latent viral infections acute or chronic?
Chronic.
Herpes simplex virus and varicella-zoster virus strains resistant to acyclovir may respond to which of the following? Famciclovir IV valacyclovir Cidofovir Foscarnet Tenofovir
Cidofovir Foscarnet
What are the two ways to classify viruses?
Classical Baltimore
Describe the classical pathway of classifying viruses.
Classical: Based on.. • Nature of the genetic material in the virion (DNA or RNA). • Symmetry of the capsid (helical or icosahedral). • Naked or enveloped. • Dimensions of the virion and capsid.
In the ointment form, which one of the following topical steroids has the highest potency? A. Triamcinolone B. Hydrocortisone C. Fluocinolone D. Clobetasol
Clobetasol
What common topical corticosteroid has superpotency and is therefore termed the 'Hercules'? When is it contraindicated?
Clobetasol Propionate .05% (class 1) Best for rapid and severe eruptions such as: contact dermatitis, acute drug eruptions. NOT for use on face, intertriginous areas, and groin.
What is the mechanism of Docosanol?
Coats virus in long chain fatty alcohol, prevents it from penetrating. Its OTC and $228 an ounce.
When fungi are in the body what do they present as? And when they are out of the body/in a colder place?
Cold = mold (outside the body) Heat = yeast (inside the body)
What are some examples of common acute local viruses?
Colds and diarrheal disease. Short incubation, short immunity -> re-infections common
What type of collagen comprises a large part of the fetal dermis but very little of the adult dermis?
Collage III
What factor, present in the dermis, provides nearly all tensile strength to the skin?
Collagen
What is the most prevalent type of collagen in the dermis?
Collagen I
What type of collagen is found in high concentration in the region of the dermal/epidermal junction(basement zone) , as well as surrounding blood vessels?
Collagen IV
What type of collagen is found in the anchoring fibrils between the epidermis and the dermis?
Collagen VII
What are the structural components of the dermis? What cell is responsible for their production?
Collagen fibers Elastic Fibers Ground substance Cell: Fibroblast.
Which histological stains (color) adhere to Collagen? And elastic fibers?
Collagen: Eosin (pink) Elastic Fibers: Argyrophilic (silver)
What are the relative functions of collagen and elastic fibers in the skin?
Collagen: tensile strength Elastic: Ability of skin to return to normal after stress/stretch.
How do you determine if a patient is an overproducer or underexcretor of uric acid?
Collect patient's urine for 24hrs, measure collective total uric acid content. < 750mg = under excretor > 750mg = overproducer.
What causes Seborrheic Dermatitis? How is it treated?
Combo of overproduction of skin oil (sebaceous glands) and increased sensitivity to a normally occurring yeast. Treated with anti fungal shampoo (kill yeast), controls it but does not cure it.
List three commonly observed cytogenetic abnormalities in B-ALL, and recall the usual patient age group and prognosis associated with these abnormalities.
- Philadelphia chromosome = worst prognosis - Translocations of 11q23; MLL = Bad prognosis (neonates and young infants) - t(12;21)(p13;q22); ETV6-RUNX1 = Very good prognosis (25% of all childhood B-ALL)
In regards to primary immunodeficiency: A patient has normal T and B cell counts, but little to no antibody is produced when prompted by an immunogen. What do they have?
Common Variable Immunodeficiency (CVID)
Describe tinea versicolor
Commonly on trunk. Asymptomatic tan or pale areas on skin. subtle, inducible scale.
Dose - response curves showing how virulence is measured.
Comparing the number of an organism needed to cause identifiable infection. 1 is more virulent than 3.
List the components and describe the function of the ground substance of the dermis.
Components: Mainly two glycosaminoglycans: Hyaluronic Acid and Dermatan Sulphate. Function: Water based environment for dissuasion to overlying epidermis, cushioning, shock absorption.
What are the Factors Influencing Absorption of Topical Medications?
Concentration - absorption is directly proportional to drug concentration Molecular size - absorption is inversely proportional to drug molecular size Lipophilicity - lipophilic is more likely to penetrate skin than hydrophilic. Composition of the Vehicle
What are the effects of congenitally acquired CMV on a baby?
Congenital CMV Syndrome Low birth weight Microcephaly Hearing loss Mental impairment Hepatosplenomegaly Skin rash (blueberry muffin spots)-due to extramedullary hematopoiesis in the skin Jaundice Chorioretinitis High mortality
What is Ehlers-Danlos syndrome? What are its general characteristics?
Congenital abnormality in collagen. • skin hyperextensibility • joint hypermobility • tissue fragility • poor wound healing
Endocrine: What disease causes Round face, moon facies with a 'buffalo hump'? What other symptoms does this have?
Cushings Disease - (prolonged exposure to cortisol) Round face, moon facies, "buffalo hump", increased fat in arms, legs and waistline, skin thinning, increased bruising(ecchymosis and purpura), striae, delayed wound healing
List the parameters that the WHO system may use to aid in the classification of hematologic malignancies.
- microscopic appearance - histologic growth pattern in the marrow, lymph node, or other tissue - presence or absence of specific cytogenetic findings or molecular findings - relative amount of malignant cells present in the blood or marrow - presence or absence of certain cell surface markers / cytoplasmic markers / nuclear markers
What are the three bulges in the primitive ectodermal germ (the origination of the hair follicle) ?
- upper = apocrine gland (+/-) - middle = sebaceous gland - lower = attachment arector pilori
Explain the concept of a "leukemic stem cell".
-root of the original perturbation -self-renew --> providing an inexhaustible source for leukemic cells that act to replace the marrow.
What are the 4 factors affecting a virus' virulence?
1) Ability of virus to replicate 2) Ability to modify host defense mechanisms 3) Ability to facilitate virus spread in and among hosts 4) Degree of direct toxicity to host cells
What are the first and second most common fibrohistocytic tumors of the skin?
1) Acrochordon 2) Dermatofibroma
What are the three most common forms of skin cancer?
1) Basal Cell Carcinoma 2) Squamous Cell Carcinoma 3) Melanoma
What are key hallmark findings of Sarcoidosis?
1) Bilateral hylar lymphadenopathy 2) Odd purple markings on the skin that ulcerate
What are the 4 main types of MPN identified by the WHO?
1) Chronic myelogenous leukemia (CML) 2) Polycythemia vera (PV) 3) Primary myelofibrosis (PMF) 4) Essential thrombocythemia (ET)
Compare and contrast the four MPNs covered in the notes with regard to blood cell counts, marrow findings, and usual cytogenetic and molecular abnormalities.
1) Chronic myelogenous leukemia (CML) - mostly neutrophilic leukocytosis 2) Polycythemia vera (PV) - inc in RBC, Neut, Platelet 3) Primary myelofibrosis (PMF) - Inc in granulocytes/megakaryocytes 4) Essential thrombocythemia (ET) - Inc in irregular megakaryocytes
What is the natural course for CML progression in a patient if left untreated?
1) Chronic phase - Leukocytosis, but no blasts. Small round megakaryocytes with round, nonlobated nuclei. 2) Accelerated phase 3) Blast phase - Essentially AML. >20% blasts in marrow/blood
What are the ways in which an infectious disease can cause tissue damage?
1) Direct damage to host: Surface components, secretables, injectables (into host cells) 2) Blocking endogenous defense mechanisms against damage
True or False 1) CD20, the marker on all mature B-cells, can also be found on B-cell lymphoblasts 2) CD3, the marker on all mature T-cells, can also be found on T-Cell lymphoblasts
1) FALSE CD20 is only on mature B-cells. B-blasts express CD19, CD22 (and/or CD79a) 2) TRUE CD3 is on all T-cells. In addition, t-lymphoblasts also can concurrently express CD4 and CD8 (in addition to other factors)
What are the 4 basic areas of available treatment for immunodeficiency?
1) Isolation: bubble.. 2) Prophylactic antibiotics: Combo, change often 3) Immunoglobulin: IVIG, SCIG 4) Transplantation: Thymus graft, marrow.
In CML all granulocytes are up regulated. Which looks the same as an infection. How can you differentiate between CML and regular infection response?
1) LAP Test Leukocyte Alkaline Phosphatase: only present in cells generated to fight infection. (CML cells = LAP negative) 2) Basophils really only go up in CML. Not a major basophil response to infection. 3) Genetics: t(9:22) = CML
What test can you perform to test for MDS?
1) Morphology of the marrow 2) Cytogenetic testing of clonal population
List two types of findings that would allow for a diagnosis of AML
1) Myeloblasts = 20%+ of nucleated cells in marrow. (Overall Blast increase) 2) Other characteristic cytogenic findings - Auer Rods, CD34, CD117, myeloperoxidase
What are the basic properties of a virus?
1) Not living. Cannot replicate outside of a host cell 2) Has genetic component (DNA/RNA), Capsid, and potentially a lipid layer. 3) Genome contains all the information to complete an infectious cycle, which is enacted by the host cell.
What are the risk factors for acute leukemia?
1) Previous chemotherapy, esp DNA-alkylating agents and Topoisomerase II inhibitors 2) Tobacco smoke 3) Ionizing radiation 4) Benzene exposure 5) Genetic syndromes - Down - Bloom - Fanconi - Ataxia-telangiectasia
Discuss possible approaches to replacing ADA.
1) Purified and stabilized ADA is available as a drug 2) Inserting the gene for normal ADA into the genome 3) Transfusion with irradiated (kill the lymphocytes) red blood cells.
What are said to be the top 2 autoimmune disorders?
1) Rheumatoid Arthritis 2) Sjogren Syndrome
Why is it important at initial diagnosis to recognize a case of AML to actually be APML?
1) Treatment is different for APML (All trans retinoic acid (ATRA), because the retinoid acid receptor gene is now fused to another gene making it inactive) 2) Disseminated Intravascular Coagulation - increased risk in APML patients. Very important to treat. NOTE: Important because you DO NOT USE CHEMO on these patients, which you want to know beforehand. You instead use ATRA. Also important because these patients are very high bleeding and clotting risks.
What systems can be affected in neonatal herpes?
1) skin, eye and mucous membrane (SEM), 2) CNS, encephalitis 3) Disseminated (spread everywhere), with disseminated being the most severe.
What are the 5 cytogenetic abnormalities for AML listed in the notes, recall their typical patient populations and prognosis.
1) t(8;21)(q22;q22): Seen in younger patients. Good prognosis 2) inv(16)(p13.1;q22) or t(16;16)(p13.1;q22): Seen in younger patients. Good prognosis. 3) APML t(15;17)(q22;q12); PML-RARA: 4) t(1;22)(p13;q13): Seen in infants with down syndrome. Good prognosis. 5) Abnormalities of 11q23: Bad prognosis
How thick is the dermis?
1-4mm depending upon body location.
What are the important functions of the micro biome?
1. Effects on tissue/organ differentiation 2. Production of vitamins by gut flora. 3. Biochemical conversions (e.g., bilirubin degradation, drug metabolism, production of potential carcinogens, etc.) 4. Competition with pathogens for colonization of body surfaces.
What fraction of melanomas develop from a pre-existing mole
1/3 2/3 are from spontaneous melanocytes.
What is the ratio of melanocytes to keratinocytes in Stratum Basale?
1:10, melanocyte:keratinocyte .
What is the ratio of RA in males Vs females?
2.5:1 Females:Males
What percentage of infants whose mothers contract primary CMV during pregnancy will NOT be infected in utero
2/3 not affected 1/3 contract CMV
How long does it take allergic contact dermatitis symptoms to manifest on the skin after exposure?
24-48 hours. Cos reaction is type IV (or delayed type, T--cell mediated) reaction.
How long does it take to fully renew the epidermis?
28 days. Time it takes for new keratinocyte to migrate to surface and slough off.
What percentage of psoriasis patients develop Psoriatic Arthritis?
5%-20%
What is the serum value of urate that marks the clinical mark/cutoff above which you do not want to see a gouty patient.
7.0 mg/dl Clinical Goal is to get the uric acid below 7.0 mg/dl
Describe the structure of the influenza virus
8 different pieces of ssRNA Surrounded by a coat with bound hemagglutinin and neuraminidase
What percentage of people in the USA are infected with CMV?
80% of the population.
A hypercellular marrow with >20% blasts is called what? And with increased blasts but <20%?
> 20% = Acute Leukemia < 20% = Myelodysplastic Syndrome.
What is the approximate number of hairs on the adult human head?
>100,000
What is the typical WBC count found in synovial fluid in RA?
>2000 WBC/uL. Significant of inflammation but not high enough for septic condition.
Zostavax is the vaccine for shingles. On what patients is it used and what it its administration schedule?
>50 years old (before then our immune systems are strong enough to suppress) 1 dose reduces likelihood of VZV reactivation and post herpetic neuralgic pain.
What are the ABCDE for melanoma, mole checking?
A = Asymmetry B = Borders (irregular) C = Color (changing, darkening) D = Diameter (no bigger than pencil eraser) E = Evolution
Primary Immunodeficiency: Where in the chain of lymphocyte maturation does Severe Combined Immunodeficiency (SCID) occur? What does this result in? Relate its level of clinical severity to other primary immunodeficiencies
A block in the development of the lymphoid stem cell from the hematopoietic stem cell. SCID = the worst of the immunodeficiencies Results in lymphopenia (both T and B). Severe cases rarely live past 1 yoa.
What is a plasma cell neoplasm?
A clonal proliferation of immunoglobulin-producing plasma cells that secrete a single class of immunoglobulin.
What is diffuse large B-cell lymphoma (DLBCL)?
A diffuse proliferation of medium to large-sized neoplastic B cells. Cells are 2x larger than normal.
What is Sarcoidosis?
A disease involving abnormal collections of inflammatory cells (granulomas) that can form as nodules in multiple organs. The granulomas are most often located in the lungs or its associated lymph nodes, but any organ can be affected
What is Burkitt's lymphoma (BL)?
A highly aggressive B-cell lymphoma, often presenting at extranodal sites or as a leukemic form
What is an apoeccrine gland?
A hybrid gland between eccrine and apocrine glands.
What is follicular lymphoma?
A lymphoma of germinal center B-cells.
What is leukemia?
A malignancy of hematopoietic cells involving blood and marrow.
What is Lymphoma?
A malignancy of hematopoietic cells, derived from LYMPHOCYTES or their precursors, which presents primarily as a solid mass
What is the link between oral allergies and other allergies such as ragweed?
A protein in the orally ingested food is similar to, and cross-reacts with proteins in certain pollens. So your body is reacting to the food as if it were the other allergen. The reason oral allergens and inhaled allergens have different symptoms is because they contact different areas and food allergens are killed once they reach the gastric acid of the stomach.
Smear and Lymph node typical to CLL/SLL
A typical blood smear of CLL. Occasional smudge cells and pro lymphocytes (larger cells with more C:N ratio) are present. A lymph node is effaced by CLL/SLL with pseudofollicles (proliferation centers).
What is Erysipelas?
A version of cellulitis that is generally caused by β-hemolytic streptococci and is confined to a sharply demarcated red areas on the face.
What is an example of an acquired disorder of eccrine function? What is an example of a congenital disorder of eccrine function?
ACQUIRED: Milaria (pic)- Blocked sweat ducts, causes prickly heat. CONGENITAL: Anhidrotic Ectodermal Dysplasia - • Severely decreased sweating • Poor temperature regulation • Other ectodermal problems - sparse hair, abnormal teeth, etc.
What is the treatment for shingles?
ACYCLOVIR given within 48-72 hours of onset may decrease lesions and pain . MAIN COMPLICATION: Neuropathic pain after the re-activation. Pain management may be needed.
What is an extra medullary myeloid tumor?
AKA Granulocytic Sarcoma - A malignancy of hematopoietic cells, derived from myeloid cells or their precursors (granulocytes, monocytes, etc.), which presents primarily as a solid mass.
A thought on Acute and Chronic Leukemia and myeloproliferative disorders
AL: Precursors CL: Mature Lymphocytes (B, T) MPD: Mature Myelocytes (Eos, Baso, Mono, RBC)
Contrast the two main categories of therapy-related AML, and compare their prognosis.
ALL t-AML= VERY POOR PROGNOSIS Alkylating agent related: - Takes 2-8 years to develop - Whole or partial loss of Chromosomes 5 and/or 7 Topoisomerase-II related: - Takes 1-2 years to develop - Rearrangement of the MLL gene (11q23)
What acute disorders can CML progress to?
AML (mostly) or ALL
Which disease does MDS usually progress to?
AML - Acute Myeloid Leukemia.
Which cell types are the origins of AML and ALL? (Original perturbations)
AML - Hematopoetic stem cell or a committed progenitor. ALL - Lymphoid stem cell.
What are the two major categories of acute leukemia?
AML and ALL (Myeloid and Lymphoblastic)
What is therapy-related AML (t-AML)?
AML arising secondary to DNA damage from a prior therapy
What is AML-NOS?
AML-not otherwise specified - it means these cases of AML dont have any of the recurring AML cytogenetic abnormalities.
Compare antibodies produced in primary and secondary responses
Ab produced in response to primary virus infections are lower affinity. B-cells must take time to undergo affinity maturation to produce Ab of higher affinity (secondary) Primary are mainly IgM (unswitched)
Antibodies to hemi-desmosomes cause which type of blister? And Ab to desmosomes?
Ab to Hemidesmosomes - bullous pemphigoid Ab to Desmosomes - pemphigus vulgaris
Endocrine: What are the common skin findings in diabetes?
Acanthosis Nigricans Yellow skin Brown patches on lower legs Foot uclers (mal perforans)
DIAGNOSE: 37 year old Hispanic Female with history of mild hypertension, hypercholesterolemia, BMI 30 and new onset of soft dark areas in skin folds, hands and neck. Has a velvety, dark pigmented neck. What is this called and what is this related to?
Acanthosis Nigricans • Majority associated with obesity and Diabetes • Can also be with endocrinopathies • Rarely inherited or with drug use • Can present with cancer (May precede (18%), accompany (60%) or follow (22%) the onset of internal cancer) 90% of all Acanthosis nigricans associated with Obesity, Diabetes, or Endocrinopathies.
What is acanthosis nigricans?
Acanthosis nigricans is a brown to black, poorly defined, velvety hyperpigmentation of the skin. It is usually found in body folds,
What is one of the only medications that can function to decrease sebum production? How does it do this?
Accutane Pretty much unknown how it does this. (Wtf?)
What molecule triggers sweating?
Acetylcholine. IT IS CRITICAL TO RECOGNIZE that even though sweating is mediated by the sympathetic portion of the autonomic nervous system it is triggered via acetylcholine secretion. Acetylcholine is a chemical otherwise associated with the parasympathetic nervous system. This is why we sweat when under stress (sympathetic control)
Describe acne and its mechanism
Acne is a ubiquitious disorder of the pilosebaceous unit (the combined hair follicle and oil glands). hyperkeratotic debris blocks the opening of the hair folicle/sebacuous gland (combined opening) then causes backup of sebum. Propionibacterium acnes, a normal bacterial commensal, then begins to multiply and converts sebum to pro-inflammatory fatty acids. (Zit)
What is the medical term for skin tags? Where are they normally present and why? How are they treated?
Acrochordon In areas of skin friction (neck, axilla, infra-mammary). Usually frozen or cut off.
What is the timing difference between acute and chronic urticaria?
Acute - present less than 6 weeks Chronic - present longer than 6 weeks.
A thought on acute versus chronic leukemia
Acute = lots of immature/blasts in marrow (either myeloid or lymphoid) Chronic = Lots of mature cells in circulation (only lymphocytes)
What are the basic functional categories for hematologic malignancies
Acute Leukemia Myelodysplastic Syndrome (MDS) Myeloproliferative Neoplasms (MPN) Classical Hodgkin Lymphoma (CHL) Non-Hodgkin Lymphoma Plasma Cell Neoplasms Other.
In which disease are Auer Rods identified in nucleated cells in the marrow?
Acute Myeloid Leukemia (AML)
Compare and contrast acute local disease versus acute systemic disease in: incubation periods virus shedding and transmission host responses likelihood of re-infection.
Acute local- usually infections of epithelial cells at body surface. Short incubation times and result in short-lived immunity, primarily via secretory IgA. Thus, re-infections are common. Shedding occurs from site of infection. Acute systemic- usually primary infection is also in epithelium, but viremia and systemic infection result in secondary replication at various sites, result in lifelong immunity and include both secretory IgA and serum IgG. Shedding occurs at any number of sites.
A 24-year-old female is diagnosed with genital herpes simplex infection. Which of the following agents is indicated for use in this diagnosis? Acyclovir Cidofovir Foscarnet Ganciclovir Valacyclovir Zanamivir
Acyclovir Valacyclovir
What are some drugs used to treat herpesviridae and what is their target?
Acyclovir and Ganciclovir - Target the thymidine kinase Foscarnet - Acts against viral DNA polymerase Thymidine kinase - essential for DNA polymerization, part of the chain introducing dTTP into DNAa
If acyclovir is activated by cellular machinery, what stops it from becoming active in non-infected cells and halting DNA replication there?
Acyclovir goes from monophosphate form to triphosphate form, but the FIRST phosphorylation is performed by a viral kinase (herpes encoded Thymidine Kinase). Non-Infected cells dont have this.
Endocrine: What disease causes full body hyper pigmentation (darker skin)? (JFK had it)
Addison's Disease. - Adrenal glands not making enough steroid hormones (glucocorticoids and mineralocorticoids).
Name the enzyme which is absent in some cases of SCID. What does a deficiency in this cause?
Adenosine Deaminase (ADA) - when deficient, adenosine accumulates in all cells but impairs lymphocyte development selectively.
What are the most common therapies that cause t-AML? Give examples of each.
Alkylating agents - Cyclophosphamide, Cisplatin Topoisomerase-II inhibitors - Doxorubicin, Etoposide Ionizing radiation
A 28-year-old woman in her 4th month of pregnancy was exposed to family members with documented influenza and she has had influenza-like symptoms for one day. When you suggest treatment with an antiviral drug, she asks whether the drug could hurt her baby. You could her that: Pregnant women are at high risk for complications of influenza Oseltamivir appears to be safe for use during pregnancy No adequate studies of oseltamivir have been done in pregnancy Oseltamivir is pregnancy category C All of the above
All of the above
Antiviral treatment is recommended for which of the following with suspected influenza? Adults ≥ 65 years old Residents of nursing homes Immunosuppressed patients All of the above
All of the above They are all at serious risk if not controlled.
Factors influencing absorption of topical medications include: A. Active drug concentration B. Composition of the vehicle C. Molecular size of the drug or prodrug D. Lipophilicity of the drug E. All of the above
All of the above.
Identify the Inflammatory Skin Disease: Delayed type hypersensitivity reaction
Allergic Contact Dermatitis
Identify the Inflammatory Skin Disease: Erythematous patch associated with the exact location of a metal bracelet.
Allergic Contact Dermatitis (nickel)
What is essential thrombocythemia?
An MPN characterized by a sustained marked thrombocytosis due to very large, irregular megakaryocytes.
What is pannus? How is it involved in the mechanism of RA?
An abnormal fibrovascular or granulous tissue forming over the cornea or over a joint in RA. Mechanism: The RA synovium (abnormal) is rich in type-A and type-B synovial cells as well as immunocytes (B, T, NK, Mast, PMNs). This abnormal synovium forms a fibrovascular structure that invades the joint and destroys adjacent cartilage and bone.
What is Sjogren Syndrome?
An autoimmune disease against exocrine glands. Mainly against tear and saliva glands.
What is viral neuraminidase?
An enzyme on the surface of influenza viruses that enables the virus to be released from the host cell.
What is an infectious disease?
An infection (see definition on last card) that causes a disease.
What are the three phases of scalp hair growth? What percentage of hairs on the scalp are in each phase?
Anagen (the growth phase) - ~85% Telogen (the resting phase) - 15% catagen (transition phase between anagen and telogen) - ~1-5%
What drug can be used to treat the symptoms associated with an immediate reaction?
Anti-histamine
What type of medication is usually used in treating urticarias? Why?
Anti-histamines. Urticaria involves IgE antibodies, Eosinophils/Basophils, and massive release of histamine causing inflammation. First exposure generates IgE antibodies. Upon re-exposure, antibody binds to IgE on mast cells and basophils causing degranulation with release of mediators such as histamine.
Review of Anti-viral state
Anti-viral state = 'poised' state with a hair trigger Cell binds interferon -> Transcription of genes activated Leaves the cell with ready, but inactive factors (capsizes, iOAS, iPKR) That can quickly progress to active forms should the cell recognize dsRNA (viral). This results in a cell that immediately halts translation, degrades mRNA, and could commit apoptosis at first sight of virus infecting cell. Halts virus progression.
What are the most common classes of drugs that cause drug eruptions?
Antibiotics and Seizure meds (anticonvulsants)
Why has the incidence of rheumatic heart disease declined in the West but not in developing countries?
Antibiotics. Early detection and treatment of strep in developed countries lead to no time for cross-reactive Ab reaction to occur.
Type II immunopathology: What is the mechanism of Complement-mediated Damage in Type II immunopathology?
Antibody binds cell, aggregates, triggers compliment -> Issues with lysis, opsonization, lysosomal enzyme release.
List the ways in which viruses can evade host defenses
Antigenic variation Inhibition of INF pathway Inhibition of apoptosis and cell cycle control Infection of immunoprivileged sites Infect the immune cells themselves 'Cloaking' - Restricted expression of viral genes Down-regulation of host proteins such as MHC class I Inhibition of TLRs, cytokines, receptors, and Ab's
What is a 'cytopathic effect' in viral infection?
Any detectable morphologic changes in the host cell
What are the two types of sweat glands and where are they located?
Apocrine sweat glands - axillary, pubic and perianal regions Eccrine sweat glands - distributed over most of the body
What is the relative sweat production of apoeccrine vs eccrine glands?
Apoeccrine make 10x more sweat than eccrine.
What are the adnexal structures of the skin?
Appendages of the skin - Sweat glands - Hair - Nails - Sebaceous glands.
What muscle causes hair to stand on end?
Arrector Pili
What are the common clinical associations with atopic dermatitis?
Asthma Allergic Rhinitis (reactions) Xerosis (dry skin, eczema)
Where is the basal lamina located in terms of skin layers?
At the dermal/epidermal junction.
When people say just 'eczema' to what disease are they usually referring?
Atopic Dermatitis
Identify the Inflammatory Skin Disease: Caused by filaggrin deficiency
Atopic Dermatitis (Eczema)
Identify the Inflammatory Skin Disease: Erythematous patch on back of knee
Atopic Dermatitis (Eczema)
Identify the Inflammatory Skin Disease: Associated with asthma and allergic reactions
Atopic dermatitis
What is the Auspitz sign? Why does it not refute the fact that there are no blood vessels in the epidermis?
Auspitz Sign - when epidermal, silvery scale of psoriasis is removed the underlying skin bleeds. This was thought to refute the fact that there were no blood vessels in the epidermis, but the area bleeding is the papillary plexus/plate of the dermis. Silvery scale can take all the layers of the epidermis with it.
Discuss how the AIRE gene is involved in preventing autoimmune disease.
Auto Immune Regulator. AIRE controls the genetic expression of thymic epithelial cells. The thymic epithelial cells produce/express major proteins from all over the body so that maturing T-cells can be exposed to them in advance of leaving the thymus and can therefore become anti-self (destroyed), a TReg cell, or a functioning T-cell that is not anti-self. When AIRE is defective, T cells can attack the body, resulting in autoimmune disease.
What is Goodpasture syndrome? What is its mechanism?
Auto-antibody destruction of the basement membranes of the lung and kidney (collagen type IV) causing bleeding from the lungs and kidney failure.
Type II immunopathology: Explain "Stimulatory hypersensitivity."
Autoimmune antibody directed against cell surface receptor, acts as antigen. So Ab binds directly to cell surface receptors and causes downstream effects.
What is pemphigus vulgaris?
Autoimmune destruction of the fibers holding desmosomes together (desmoglein 1 and 3). Blistering.
Discuss immunological aspects of celiac disease that are non-autoimmune and autoimmune.
Autoimmune: Ab against TG2, Ab against TG3, T-cell reaction to TG2/giladin hybrid antigen Non-AutoImmune: T-cell immunity against giladin
What is Type II immunopathology?
Autoimmunity involving antibody.
Immunodeficiency: What test can you perform to determine if there is a T, B, or combined immunodeficiency?
B - Test for presence of antibody (IgG, IgM, IgA) T - Test for CD3, CD4, CD8 Can combine the tests, can also look at mitogen reactions, and sequence specific genes. (more in pic)
Which is more common, B-Cell Acute Lymphoblastic Leukemia or T-Cell Acute Lymphoblastic Leukemia?
B-ALL. Accounts for 80-85% of cases of ALL
Contrast B-ALL and T-ALL in regards to patient age, sex, manner of manifestation, and prognosis.
B-ALL: - Philadelphia chromosome = worst prognosis - Translocations of 11q23; MLL = Bad prognosis (neonates and young infants) - t(12;21)(p13;q22); ETV6-RUNX1 = Very good prognosis (25% of all childhood B-ALL) T-ALL: More common in adolescents/young adults than Males affected over females. Worse prognosis overall (compared to B-ALL) Manifests as large mediastinal mass (B-ALL does not)
Characterize the infections you would expect in a pure B cell deficiency and in a pure T cell deficiency.
B-Cell deficiency: Extracellular pathogens (high grade, pus-producing bacteria) T-Cell Deficiency: Intracellular pathogens (virus, fungi, yeast, some bacteria)
What is the immunophenotype for DLBCL?
B-cell markers positive: CD19+, CD20+
What is the relative role of T and B cell mediated defenses against viruses in regards to a virus that is inside or outside of a cell?
B-cell: Antibodies attack/bind free virus outside of cells or at initial site of infection. Ab CANNOT directly attack/see a virus once it has entered/infected a cell so..... T-cells (CD8) must work to recognize and kill infected cells. !!! - Humoral response is critical for recognition of virions !!! - Cell-mediated response is critical for recognizing and eliminating virally infected cells.
In which cell type does EBV remain latent?
B-cells This is why it is linked to B-cell diseases (leukemia, lymphoma)
Which of the following would you use for a rash on a chips face? A. Triamcinolone B. Hydrocortisone C. Fluocinolone D. Clobetasol
B. Hydrocortisone Want to go gentle
What is more irritating, creams or gels?
Gels are drying and more of an irritant.
A simple way to think about leukemia/lymphoma/EMMT presentation.
Generally speaking (there are always exceptions): Leukemia = No solid masses, loose in circulation, myeloid OR lymphoid origin. Lymphoma = Solid masses of LYMPHOID origin Extra Medullary Myeloid Tumor = Solid masses of MEYLOID origin.
Contrast basic concepts of high, low, acute, and chronic leukemias
Generally: ACUTE = HIGH GRADE CHRONIC = LOW GRADE Acute is very high spike in WBC, often coupled with failing of marrow to produce all other normal marrow cells. Fatal without therapy.
Explain why there is a need for a second and third generation of protein tyrosine kinase inhibitors (PTKIs).
Gleevec was extremely successful, but mutant PKs continue to mutate active sites requiring more generations of PKTIs.
What is giladin and where is it found?
Gliadin is a class of proteins present in wheat and several other cereals. Gliadins and glutenins are the two main components of the gluten fraction of the wheat seed.
What type of crystals form in: Gout CPDD
Gout: Monosodium urate crystals CPDD: calcium pyrophosphate dihydrate crystals
What is the morphological difference between gout crystals and pseudo gout crystals?
Gout: Needle shaped Pseudogout: Rhomboid
Compare and contrast the immunopathologic mechanisms of Graves and Hashimoto thyroiditis.
Graves => Hyperthyroidism, stimulatory Ab to TSH receptor Hashimoto => Hypothyroidism, Ab bind thyroglobulin and thyroid peroxidase Tend to be on spectrum with one another and linked in many ways.
In what patients will you typically see Immunodeficiency-associated BL?
HIV patients.
What HLA alleles are correlated with Celiac?
HLA-DQ2 HLA-DQ8 NOTE: Ninety percent of people with this condition are HLA-DQ2, and most of the rest are HLA-DQ8; BUT most HLA- DQ2 or 8 people don't get celiac disease, implicating other genetic and environmental factor
What is the most common cause of encephalitis in the USA? Which lobe is most affected?
HSV 1 and 2 Temporal lobe
Identify which herpesviruses have asymptomatic shedding associated with reactivation.
HSV 1, HSV 2, CMV ALL BUT VZV (Chickenpox/shingles)
Explain the clinical manifestations of primary infection and reactivation for HSV 1 and 2
HSV1 and 2 Primary: Most are asymptomatic but the rest depend on the site of initial infection • Gingivostomatitis: Mouth (MOST COMMON SYMPTOM) • Herpetic Whitlow: Fingers • Genital: STD • Herpes Keratitis: Cornea of the eye • Encephalitis: Either primary or reactivation. • Neonatal Herpes: Infection of a baby in utero, peripartum, or postpartum. Reactivation: Most are asymptomatic or have viral shedding. • Herpes Labialis - cold sores • Keratitis - eye • Recurrent genital herpes • Encephalitis
In which cell type do HSV1, HSV2, VZV, and CMV remain latent?
HSV1, HSV2, VSV - Sensory neurons (alpha subfamily) CMV - Monocytes and Lymphoytes (beta subfamily)
Mutations in which pathway account for nearly all BCC?
Hedgehog pathway
What are the two general geometric shapes adopted by viral capsids?
Helical Icosahedral
What is myelodysplastic syndrome (MDS)?
Hematological condition with ineffective production of all blood cells.
What type of junction protein connects basal keratinocytes to the basal lamina?
Hemi-desmosomes.
What family of virus are HSV1, HSV2, VZV, and CMV? What type of genome do they all have? What infectious property do they all have in common?
Herpesviridae - ALL ARE ds DNA! They all infect then undergo a latent period.
Contrast basic concepts of high and low grade lymphomas
High Grade - Rapidly enlarging mass. Low Grade - Mildly enlarged lymph nodes. Perhaps that way for years, not rapidly growing
Why are sneezes such an effective method to pass infectious disease?
High pressure air movement practically vaporizes bodily fluids resulting in some droplets that are small enough (<10microns) to stay suspended in the air for a long time (carrying infectious agent) and if inhaled are ALSO small enough to travel all the way down to the alveoli (highly vascular) without getting trapped.
What factors are considered the 'encounter' of an infectious disease?
How the agent meets the host What was the route of infection What was the infectious dose
Why is the ground substance so full of water?
Hyaluronic acid and dermatan sulphate can absorb >10,000x their own weight in water.
What common topical corticosteroid is very low in potency and is therefore termed the 'gentle touch'?
Hydrocortisone. 2.5% (class 7) Best on face, intertriginous areas, groin.
Outline the Hygiene or Old Friends Hypothesis, and the observations that support it.
Hygiene hypothesis: Lack of exposure to environmental factors increases susceptibility to disease, allergy, etc Observation: Allergies and Asthma are LESS increased in rural/poor/slums versus urban/rich/neighborhoods. Old Friends Hypothesis: Harmless microorganisms live in humans and instruct the body NOT to overreact agains commensals or low-grade pathogens. This establishes a healthy balance between T-activation and T-regulation. T-reg impart tolerance. If T-reg not developed by 'old friends' exposure then body has increased Th1, Th2, and Th17 response to potentially harmless factors.
What eventually occurs if you keep placing grafts onto a patient that already underwent first and second set rejections?
Hyperacute or 'white graft' reaction: So intense a rejection the graft receives no blood supply and is immediately rejected. Cause by preexisting Ab against this graft either developed during the earlier rejections or, in the case of xenografts, due to direct B-cell response to foreign carbohydrates from other species.
What effect does the number of chromosomes have on ALL?
Hyperdiploidy (between 50 and 66 chromosomes) = good prognosis. Hypodiploidy <46 = bad prognosis.
Endocrine: What are the common skin findings in hyper and hypothryoidism?
Hyperthyroidism • Smooth, warm, moist skin. Pretibial myxedema Hypothyroidism • Dry skin, brittle nails, sparse hair, delayed wound healing, puffy madarosis (loss of lateral 3rd of eyebrow)
What are the Fitzpatrick Skin Types?
I-VI ranging from very fair to vary dark with accompanying attributes.
Which interleukin, secreted by Th2 cells, is highly chemotactic to eosinophils?
IL-4
The drug of choice for the treatment of serious or disseminated varicella-zoster infections is: Famciclovir Valacyclovir IV acyclovir Cidofovir Foscarnet Tenofovir
IV acyclovir
What treatments are utilized for B-cell (immunoglobulin) deficiencies?
IV or SC administered concentrated IgG. (that somehow magically does not induce complement)
What results from a loss of function mutation in the gene for filaggrin?
Icthyosis Vulgaris and Atopic Dermatitis. Increased transepidermal water loss.
What is the primary cause for chronic urticaria?
Idiopathic/autoimmune.
What are a couple risk factors involving the gut lining in IBD?
If the gut is predisposition to be leaky OR If the gut does not repair when damaged, leading to more leakiness. In either case, more organisms can pass through the epithelial GI wall, causing potential for increased. reaction. NOTE: also seen that bowel will be fine, virus attacks that causes leaky gut, triggers immunization (initiation) against gut flora then gut heals. Then at a later incidence (of permeable gut) the memory cells trigger aggressive response (Effector) to flora of gut leading to chronic inflammation.
Infantile hemangioma are usually left alone, however, when can they cause problems or alert to other issues?
If the location or the size of the hemangioma is harmful to other tissues (eye, lip, ear, breast, anogenital area) (can close the throat or block other function) Also if multiple hemangioma, could denote internal hemangioma in the liver, GI tract, lungs and CNS.
What signals mast cells to dump their granules (when IgE bound)?
IgE, bound to mast cells in close proximity, are cross-linked by antigen. This is the signal for mast cells to degranulate.
Discuss the roles of IgG, IgE, M2 macrophages, and eosinophils in helminth immunity.
IgG - Coat the helminth, signal eosinophils to opsonize worm IgE - Trigger mast cell degranulation -> aggressive peristalsis and attraction of eosinophils M2 macrophage - surround/wall off invader, heal damage Eosinophils - Engulf helminth, digest with Major Basic Protein.
Describe findings that might be seen in a peripheral blood smear of a patient with leukoerythroblastosis and how these findings relate to patients with marrow fibrosis.
Immature granulocytes, nucleated RBC, dacrocytes The fibrosis of the marrow constitutes a lesion that crowds out hematopoietic tissues causing release of immature precursors to maintain blood cell levels.
Type 1 reactions are described as having two phases, immediate and late: What is the 'immediate reaction' in type 1 response? What is its mechanism and mediators?
Immediate reaction: HISTAMINE mediated IgE binds mast cells -> Allergen cross links IgE -> Mast cell release histamine -> blood-vessel dilation/leakiness, swelling, itch
What is the general role of immune response and humoral response in viral infections?
Immune: clears the body of the infection Humoral: Prevents re-infection.
What is the primary clinical presentation for a primary CMV infection
Immunocompetent: Asymptomatic In the immunocompromised: Infection of most organs.
List methods for immunophenotyping in acute leukemias (covered in notes for previous Introduction lecture), and list a few basic markers (bolded in notes) that would help to assign blasts to a precursor-B, precursor-T, or myeloid lineage.
Immunophenotyping - This refers to the use of antibodies to detect whether certain substances are being expressed by cells. Lymphoblasts and Myeloblasts/HSC- CD34 (not on mature cells) Myeloblasts- MPO, CD117 CKIT Lymphoblasts - TdT (Not on mature cells) B-precursor - CD19, CD22 T-Precursor - range from CD2-CD8
Describe the graft-versus-leukemia phenomenon.
In severe cases of leukemia: Wipe out the marrow of the patient (radiation, or drugs) then replace it with (donor) allogenic marrow that contains some T-cells. These T-cells then attack the leukemia in the host. Research now trying to maximize the graft Vs Leukemia effect while limiting the graft vs host effect.
What are the 2 types of influence vaccines and their characteristics?
Inactivated Influenza Virus (IIV) - injectable killed, tri and quadrivalent. Live attenuated Influenza virus (LAIV) - live, nasal spray, Don't use live attenuated in pregnancy or on the imunocomprimised.
Contrast the incidences of leukemia and lymphoma in adult populations versus childhood populations.
Incidence (of cancers cancers). Adults: Leukemia 10th, Lymphoma 7th Kids: Leukemia 1st, Lymphoma 3rd
Which has a higher incidence rate in adults: leukemia or non-hodgkins lymphoma? Which has a higher death rate?
Incidence: Non-hodgkins lymphoma Death: Leukemia However, in adults, both occur (incidence) at rates 4-5 times less than prostate (number 1 in men) or breast cancer (number 1 in women).
How long is the incubation period for VZV? When is a VZV patient contagious?
Incubation: 10-21 days. Transmission: They are contagious from 1-2 days before rash starts until blisters form scabs.
Define indolent and aggressive as these terms relate to lymphoma.
Indolent: 'Lazy' or slowly proliferating, may not treat when first diagnosed Aggressive: Rapid proliferation, immediate treatment.
What are some common types of indolent and aggressive lymphomas?
Indolent: CLL/SLL, FL (both are leaning towards indolent though this was never fully discussed), NLPHL Agressive: Mantle cell lymphoma, Plasma cell myeloma (can be) Highly Aggressive: Burkitt's Lymphoma,
What is the most common benign tumor of childhood?
Infantile Hemangioma.
Describe the mechanism of rheumatic heart disease
Infection with a certain strain of Streptococcus followed by neutrophil-mediated destruction of heart valves. Streptococcus M-protein antigen exposure causes cross-reaction with heart valves (thought to be laminin), Ab binds, activates complement -> destruction. Rheumatic fever are these same self-destructive symptoms but found in more places (skin, CNS, ..)
What are the clinical characteristics and etiologic agents for Cellulitis?
Infections occur through breaks in skin or post-surgical. Responsible bacteria: β-hemolytic streptococci, Staphylococcus aureus, and Haemophilus influenzae Clinical: Ill-defnied, and not palpable erythematous area that is warm to touch. May progress to septicemia
What is arthritis?
Inflammation in joints causing pain and stiffness that can worsen with age. (notice nothing was said about cartilage, ligaments, etc...)
What is enthesitis?
Inflammation of ligamentous, osseous junctions.
What is endocarditis?
Inflammation of the inner layer of the heart. Heart valves, intraventricular septum and chord tendinae may all be involved (mostly heart valves)
What is Dermatitis?
Inflammation of the skin. Thickening, spongiosis but not blistering.
Why is it SUPER important in asthma patients to treat the inflammation in addition to the bronchoconstriciton?
Inflammation, in this case mediated by M2 macrophages, can cause tissue fibrosis. This results in permanent damage of the lung tissue. Broncho constriction is reversible, the damage from inflammation is not. This is the reason for using glucocorticoids in asthma treatment.
What is the target virus for Oseltamivir, Zanamivir, and Peramivir? What are their mechanism and target?
Influenza They block Neuraminidase activity which stops formed flu virus from leaving the host cell. In addition, blocking NA blocks virus penetration through mucin secretions. So they can't bud off and they can't penetrate.
What is the target virus for Amantadine and Rimantadine? What is their mechanism?
Influenza A, but only if susceptible, these are hardly used due to large resistance to them. Blocks the VIRALLY encoded M2 ion channel, preventing changes in intracellular pH, NECESSARY for uncoating. Virus does not uncoat, does not infect.
A patient receives a drug that is converted to acyclovir in the body. Which antiviral action is exerted by this agent? Inhibition of viral uncoating Inhibition of DNA polymerase Inhibition of viral entry DNA chain termination Prevention of viral maturation
Inhibition of DNA polymerase AND DNA chain termination
What drugs are used for herpes viruses and what are their affects?
Inhibition of viral genome replication (via various mechanisms) Acyclovir (HSV 1, 2) Valacyclovir (the prodrug of Acyclovir) (HSV 1, 2) Gancyclovir (CMV) Valgancyclovir (prodrug for Gancyclovir) (CMV) Foscarnet (CMV) cidofivir (CMV) Inhibitors of viral penetration Docosanol
When in the life cycle is Varivax administered? (Initial dose and booster)
Initial dose: 12-15 months Booster: 4-6 years of age
Distinguish between innate and adaptive anti-viral responses.
Innate immunity primes and initiates the adaptive immune response. Innate: • Natural barriers: skin, mucus, ciliated epithelium, gastric acid, tears, and bile. • Cells: macrophages, neutrophils, dendritic cells, and NK cells. • Soluble factors: interferons, cytokines, complement, chemokines. Adaptive response is acquired over time and specifically tuned to particular molecules. Acquired during infection and results in immunological memory.
What factor induces a cell to enter an anti-viral state?
Interferons. Anti-viral cells are bound, and have responded, to interferon
The C-reactive protein is an acute phase reaction (inflammation) protein of hepatic origin used to assay for levels of inflammation in the body. What is its normal role in the body?
It binds to dead or dying cells to activate complement. Unregulated during times of inflammation to help rid the body of dead or dying cells.
Why is it dangerous for women to contract VZV while pregnant (first 8-20 weeks)?
It can present as pneumonia or death in the mother. Also can cause serious issues with baby: Congenital Varicella Syndrome (microcephaly, atrophic limbs, mental retardation, etc..)
Describe the appearance of collagen under a high power microscope
It is an alpha helical structure, which when viewed looks like a striated fiber.
What is the 'eosinophil chemotactic factor of anaphylaxis' or ECF-A?
Its the combination of prostaglandins and leukotrienes produced by activated mast cells. They are called this because they are very good at attracting eosinophils.
Epidermis: What is the cornified envelope?
Its the stratum corneum. Formed of crosslikned dead keratinocytes. Cornification is the process by which a living keratinocyte becomes a dead, dried up, anueleic corneocyte.
What is the latent period in viral progression? What steps occur there?
Its the time between the initial viral infection of a cell and when that virus is again noted extracellularly (whole, mature virus export) • Attachment of virus to the cell. • Entry of virus into the cell and uncoating of the viral genome. • Viral gene expression. • Viral genome replication. • Assembly of new viruses and egress of new virus particles from the cell.
What is a Mantoux test?
Its the typical TB, PPD intra-dermal skin test. Creates hard bump called an induration, size of induration is measures for diagnosis.
What gene is mutated in nearly all cases of PV? What other myeloproliferative neoplasms have this mutation?
JAK2 Primary Myelofibrosis (Mutated in 50% of cases) Essential Thrombocythemia (Mutated in 50% of cases)
Why are tanning beds so awful?
JUST ONE USE increases chance of melanoma by 20%. Each additional use increases risk by 2%.
What signaling pathway do interferons activate in order to alter gene expression in the cell?
Jak/Stat pathway
What is the difference between junctional nevi, compound nevi, and intradermal nevi?
Junctional - nest of melanocytes at Derm/epiderm junction. Flat nevus Compound - nest at junction and in dermis. Partially raised nevus. Intradermal - nest in dermis. Raised nevus
Explain how a microbe is shown to be the cause of a specific disease. (Koch's Postulates)
Koch's Postulates 1. Specific microbes are present regularly in characteristic lesions of the disease. host. 2. The specific microbes can be isolated and grown in vitro. 3. Injection of the cultured microbes into animals reproduces the disease seen in humans. 4. The specific microbes can be re-isolated from lesions of the disease in animals.
DIAGNOSE: 32 year old Hispanic woman with hair loss over 6 months "filling her brush" daily, with heavy and irregular menses and now nail changes (spoon nail). Reports heavy menses.
Koilonychia Associated with heavy menses in women. Seen with chronic iron deficiency.
Which type of viruses are more prevalent: highly pathogenic/virulent strains or low pathogenic/virulent strains?
LOW pathogenicity/virulence. Natural selection. If the virus kills the host, the virus dies too. Those that dont kill the host have greater survival.
What is the appearance of megakaryocuytes in PV?
Large and bizarre.
Type 1 reactions are described as having two phases, immediate and late: What is the 'Late-stage reaction' in type 1 response? What is its mechanism and mediators?
Late-stage reaction: PROSTAGLANDIN/LEUKOTRIENE mediated This is all happening AFTER a mast cell has been activated in the immediate reaction Activated mast cell -> Activated phospholipase 2 -> Clevage of AA -> Prostaglandins and Leukotrienes -> Inflammation, constrict bronchioles, recruitment of eosinophils
What is the hallmark clinical finding for a rash due to VZV?
Lesions in multiple stages at same time: vesicles, pustules, crusts, and scabs
DIAGNOSE: 44 year old Dutch man with new onset of itchy rash on wrists and lower legs, sores in mouth
Lichen Planus Arising from hepatic Issue: Hep B, or C Purple, polygonal, pruritic papules Mucosal lesions Sometimes the oral findings are just associated with gold fillings (just alter the fillings)
DIAGNOSE: Concentric erythematous rings emanating from a single papule. Growing in size.
Lime Disease. Papule is tick bite.
Review methods of skin cancer prevention.
Limit UV exposure - thats the bulk of it. Limit Arsenic exposure.
What is a benign tumor of adipose cell origin? How are they treated?
Lipoma. They are deep, so they are only removed surgically.
Which flu vaccine (IIV, LAIV) has proven more effective in people < 59?
Live Attenuated, especially in years when the vaccine is mismatched with the prevalent virus.
What are the primary differences between Seborrheic Dermatitis and psoriasis clinical presentation?
Location: SD usually scalp, face, torso. Psoriasis usually on extensor surfaces (elbows, back, knees) Lesions: Psoriasis - thicker silvery scale. SD - thiner, greasy scale.
How do you characterize low and high grade MDS
Low grade = Myeloblasts < 5% of marrow cells, and < 2% of peripheral blood cells. High grade = Myeloblasts > 5% of marrow cells, and/or > 2% or more of peripheral blood cells.
Why do you typically see gout in the far extremities, especially the great toe?
Lower temp decreases solubility of urate, the further from the heart, the colder the area, the more MSU crystals form. Typically coldest area of the body = feet -> toes.
DIAGNOSE: Erythematous wood grain pattern in skin with negative fungal testing. Coupled with weight loss
Lung Cancer skin condition called Erythema gyratum repens
What is the appearance of the lymph node and the cytology involved in CLL/SLL?
Lymph node: effacement of the lymph node with diffuse infiltration. Pseudo follicles present (partial looking follicles spread all over). Cytology: Predominantly small cells, slightly larger than normal lymphocytes; round nuclei with clumped chromatin
What is lymphadenopathy?
Lymph nodes which are abnormal in size, number, or consistency.
What is a common WBC (lymphocyte) measurement for a CLL/SLL peripheral blood CBC?
Lymphocytosis, Lymphocytes ≥ 5 × 10^9/L
What are the radiologic findings for plasma cell myeloma?
Lytic bone lesions (eaten away areas), osteoporosis or fractures in 70-85% of myeloma patients at diagnosis
What are the diagnostic criteria for plasma cell myeloma?
M protein in serum or urine Bone marrow clonal plasma cells or plasmacytoma Related organ or tissue impairment: Hypercalcemia, renal insufficiency, anemia, bone lesions (CRAB).
Compare and contrast myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN)?
MDS - marrow overtaken by clonal growth that makes ABNORMAL/NON FUNCTIONING myeloid cells. (dec blood cell counts in periphery) MPN - marrow overtaken by clonal growth that makes FUNCTIONING myeloid cells. (inc blood cell counts in periphery)
Briefly describe each of the following plasma cell neoplasms: Monoclonal gammopathy of undetermined significance (MGUS) Plasma cell myeloma Solitary plasmacytoma of bone Extraosseous (extramedullary) plasmacytoma
MGUS - presence of a monoclonal immunoglobulin (M-protein) in the serum or urine of a patient with no evidence of plasma cell myeloma Plasma cell myeloma - bone marrow based plasma cell neoplasm. (M-protien in urine and serum) Solitary plasmacytoma of bone - localized tumor of the bone, which is composed of clonal plasma cells identical to those found in plasma cell myeloma Extraosseous Plasmacytoma - localized plasma cell tumors that arise in tissues outside of the bone marrow. They appear to be biologically distinct from solitary plasmacytoma of bone and plasma cell myeloma.
What is the function of melanocytes?
Make melanin which protects DNA from UV damage, package melanin for transfer to basal keratinocytes.
What is hyperhidrosis? What is this a disorder of? What are treatment options?
Marked increase in sweating Abnormal Eccrine glands (if sweating = palms, feet) or abnormal Apoeccrine glands (axilla) Aluminum chloride gels (like a really strong antiperspirant) Botox - blocks the Ach release from nerves. stops sweating.
What are some examples of common acute systemic viruses?
Measles and smallpox. Long incubation time, lifelong immunity.
If PMF is diagnosed in the fibrotic stage, what is the prognosis?
Median survival of ~5 years. Death due to bone marrow failure.
What are the function and location of Meissner's corpuscles, Pacinian corpuscles, and Merckels cells?
Meissner's corpuscles - Papillary dermis of thick skin. Sense delicate touch Pacinian corpuscles - Reticular Dermis of thick and thin skin. Sense deeper sensation -> vibration, pressure, and touch Merckels cells - Stratum Basale. Light touch discrimination.
Describe the function of the melanocyte, melanogenesis, and melanin.
Melanocyte - deposit melanin into keratinocytes. Melanin - absorbs up to 99.9% of UVR, protective of keratinocytes against UVB. Melanogenesis - UVB triggers melanocytes to make more melanin.
What skin cancers are caused by UVR?
Melanoma Basal Cell Carcinoma Squamous Cell Carcinoma
How are minor and major cellulitis treated?
Minor: oral antibiotics Major: IV antibiotics, hospitalization.
What are benign tumors (growths) of melanocytes called?
Moles ('Nevi' in med terms)
Describe the incidence of skin cancer in the US
More than 3.5 million skin cancers in over 2 million people diagnosed annually More cases of skin cancer than the next three most frequent cancers combined.
What is the most common point of entry for most viral pathogens?
Mucosal surfaces.
What tissues are more commonly affected by candida?
Mucous membranes and skin.
How do you diagnose atopic dermatitis?
Must have: Itchy skin AND Three or more of the following: • History of involvement of skin creases (or face if pt < 10 yrs) • Personal history of asthma or hay fever (or FH of atopic disease if pt < 4 yrs) • History of dry skin within the last year • Visible flexural eczema (or face if pt < 4 yrs) o Onset under 2 years of age
Describe PXE and its mechanism
Mutation in the gene encoding the Multi Drug Resistance complex. Pathway unknown but this somehow leads to enlarged, tangled and calcified elastic fibers. histology looks purple blue (elastic fibers gnarled and everywhere)
Hematologic malignancy: What is Myelodysplastic Syndrome?
Myelodysplastic Syndrome (MDS): Neoplastic clonal population (many blasts) takes over marrow. Marrow NOT CAPABLE of making normal blood cells in one or more lineages.
Hematologic malignancy: What is MPN?
Myeloproliferative Neoplasms: Neoplastic clonal population in marrow where the clone makes NORMAL functioning blood cells. But makes too many of them in one or more lineages.
Which types of cells are morphologically characteristic of: Nodular lymphocyte-predominant subtype of Hodgkin's lymphoma Classical Hodgkins Lymphoma
NLPHL: lymphocyte-predominant (LP) cells CHL: Reed-Sternberg (RS) cells (pic)
The tanning industry uses UV-A rays which they claim induces a protective tan with little to none of the adverse side effects. Is this true?
NO UVA implicated in melanoma. Also implicated in ROS production, and immune suppression.
Discuss the three requirements for graft-versus-host disease to occur.
NOTE: We are talking about the GRAFT rejecting the HOST here. This happens when the graft has its OWN T-cells that will reject the host. These are for a rejection to OCCURR: 1) The graft must contain immunocompetent T-cells 2) Their must be an antigen in the host the T-cells can recognize 3) The host must not reject the graft too rapidly (immunoINcompetent)
Describe the appearance of the lymph follicles in follicular lymphoma
Neoplastic follicles are relatively uniform in size and evenly distributed in the lymph node cortex and medulla. Packed back to back.
From which embryonic cells do melanocytes arise?
Neural Crest.
What are axial and inguinal freckling a potential indicator of?
Neurofibromatois
What are the basic classes of ways in which Type II immunopathology can damage tissues?
Neutralization Complement-mediated Damage "Stimulatory hypersensitivity."
What is a benign tumor of melanocytes?
Nevi (moles)
DIAGNOSE: A hamartoma that most commonly presents as a papillomatous, yellow-orange linear plaque on the face or scalp. Lesions on the scalp are associated with alopecia. Rapid growth occurs at puberty with enlargement of sebaceous glands and epidermal hyperplasia.
Nevus sebaceous Hyperplasia of sebaceous glands, Crowds out hair follicles.
What are the primary differences between nevus sebaceous and sebaceous hyperplasia?
Nevus sebaceous is mostly on the scalp and present in large continuous patches. Sebaceous hyperplasia are usually on the face and are single points.
What are the most common causes of allergic contact dermatitis?
Nickel Fragrance Neomycin Sulfate - in neosporin, Bacitracin
What is the most common cause of allergic contact dermatitis?
Nickel (contact) = (nearly 20% of all cases)
What is an NBT test and how is it used? What is an example of a disease that this test is used for?
Nitroblue tetrazolium test - NBT test is used to assay the ability of WBC to make ROS. NBT test forms a blue compound when the tested cell is making ROS. No blue = no ROS. Chronic Granulomatous Disease - diminished ROS production by cells (NBT test does not turn blue). Inability to kill phagocytosed pathogens.
What is the treatment for CMV?
No treatment in immunocompetent. Immunocompromised: Gancyclovir, Foscarnet,
What is the eclipse period of a virus?
No viral products produced. Virus is being disassembled, releasing its genome for future replication.
Where can lymphoma present?
Nodal - presenting as enlarged lymph node Extranodal - presenting at other sites (skin, brain, GI) Can also present in both.
What are the 4 subtypes of CHL? Which is most common?
Nodular sclerosis (most common) - young adults, females Lymphocyte-rich - children, elderly Mixed cellularity Lymphocyte-depleted
What are the two types of impetigo and which is more common?
Non-bullous impetigo - More common (70-80%) Bullous Impetigo - Less Common (20-30%)
What are the clinical characteristics and etiologic agents for impetigo (both versions)?
Non-bullous: Most common on face. Erythematous macule with superficial blister, progresses to honey-colored yellow crust. Etiology: β-hemolytic streptococci and/or Staphylococcus aureus Bullous Impetigo: Affects any area of body. Superficial, flaccid blister that may occasionally demonstrate layered pus. Eventually collapsed blisters, look like 'varnish'. Etiology: Staphylococcus aureus Both start as single lesion then develop into multiple adjacent lesions.
54 yr old patient has knee pain that hurts more with activity and has crepitance. Is this inflammatory or non inflammatory? What type of fluid would you expect to aspirate from the knee joint? What WBC count (range) would you expect from this fluid?
Non-inflammatory. Structural issue, worse with activity = non-inflammatory. Better with movement = usually inflammatory Type 1 fluid (non-inflammatory): WBC = 200-2000, 25% polymorphonuclear leukocytes, normal viscosity
What is the cellular origin of a neurofibroma? What characterizes a neurofibroma?
Nonmyelinating Schwann cells Characteristics: Button hole sign (can push it flat with skin then it pops back up, soft)
What is the ~normal range for WBC? What range is Leukopenia? What range is Leukocytosis?
Normal: 5-10k Leukopenia < 5000 Leukocytosis > 10,000
What is the morphological difference between an activated follicle in a normal lymph node and a follicle in follicular lymphoma?
Normal: various cells in reactive follicle. (macrophages, T-cells, etc). Better defined mantle zone FL: homogenous tumor cells. poorly defined mantle zone
What are creams?
Oil in a water emulsion
Which of the following correctly describes the emulsion properties of creams? A. Oil in water emulsion B. Semisolid emulsion in alcohol base C. Powder in water D. Pressurized collections of gaseous bubbles in a matrix of liquid film
Oil in a water emulsion. B. Semisolid emulsion in alcohol base = GEL C. Powder in water = LOTION D. Pressurized collections of gaseous bubbles in a matrix of liquid film = FOAM
What are the sites on the body must suited for Ointments Creams Gels Lotions Foams
Ointments - non-intertregenous areas. Not on face, hands or groin. Very hydrating Creams - Pretty much anywhere. Hydrating Gels - oral mucosa and scalp. Do not put on fissures, erosions. Drying. Lotions - Scalp, intertregenous areas . Foams - scalp, hair-bearing areas.
What type of vehicle would you use for a patient exposed to poison ivy? A. Ointment B. Cream C. Lotion D. Foam
Ointments would be better. Increased absorption.
If a virus has a (+) stranded RNA genome, and that genome is directly translated into protein, how does the viral genome get replicated?
One of the proteins/enzymes encoded by the mRNA genome is the RNA-dependent RNA polymerase (RdRp) which acts to replicate the RNA genome (by first making (-) RNA from the (+) RNA, then vice versa)
What is the risk that a newborn will have an allergy if one parent has one? And if both parents?
One parent : 35% Both: 65%
What is a slow virus?
One that infects, causes no symptoms, has a very long incubation period (may or may not induce an immune response) Eventual disease is followed by progressive deterioration and death. EX: AIDS, Cancer
What is the treatment for infantile hemangioma?
Options: Leave it alone, moisturize it, beta-blockers, pulsed-dye laser
What is thrush?
Oral candidiasis. White, non scaly.
Describe Squamous Cell Carcinoma
Origin: Upper epidermis b/m: More malignant than BCC. Squamous cell carcinoma may appear as growing lumps, often with a rough surface, or as flat, reddish patches that grow slowly. Both BCCs and SCCs may develop as a flat area showing only slight changes from normal skin.
A 75-year-old man with chronic obstructive pulmonary disease is diagnosed with suspected influenza based on his complaints of flu-like symptoms that began 24 hours ago. Which of the following agents is most appropriate to initiate for the treatment of influenza? Ribavirin Oseltamivir Rimantadine Acyclovir Zanamivir Tenofovir
Oseltamivir (Tamiflu) Because Zanamivir has adverse affects = cough and bronchospasm.
What 4 drugs that we discussed are used to treat influenza?
Oseltamivir - Block entry and exit Zanamivir - Block entry and exit Amantadine - block uncoating Rimantidine - block uncoating
What are the adverse reactions to Oseltamivir and Zanamivir?
Oseltamivir - N/V and abd pain Zanamivir - Cough, bronchospasm.
What is the route of administration for: Oseltamivir, Zanamivir
Oseltamivir - oral Zanamivir - Low F, so inh
What is PV?
Overproduction of RBC
Via which factors does INF signaling shut down translation?
PKR - blocks translation initiation OAS - degrades mRNA
MPN: A patient has large, irregular Megakaryocytes in the marrow. What MPN disorders can this signify?
PMF, ET, and PV
What are some modalities that Rheumatologists use to assess patients?
PMH: inflammatory vs not Inflammation: Erythrocyte Sedimentation Rate, C-Reactive Protein Physical Exam: visible characteristics Autoantibody Testing: titers Synovial Fluid analysis: infection, crystals Imaging
Immunodeficiency: What tests can you perform to determine if there is a PMN, macrophage, or complement problem in immunodeficiency?
PMN: WBC count, morphology and diff. NBT test, oxidative burst Complement: C1 inhibitor and individual complement factor levels.
What is the mechanism of leukocytoclastic vasculitis? How does this relate to its clinical presentation?
PPT of immune complexes along vessel walls causes recruitment of neutrophils and inflammation along the interior wall of the blood vessel. This leads to extravasation of red blood cells into the dermis. Clinical Presentation: Palpable purpura. Palpable cos of inflammation and purpuric cos of extravasation of RBC into dermis.
Explain the clinical manifestations of primary infection and reactivation for VZV
PRIMARY: Can present as chickenpox, but can also have much more severe symptoms. CHICKENPOX - less severe • Fever, malaise, headache • 'Dew drop on a rose petal' blisters on erythematous base. These progress to pustules, which then rupture to form scabs. • Rash first on trunk (more on trunk overall) then to extremities • HALLMARK: lesions in multiple stages at same time: vesicles, pustules, crusts, and scabs MORE SEVERE: Primary infection symptoms. • Cellulitis • Pneumonia • Necrotizing Fascitis • Encephalitis • Hepatitis • In Pregnancy: Death of mom or damage to fetus Reactivation: • Shingles: rash on dermatome pre cursed by pain
What are Pacinian corpuscles and Messiner corpuscles? What is their function? What is their primary location?
Pacinian - pressure and vibratory sensation. most concentrated in genital area. Messiner - fine touch and tactile discrimination. most concentrated in distal aspects of digits.
What is arthralgia?
Pain in a joint without detectable inflammation.
What are Osler nodes?
Painful, red, raised lesions (inflamed vasculature) found on the hands and feet. NOT infection related (will not grow in culture)
What does a sister mary joseph node usually signify?
Pancreatic or GI cancer. Node near umbilicus.
What are the two layers of the dermis?
Papillary Dermis - more superficial. loose connective tissue Reticular Dermis - more deep, sweat glands, dense connective tissue.
In what layer of the dermis are the capillary structures of the skin located?
Papillary layer. This area is sometimes called the supra papillary plate (plexus).
High serum levels of eosinophils can mean what?
Parasitic infection Type 1 hypersensitivity reaction
What is the most common gene mutation in BCC and what drug is used to treat this? What is its basic mechanism?
Patch 1 gene function: tumor suppressor by inhibiting smoothened which is a tumor promoter Mutation in Patch 1 causes DIMINISHED Patch 1 activity Rx: Vismodegib: Acts to inhibit smoothened (same function as patch 1).
What are the 4 types of immunopathology? Describe the classification of each
Pathologies due to.... TYPE 1 - IgE (allergies), Th2, AND PARASITES TYPE 2 - IgG, IgA, or IgM against self-cells -> MAC lysis TYPE 3 - IgG against soluble antigen, forms immune complexes on vessel walls -> inflammation TYPE 4 - T-cell mediated Chronic Frustrated Immune Response - Adaptive immune response to pathogen that can not be rid of.
What causes the pathology in RA?
Pathology is caused by an immune response.
What is androgenic alopecia? What causes it?
Pattern baldness. The process is not understood completely, but it is known that conversion of testosterone (androgen) to 5-dihydrotestosterone is important in promoting this change.
Describe the problem that HLA-B*5701 people may have with the HIV drug abacavir.
People with this allele of HLA-B (component of of MHC I complexes) generate an MHC I that can be structurally altered by the drug abacavir. This structural alteration causes the MHC I to bind and present self-peptides to CTL cells in a conformationally awkward manner, causing an auto-immune reaction to the self. NOTE: MHC I are constantly presenting the self to CTL cells, and there is no reaction because the adaptive immune system has adapted to the self. The altered confirmation of the HLA-B*5701-MHC I causes altered presentation of the self to the CTL, so the self-peptide looks abnormal, triggering an abnormal response.
Where in the body does the original transformation/mutation event usually occur in lymphoma?
Peripheral lymphoid tissues. (not the marrow)
Detail two differences between persistent and latent infection.
Persistent: continue to produce new virus over a long period of time. Latent - can infect host and cause no symptoms for a long 'quiet' period. Termed latent (not 'dead') because at any time they can re-initiate transcription and replication to produce new virus
Given patient's serum, fluorescent antibody to human immunoglobulins, and slices of normal kidney, describe how you could tell if the patient's glomerulonephritis was due to Goodpasture's Disease.
Pic: Glomerulus with stain against human IgG. Linear pattern, nicely painted basement membrane = signifies type II anti-Ab even lining of the basement membrane.
What is the difference between polycythemia and polycythemia vera?
Polycythemia = increase in the hematocrit. Can be due to either more RBC or less plasma Polycythemia Vera = Increased RBC production.
MPN: A patient has RBC, neutrophil, and platelet hyperplasia. What MPN disorder does this signify?
Polycythemia Vera
MPN: A patient has a JAK2 mutation and thrombosis noted in the splenic, mesenteric or portal veins. What MPN disorder does this signify?
Polycythemia Vera
What are the genes or genetic mutations commonly associated with RA?
Polygenic disease with possibly different sets of predisposing genes in different population groups * 'The Shared Epitope' = QKRAA = HLA-DRB1 PTPN22 STAT4
DIAGNOSE: Patient: Findings are blistering lesions on hands with SUN exposure, hypertrichosis and atrophic scars with milia. Associated with hepatitis.
Porphyria Cutanea Tarda
What are lotions/solutions?
Powder in water
Identify treatment options for premalignant and malignant skin tumors.
Pre-malignant treatment: Topical treatments Cryotherapy Curettage with Electrodesiccation (scrape n burn) Excision Radiotherapy Malignant: Immunotherapy - Targets programmed death receptors on T-cells. Inhibits lymphocyte death, they are fighting the cancer. Targeted Therapy - Rx targeting specific pathways (BRAF, MEK) Chemotherapy - last resort Palliative Local Treatment - Drugs/treatment that cause tumor shrinkage, better life, but not longer life expectancy.
What are primary and secondary immunodeficiency?
Primary - Congenital. Mutations in immune system genes Secondary - Acquired. Following treatment with immunosuppressive drugs. Or seen in patients with advanced cancer, measles, AIDS...
MPN: A patient has megakaryocytic and granulocytic hyperplasia, but no marked increase in RBC. What MPN disorder does this signify?
Primary Myelofibrosis.
MPN: A patient has a JAK2 mutation and the peripheral blood is hypercellular. What MPN disorders can this signify?
Primary Myelofibrosis. REMEMBER: ET also has JAk2 mutation, but blood is mostly normocellular.
Describe collagen formation
Pro collagen synthesized intracellularly consisting of three separate chains. Each chain is string of Gly-X-Y where X and Y are usually proline and hydroxyproline. Then the pro collagen are exported from the cell and assembled outside the cell into collagen fibrils.
What is primary myelofibrosis?
Proliferation of the granulocytic and megakaryocytic lineages, with eventual progression to myelofibrosis
Which factors, released by mast cells, lure eosinophils to the site of helminth infestation?
Prostaglandins and leukotrienes.
What are Tonofilaments?
Protein structures (keratin filaments) that insert into the dense plaques of desmosomes on the cytoplasmic side of the plasma membrane
What feature is present on the nails of HIV patients?
Proximal superficial Fungal infection.
What is the derm term for itching?
Pruritus
Identify the Inflammatory Skin Disease: Silvery, thick scale on elbow
Psoriasis
What are two disorders of capillary loops in the dermal plexus that we discussed?
Psoriasis and Verruca.
Identify the Inflammatory Skin Disease: May be associated with increased risk of CV disease
Psoriasis.
What are the two main factors that prevent viral infection?
Public Health Measures Vaccines.
What is Restylane?
Pure hyaluronic acid derived from yeast. Used for cosmetic purposes.
Describe the cellular and molecular events following intradermal injection of tuberculin antigen into a person who has cell-mediated immunity to it. Justify calling the process 'delayed hypersensitivity'. Characterize the cells that would be seen in a 48-hour biopsy of the site with regard to whether T cells or macrophages predominate
Purified Protein Derivative injected intra-dermally Antigen presented by APC. If patient already exposed to TB this will elicit the effector phase, inflammation response will occur, and site will be full of macrophages (cos each Th1 cell recruits 1000 macrophages). Test is read after 48 hours. (delayed response)
DIAGNOSE: 49 year old Caucasian female with rapidly enlarging ulcer for 2 weeks. Went to urgent care where it was debrided and placed on antibiotics. Now in ER, painful and enlarging. to NOTE: Rapid enlargement, painful
Pyoderma Gangrenosum Bunch of neutrophils attacking. DONT DEBRIDE NORMALLY associated with underlying syndrome: • Inflammatory GI: Chrons or Ulveritive colitis. • Arthritis • Monoclonal Gammopathy Essential to differentiate from necrotizing fascitis
What test for TB can you administer if the patient has a BCG vaccine? Why does this work?
QuantiFERON-TB gold test. This test exposes patient blood or WBC to purified human TB epitopes, then INF-g is measured in the sample using ELISA. Will remain negative in people without TB that have the BCG vaccine cos that vaccine uses attenuated bovine tuberculosis bacteria.
A patient presents with Acanthosis Nigricans. What would be a red flag for it being associated with cancer?
RAPID onset of Acanthosis Nigricans COUPLED with weight loss.
What percentage of genital HSV is transmitted during and asymptomatic reactivation?
Reactivated lesions are infectious 70% of genital HSV transmission occurs during asymptomatic reactivation.
What are the clinical characteristics and etiologic agent of lice?
Redness on skin (scalp, body, axilla, brows), egg (translucent pouch) stuck to hairs away from scalp (called nits). Etiologic agent: the louse. 1) Pediculus humanus var. capitis- bloodsucking, wingless insect that preferentially infest the scalp 2) Pediculus humanus var. corporis- preferentially infests the trunk 3) Phthirus (Pthirus) pubis- preferentially affects the hair of the genital area
What are the two types of high grade MDS?
Refractory Anemia with Excess Blasts-1 (RAEB-1): 5-9% blasts in marrow or 2-4% blasts in the peripheral blood. (Bad. Median survival 16 months) Refractory Anemia with Excess Blasts-2 (RAEB-2): 10-19% blasts in marrow or 5-19% blasts in the peripheral blood. (Worst. Median survival 9 months)
What are the two types of low grade MDS?
Refractory Cytopenia with Unilineage Dysplasia (RC-UD) - Dysplasia in ONE cell lineage Refractory Cytopenia with Multilineage Dysplasia (RC-MD) - Dysplasia in Two or more cell lineages. (worse prognosis, Median survival 2.5 yrs.
What is meant by 'plus strand' and 'minus strand' in viral genomes?
Remember that the goal of the virus, regardless of starting with DNA or RNA, is to end up with a specific mRNA to be turned into protein. This final mRNA has the sequence desired for the protein so it is a plus strand, the complimentary RNA sequence to this mRNA is the minus strand because it does not contain the desired RNA sequence to produce the desired protein. These same rules apply to DNA. If the sequence of the DNA matches that of the final target mRNA (disregarding T/U substitutions) then that DNA is the plus strand. Same principle as the coding strand (+) and the template strand (-). Not sure why they dont just use that.
Why don't viruses typically infect dead cells?
Remember, the virus is not alive and has no metabolic activity. It ATTACHES to the cell via receptor/ligand affinity (no energy required), however, ENTRY is an energy dependent mechanism. This energy cannot come from the virus, it must come from the cell. Therefore the cell must be alive to provide this energy.
Via what pathway does VZV enter the body?
Respiratory
How long is a hair on the scalp engaged in each of the phases of growth?
Rule of threes Anagen - 3 years Telogen - 3 months Catagen - 3 weeks or less
What is the clinical pearl for scabies regarding their location on the body?
SOFT SKIN DISTRIBUTION Distribution- symmetric- interdigital web space, flexural wrist, waist, axillae, genitalia and breast
What two enzymes can be involved in Uric acid overproduction and how?
SUPER ACTIVITY of PRPP (phosphoribosyl-pyrophosphate) synthetase or DEFICIENCIES of HGPRT (hypoxanthine- guanine phosphoribosyltransferase)
What is the vector for scabies? What is the main symptom caused by these?
Sarcoptes scabiei variety hominis- highly host specific mite confined to humans. Burrows into epidermis and lays eggs. Primary symptom: Intense, miserable pruritus - worse at night or when hot bath/shower.
What is the most absorptive area of the skin for topical drug administration?
Scrotum. Yay.
DIAGNOSE: 1-6 mm yellowish-white papule on the face (globules) with central dell. (is not basal cell skin cancer)
Sebaceous Hyperplasia
Identify the Inflammatory Skin Disease: Oily scale located on scalp
Seborrheic Dermatitis
Identify the Inflammatory Skin Disease: Triggered by Malassezia Furfur
Seborrheic Dermatitis
DIAGNOSE: 67 year old Caucasian gentleman, otherwise is good health with only mild hypertension present for "dandruff" and hand tremor.
Seborrheic Dermatitis - Dandruff coupled with a neurological disfunction.
What are some examples of neurologic disorders causing skin signs?
Seborrheic Dermatitis - seen with parkinsons, after head trauma, in HIV, and cerebral palsy Neurofibroma - Neurofibromatosis Angiofibroma - Tuberous Sclerosis
What is Seborrheic Dermatitis?
Seborrheic dermatitis is an inflammatory skin disorder affecting the scalp, face, and torso Typically presenting with scaly, flaky, itchy, and red skin. Pic is 'Cradle Cap', just SD in infants.
What is a benign neoplasm of keratinocytes?
Seborrheic keratosis "barnacles of life" Most common in older age.
What are gels?
Semisolid emulsion in an alcohol base
What is a Janeway Lesion?
Septic micro emboli (spots). Infection related (will grow in culture). Non-tender
What is the most common treatment for PV?
Serial bloodletting and administration of aspirin
What is serology and how is it used in CMV diagnosis?
Serology: The study of serum. If they have CMV IgM its the primary, if IgG its recurrent. a. Positive IgM, negative IgG= acute CMV disease b. Negative IgM, negative IgG= patient has never been infected with CMV c. Negative IgM, positive IgG= patient has previously been infected with CMV at some time in their life d. PositiveIgM, positive IgG=recent CMV reactivation
Why do sebaceous glands not become highly active until puberty?
Sex hormones are requisite to sebum secretion. Therefore sebaceous glands are not highly active until adrenarche (puberty).
What is an adult-onset SECONDARY activation of chickenpox? (second activation of the same initial infection)
Shingles So primary infection = chicken pox REactivation = shingles (you dont CATCH shingles), it reappears when you are immune suppressed.
What constitutional symptoms can a viral infection produce that are directly owing to INF production and release?
Side effects of anti-viral response lead to constitutional symptoms (fever, chills, nausea, malaise)
Type II immunopathology: What is neutralization and how can it lead to damage?
Single human protein inactivated by an antibody. EX: Ab Neutralization of INF-g (observed in SE asia), leads to no M1 macrophage activation by Th1 cells -> issues with micro bacteria.
What organs are required to make the final active form of sunshine derived Vitamin D?
Skin -> Liver -> Kidneys
What is an adnexal structure?
Skin associated features, generally protective or involved in homeostasis: hair follicles, sebaceous glands, sweat glands.
What is the rash difference between small pox and chicken pox?
Small pox concentrated at extremities Chicken pox concentrated at trunk
How can stained elastic fibers, when viewed under the microscope, clue you in to the relative age of the patient and location of the skin sample?
Solar elastosis - exposure to the sun causes elastic fibers to bundle together. The more bundling, generally the older the patient and the more sun-exposed the area of the skin.
What is leukocytoclastic vasculitis? Where does it present? What causes it?
Some type of insult leads to the formation and precipitation of immune complexes on the walls of the post capillary venules.
What is tissue tropism in regards to virus?
Specifying the types of tissues that the virus typically infects. (Specificity Largely due to the interaction of a virus attachment protein with a specific receptor molecule on the surface of a cell) EX: Enterotropic viruses replicate in the gut and neurotropic viruses in nervous system tissue
Which factors help an infectious disease spread through tissues: 'spreading factors'? Which factors can inhibit microbial spread: 'wall off'?
Spreading factors: Hyaluronidase, elastase, collagenase, etc Blocking factors: Coagulase
Of the two etiologies for impetigo, which is the more common perpetrator?
Staphylococcus aureus
Jane has bilateral lower extremity edema and itchy rash. What is the most likely diagnosis? Allergic Contact Dermatitis Cellulitis Erysipelas Rosacea Stasis Dermatitis
Stasis Dermatitis: Key words = lower extremity, itchy, edema.
Identify the Inflammatory Skin Disease: Itchy lesions located in distal lower extremities.
Stasis Dermititis
Identify the Inflammatory Skin Disease: Lesion on medial malleolus coupled with edema
Stasis Dermititis
What is Graves Disease?
Stimulatory Hypersensitivity: An IgG antibody that binds and activates the Thyroid Stimulating Hormone (TSH) receptor, causes thyroid cells to over-secrete thyroid hormones -> Hyperthyroidism
What are the different layers of the epidermis? What does each contain?
Stratum Corneum - Outter layer. Dead cells, no nuclei. Stratum Granulosum - Migrating keratinocytes (called granular cells in this area) Stratum Spinosum - Contains keratinocytes (polygonal shapes) and Langherans cells (though these are found in all layers) Stratum Basale - Basal layer. contains Merckel cells, melanocytes, basal keratinocytes (columnar cuboidal)
What is the layer of epidermis where keratinocytes begin to lose their nuclei?
Stratum Granulosum
What is the thickest layer of the epidermis?
Stratum Spinosum.
Which layer of the epidermis has a 'prickly' appearance and why?
Stratum spinosum - many desmosome attachments between migrating keratinocytes here, desmosome attachments look 'prickly' due to their tonofilaments.
What bacteria is most commonly associated with infective endocarditis?
Streptoccoci Viridans. -> Bacteria on the heart valves -> infective endocarditis
What are the common causes of irritant dermatitis?
Strong Irritants - strong chemicals. Weak Irritants - soap, skin products, perfumes, wool, raw foods, body secretions (this is why babies with poop-diapers get rashes) Friction - (skin folds cause increased risk of irritant dermatitis. )
What is the overall immunophenotype for CLL/SLL?
Strongly positive: CD5, CD19, CD23 Weakly positive: CD20, surface immunoglobulin Negative: CD10, FMC7
Describe the virion structure and replication cycle of herpesviruses
Structure: dsDNA genome in an icosahedral capsid, which is surrounded by an envelope
What is mantle cell lymphoma?
Sub type of B-cell lymphoma. Mainly affects the mantle zone that surrounds normal germinal center follicles
Which types of ultraviolet radiation cause these conditions: Sunburn Photoaging, wrinkles Corneal burns
Sunburn - Mainly UVB Photoaging/Wrinkles - UVA Corneal Burns - UVB
What is the primary function of the Eccrine glands?
Sweat. Thermoregulation.
DIAGNOSE: 37 year old female with 5 month history of transient scaly eruption on arms and chest, "mouth sores", arthralgias, one ER visit for possible seizure, now with new rash on face
Systemic Lupus Erythematosus
DIAGNOSE: Lost Smile: 42 year old Caucasian Female with pain in finger tips, reduced range of motion with tight feeling, shortness of breath, difficulty eating and tightness around her mouth and salt and pepper skin changes
Systemic Scleroderma Skin findings: •thickened skin over fingers and hands •skin tightening around mouth •Raynaud's •Esophogeal/GI dysmotility and strictures (trouble eating, swallowing) •Commonly develop pulmonary hypertension with bad prognosis •pericarditis has poorest prognosis •Autoimmune: ANA+ 80-90%, anti-centromere ab in limited, anti-scl70 in systemic
What is scleroderma?
Systemic auto immune disease characterized by hardening of the skin. This is not just a disease of the skin, it is also affecting a wide array of internal organs and MSK functionality. CREST mnemonic describes symptoms (pic) Scleroderma is caused by genetic (HLA mutations) and environmental (chemical) factors. Result is increased synthesis of collagen (leading to the sclerosis), damage to small blood vessels, activation of T lymphocytes and production of altered connective tissues.
Define Type IV immunopathology
T-cell mediated events that are undesirable or injurious.
Discuss the idea that it may be possible to switch Th1/Th2/Th17 responses to Treg instead.
T1 and T2 regulate and suppress one another. T reg can suppress Th1/Th2/Th17. Can have clinical use. Example from notes is that Crohn Disease patients were given worms to try to switch the T cell response from Th1 to Th2 (since Th2 responses mediated parasitic infections and were more protective where Th1 responses were more destructive). In fact, the switch was not from Th1 -> Th2, but rather to Tregs - which suppressed the other responses and lead to an improvement in symptoms. However, therapy needs to make sure Tregs don't get out of balance as this could suppress the immune system in fighting off legitimate threats
True or False Gout, axial arthropathies, and hemochromatosis are more common in males
TRUE
True or False In general, potent or superpotent topical steroids should be avoided for use on the face, skin folds (axillary and intertriginous folds), and groin areas due to the risk of epidermal atrophy and potential for steroid-induced rosacea/perioral dermatitis on the face.
TRUE
True or False Nearly all hematopoietic neoplasms are considered malignancies .
TRUE
True or False ONE exposure to Beryllium can give you Chronic Beryllium Disease for the rest of your life
TRUE
True or False The terms Dermatitis and Eczema are used interchangeably
TRUE
True or False Urticaria resulting from food allergies are usually acute
TRUE
True or False AML-NOS patients often have a normal karyotype
TRUE
True or False Atopic dermatitis is typically located in the flexor creases of the body
TRUE
True or False Both erysipelas and cellulitis cause local lymphadenopathy which is a good sign that what you are seeing is in fact an infection.
TRUE
True or False Erysipelas and Cellulitis are both variations of cellulitis that affect different parts of the body
TRUE
True or False In CHL, the malignant cells usually represent only a small minority, between 0.1% and 2%, of the total cellular population of involved tissues
TRUE
True or False It is thought that our bodies play host to a crap load of viruses that dont cause a disease state, similar to commensal bacteria
TRUE
True or False Men are more at risk for BCC and SCC than women
TRUE
True or False Port Wine stains and Nevus Sebaceous both grow in size with the patient.
TRUE
True or False RA is a systemic autoimmune disease that affects multiple organ systems but is prevalent in the joints
TRUE
True or False RA labs are positive for RF/CCP and have high ESR/CRP
TRUE
True or False RA, SLE, and scleroderma are more common in females
TRUE
True or False T-ALL presents more often in Males than females
TRUE
True or False The closer your mouth is to the ground, the more likely you are to have parasites
TRUE
True or False The major component of creams is water and the major component of ointments is oil
TRUE
True or False Thrush is commonly seen in infants
TRUE
True or False Treatment of surface tinea infections is ill advised as this will cause the infection to travel into the hair follicle and go deep, causing need for use of systemic treatments .
TRUE
True or False Viral genomes can be DNA or RNA and can contain either single stranded DNA or double stranded DNA
TRUE
True or False non-enveloped (lipid membrane) viruses generally escape by lysis of the infected cell while enveloped viruses can escape without lysing the host
TRUE
True or False You will not get IBD symptoms if you have no micro biome in your gut
TRUE But that leads to all sorts of other problems.
True or False The flora are abnormal in IBD
TRUE DEBATE: between whether the abnormal flora cause the IBD or if the IBD reaction causes abnormal flora.
True or False Enveloped viruses are more fragile and non-enveloped viruses are more robust
TRUE Enveloped viruses are fragile and sensitive to many environmental stresses, such as pH, and they are most often transmitted by close contact. Non-enveloped viruses are hardier, and can sustain drying, low pH, detergents, and high temperature, and therefore are often transmitted via virus-associated objects or fomites and use respiratory or fecal/oral routes.
True or False Virus particles themselves are not alive and do not grow or undergo division.
TRUE One view is that they can be thought of as chemicals.
True or False CMV can be transmitted through breast milk
TRUE Transmitted via • Saliva, breast milk, sexual contact, blood, tears, respiratory secretions, contact with urine, stool etc. • Blood transfusions and organ transplantations • Infected pregnant women can pass the virus to their unborn babies
True or False For pregnant women with chronic genital HSV flares, C-section is recommended for birth.
TRUE Vaginal birth risks transmission to the baby.
True or False The modern-day vertebrate innate immune system is optimized to defend against ancient, extinct viruses, rather than our modern viral threats.
TRUE Viruses evolve faster than mammals. We can't keep up.
True or False CLL/SLL disease has a male predominance
TRUE 2:1, M:F
True or False In AML you will generally see a large drop in the CBC for any of the following: platelets, RBC, non-leukemic WBC
TRUE AML is ACUTE. This causes a drop in other cells produced in the marrow aside from the leukemic cells.
True or False In acute leukemia the leukemic cells are most often blasts.
TRUE Accumulation of precursors (blasts) due to a block in maturation.
True or False The WBC seen in a peripheral smear of a CHRONIC leukemia are generally more mature than those seen the smear of an ACUTE leukemia?
TRUE Acute - generally blasts Chronic - generally mature
True or False Rheumatoid arthritis and systemic lupus erythematosus (SLE) usually present in a symmetrical manner in joints of the body.
TRUE And osteoarthritis and gout are usually asymmetric.
True or False In DiGeorge syndrome, B-cells have diminished ability to produce IgA and IgG antibodies.
TRUE DiGeorge affects T-cell development. This includes T-follicular helper cells, so B-cells can not class switch and humoral immune response is diminished.
True or False Just about any damage to the dermis will also present in the epidermis.
TRUE Epidermis is nourished entirely by the dermis. Damage to the dermis almost always presents as accompanying damage to the epidermis.
True or False A high cortisol state can cause a high neutrophil count AND a low lymphocyte count
TRUE High Cortisol breaks neutrophils off the vascular endothelium in the lung, puts em into circulation -> peripheral Neutrophils up High Cortisol causes apoptosis of lymphocytes -> peripheral lymphocytes down.
True or False Autoimmune disorders are more common in females than males
TRUE Hormonre related reasons, but not sure of the mechanism.
True or False MDS can progress to Acute Leukemia
TRUE MDS and AL are pretty much the same thing (cytopenias with hyper cellular bone marrow). But AL = >20% blasts and MDS <20% blasts.
True or False Germinal center b-cells in a normal lymph node test negative for BCL2
TRUE So low that it is not positive.
True or False Leukemia and Lymphoma are BOTH disorders of hematopoetic cells
TRUE The common thread is the presence of a clonal malignant population of cells derived from a transformed cell of marrow derivation
True or False The nervous sensations of itch and burn travel to the CNS more slowly
TRUE They involve small unmyelinated fibers that conduct signal slowly.
True or False Most Urticaria cases will resolve within 6 weeks.
TRUE most are acute reactions.
True or False Low income people are less likely to develop asthma
TRUE Old friends hypothesis.
True or False The presence or absence of certain receptors can affect the outcome of a viral infection.
TRUE People lacking certain cellular receptors (abnormal, disease, or otherwise) may be entirely resistant to a virus that infects and is harmful to others.
True or False The number of bacteria in a human gut outnumber the endogenous cells in the entire human body
TRUE 10^13 cells in the body 10^14 bacteria in the gut flora
True or False Acyclovir requires cellular activation
TRUE Converted from monophosphate form to triphosphate form and is incorporated into DNA as an nt analog, which terminates elongation.
True or False In X-linked (Bruton's) Agammaglobulinemia, little to no antibody are made
TRUE. Pre-B-Cell can not mature, can not make Ab.
Describe a KOH prep. What specific fungi is this testing for?
Take a skin biopsy, expose it to KOH which eats away all epithelial cells, allows fungus to be easily identified. Test will be positive or negative for fungi, you will never see (dermatophytes) in normal skin. (but you will see candida) Testing for many fungi.
What is the brand name for Oseltamivir?
Tamiflu
What immunophenotyping marker distinguishes immature lymphocytes from other cells?
TdT
Which factors affect urate solubility?
Temperature Dehydration Trauma Proteoglycan abnormalities pH a) Temperature - lower temp = less solubility, higher temp = higher solubility. b) Dehydration or volume fluxes: overnight intra-articular dehydration may concentrate uric acid and crystallization promotors leading to the onset of acute gouty arthritis in the awakening morning hours. c) Trauma: release of articular MSU crystals, which trigger an attack. d) Intact proteoglycans bind and solubilize MSU. Proteoglycan abnormalities (as seen in osteoarthritis) may alter local urate levels and precipitate an attack. e) pH: MSU crystals are less soluble at a lower pH.
What is pseudogout?
Term for acute arthritis due to CPDD crystals.
Adnexal Structures: What are the two different types of hair on the body?
Terminal Hairs - Large, thick, coarse, pigmented. Scalp, beard, pubic area. Vellus Hairs - Small, fine, and apigmented. Located diffusely on the body - represented by hairs often on the ear, the lateral face of women, and the body in general.
Describe the factors that regulate the differentiation of Th0 cells in the Peyer's Patches to Th1, Th2, or Th17 versus into Treg cells.
Th0 -> Treg = TGFß (alone) or IL-10 Treg down, Th1, Th2, Th17 up = TFGß AND IL-6 Normal commensal gut organisms have evolved to live in the lumen and not try to invade; the immune response to them, taking place in an environment dominated by TGFß, is mostly by Treg at a steady level. When the innate response indicates a threat, it makes stress cytokines like IL-6 and the response switches from Treg production to defensive Th1, Th17, or Th2.
What happens when a Th2 cell recognizes a helminth?
Th2 is presented with helminth antigens by an APC and secretes IL-4, IL-5 and IL-13 which turn the macrophages into alternatively activated M2 macrophages which wall off the invader.
Which Strand of a viral DNA genome must be transcribed into the target mRNA?
The (-) strand. This results in a (+) strand mRNA
What is the most important factor in determining the prognosis of melanoma?
The Breslow measurement of thickness.
Which end of the IgE antibody sticks to the mast cell?
The Fc Portion.
What system is used to classify hematologic malignancies?
The WHO system: World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues
What does 'grade' refer to in all cancers? DELETE
The clinical aggressiveness of a malignancy
What are epidermal rete and dermal papillae? Why are these features important for dermal/epidermal interaction? What surface feature do these give rise to?
The downward projections of epidermis (rete) interlocked with the upward projections of dermis (papillae). Important to increase the contact surface area between epidermis and dermis due to the fact that the dermis is the only nutrient supply source for the epidermis, which has no blood vessels. Surface Feature: finger prints (epidermal ridges)
What is a commensal organisms of the gut?
The microbiome. Organisms that are in a relationship in which one organism derives food or other benefits from another organism without hurting or helping it
Discuss the incidence of selective IgA deficiency, and the associated syndromes.
The most common immunodeficiency disease. 200 in every 100,000 live births. 10-15 times more frequent in Celiac patients. Is usually asymptomatic, but can have diarrhea, sinopulmonary infections, increased frequency and severity of all allergies.
Where on the body are sebaceous glands more prevalent?
The sebaceous glands are more prominent in the "oily" areas of the body, such as the face, neck, and chest and upper back
List two reasons for the frequent occurrence of splenomegaly and hepatomegaly in patients with MPNs.
The spleen/Liver are sequestering excess RBC as well as making RBC on its own. 1) Sequestration of RBC 2) Extra Medullary hematopoiesis (hematopoiesis occurring outside the bone)
What is the anti-viral state? Describe its effects
The state a cell goes into when it has responded to interferon signaling. Effects: -alters transcription of > 100 cellular genes -is facilitated (triggered) by dsRNA -results in temporary blockade of cell proliferation
Where do most drug-related rashes present?
The trunk
Explain why a person usually has no observed symptoms when first exposed to a "contact sensitizer" like poison ivy.
There is an initiation (immunization) phase and an elicitation (effector) phase. This first exposure is the initiation phase (DC show antigen on MHC I/II to generate a t-cell response that generates memory t-cells (immunization)) Subsequent exposures trigger memory t-cells which have a lower threshold for reactivity and a stronger response. Secretion of INF-g attracts M1 macrophages resulting in strong, potentially self-damaging immune response.
Describe the mechanism of (+) RNA production in Viral genomes with a ss(+)RNA requiring a DNA intermediate.
These are called Retroviruses. They rely on reverse transcriptase which makes DNA from the initial ssRNA. The produced DNA then inserts itself into the host genome.
What are Intracellular restriction factors? What are some examples?
These are cellular proteins that act to block post-entry steps of viral infection (replication, translation, etc..) Examples: Trim5 blocks retroviruses. APOBEC blocks HIV and HCV.
DIAGNOSE: funny red bumps/growths on skin, growing, bleed when touched. Can be quite pronounced.
These are metastases to skin. commonly seen in renal, lung and breast cancer.
Describe the pathway to translation for (+) stranded RNA viruses
These genomes have the (+) RNA, which IS the final mRNA so this can be directly translated into protein.
What role do diuretics and low dose aspirin play in hyperuricemia?
They are URAT1 ACTIVATORS. Increased URAT 1 activity results in increased Uric Acid reabsorption and decreased excretion, increasing risk of hyperuricemia.
What is the function of the glycoprotein 'spikes' seen on some viruses?
They are involved in attachment to new host cell.
What causes verruca? With is the physiological appearance of a wart.
They are virally induced. They need a blood supply so they recruit it from the papillary plexus causing thrombosed capillaries to be visible from the surface. Indeed, the presence of central thombosed capillary loops is a reassuring sign that the lesion is in fact a wart.
Describe the immunological problem of the Nude mouse, and name the human immunodeficiency condition it resembles.
They have a very different mutation buy they also fail to make thymic stroma (no t-cells) and are therefore phenotypically similar to DiGeorge Syndrome patients.
In the case of (-) ssRNA viral genomes, the RNA is not ready for coding (Cos is (-) strand) and can therefore not encode for/make the necessary RdRp needed to produce (+) ssRNA. How do (-) ss RNA viral genomes progress?
They have pre-formed RdRp present in their capsid when they infect a new cell.
In which types of skin is the stratum lucidum found? What is its function?
Thick skin. Reduction of friction between stratum corneum and stratum granulosum.
What factors in the patient can affect uptake of topical medications
Thickness of skin - bottoms of feet, thickness of stratum corneum. Skin Hydration - wetter = more absorption Occlusion - covering area of administration increases uptake.
Discuss the mechanism of chronic beryllium disease.
This is a pulmonary inflammatory and fibrotic disease caused by exposure to inhaled beryllium (Be) dust. Be covalently binds to endogenous peptides which forms a new epitope against which a Th1 and later a Th2 response are made. Macrophages cannot remove the Be so an immediate inflammatory response is generated, even after one exposure.
What is the most common method of death attributable to disease in polycythemia vera (PV) patients?
Thrombotic events (due to massively inc platelets)
Acyclovir would be ineffective against HSV strains with loss of expression of: M2 proton channel Dihydrofolate reductase Reverse transcriptase Thymidine kinase Neuraminidase
Thymidine kinase This is needed for the initial activation of acyclovir.
Describe the common locations for the following Tinea capitis Tinea faciei Tinea barbae Tinea corporis Tinea Cruris Tinea manuum Tinea Pedis Tinea unquium
Tinea capitis - scalp or hair (most common) Tinea faciei - face Tinea barbae - version of tinea faciei limited to beard Tinea corporis - non hair-bearing skin Tinea Cruris - genital region Tinea manuum - hands, palms Tinea Pedis - feet Tinea unquium - nails
What is the category of the pathogenic mechanism of Cholera?
Toxin-mediated
Against what gut component do Celiac patients form Ab? What does this do?
Transglutaminase 2 (TG2) (tTG in pic) Enzyme, breaks down gluten into components.
What is the genetic mutation in FL that allows BCL2 to be increased in activity?
Translocation of t(14;18), involving the long arms of chromosomes 14 and 18, which places the BCL2 gene on chromosome 18 under the influence of the IGH promoter on chromosome 14 .
What is the underlying genetic cause and mechanism of Burkitt's Lymphoma?
Translocation t(8;14) puts the MYC gene next to IGH => Constitutively activated MYC => MYC activates many gene, some of which are in evolved in cell proliferation => cell proliferation increased/uncontrolled.
How is BCL1 affected in mantle cell lymphoma?
Translocation, t(11;14), (BCL1 gene and IGH gene) = induces consistent over expression of BCL1
What is Ribavirin used for? What is it? What is its mechanism?
Treatment for Respiratory Syncytial Virus A nucleoside analoge Blocks capping of viral mRNA
What common topical corticosteroid has midlevel potency and is therefore termed the 'The all purpose weapon'? When is it contraindicated?
Triamcinolone Acetonide .1% (class 4) Best for moderate spongiotic dermatoses in trunk and extremities. NOT recommended for long term use on face, intertriginous areas, groin.
What are the most common dermatophytes?
Trichophyton - head, feet, and cutaneous Microsporum - fluorescent tinea capitis Epidermophyton - most common in genital region
True or False Unlike other tests in herpesvirus infections, serology CAN distinguish between primary and recurrent infection
True
What are some examples of type 1 and type 2 interferons?
Type 1 - INFa, INFb Type 2 - INFg Different receptors on targets cells, very similar pathways.
What are the two types of nerve fibers to be aware of and their basic characteristic?
Type A - Heavily Myelinated. Conduct rapidly. Initial localized pain, proprioception, touch, muscle stretch Type C - Un-myelinated. conduct slowly. Temperature and itching
What type of hypersensitivity is involved in urticaria? What mediates this reaction?
Type I, Immediate type. IgE antibodies.
What type of hypersensitivity is involved in allergic contact dermatitis? What mediates this reaction?
Type IV, delayed type. Cell mediated, T-cells
What is URAT1 and what is its function?
URAT1: Urate/organic anion exchanger. Sits in proximal tubule of kidney and reabsorbs Uric acid in exchange for unwanted organic acids such as: lactate, acetoacetate, hydroxybutyrate and succinate.
Describe actinic Keratosis. What, if left untreated, can this progress to?
UV induced (typically) pre-cancerous patch of thick, scaly, or crusty skin. Can progress to Squamous Cell Carcinoma (more common progression) or Basal cell carcinoma. 65% of all SCC arise from AK 36% of all BCC arise from AK
Which class of UV more deeply penetrates the skin?
UVA
Which class of UVR causes thymine dimers?
UVB
Describe vitamin D metabolism in the skin. How does this compare to VIt D3 taken in from diet?
UVR induces synthesis of Cholecalciferol (D3) and ergocalciferol (D2) which travel to liver and kidney where they are converted into the active form - Di-hydroxy D3). D3 taken in from diet IS Cholecalciferol. So both the exogenous and endogenous forms travel to liver and kidney to become active.
Hyperuricemia can lead to gout and is caused by either overproduction of urate or decreased excretion of urate. Which (overproduction , under excretion) predominates as the cause of primary gout?
Under-excretion. ~90% of all cases.
Describe the clinical features which, although not immunological, are part of DiGeorge syndrome.
Unexplained convulsions in infancy and abnormal development of the great vessels of the heart.
What are fungi?
Unicellular eukaryotes: mold, yeast, mildew Multicellular eukaryotes: mushrooms Fungi are their own kingdom separate from plants, animals, protists, and bacteria.
What is the difference between unscented and fragrance-free products? Why does one of these still cause a reaction?
Unscented still uses fragrance, just a masking fragrance. Fragrance-free uses no fragrance at all. There are 100 known contact allergens in fragrances.
What type of crystals accumulate in gout? What causes their formation?
Urate Crystals: Over production or under-excretion of uric acid. Inc conc in blood -> precipitates into urate crystals. Exact mechanisms are complex but has to do with genetics, drugs, diet, and metabolic issues.
Identify the Inflammatory Skin Disease: Type I hypersensitivity reaction, IgE involvement.
Urticaria.
What is a physical urticaria?
Urticarias caused by various physical affront to the skin. • Dermagraphism • Delayed Pressure Urticaria • Vibratory Angioedema • Exercise-induced urticaria • Cold Urticaria • Solar Urticaria • Aquagenic Urticaria
What drug is used to treat late-stage reactions? What drug is NOT used?
Used: Corticosteroids, shut down phospholipase A2 (Prostaglandin and leukotriene synthesis) NOT used: Antihistamine. Late stage reaction is NOT histamine mediated.
Infantile Hemangioma: What is it? What are its clinical features? What is the cell of origin? Where on the body is it typically located? Is it typically benign, malignant, or potentially malignant? More common in children or adults?
Usually a lesion at birth, but rapidly grows in first couple months. Grows over first year of life. they then involute, 50% have resolved by age 5 and 90% have resolved by age 9. Origin: Endothelial cells Location: anywhere b/m: Benign Infantile onset.
What type of arthritis has a very rapid onset (hours)
Usually gout or pseudo gout.
Port Wine Stain: What is it? What are its clinical features? What is the cell of origin? What is its progression and treatment?
Vascular anomaly causing coloring of the skin Cell: Endothelial Present at birth and persists into adulthood, growing in size with the patient. Treatment: Vascular lasers. Can be alluding to venous or arterial malformation under the skin in deeper vessels. Can be treated with compression stalkings.
What is the medical term for a wart?
Verruca
How can you distinguish between drug eruptions and viral exanthematous eruptions?
Very difficult to tell apart. Mix of macules and papules all over. Main way to determine: ask patient - Feeling sick otherwise (viral symptoms)? - Recently started any new meds?
What is Viremia? What is the difference between primary and secondary viremia?
Viremia: Presence of virus in the blood. Primary viremia refers to the initial spread of virus in the blood from the first site of infection. Secondary viremia occurs when primary viremia has resulted in infection of additional tissues via bloodstream, in which the virus has replicated and once more entered the circulation.
What characterizes a viral acute infection?
Virus acute infection is characterized by a high viral replication rate and the production of a large number of progeny. Replication is transient in an individual host, as it is limited either by the death of the host (and/or cells inside the host) or by the host immune responses.
What is the clinical presentation of atopic dermatitis.
Visible flexural eczema (antecubital fossa, popliteal fossa, neck, wrists, ankles) OR Eczema on face if <4 yoa.
What happenes to collagen in the absence of Vitamin C? What physiological phenomena result?
Vit C is essential for proper extracellular collagen fibril assembly. No vitamin C yields WEAK COLLAGEN -> • wounds fail to heal • hair grows abnormally • gums recede and teeth fall out • blood vessels become fragile. Vit C deficiency = scurvy.
What is the predominant component of hyaline cartilage?
WATER but then Collagen type 2 and proteoglycans (holding water)
What are the usual causes for polyarticular arthritis?
Want to think: Systemic issues and/or autoimmune. Causes: rheumatoid arthritis, lupus, psoriatic arthritis, reactive arthritis, hep B.
What are the usual causes for monoarticular arthritis?
Want to think: something happened to this exact joint, this is not systemic. Causes: septic arthritis, gout, traumatic arthritis, mechanical derangement of joint
What are ointments?
Water in an oil emulsion
What are the most common vectors for fungal infection?
Wetter = worse. Direct contact: Animals (cats and livestock worst), people, gym floors, etc
Cherry Hemangioma: What is it? What are its clinical features? What is the cell of origin? Where on the body is it typically located? Is it typically benign, malignant, or potentially malignant? More common in children/adults/men/women?
What: Skin papule, abnormal proliferation of blood vessels. Clinical: Multiples, 1.4 mm in size, bright red smooth top papule. Origin: Endothelial cell Where: Typically on the trunk b/m: Completely Benign Middle aged onset.
What is the ultimate reason that the bowel becomes inflamed in IBD?
Whatever the prior mechanism, the gut now has activated Th1, Th17, and Th2 against normal commensal organisms (Microbiome) as if trying to rid the gut of these creatures; but they never can, so the inflammation goes on and on. Chron and Ulcerative Colitis are both attacks against the normal, commensal organisms of the gut.
What is the basic mechanism of interferons in viral infection?
When a cell is infected with a virus is produces and secretes interferons which 'warn' neighboring cells of the virus, making those neighboring cells harder for the virus to infect. Two types: Type 1 INF - made by any infected cell Type 2 INF - made by T-cells and NK cells
When, diagnostically, do you consider the diagnosis for MDS?
When there has been one observed, persistent cytopenia of two or more cell lineages. Cytopenia of a single lineage is almost alway just anemia
When do congenital nevi become concerning for potential melanoma?
When they are large (>10cm)
Neuraminidase inhibitors are most effective when started how long after symptom onset? Within 24 hours Within 48 hours Within 72 hours Within 96 hours Within 5 days
Within 48 hours.... But ASAP. As soon after symptoms as possible.
Where geographically is endemic BL most common? Where on the body does BL most commonly present?
World: malaria belt of equatorial Africa Body: Jaw and abdomen
Which type of arthritis is worse with activity, at the end of a day? And which type is worse with rest, at the beginning of a day?
Worse with activity/end of day: Osteoarthritis Worse with rest/Beginning of day: Rheumatoid arthritis
In regards to primary immunodeficiency: A patient has normal pre-B cells but little to no normal mature B-cells. What do they have?
X-linked (Bruton's) Agammaglobulinemia
In regards to primary immunodeficiency: A patient has normal T and B cell counts. When prompted by an immunogen, B-Cells produce large amounts of IgM, but little to no IgG. What do they have?
X-linked hyperIgM Syndrome
What problems arise with therapeutic gene insertion into a genome?
You can insert the gene near or in a pro-oncogene, thereby activating it into an oncogene.
What is impetigo?
a contagious bacterial skin infection most common among preschool children.
What are the two main features that characterize myelodysplastic syndrome (MDS)?
a) Ineffective hematopoiesis b) Increased risk of transformation to acute myeloid leukemia
Relate the importance of specific recurrent translocations (EX: t(9;22) in certain hematologic malignancies in regard to the clinical care of patients.
a) diagnostic markers for certain hematologic malignancies b) critical role in the development of the hematologic malignancy they are associated with
For Cytomegalovirus (CMV), list the following: a. Type of virus (DNA vs. RNA, double strand versus single strand) b. Cells targeted for primary infection and latency c. Transmission and incubation period d. Disease entities and their clinical presentations e. Diagnosis and key diagnostic tests f. Treatments g. Prophylaxis-including vaccines
a. Type: dsDNA b. Primary: Epithelia, monocytes, Lymphocytes, others Latency: Monocytes and lymphocytes c. T/I: Contact, blood transfusions, transplantation, congenital. Incubation: d. D/C: Infectious, mononucleosis like syndrome. e. Diagnosis: f. Treatment: g.
For Varicella Zoster virus (VZV), list the following: a. Type of virus (DNA vs. RNA, double strand versus single strand) b. Cells targeted for primary infection and latency c. Transmission and incubation period d. Disease entities and their clinical presentations e. Diagnosis and key diagnostic tests f. Treatments g. Prophylaxis-including vaccines
a. Type: dsDNA b. Primary: Mucosal epithelium, Latency: Neuron c. T/I: Contact or respiratory. Incubation: d. D/C: Chicken Pox (varicella), Shingles (Zoster) e. Diagnosis: f. Treatment: Options: None, Acyclovir, Varivax, Zostavax g.
For Herpes simplex type 2 (HSV2), list the following: a. Type of virus (DNA vs. RNA, double strand versus single strand) b. Cells targeted for primary infection and latency c. Transmission and incubation period d. Disease entities and their clinical presentations e. Diagnosis and key diagnostic tests f. Treatments g. Prophylaxis-including vaccines
a. Type: dsDNA b. Primary: Mucosal epithelium, Latency: Neuron c. T/I: Contact, sexual. Incubation: 2-12 days d. D/C: Orofacial and/or genital lesions, encephalitis. e. Diagnosis: f. Treatment: g.
For Herpes simplex type 1 (HSV1), list the following: a. Type of virus (DNA vs. RNA, double strand versus single strand) b. Cells targeted for primary infection and latency c. Transmission and incubation period d. Disease entities and their clinical presentations e. Diagnosis and key diagnostic tests f. Treatments g. Prophylaxis-including vaccines
a. Type: dsDNA b. Primary: Mucosal epithelium, Latency: Neuron c. T/I: Contact. Incubation: 2-12 days d. D/C: Orofacial and/or genital lesions, encephalitis. e. Diagnosis: f. Treatment: g.
What is M protein?
an abnormal immunoglobulin fragment or immunoglobulin light chain that is produced in excess by an abnormal clonal proliferation of plasma cells. Basically a crap load of neoplastic plasma cells make a weird immunoglobulin light chain in excess (M-protein) which can be detected. (its the band in the gamma region in the pic, it is not normally that tall of a spike)
What is a melanosome?
an organelle found in animal cells and is the site for synthesis, storage and transport of melanin
What is the name of the muscle attached to each hair that raises it making goose bumps?
arrector pili
Define: atopic immediate hypersensitivity allergy allergen anaphylaxis asthma hives wheal-and-flare reaction.
atopic - 'prone to develop any of the range of allergic syndromes' immediate hypersensitivity - Usually tied to immediate mast cell degranulation symptoms. allergy - hypersensitivity by the immune system to something in the environment. allergen - the antigen in a type 1 reaction anaphylaxis - serious allergic reaction, multiple symptoms asthma - bronchoconstrictive and inflammatory response to allergen hives - wheal-and-flare reaction - is a hive
What is the most common location of initial viral replication?
epithelial cells near body surface or barriers.
What are foams?
gas in a matrix of liquid film.
List three sites where thrombosis should always make one consider the possibility of PV.
mesenteric vein, portal vein, or splenic vein.
Give an example of a Type II mechanism disease of: muscle kidney heart red cells platelets lung thyroid
muscle - Myasthenia Gravis kidney - Goodpasture heart - Dressler, Rheumatic Heart Disease, red cells - Autoimmune hemolytic anemia. platelets - Autoimmune Thrombocytopenic Purpura lung - Goodpasture thyroid - Graves, Hashimoto
What are the features of the afferent free nerves in the dermis that conduct pruritus?
small, unmyelinated C fibers with a slow conduction rate.
What is the Philadelphia chromosome? In what diseases is it found (that we discussed do far)
t(9;22) CML and B-ALL
What chromosomal translocation is seen in CML?
t(9;22). BCR-ABL, The Philadelphia chromosome
What are some important anti-microbial peptides present in skin as part of its innate defense system?
α-defensins β-defensins cathelicidin (HCAP-18) psoriasin RNase7
What are centrocytes and centroblasts?
• Centrocytes: small to medium size with scant cytoplasm; angulated, elongated, twisted or cleaved nuclei; inconspicuous nucleoli • Centroblasts: large transformed cells with round or oval nuclei and vesicular chromatin; a narrow rim of cytoplasm; one to three peripheral nucleoli
What are the functions of Langherans cells?
• Dendritic cells in the epidermis derived from a bone marrow stem cell • Participate in cell-mediated immune reactions by processing and presenting antigens (circulate back and forth between skin and lymph nodes)
What are the functions of keratinocytes?
• Form a barrier • Synthesize Keratin - the major intracellular fibrous protein of the skin • Involved in a defined cycle of proliferation, differentiation, and programmed cell death (apoptosis).
In viral assembly, what are the two ways the viral genome can get into the capsid?
• The capsid assembles around the virus genome. • The genome is "fed" into preformed capsids.
Aside from clear clinical diagnostic tactics (possible with Herpes gingivostomatitis and herpes labialis) how else is HSV diagnosed?
• Viral culture of lesions (easiest and best bet for oral or genital lesions) • Direct fluorescent antibody stain of lesions (fluorescent stain adheres to HSV antigens in a sample indicating their presence) • PCR of lesions (most expensive) Shown, staining of the eye for HSV - leaves 'dendritic' pattern.
List the seven basic virus genomes
• dsDNA • gapped circular dsDNA • ssDNA • dsRNA • ss(+)RNA • ss(-)RNA • ss(+)RNA with DNA intermediate
