Flashcards in Immunlogy Deck (154):
site of B cell localization and proliferation in lymph nodes?
Follicle - in outer cortex
Which part of lymph node houses T cells?
Paracortex - area of cortex between follicles and medulla
-becomes enlarged during extreme immune responses
-not well developed in DiGeorge syndrome pts (b/c no T cells...)
lymph node drainage from upper limb, lateral breast?
Axillary lymph nodes
lymph node drainage from stomach
lymph node drainage from duodenum and jejunum
superior mesenteric node
lymph node drainage from sigmoid colon
colic --> inferior mesenteric node
lymph node drainage from rectum?
internal iliac node
lymph node drainage from anal canal?
superficial inguinal node
lymph node drainage from testes
superficial and deep plexuses --> para-aortic nodes = retroperitoneal nodes
lymph node drainage from thigh (superficial)
superficial inguinal nodes
lymph node drainage from lateral side of dorsum of foot
lymph node drainage of prostate
internal iliac nodes
right lymphatic duct vs thoracic duct drains?
right lymphatic ducts drains: right arm and right half of head
thoracic duct drains: everything else
Where are B cells found in the spleen?
Follicles within white pulp of spleen
Where are T cells found in spleen?
PALS = periarterial lymphatic sheath within white pulp of spleen
immunlogic results of/response to splenic dysfunction?
splenic dysfunction: decreased IgM-->decreased complement activation --> decreased C3b opsonization --> increased susceptibility to encapsulated organisms (SSHiNK: Salmonella, S. pneum, H. influenza, N. meningitidis, K. pneumonia)
Howell-Jolly bodies, Target cells, and thrombocytosis
Thymus is derived from what branchial pouch?
3rd branchial pouch
Where in thymus does positive selection occur? Negative selection?
positive --> corex
negative --> medulla/corticomedullary jxn
beta-2-microglobulin is found on which class of MHC molecule?
MHC I: has a heavy chain and a beta-2-microglobulin chain
Which HLA genes code for MHC I? MHC 2?
MHC I: HLA-A, HLA-B, HLA-C
MHC II: HLA-DR, HLA-DP, HLA-DQ
which cell types express MHC I? MHC II?
MHC I --> expressed on almost all nucleated cells (not expressed on RBCs)
MHC II: expressed only on APCs
-Inflammatory bowel disease
Diabetes type I
-Diabetes type I
-Pernicious anemia --> B12 deficiency
steroid-responsive nephrotic syndrome
only lymphocyte member of innate immune system?
natural killer cells
What CD-?'s are expressed on NK cells?
Which cytokines activate natural killer cells?
which cytokine induces Th2 formation? which cytokines are secreted by Th2 and what are their actions?
*IL-4 induces Th2
-IL-4 --> stimulates B-cells
-IL-5 --> stimulates B-cells
-IL-10 --> inhibits Th-1 cells and macrophages
which cytokine induces Th1 formation? which cytokines are secreted by Th1 and what are their actions? Which cytokine inhibits Th1?
*IL-12 induces Th1
-IL-2 --> stimulates T-cells
-IFN-gamma --> stimulates macrophages
*IL-10 (secreted by Th2 cells) inhibit Th1 cells
What are the antigen presenting cells?
What are the 2 signals needed for Helper T-cell activation?
signal 1: foreign antigen, after being phagocytosed by APC, is presented on MHC II of APC and is recognized by TCR on the Th cell
signal 2 = "co-stimulatory signal": interaction between B7 (on APC) and CD28 (on Th cell)
2 signals needed for cytotoxic T-cell activation?
signal 1: viral or self proteins are presented on MHC I and recognized by TCR on cytotoxic T-cell
signal 2: IL-2 from Th1 cell activates cytotoxic T-cell to kill the virus-infected cell
2 signals needed for B-cell activation and class-switching?
First, helper T-cells are activated LOOK UP IN IMMUNO BOOK!
-secrete which cytokines?
-regulate cell-mediated response
-secrete Th1 cytokines: IL-2, IFN-gamma
-activate macrophages and CD8+ T-cells
-inhibited by IL-10 (from Th2 cell)
-secrete which cytokines?
-another action they do?
-regulate humoral response
-secrete Th2 cytokines: IL-4, IL-5, IL-6, IL-10
-help B-cells make antibody (IgE> IgG)
-inhibited by IFN-gamma (from Th1 cell)
How do natural killer cells induce apoptosis?
use perforin and granzymes to induce apoptosis
How do cytotoxic T-cells induce apoptosis?
release cytotoxic granules containing preformed proteins:
-perforin (delievers granules into target cell)
-granzyme (activates apoptosis inside target cell)
-granulysin (antimicrobial, induces apoptosis)
Natural Killer vs Cytotoxic T-cells
Both induce apoptosis of virally-infected or tumor cells
*NK cells --> Recognize ABSENCE of MHC-1 on target cell surface
*Cytotoxic T-cells --> have CD8, which BINDS to MHC-1 on virus-infected cells
What part of the antibody is recognizes antigens?
the antigen binding fragment on the Fab part of the antibody; the VL and VH (variable light and variable heavy) chains recognize antigens.
Which part of the antibody fixes complement?
Complement binding is at CH2 of the Fc part of the antibody (of IgG and IgM only)
Which part of antibody do macrophages bind to?
Fc fragment, below the complement binding area
Which part of the antibody determines the isotype (ie IgG, IgM, IgD, IgE, IgA)? idiotype (ie unique antigen-binding pocket)?
Isotype --> determined by the Fc
Idiotype --> determined by Fab
opsonization vs neutralization vs complement activation:
opsonization - antibody promotes phagocytosis
neutralization - antibody prevents bacteral adherence
complement activation - antibody activates complement, enhancing opsoninzation and lysis
Main antibody in secondary/delayed response to an antigen, and most abundant antibody in blood?
IgG (t1/2 of IgG = 21 days; one reason it's most abundant!)
Which antibodies can fix complement?
IgM and IgG
Which antibody can cross the placenta?
Which antibody is found in secretions (tears, saliva, mucus) and breast milk ("colustrum")?
Which antibody is a monomer in circulation, but a dimer when secreted?
Which antibody is produced in primary/immediate response to an antigen?
Which antibody can exist as a pentamer (as well as a monomer)?
Which antibody mediates immediate/type I hypersensitivity reactions through release of histamine?
Which antibody mediates immunity to worms by activating eosinophils?
which antibody is in lowest concentration in serum?
Which blood types of mothers may lead to erythroblastosis fetalis and hemolytic disease of newborn?
Type O mothers; because in type O mothers, antibodies are mostly IgG, so can cross placenta and cause fetal hemolysis.
But, maternal blood types A and B: anti-A and anti-B antibodies are IgM, so can't cross placenta...
3 complement pathways:
1) Classic: IgG or IgM mediated; form antigen-antibody complexes
2) Alternative: stimulated by spontaneous and microbe surface molecules
3) Lectin: mannose
Which 2 complement factors are involved in anaphylaxis?
C3a and C5a
Which 2 complement factors are involved in opsonization of bacteria?
C3b and IgG
What complement complex stimulates cytolysis by MAC?
Hereditary angioedema: have increased bradykinin (so increased vasodilation and vascular permeability), episodes of painless, non-pitting, well-circumscribed edema
C1 esterase inhibitor deficiency (C1 esterase inhibitor prevents complement activation on self cells; but, in this case, it is deficient)
recurrent pyogenic sinus and respiratory tract infections (esp S. pneum and H. infl), and increased susceptibility to type III hypersensitivity rxns (esp glomerulonephritis)
C3 complement deficiency
Recurrent Neisseria bacteremia (N. gonococcal and N. meningococcal)
C5-C9 complement deficiency
DAF (decay accelerating factor) deficiency may cause?
DAF is a complement inhibitor, meant to prevent complement activate on self-cells. If deficient, may lead to Paroxysmal Nocturnal Hemoglobinuria and to complement-mediated lysis of RBCs
IL-1 and IL-6 --> pro-inflammatory
IL-10 and TGF-Beta --> anti-inflammatory
functions IL-1 through IL-5
"Hot T-Bone stEAk"
IL-1: Hot --> pyrogen, fever, acute inflammation
IL-2: T --> stimulates growth of helper and cytotoxic T-cells (note: lots of immunosuppressants block IL-2)
IL-3: B--> stimulates Bone marrow stem cells (functions like GM-CSF = granulocyte macrophage colony stimulating factor)
IL-4:E -->stimulates class-switching to IgE and IgG. Also: induces differentiation into Th2 cells, and promotes growth of B cells
IL-5: A --> stimulates class-switching to IgA and stimulates eosinophil production (it's the mucus-producing IL!); also: promotes differentiation of B cells.
Which cytokines are secreted by macrophages?
IL-1, IL-6, IL-8, IL-12, TNF-gamma
Which cytokines are secreted by all T-cells? by Th1 only? by Th2 only?
*all T-cells secrete IL-3
*Th1 secrete: IL-2, IFN-gamma
*Th2 secrete: IL-4, IL-5, IL-10
Which cytokine is the major chemotactic factor for neutrophils?
IL-8 ("clean up on aisle 8!" --> neutrophils come clear infections!)
Interferons alpha, beta, and gamma functions:
-all activate NK cells and kills virus-infected cells
-alpha and beta --> inhibit viral protein synthesis
-gamma --> stimulate MHC I and II expression and antigen presentation in all cells
All T-cells express:
-TCR (binds antigen-MHC complex)
-CD28 (binds B7 on APC)
*Th cells --> CD4 also
*cytotoxic T-cells --> CD8
CD19, CD20, CD21 --> all present on what cell type?
CD14, CD16, and CD40 are present on what cell type?
CD16, CD56 are present on what cell type?
NK cells (CD16 is also on macrophages; but CD56 is a unique marker for NK cells)
How do superantigens work?
Superantigens (like from S. aureus, and Group A Strep) --> cross-link the TCR on T-helper cells to the MHC class II on APCs: So, get uncoordinated release of IFN-gamma from Th1 cells; IFN-gamma stimulates macrophages, so get release of IL-1, IL_6, and TNF-alpha from macrophages
How do endotoxins/lipopolysaccharides work?
ie in gram (-) bacteria --> stimulate macrophages directly (Th cells not involved, unlike with superantigens) by binding to CD14 receptor --> release of acute phase cytokines (IL-1, IL-6, TNF-alpha)
After exposure to which diseases/microbes should a person be given preformed/passive antibodies?
"To Be Healed Rapidly"
(also: should give RSV abs to premature babies born during winter months)
What kind of immune response is induced by live attenuated vaccines? inactivated or killed vaccines?
-live attenuated --> cellular response
-inactivated or killed -->humoral imunnity (weaker response; usually need booster shots)
4 types of hypersensitivity reactions (briefly)
(types 1-3 = antibody-mediated)
Type 1 - Anaphylactic and Atopic
Type 2 - Cytotoxic
Type 3 - Immune complex
Type 4 - Delayed (cell-mediatedd)
What type of hypersensitivity reaction is this: anaphlaxic ("wheal and flare"), atopic; free-antigen cross-links IgE on pre-sensitized mast cells and basophils --> release of histamine, etc. How quickly does this reaction develop?
Type I --> happens very rapidly after antigen exposure to pre-formed antibody
Hypersensitivity type: IgM, IgG bind fixed antigen on an "enemy" self cell --> lysis by complement or phagocytosis = cytotoxic
Hypersensitivity type: Immune complex (antigen-antibody) activates complement--> neutrophils --> release lysosomal enzymes
What type of hypersensitivity reaction is serum sickness?
type III: serum sickness-->antibodies to foreign proteins form over about 5 days --> form immune complexes --> deposit in membranes --> fix complement --> tissue damage
fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure?
serum sickness (type III hypersensitivity)
Type III hypersensitivity reaction
-test by immunofluorescent staining
-intradermal injection of antigen induces antibodies-->form antigen-antibody complexes in the skin --> edema, necrosis, activation of complement
*ex = swelling and inflammation following tetanus vaccine.
Type IV hypersensitivity? How long does it take?
--> sensitized T-cells encounter antigen--> release lymphokines --> macrophage activation...
-takes about 48 hours
-TB skin tests
-Touching (contact dermatitis)
Direct and Indirect Coombs' test --> tests for what kind of hypersensitivity rxn?
Type II = antibody-mediated
List 8 disorders/situations with type IV hypersensitivity:
-diabetes - type I
List 7 disorders/situations with type III hypersensitivity
-Hypersensitivity pneumonitis (ie Farmer's lung)
List examples of type II hypersensitivity disorders/reactions
-Anemias (hemolytic anemia, pernicious anemia)
-erythroblastosis fetalis (Rh incompatibility)
-acute hemolytic transfusion rxns
-idiopathic thrombocytopenic purpura
-Bullous pemphigoid, Pemphigus vulgaris
What type of hypersensitivty reaction is Goodpastures? PSGN?
Goodpastures--> type 2
PSGN--> type 3
what type of hypersensitivity rxn is Grave's disease? Hashimoto's?
Hashimoto's --> type 4
ANA (anti-nuclear antibodies)
-nonspecific (Sjogren's, scleroderma, polymyositis, dermatomyositis, rheumatoid arthritis,juvenile arthritis, MCTD)
SLE (anti-dsDNA=specific for renal disease)
=Rheumatoid facor = IgM antibodies that attack IgG --> Rheumatoid arthritis
primary biliary cirrhosis
anti-microsomal, anti-thyroglobulin antibodies
=anti-Ro antibodies --> Sjogrens
=anti-La --> Sjogrens
mixed connective tissue disease
anti-smooth muscle antibodies
anti-glutamate decarboxylase antibodies
type 1 diabetes
anti-TSH receptor antibodies
anti-Ach receptor antibodies
Boys with recurrent bacterial infections after 6 months, B-cell deficient, and deficient in all classes of Ig's. What's the condition and what gene is defective?
Bruton's agammaglobulinemia; defect in BTK, a tyrosine kinase gene. can form pro-B cells, but not beyond that. X-linked recessive, so increased in males
Defect in BTK gene
BTK = a tyrosine kinase gene --> defect = Bruton's agammaglobulinemia
Defect that causes hyper-IgM syndrome?
defective CD40L on helper T-cells--> can't class switch
anaphylaxis on exposure to blood products with IgA; and: sinus and lung infections, milk allergies, and diarrhea...
Selective Ig deficiency, usually to IgA
-caused by a defect in isotype switching to a specific class
normal # of B cells, but decreased plasma cells, decreased Immunoglobulin...
Defect in B-cell maturation --> CVID = common variable immunodeficiency
90% of pts with DiGeorge syndrome (thymic aplasia) --> failure to develop 3rd and 4th pharyngeal pouches (so, no thymus)
absent thymic shadow
-DiGeorge syndrome (thymic aplasia)
tetany, recurrent viral infections, congenital heart and great vessel/aortic arch defects, cleft palate, mandible deformities...
DiGeorge syndrome = thymic aplasia: no thymus or parathyroids, so: deficient T-cells, PTH, Calcium
-absent thymic shadow on CXR
Disseminated mycobacterial infections, decreased levels of IFN-gamma
IL-12 receptor deficiency --> so decreased Th1 response --> decreased IFN-gamma secretion
-Th cells don't produce IFN-gamma --> neutrophils can't respond to chemotactic stimuli
-increased levels of IgE
-presentation = FATED:
--non-inflamed staph Abscesses
--retained primary Teeth
--Dermatological problems = eczema
Abscesses + still have primary teeth + eczema + high levels of IgE
think Job's syndrome = Hyper-IgE syndrome
Recurrent infections, Chronic diarrhea, FTT; have NK cells, but no B or T cells
-defective IL-2 receptor (most common, X-linked)
-Adenosine Deaminase deficiency
-failture to synthesize MHC II antigens
Most common cause of SCID?
-defective IL-2 receptor (X-linked)
Cerebellar deficits + spider angiomas + IgA deficiency (so increased risk of sinopulmonary infections)
=Triad of symptoms in Ataxia-telangiectasia:
-cerebellar deficits =ataxia
-spider angiomas = telangiectasia
-->d/t defects in ATM (Ataxia Telangiectasia Mutated) gene, which codes for DNA repair mechansims --> so, also hypersensitive to x-ray radiation, b/c causes chromosomal breaks
In which immune deficiency are patients hypersensitive to X-ray radiation (b/c it causes chromosomal breaks)?
Ataxia-Telangiectasia --> mutation in ATM gene, which codes for DNA repair enzymes
Thrombocytopenic purpura, recurrent pyogenic Infections, Eczema; Low IgM
Triad of symptoms in Wiskott-Aldrich syndome --> "TIE" = Thrombocytopenic purpura, Infections, Eczema
-get progressive deletion of B and T cells
-decreased IgM; increased IgE and IgA
Defect in LFA-1 integrin/CD18 protein; poor wound healing -- no pus formation, delayed separation of umbilicus
Leukocyte adhesion deficiency (type 1)
-->defect in LFA-1 integrin (CD18) protein on phagocytes
recurrent infections with staph and strep, partial albinism, peripheral neuropathy/neuro defects; defect in LYST gene
-defect in LYST: lysosomal trafficking regulator gene
-microtubule dysfunction in phagosome-lysosome fusion
-see abnormal giant lysosomal inclusions on LM of peripheral smear
absent respiratory burst in neutrophils, increased susceptibility to catalase positive organisms (ie S. aureus, E. coli, Aspergillus, Serratia, Nocardia...); negative nitroblue tetrazolium dye reduction test
Chronic granulomatous disease
vascular fibroid necrosis, neutrophil infiltration, and infarction of graft within minutes after a transplant:
-what type of hypersensitivity reaction is this?
Hyperacute transplant rejection: antibody-mediated (type II hypersensitivity) d/t prefored anti-donor antibodies in the recipient
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate, weeks after a transplant:
-is this reversible?
Acute transplant rejection
-cell-mediated: Cytoplasmic T-cells reacting against foreign MHCs
-can reverse with immunosuppressants
obliterative vascular fibrosis; fibrosis of graft tissue and blood vessels, months to years after a transplant:
-is this reversible?
Chronic transplant rejection
-cytoplasmic T-cells see non-self-MHC I as self-MHC I presenting a non-self antigen--> get T-cell and antibody-mediated vascular damage
Maculopapular rash, jaundice, hepatosplenomegaly, diarrhea at variable point after a transplant:
-what's the pathogenesis?
-what types of transplants is this most common in?
-usually follows a bone marrow or liver transplant (b/c they're organs rich in lymphocytes)
-Pathogenesis: grafted immunocompetent T-cells proliferate in the irradiated immunocompromised host/pt --> graft cells reject cells with "foreign" proteins (ie self) --> get severe organ dysfunction
Which immunosuppressant drug is a precursor of 6-mercaptopurine?
Mannitol diuresis may prevent nephrotoxicity caused by what immunosuppressant drug?
Which immunosuppressant drug is a monoclonal antibody that binds to CD3 on T-cells?
Which immunosuppressant drug is a monoclonal antibody that binds IL-2 receptor on activated T-cells?
Which immunosuppressant drug inhibits IMP (inosine monophosphate dehydrogenase)?
Which immunosuppressant drug inhibits calcineurin-->loss of IL-2 production --> blockage of T-cell differentiation and activation?
Which immunosuppressive drug binds FK-binding protein--> get loss of IL-2 production?
Which immunosuppressive drug inhibits mTOR (mammalian target of rapamycin)--> inhibits T-cell production?
Which immunosuppressive drug is metabolized by xanthine oxidase, so allopurinol increases its toxicity?
Clinical use of Filgrastim and Sargramostim?
-->recombinant cytokines, used to treat post-chemo patients for recovery of bone marrow
-Filgrastim =granulocyte-colony-stimulating factor
-Sargramostim =granulocty-macrophage colony stimulating factor
Clinical use for recombinant erythropoietin?
-renal failure --> because EPO comes from kidneys
-pts undergoing chemo
clinical use for recombinant alpha-interferon?
-Hepatitis B and C
clinical use for recombinant Beta-interferon?
clinical use for recombinant gamma-interferon?
Chronic granulomatous disease
Infliximab: target? uses?
-used to treat: Crohn's disease, Rheumatoid arthritis, Psoriatic Arthritis, Ankylosing spondylitis
Adalimumab: target? uses?
-used to treat: Crohn's disease, Rheumatoid arthritis, Psoriatic arthritis
Abciximab: target? uses?
targets Glycoprotein IIb/IIIa
-clinical uses: prevent cardiac ischemia in unstable angina, and in pts treated with percutaenous coronary intervention
Herceptin = Trastuzumab: target? clinical use?
-used to treat HER-2-overexpressing breast cancer
Rituximab: target? uses?
-targets CD20 (so, B-cells!)
-used to treat B cell-non Hodgkin's lymphoma