Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
385 Cards in this Set
- Front
- Back
|
Innate immunity
|
first defense against pathogens
|
|
|
Natural killer cells
|
large granular lymphocytes in peripheral blood
|
|
|
TLRs
|
recognize non-self antigens on pathogens
|
|
|
NF kB
|
"master switch" to the nucleus
|
|
|
IgM and IgG synthesis
|
begins at birth
|
|
|
where are T-cells derived from?
|
bone marrow
- lymphocyte stem cells mature in the thymus |
|
|
where are T-cells located at in the body?
|
peripheral blood and bone marrow, thymus, paracortex of lymph node, Peyer's patches
|
|
|
what are the two types of T-cells?
|
CD4 (helper)
CD8 (cytotoxic) |
|
|
what is the function of a CD4 cell?
|
1. secrete cytokines: IL-2 > proliferation of CD4/CD8 T-cells
2. INF-g > activation of macrophages 3. Help B cells become antibody producing plasma cells |
|
|
what is the function of CD8 cells?
|
kill virus-infected cells, neoplastic and donor graft cells
|
|
|
where are B-cells located?
|
Peripheral blood
Bone marrow Germinal follicles in lymph nodes Peyer's patches |
|
|
what is the function fo the B-cell?
|
differentiate into plasma cells that produce immunoglobulins to kill encapsulated bacteria
|
|
|
where area Natural Killer cells located?
|
peripheral blood
- large granular lymphocyte |
|
|
what is the function of NK cells?
|
kill virus infected and neoplastic cells
Release INF-g |
|
|
where are macrophages derived?
|
Conversion of monocytes into macrophages occurs in the connective tissue
|
|
|
what is the function of a macrophage?
|
involved in the phagocytosis and cytokine production
Acts as Antigen Presenting cell (APC) |
|
|
where are Dendritic cells found?
|
skin (Langerhn's cells)
Germinal follicles Act as APC |
|
|
APCs
|
B cells
Macrophages Dendritic cels |
|
|
HLA-B27 is associated with what disease?
|
Ankylosing spondylitis
|
|
|
what HLA is associated with Multiple sclerosis?
|
HLA-DR2
|
|
|
what HLAs are associated with Type I DM?
|
HLA-DR3 & DR4
|
|
|
HLA-B27
|
ankylosing spondylitis
|
|
|
APCs
|
B cells
macrophages dendritic cells |
|
|
Type I HSR
|
IgE activation of mast cells
|
|
|
Mast cell activation
|
allergens cross link allergen specific antibodies
|
|
|
IgE antibody mediated activation of mast cells producing an inflammatory response
|
Type I (immediate) Hypersensitivity reaction
|
|
|
what cells do APCs interact with causing interleukins to stimulate B-cell maturation in a Type I HSR?
|
APCs interact with CD4 TH2 cells causing interleukins to stimulate B-cell maturation
|
|
|
what does IL-4 do?
|
IL-4 causes plasma cells to switch from IgM to IgE synthesis
|
|
|
what does IL-5 stimulate?
|
IL-5 stimulates the production & activation of eosinophils
|
|
|
what causes the release of preform mediators by the mast cell in a type I HSR?
|
IgE triggering causes mast cell to release preformed mediators
|
|
|
what is the early phase of mast cell reaction
|
release of histamine, chemotactic factors for eosinophils, and proteases
Produces tissue swelling and bronchoconstriction |
|
|
late phase reaction of mast cells in Type I HSR
|
mast cells synthesize and release prostaglandins and leukotrienes
enhances and prolongs acute inflammatory reaction |
|
|
what is desensitization therapy
|
desensitization therapy involves repeated injections of increasingly greater amounts of allergen, resulting in production of IgG antibodies that attach to allergens and prevent them from binding to mast cells
|
|
|
scratch test
|
best overall sensitivity for Type I HSR
positive response is a histamine mediated wheal and flare reaction after introduction of an allergen into the skin |
|
|
what is a potentially fatal type I HSR?
|
Anaphylactic shock
|
|
|
Type II HSR
|
antibody-dependent cytotoxic reactions
|
|
|
pathogenesis of Type I HSR
|
IgE dependent activation of mast cells
|
|
|
Atopic disorders are examples of what HSR?
|
Type I HSR:
- hay fever - eczema - hives - asthma - reaction to bee sting |
|
|
Drug Hypersensitivity from penicillin producing a rash or anaphylaxis is an example of what type of HSR?
|
Type I
|
|
|
Hay fever
HSR? |
Type I
|
|
|
Eczema
HSR? |
Type I
|
|
|
Hives
HSR? |
Type I
|
|
|
Asthma
HSR? |
Type I
|
|
|
REaction to bee sting
HSR? |
Type I
|
|
|
pathogenesis of Type II HSR?
|
antibody dependent reaction
|
|
|
Type II complement dependent reactions
|
IgM or IgG mediated
|
|
|
describe an IgM mediated Type II HSR.
|
Lysis
- antibody (IgM) directed against antigen on the cell membrane activated the complement system leading to lysis of the cell by the MAC |
|
|
Example of IgM mediated Type II HSR
|
ABO mismatch
Cold immune hemolytic anemia |
|
|
describe IgG mediated Type II HSR.
|
IgG attaches to basement membrane/matrix > activates complement system > C5a is produced > recruitment of neutrophils/monocytes to the activation site > release enzymes, reactive oxygen species > damage to tissue
|
|
|
example of IgG mediated Type II HSR
|
Goodpasture's syndrome
Pernicious anemia |
|
|
describe Goodpastures Type II HSR.
|
with IgG antibodies directed against pulmonary and glomerular capillary basement membrane s
|
|
|
what occurs in phagocytosis in a type II HSR?
|
fixed macrophages phagocytose hematopoietic cells coated by IgG antibodies or complement (C3b)
|
|
|
example of Type II HSR phagocytosis.
|
Warm (IgG) autoimmune hemolytic anemia
ABO and Rh hemolytic disease of a newborn ITP |
|
|
what is natural killer cell destruction of neoplastic cells and virus infected cells an example of?
|
Antibody (IgG) dependent cell mediated cytotoxicity Type II HSR
|
|
|
what is eosinophil destruction of helminths an example of?
|
antibody (IgE) dependent cell mediated cytotoxicity type II HSR
|
|
|
what is Myasthenia gravis an example of HSR?
|
Type II HSR
antibodies directed against cell surface receptors |
|
|
what type of HSR is Graves disease an example of?
|
antibodies directed against cell surface receptors TYPE II HSR
|
|
|
what is the pathogenesis of Type III HSR?
|
deposition of antigen-antibody complexes
|
|
|
what type of HSR is SLE?
|
Type II HSR
- DNA-anti-DNA |
|
|
what type of HSR is Serum sickness an example of?
|
Type III HSR
- horse antihymocyte globulin antibody |
|
|
what type of HSR is Poststreptococcal glomerulonephritis?
|
Type III HSR
|
|
|
Type IV HSR pathogenesis
|
antibody-independent T-cell mediated reactions
|
|
|
example of delayed type IV HSR
|
Tuberculous granuloma
PPD reactions MS |
|
|
Cell mediated cytotoxicity Type IV HSR example
|
killing of tumor cells and virus infected cells
contact dermatitis: nickel & poison ivy |
|
|
Does Type IV HSR involve immunoglobulins?
|
NO
|
|
|
Myasthenia gravis, Graves disease are examples of what?
|
antibodies against receptors
type II HSR |
|
|
Type III HSR
|
complement activation by circulating antigen-antibody complex
|
|
|
describe the mechanism of a type III HSR
|
1. first exposure to antigen
- synthesis of antibodies 2. Second exposure to antigen - deposition of antigen-antibody complexes - complement activation, producing C5a, which attracts neutrophils that damage the tissue |
|
|
what is an arthus reaction?
|
localized immunocomplex reaction
- example: farmers lung from exposure to thermophilic actinocycetes or antigens in the air |
|
|
what test are used to evaluate a Type III HSR
|
Immunofluorescent staining of tissue biopsies
|
|
|
what are the antibody mediated HSRs?
|
Types I, II, III
|
|
|
Type IV HSR
|
cellular immunity
- antibody independent T cell mediated reactions |
|
|
Functions of Cell Mediated immunity (TYPE IV HSR)
|
1. control infections caused by viruses, fungi, helminths, mycobacteria, intracellular bacterial pathogens
2. Graft rejection 3. tumor surveillance |
|
|
Delayed reaction hypersensitivity
Type IV HSR |
DRH: CD4 cells interact with macrophages (APCs with MHC class II antigens) resulting in cytokine injury to tissue
|
|
|
Cell mediated cytotoxicity
Type IV HSR |
CD8 T cells interact with altered MHC class I antigens on neoplastic, virus infected, or donor graft cells causing cell lysis
|
|
|
what is contact dermatitis an example of?
|
Type IV HSR
Cell-mediated cytotoxicity - activated CD4 and CD8 T-cells damage antigens in skin (poison ivy, nickel) |
|
|
what is the patch test used for?
|
to test for Type IV HSR contact dermatitis
- suspected allergen in placed on an adhesive patch is applied to skin to see if a skin reaction occurs |
|
|
what is the primary mediator of contact dermatitis?
|
CD4 T-cells
|
|
|
what is the most important requirement for successful transplantation?
|
ABO blood group compatibility between recipient and donor
|
|
|
what must a patient been exposed to in order to have anti-HLA cytotoxic antibodies?
|
people must have had previous exposure to blood products to develop anti-HLA cytotoxic antibodies
|
|
|
what type of graft is associated with the best survival rate?
|
autograft (self to self)
|
|
|
what is a syngenic graft?
|
isograft
- between identical twins |
|
|
Allograft
|
between genetically different individuals of the same species
|
|
|
what type of graft is a human fetus an example of?
|
allograft that is not rejected by mother
|
|
|
Xenograft
|
between two species
- transplant of heart valve from pig to human |
|
|
Hyperacute rejection
|
irreversible
type II HSR |
|
|
how long does it take for a hyperacute rejection to take place?
|
irreversible reaction occurs within minutes
|
|
|
pathogenesis of HYPERacute rejection
|
1. ABO incompatibility or action of preformed anti-HLA antibodies in the recipient directed against donor antigens in vascular endothelium
|
|
|
what type of HSR is a HYPERacute rejection?
|
type II HSR
|
|
|
a patient with blood group A receives a heart from a blood group B patient. what type of rejection would this cause?
|
HYPERacute reaction
- pathological finding of vessel thrombosis |
|
|
what is the most common transplant rejection?
|
Acute rejection
|
|
|
is an acute rejection reversible?
|
YES
- reversible reaction that occurs within days to weeks |
|
|
what type of HSR is an acute rejection?
|
1. Type IV cell mediated HSR
- host CD4 T cells release cytokines, resulting in activation of host macrophages, proliferation of CD8 T-cells, and destruction of donor graft cells - extensive interstitial round cell lymphocytic infiltrate in the graft, edema, and endothelial cell injury 2. Antibody-mediated type II HSR - cytokines from CD4 T cells promote B cell differentiation into plasma cells producing anti-HLA antibodies that attack vessels in the donor graft. - vasculitis with intravascular thrombosis in recent grafts - intimal thickening with obliteration of vessel lumens in older grafts |
|
|
how are acute rejections potentially irreversible?
|
acute rejections are potentially reversible with immunosuppressive therapy, such as cyclsporine, OKT3, and corticosteroids.
Immunosuppressive therapy is associated with an increased risk of cervical squamous cell cancer, malignant lymphoma, and squamous cell carcinoma of the skin |
|
|
what is the most common cancer associated with immunosuppression?
|
squamous cell carcinoma
|
|
|
acute rejection
|
most common type
type IV and type II HSR |
|
|
is a chronic rejection reversible?
|
NO
irreversible reaction that occurs over months to years |
|
|
pathogenesis of chronic rejection.
|
involves continued vascular injury with ischemia to tissue
- blood vessel damage with intimal thickening and fibrosis |
|
|
clinical findings in graft vs. host reaction
|
jaundice - bile duct necrosis
diarrhea - GI mucosa ulceration dermatitis |
|
|
what do you treat a GVH reaction.
|
Treat with anti-thymocyte globulin or monoclonal antibody before grafting
cyclosporine reduces the severity of the reaction |
|
|
what type of transplant has the best allograft survival rate?
|
Corneal transplants
|
|
|
what is a risk of a cornea transplant?
|
transmission of Creutzfeldt Jakob disease
|
|
|
describe the findings associated with a bone marrow transplant
|
graft contains pluripotential cells that repopulate host stem cells
host assumes ABO group of donor Danger of GVH reaction and CMV infection |
|
|
examples of organ specific autoimmune disorders
|
Addison's disease
Pernicious anemia Hashimoto's thyroiditis |
|
|
examples of systemic autoimmune disorders.
|
SLE
rheumatoid arthritis systemic sclerosis |
|
|
what is the most useful screening test for autoimmune disease?
|
Serum antinuclear antibody (ANA) test
|
|
|
what antibodies does the serum ANA detect?
|
antibodies against DNA, histones, acidic proteins, and nucleoli
|
|
|
anti-dsDNA antibodies
|
SLE with glomerulonephritis
|
|
|
antihistones antibodies
|
antihistones antibodies present in drug induced lupus
|
|
|
acidic proteins antibodies
|
anti-Smith present in SLE
anti-ribonucleoprotein antibodies in systemic sclerosis |
|
|
Nucleolar antigens antibodies
|
anti-nucleaolar antibodies present in systemic sclerosis
|
|
|
what does the RIM pattern of the serum ANA test correlate with?
|
anti-dsDNA antibodies and the presence of renal disease in SLE
|
|
|
what is systemic lupus erythematosus?
|
connective tissue disease that mainly affects the blood, joints, skin, and kidneys
|
|
|
what do environmental factors play an important role in SLE?
|
Environmental factors are important in exacerbating SLE or triggering the initial onset
|
|
|
what type of HSR is involved in SLE?
|
Type II HSR
immuncomplexes |
|
|
autoantibodies: anti-ACh receptor
|
disease: myasthenia gravis
|
|
|
autoantibodies: anti-basement membrane
|
Goodpastures syndrome
|
|
|
anticentromere antibodies
|
CREST syndrome
|
|
|
antiendomysial IgA antibodies
|
Celiac disease
|
|
|
Antigliadin IgA antibodies
|
Celiac disease
|
|
|
Antihistone antibodies
|
drug induced lupus
|
|
|
anti-insulin antibodies
|
Type 1 Diabetes
|
|
|
anti-islet cell antibodies
|
Type 1 DM
|
|
|
Anti-intrinsic factor antibodies
|
Pernicious anemia
|
|
|
anti-parietal cell antibodies
|
pernicious anemia
|
|
|
antimicrosomal antibodies
|
Hashimotos thyroiditis
|
|
|
Anti-Smith antibodies
|
SLE
|
|
|
Anti-SS-A (Ro) antibodies
|
Sjogren syndrome
SLE |
|
|
Anti-SS-B (La) antibodies
|
Sjogren's syndrome
|
|
|
Antithyroglobulin antibodies
|
hashimoto's thyroiditis
|
|
|
anti-tissue transglutaminase IgA antibodies
|
Celiac disease
|
|
|
anti-topoisomerase antibodies
|
Systemic sclerosis
|
|
|
antimitochondrial antibodies
|
primary biliary cirrhosis
|
|
|
anti-myeloperoxidase antibodies
|
microscopic polyangiitis
(p- ANCA) |
|
|
Anti-nuclear antibodies
|
SLE
Systemic sclerosis Dermatomyositis |
|
|
Anti-proteinase 3 antibodies
|
Wegener's granulomatosis (c-ANCA)
|
|
|
Anti-ribonucleoprotein antibodies
|
MCTD
|
|
|
anti-TSH receptor antibodies
|
Graves disease
|
|
|
what is the function fo STAT4 and its importance in SLE?
|
An allele on STAT4 is associated with increased risk for developing SLE
STAT4 is part of a family of transcription factors Protein products of STAT4 are essential for mediating responses to IL-12 in lymphocytes and in regulating the differentiation of T helper cells |
|
|
most common cardiac findings in SLE.
|
fibrinous pericarditis with effusions
|
|
|
most common drug associated with drug induced lupus.
|
Procainamide
|
|
|
Drug induced lupus
|
antihistones antibodies
|
|
|
screen for SLE
|
serum ANA
|
|
|
confirm SLE
|
anti-dsDNA and anti-Sm antibodies
|
|
|
LE cell
|
neutrophil with phagocytosed, altered DNA
|
|
|
is serum complement increased or decreased in SLE?
|
usually decreased because of activation of complement system by immunocomplexes
|
|
|
what is the most common cause of death in SLE?
|
infection due to immunosuppression
|
|
|
systemic sclerosis
|
excess collagen deposition, digital vasclitis
|
|
|
Raynaud's phenomena
|
most common initial sign of systemic sclerosis
|
|
|
what type of dysphagia do patients with systemic sclerosis have?
|
dysphagia for solids and liquids because the lower two thirds of the esophagus doesn't have peristalsis due to smooth muscle replaced by collagen
|
|
|
what is the most common cause of death in patients with systemic sclerosis?
|
respiratory failure
|
|
|
what would your laboratory findings be in a patient with systemic sclerosis?
|
Serum ANA positive in 70-90%
Anti-topoisomerase antibody is positive in 30% Extractable nuclear antibody to Scl 70 |
|
|
anti-topoisomerase antibodies
|
Systemic sclerosis
|
|
|
what is CREST syndrome
|
limited sclerosis
|
|
|
where is the sclerosis limited to in CREST syndrome?
|
C: calcification, centromere antibody
R: Raynaud's phenomena E: Esophageal dysmotility S: Sclerodactyly T: telangiectasias |
|
|
what laboratory findings might you have with a patient who has CREST syndrome?
|
anticentromere antibodies
|
|
|
treatment of CREST syndrome
|
D-Penicillamine
recombinant human relaxin |
|
|
Dermatomyositis
|
skin involvement
|
|
|
Polymyositis
|
NO skin involvement
|
|
|
what is Dermatomyositis associated with?
|
antibody mediated damage involving the vasculature
|
|
|
what is Polymyositis associated with?
|
T cell mediated damage
involves musculature |
|
|
patient presents with Heliotrope eyes and Gottron's patches
|
patient has dermatomyositis or polymyositis
|
|
|
Gottron's patches
|
purple papules over the knuckles and proximal interphalangeal joints
|
|
|
DM/PM
|
increased serum CK
|
|
|
T/F
Renal disease is uncommon in patients with mixed connective tissue disorders. |
True
|
|
|
what laboratory findings would be present in mixed connective tissue disease?
|
Anti-ribonucleoprotein antibodies are positive in almost 100% of cases
|
|
|
what is the most common congenital immunodeficiency?
|
IgA deficiency
|
|
|
what is a significant clinical finding in patients that have a B-cell immunodeficiency?
|
recurrent encapsulated bacterial infections
- Streptococcus pneumonia |
|
|
what type of disorder is Bruton's agammaglobulinemia?
|
B-cell disorder
|
|
|
defect in Bruton's agammaglobulinemia
|
Failure of B cells to become mature B cells
Mutated tyrosine kinase X linked recessive disorder |
|
|
what are the clinical features of Bruton's agammaglobulinemia?
|
Strep pneumonia infections
Maternal antibodies protective from birth to age 6 months of age decreased Immunoglobulins HYPOplasia of lymph nodes Flat gamma globulin peak upon electrophoresis |
|
|
what is the defect in IgA deficiency?
|
B-cell disorder
- Failure of IgA B cells to mature to plasma cells (defect in the final step in producing plasma cells that develop IgA) |
|
|
what are clinical features of IgA deficiency?
|
Strep pneumonia infections
Giardiasis anaphylaxis if exposed to blood products that contain IgA decreased IgA and secretory IgA |
|
|
what type of disease is Common variable immunodeficiency?
|
B-cell disorder
- diagnosis of exclusion |
|
|
what is the defect found in common variable immunodeficiency?
|
defect in B-cell maturation to plasma cells
- maturation arrest is before the plasma cell > HYPERplastic lymph node - ADULT immunodeficiency disorder |
|
|
Clinical findings with common variable immunodeficiency.
|
Sinopulmonary infarctions
Gi infections (Giardiasis) Pneumonia Autoimmune disease (ITP, AIHA) Malignancy decreased immunoglobulins |
|
|
Severe Combined Immunodeficiency (SCID)
|
combined T-cell and B-cell disorder
- no B-cells > no Immunoglobulins - no T-cells > no cellular immune response |
|
|
Clinical features of SCID.
|
defective Cell mediated immunity
decreased immunoglobulins |
|
|
treatment of SCID
|
gene therapy
bone marrow transplant - patients with SCID do not reject allografts |
|
|
DiGeorge syndrome
|
T-cell disorder
|
|
|
defect in DiGeorge syndrome
|
failure of third and fourth pharyngeal pouches to develop
- Thymus and parathyroid glands fail to develop |
|
|
clinical findings in DiGeorge syndrome
|
HYPOparathyroidism (tetany)
Absent thymic shadow on radiograph Danger of GVH reaction Deletion of 22q11 |
|
|
Wiskott-Aldrich syndrome
|
combined B and T cell disorder
|
|
|
defect in Wiskott-Aldrich syndrome
|
progressive deletion of B and T-cells
X linked recessive disorder |
|
|
what is the symptom triad of Wiskott-Aldrich syndrome
|
Eczema, thrombocytopenia, SP infections
|
|
|
what are clinical findings of wiskott-aldrich syndrome?
|
Symptom triad: eczema, thrombocytopenia, SP infections
associated with risk of malignant lymphoma defective CMI decreased IgM NORMAL IgG Increased IgA and IgE |
|
|
Ataxia telangiectasia
|
combined B- and T-cell disorder
|
|
|
defect in ataxia telangiectasia
|
mutation in DNA repair enzymes
thymic HYPOplasia Autosomal recessive disorder |
|
|
Clinical features of ataxia telangiectasia
|
Cerebellar ataxia
telangiectasia of eyes and skin increased risk of lymphoma/leukemia; adenocarcinoma increased serum AFP decreased IgA decreased IgE IgM low molecular weight variety Decreased IgG2 or total IgG Decreased T-cell function |
|
|
what is the most common acquired immunodeficiency disease worldwide
|
AIDs
|
|
|
what is the most common cause of death due to infection worldwide?
|
AIDs
|
|
|
how does the AIDS virus enter blood vessels and dendritic cells?
|
virus enters blood vessels or dendritic cells in areas of mucosal injury
|
|
|
Pediatric AIDS
|
most due to vertical transmission
|
|
|
what is the most common mode of infection of AIDs in healthcare workers?
|
accidental needlestick
|
|
|
body fluids containing HIV
|
blood, semen, breast milk
|
|
|
T/F
AIDs virus cannot enter intact skin or mucosa |
True
|
|
|
what is the risk per unit of blood to contract AIDs from a blood transfusion?
|
risk per unit of blood is 1 per 2 million units of blood transfused
|
|
|
HIV
|
Cytotoxic to CD4 T-cells
loss of cell mediated immunity |
|
|
what is detected in the ELISA test to screen for HIV?
|
anti-gp120
|
|
|
what is the confirmatory test for HIV?
|
Western blot
|
|
|
what will a positive western blot show for HIV?
|
presence of p24 antigen and gp41 antibodies
& either gp120 or gp160 antibodies |
|
|
p24 antigen
|
indicator of active viral replication in HIV and AIDS
Present before anti-gp120 antibodies |
|
|
what is the CD4 T-cell count used for in HIV and AIDs
|
monitoring immune status
- useful in determining when to initiate HIV treatment and when to administer prophylaxis against opportunistic infections |
|
|
HIV viral load
|
detection of actively dividing virus
marker of disease progression most sensitive test for diagnosis of acute HIV before seroconversion |
|
|
reservoir cell for HIV
|
follicular dendritic cells in lymph nodes
|
|
|
what defines the early symptomatic phase of AIDS
|
1. CD4 T cell count 200 to 500
2. Generalized lymphadenopathy 3. NON-AIDs defining infections 4. Fever, weight loss, diarrhea |
|
|
Examples of non-AIDS defining infections
|
hairy leukoplakia
EBV caused glossitis Oral candidiasis |
|
|
most common CNS fungal infection in AIDS
|
cryptococcosis
|
|
|
most common malignancy in AIDs
|
Kaposi's sarcoma
|
|
|
most common cause of blindnes in AIDS
|
CMV
|
|
|
Criteria for diagnosis of AIDS
|
1. HIV-positive with CD4 T-cell count of 200 cell/mm or less or an AIDS defining condition
|
|
|
Most common AIDS defining infections
|
Pneumocysitis jiroveci pneumonia
systemic candidiasis |
|
|
AIDS defining malignancies
|
Kaposi's sarcoma
Burkitt's lymphoma (EBV) Primary CNS lymphoma (EBV) Cervical carcinoma disseminated candidiasis |
|
|
death in AIDs
|
disseminated infection
|
|
|
CD4 count 700-1500
|
normal
|
|
|
CD4 count 200 to 500
|
oral thrush
herpes zoster hairy leukoplakia |
|
|
CD4 count 100 to 200
|
Pneumocystis jiroveci pneumonia
dementia |
|
|
CD4 count below 100
|
toxoplasmosis
cryptococcosis cryptosporidiosis |
|
|
CD4 count below 50
|
CMV retinitis
Mycobacterium avium complex Progressive multifocal leukoencephalopathy primary central nervous system lymphoma |
|
|
what helps prevent the transmission of AIDS from mother to fetus?
|
treatment with reverse transcriptase inhibitor reduces transmission to newborn to less than 8%
|
|
|
what activates complement?
|
IgM, IgG-antigen complexes, endotoxin
- only complement cleavage products are functional |
|
|
C3a, C5a
|
anaphylatoxins
Stimulate mast cell release of histamine |
|
|
C3b
|
opsonization
|
|
|
C5a
|
activation of neutrophil adhesion molecules
neutrophil chemotaxis |
|
|
C5-C9 (membrane attack complex)
|
cell lysis
|
|
|
what complement components are found in the classical pathway?
|
C1, C4, C2
|
|
|
C1 esterase inhibitor
|
inactivates the protease activity of C1
- protease normally cleaves C2 and C4 to produce C4bC2b complex |
|
|
what disorder is C1 esterase inhibitor deficient in?
|
hereditary angioedema
|
|
|
DAF
|
deficient in PNH
|
|
|
Test indicating activation of the classic system
|
Decreased C4, C3
Normal factor B |
|
|
Test indicating activation of the alternative pathway
|
Decreased factor B, C3
Normal C4 |
|
|
test indicating activation of both complement cascades
|
Decreased C4, Factor B, C3
|
|
|
Describe hereditary angioedema
|
Autosomal dominant disorder
deficiency of C1 esterase inhibitor Continued C1 activation decreases C2 and C4 and increases their cleavage products which have anaphylactoxic activity NORMAL C3 Swelling of face and oropharynx |
|
|
C2 deficiency
|
most common complement deficiency
associated with septicemia and lupus like syndrome in children |
|
|
C6-C9 deficiency
|
increased susceptibility to disseminated Neisseria gonorrhea or N. meningitidis infections
|
|
|
Paroxysmal nocturnal hemoglobinuria
|
acquired stem cell disease
Defect in molecule anchoring decay accelerating factor which normally degrades C3 and C5 convertase on hematopoietic cell membranes Complement mediated intravascular lysis of red blood cells, platelets, and neutrophils |
|
|
a 42 year old woman who is under treatment for an arrhythmia, develops a facial rash, photophobia, and joint pains with morning stiffness. What test would most likely be abnormal in this patient?
|
anti-histone antibody because the patient has drug induced lupus most likely caused by procainamide
|
|
|
best test for drug induced lupus
|
anti-histone antibody
|
|
|
anti-double stand DNA antibodies
|
SLE with glomerulonephritis
|
|
|
Anti-ribonucleoprotein antibody
|
marker for mixd connective tissue disease
|
|
|
anti-centromere antibody
|
marker for CREST syndrome mainly and systemic sclerosis
|
|
|
anti-SS-B (La) antibody
|
marker for Sjogren's syndrome
|
|
|
what test results would be expected in a patient with reduced lung compliance, renal disease, hemolytic anemia, and pericardial effusion?
|
The patient has SLE
- Serum ANA with rim pattern: sign of SLE with renal disease - Direct Coomb's tes: warm autoimmune hemolytic anemia |
|
|
rheumatoid factor
|
rheumatoid arthritis
|
|
|
anti-ribonucleoprotein antibody
|
associated with MCTD
|
|
|
list features of SLE vs. Systemic sclerosis
|
SLE:
- endocarditis: Libman Sacks endocarditis. Sterile vegetations on mitral valve. - False positive syphilis serology: due to anti-cardiolipin antibodies that cross react with beef cardiolipin in the test system Systemic Sclerosis: - Dysphasia for solids and liquids |
|
|
systemic sclerosis
|
excessive collagen production and digital vasculitis
primarily targets the skin, GI, lungs, kidneys, commonly begins with Raynauds phenomenon. digital infarcts. sclerodactyly. dystrophic calcification in SC tissue. tightened facial features. Telangiactasia. Interstitial fibrosis of lungs with respiratory failure. Malignant HTN from renal disease. Serum ANA positive 70-90% |
|
|
a 42 year old woman develops Raynaud's phenomenon and dysphagia for solids and liquids. Her fingers are tapered and exhibit focal areas of dystrophic calcification at the tips as well as telangiectasias over the skin surface. The results of a serum ANA study are pending. What additional test would be useful if the serum ANA returns positive?
|
the patient has systemic sclerosis or CREST syndrome.
- anti-centromere antibody: is good for CREST syndrome and systemic sclerosis - Anti-Scl-70 antibody (topoisomerase) is the characteristic antibody of systemic sclerosis |
|
|
anit-SS-A (Ro) antibody
|
antibody noted in SLE and Sjogrens syndrome
|
|
|
anti-DS DNA- antibody
|
specific for SLE
|
|
|
anti-smith antibody
|
specific for SLE
|
|
|
what is CREST syndrome
|
limited sclerosis
C: calcinosis R: Raynaud's phenomenon E: Esophageal dysfucntion S: sclerodactyly T: telangiectasia anti-centromere antibodies in 50-90% cases renal disease and interstitial lung disease are not as common as in systemic sclerosis |
|
|
Neutrophil with phagocytosed DNA associated with:
|
SLE
|
|
|
Neutrophil with phagocytosed immunocomplexes associated with:
|
rheumatoid arthritis
|
|
|
Body cavity effusions associated with?
|
SLE and rheumatoid arthritis
|
|
|
Cavitating nodules in the lungs associated with
|
Caplan's syndrome with rheumatoid nodules in the lungs in patients with pneumoconiosis
|
|
|
Postitve serum antinuclear antibody test associated with?
|
SLE and rheumatoid arthritis
|
|
|
Anemia of chronic disease associated with?
|
rheumatoid arthritis and SLE
|
|
|
Destructive joint disease associated with:
|
Rheumatoid arthritis is destructive
|
|
|
Elevated sedimentation rate associated with:
|
RA and SLE
|
|
|
High serum complement levels associated with:
|
Rheumatoid arthritis
- has high levels of complement and SLE has low levels of complement |
|
|
wide-mouthed diverticula associated with:
|
systemic sclerosis/CREST
|
|
|
relaxed lower esophageal sphincter associated with:
|
systemic sclerosis/CRESt
|
|
|
pericardial friction rub associated with:
|
SLE
- MC cardiac lesion in SLE |
|
|
Raynaud's phenomenon associated with:
|
systemic sclerosis/CREST
|
|
|
dysphagia for solids and liquids associated with:
|
systemic sclerosis/CREST
- smooth muscle is replaced by collagen in the mid and lower esophagus |
|
|
Glomerulonephritis associated with?
|
systemic sclerosis/CREST
SLE |
|
|
Positive band test associate with?
|
SLE has positive band test
|
|
|
Unexplained pleural or pericardial effusion associated with:
|
characteristic of SLE
- inflammation of serosal membranes |
|
|
Autoimmune warm hemolytic anemia associated with:
|
SLE
|
|
|
anti-topoisomerase
anti-Scl-70 antibodies |
these are the same antibodies and are seen in systemic sclerosis
|
|
|
anti-Sm-antibodies
anti-ds-DNA antibodies |
both are present in SLE
|
|
|
anti-glomerular basement membrane antibodies
|
Goodpasture's syndrome
|
|
|
anti-ribonuclearprotein
|
MCTD
|
|
|
anti-Jo-1 antibody
|
PM/DM
|
|
|
anti-phospholipid antibody
|
SLE
|
|
|
anti-gliadin antibody
|
Celiac disease
|
|
|
anti-mitochondrial antibody
|
primary biliary cirrhosis
|
|
|
anti-microsomal antibody
|
Hashimoto's thyroiditis
|
|
|
a 23 year old woman with a 2 year history of arthralgia and facial rash delivers a child with complete heart block. What best explains the pathophysiology of the newborn's cardiac abnormality?
|
Vertical transmission of anti-Ro antibodies
the mother has SLE and IgG anti-SS-A (Ro) antibodies, which have crossed the placenta and attacked the babies conduction system |
|
|
Dysphagia for solids and liquids, scaly patches over the PIP joints, raccoon eyes, and muscle pain/atrophy of the shoulder muscles with an elevated serum CK characterizes:
|
Dermatomyositis
- the patches are called Gottron's patches. A muscle biopsy is confirmatory when it shows a lymphocytic infiltrate |
|
|
MSU crystals
|
negative birefringence
yellow when parallel to slow ray |
|
|
calcium pyrophosphate
|
positive birefringence
blue when parallel to slow ray |
|
|
morning stiffness
|
RA
SLE polymyalgia rheumatica |
|
|
joint effusion
|
blood
exudate |
|
|
hot joint
|
acute inflammation
septic arthritis |
|
|
joint crepitus
|
crackling feeling
osteoarthritis |
|
|
osteoarthritis
|
most common disabling joint disease
|
|
|
Alkaptonuria
|
homogentisic acid deposits in intervertebral disks
black color - deficiency of homogentisic acid oxidase |
|
|
OA primary sites
|
femoral head
knee cervical/lumbar vertebrae hands |
|
|
Ochronosis
|
AR
deficiency homogentisic acid osteoarthritis |
|
|
articular cartilage
|
proteglycans
type II collagen |
|
|
OA
|
wearing down of articular cartilage
bone rubs on bone |
|
|
osteophytes at joint margins
|
OA
|
|
|
clefts, subchondral cysts
|
OA
|
|
|
no fusion of the joint
|
OA
|
|
|
pain is the most common complaint
|
OA
|
|
|
joint stiffness after inactivity
|
OA
|
|
|
Heberden's nodes
|
OA fingers
DIP joint enlargement/pain |
|
|
Bouchard's nodes
|
OA fingers
PIP joint enlargement/pain |
|
|
OA vertebral column
|
cervical/lumbar
degenerative disk disease compressive neurpathies |
|
|
neuropathic joints
|
loss of proprioception, deep sensation leading to recurrent trauma
|
|
|
common causes of neuropathic joints
|
diabetes
syringomyelia tabes dorsalis |
|
|
RA lung
|
interstitial fibrosis
effusions |
|
|
RA blood
|
ACD
AIHA Felty's syndrome (autoimmune neutropenia, splenomegaly) |
|
|
RA cervical spine
|
subluxation of atlantoaxial joint
cord/vertebral artery compression |
|
|
Caplan syndrome
|
rheumatoid nodules in lung plus pneumoconiosis
|
|
|
RA cardiovascular
|
pericarditis
aortitis Vasculitis |
|
|
Baker's cyst
|
outpouching of posterior joint space in knee
|
|
|
RA lab
|
positive for serum FR
positive serum ANA normal to increased serum C3 decreased synovial C3 increased serum total protein |
|
|
Sjogren's syndrome
|
destruction of minor salivary glands and lacrimal glands
|
|
|
dry mouth
dry eyes |
Sjogren's syndrome
|
|
|
Lab Sjogren's syndrome
|
positive serum ANA
positive serum RF anti-ss-A antibodies (Ro) anti-ss-B antibodies (La) lip biopsy for confirmation |
|
|
JRA
|
RF is usually negative
|
|
|
JRA Still's disease
|
fever
rash polyarthritis |
|
|
JRA polyarticular disease
|
disabling arthritis predominates
|
|
|
JRA pauciarticular
|
limited arthritis
uveitis and potential for blindness |
|
|
T/F
Gout is a female dominant disease |
False
Gout is a male dominant disease |
|
|
T/F
most cases of gout are due to overproduction of uric acid |
False
most cases of gout are due to underexcretion of uric acid |
|
|
what clinical conditions is gout associated with?
|
urate nephropathy
renal stones HTN artery disease Pb poisoning |
|
|
what joint is most often involved in acute gout?
|
1st metatarsophalangeal joint
|
|
|
what is responsible for initiating the attack in acute gout?
|
free uric acid crystals
|
|
|
confirmatory test of acute gout
|
must confirm with joint aspiration
hyperuricemia does NOT define gout |
|
|
Tophus
|
MSU deposits in soft tissue around the joint
|
|
|
Nonpharmacological treatment of gout
|
eliminate high purine diet
moderation in alcohol intake |
|
|
Pharmacological treatment of acute gout
|
NSAIDS or colchicine
|
|
|
Drugs to prevent gout
|
uricosuric agents for underexcretors
allopurinol for overproducers |
|
|
calcium pyrophosphate dihydrate deposition disease
|
deposition of calcium pyrophsophate in tissues
|
|
|
a febrile 56 year old male alcoholic has pain in his right big toe that woke him up at night. He has been taking low doses of ASA to relieve the pain without relief. His mother has severe osteoarthritis. The right toe is swollen, hot, and exquisitely sensitive to touch. Laboratory studies show a neutrophilic leukocytosis and left shift. A synovial tap is performed. Based on this history what else most likely applies to this case?
|
the patient has gout
negative birefringent crystals: yellow and parallel to slow ray underexcretion of uric acid: most cases of gout are underexecretion rather than overproduction of uric acid |
|
|
what is chronic gout characterized by?
|
tophi which are deposits of MSU in soft tissue around joints that incite a granulomatous reaction with multinucleated giant cells.
Tophi destroy the subjacent bone causing erosive arthritis. |
|
|
Clinical conditions that are associated with gout.
|
urate nephropathy: rx of disseminated cancer with increased purines
renal stones hypertension coronary artery disease lead poisoning leading to interstitial nephritis |
|
|
list common findings of both rheumatoid arthritis and osteoarthritis.
|
Female dominance
Proximal interphalangeal joint involvement |
|
|
list some common findings in osteoarthritis
|
Cartilage fibrillation
osteophytes subchondral bone cysts |
|
|
list some common findings in rheumatoid arthritis
|
inflammatory joint disease
ankylosis of the joint symmetric joint involvement |
|
|
T/F
rheumatoid arthritis is a non-inflammatory disease. |
false
osteoarthritis is a non-inflammatory joint disease |
|
|
is there ankylosis of the joint in osteoarthritis
|
NO
|
|
|
what type of arthritis has an HLA-DR4 association
|
Rheumatoid arthritis
|
|
|
what type(s) of HSR are involved in rheumatoid arthritis?
|
Type IV: initial inciting agent may be EBV > activated B/T cells damage synovium synovium expresses antigens to which B cells synthesize RF(IgM against FcIgG)
RF + IgG form immuncomplexes > type III HSR > activate complement system > C5a chemotactic to neutrophils > acute inflammation of synovium > pannus formation releases cytokines that damage articular cartilage > fusion of joint |
|
|
a 28 year old man who works in a summer camp in upstate NY develops bilateral facial weakness involving both the upper and lower facial muscles. He also complains of joint pains in both knees. He has a history a few months ago having an erythematous rash on his right thigh that was circular, and had a central clearing. A CBC show a mild hemolytic anemia and intraerythrocytic parasites. What would you find in his serological test? Why does he have facial weakness?
|
the patient has Lyme's disease with erythema chronicum migrans, bilateral bell's palsy, and hemolytic anemia due to BAbesia microti
there would be a positive serological test for a spirochete: Borrelia burgdorferi Cranial nerve VII palsy: bilateral Bell's palsy is very characteristic of Lyme's disease Joint disease is the most common late manifestation of disease and is destructive |
|
|
x-ray finding of Reiter's syndrome
|
periostitis at insertion of Achilles tendon
|
|
|
x-ray finding in Gout
|
erosive arthritis with overhanging margins
|
|
|
x-ray finding of rheumatoid arthritis
|
ankylosis of MCP and/or PIP joints
|
|
|
x-ray finding in Calcium pyrophosphate deposition arthropathy
|
linear calcification in the articular cartilage, usually the knee
|
|
|
x-ray finding in psoriatic arthritis
|
pencil in cup deformity
|
|
|
x-ray findings in ankylosing spondylitis
|
sacroilitis and eventually ankylosis of the vertebra (bamboo spine)
|
|
|
what triggers Reiter's syndrome?
|
Chlamydia urethritis trigers disease
|
|
|
A febrile, sexually active 23 year old woman has a hot, swollen right knee, and pustular lesions on the palm of her hand. She recently returned from a camping trip in Colorado. What would apply to this case?
|
the patient has disseminated GC
Septiciemia occurs in 40% Complement deficiencies C6-C9 may be present |
|
|
gram stain of GC
|
gram negative diplococci
|
|
|
what is the MCC of septic arthritis in urban areas?
|
Neisseria gonorrhoeae
|
|
|
what predisposes an individual to dissemination of Neisseria gonorrhoeae?
|
deficiency of C6-C9
|
|
|
synovial fluid aspirated from an inflamed right knee joint of a 45 year old man shows a triclinic crystal that is blue when parallel to the slow ray of the compensator. An x-ray of the knee shows linear calcification in the articular cartilage. What is the diagnosis?
|
the patient has chondrocalcinosis (calcium pyrophosphate disease) associated with hemochromotosis.
Inflammatory joint disease secondary to a positively birefringent crystals |
|
|
disorder of purine metabolism
|
gout
|
|
|
pseudogout
|
Chondrocalcinosis
- degenerative joint disease usually involves the knee. - may be associated with hemochromatosis - crystals produce linear deposits in articular cartilage - crystals phagocytosed by neutrophils show positive birefringence |
|
|
your patient has ankylosing spondylitis. He is also found to have a murmur and S3 heart sound.
What type of murmur is associated with AS and what is the HLA relationship? |
Aortic regurgitation: diastolic blowing murmur off the second heart sound in the right second intercostal space
S3 heart sound: LV overload Relationship with HLA-B27 |
|
|
Is ankylosing spondylitis a rheumatoid arthritis variant?
|
NO
- seronegative (RF negative) spondyloarthropathy |
|
|
what type of lung disease does ankylosing spondylitis cause?
|
kyphosis produces a restrictive type of lung disease
|
|
|
a 32 year old man with a long history of UC develops joint pains in his knees and lower back pain. What is the diagnosis? what would additional findings be?
|
patient has ankylosing spondylitis
- AS is associated with UC - AS is an inflammatory joint disease - HLA-B27 halplotype: the UC was the environmental trigger that prompted AS |
|
|
A 5 year old girl has an acute onset of fever, generalized rash, generalized painful lymphadenopathy, and polyarthritis. the cardiac exam is normal. A CBC shows an absolute neutrophilic leukocytosis, mild normocytic anemia, and normal platelet count.
Diagnosis? Additional findings? |
the patient has juvenile rheumatoid arthritis specifically Still's disease
- inflammatory joint disease - negative for rheumatoid factor |
|
|
what are Bouchard's nodes and a relationship with obesity related to?
|
osteoarthritis
|
|
|
what are blurry vision, inflammatory joint disease, restrictive lung disease associated with?
|
ankylosing spondylitis
|
|
|
in osteoarthritis, what is the pain in the DIP and PIP joints related to?
|
secondary synovitis.
|
|
|
what is commonly associated with hyperuricemia?
|
Disseminated cancer: increased production of purines
Alcoholic: decreased excretion of uric acid due to competition with lactate and b-OHB for excretion in the proximal tubule. - Lead poisoning: interferes with excretion of uric acid - Thiazides: increased reabsorption from volume depletion - low dose aspirin inhibit uric acid secretion and may cause hyperuricemia |
|
|
you have diagnosed your patient with Reiter's syndrome with Chlamydia. What will be your findings?
|
Sterile conjuctivits
Achille's tendon periostitis arthritis (HLA-B27 positive type) Urine sediment exam: a sterile pyruia is present with Chlamydia urethritis |
|
|
What does a Bamboo spine and kyphosis characterize?
|
ankylosing spondylitis
|
|
|
what do the following characterize?
HLA-DR4 haplotype Carpal tunnel syndrome Subcutaneous nodules Autoantibody against IgG |
rheumatoid arthritis
|
|
|
what is the pathognomonic lesion for chronic gout?
|
erosive arthritis with overhanging margins: tophus deposition
- presence of tophi indicates gout |
|
|
describe the nodular masses found in rheumatoid arthritis?
|
fibrinoid necrosis
|
|
|
describe the nodular masses found in tophi.
|
multinucleated giant cells and negatively birefringent crystals
|
|
|
restrictive lung disease, pleural effusion with low glucose, splenomegaly, absolute neutropenia, and xerostomia would most likely be associated with what laboratory findings?
|
Positive rheumatoid factor
anti-SS-B antibodies Lymphocytic destruction of minor salivary glands |
|
|
a 65 year old woman with RA complains of inability to swallow dry crackers. She also states that her eyes "feel like they have sand in them." You would most expect this woman to have what abnormal test?
|
the patient has Sjogren's syndrome
Xerostomia, keratoconjunctivitis sicca lymphocytic destruction of minor salivary glands biopsy is the confirmatory test for Sjogren's syndrome |
|
|
what type of joint disease are osteoarthritis and neurogenic joint?
|
NON-inflammatory joint disorders
|
|
|
what is degenerative cartilage and joint mice associated with?
|
Osteoarthritis
- degeneration of cartilage: OA is non-inflammatory reaction - joint mice: pieces of articular cartilage break off from cartilage fibrillation |
|
|
Pannus
|
granulation tissue that grows over and destroys articular cartilage in RA
|
|
|
describe rheumatoid factor
|
ICs formed by IgM antibodies against IgG (rheumatoid factor)
|
|
|
Baker's cysts
|
occur in RA
represent synovial cysts in the popliteal space. When they rupture in the calf muscles it simulates thrombophlebitis |
|
|
Extension of DIP joint
|
boutonniere deformity in RA
|
|
|
Painful MCP joint
|
characteristic of RA
particularly 2 and 3 MCPs |
|
|
Atlantoaxial subluxation
|
charcaterizes RA
|
|
|
Flexion of DIP joint
|
swan's neck deformity of RA
|
|
|
Splenomegaly with neutropenia
|
Felty's syndrome which is commonly seen in RA
|
|
|
A veterinarian is bitten in the finger by a cat. A few days later she develops a septic arthritis in her finger. What is the most likely pathogen?
|
Pasteurella multocida
|
|
|
MCC of non-GC septic arthritis
|
Staphylococcus aureus
|
|
|
Borrelia burgdorferi
|
Lyme's disease
|
|
|
Salmonella paratyphi
|
osteomyelitis in sickle cell disease
|
|
|
Bartonella henselae
|
cause of cat scratch disease and bacillary angiomatosis
|
