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;
223 Cards in this Set
- Front
- Back
|
Lymph Node Follicle
|
Site of B-cell localization and proliferation.
|
|
|
Lymph Node- Medulla
|
Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses.
|
|
|
Medullary sinuses
|
Communicate with efferent lymphatics and contain reticular cells and macrophages.
|
|
|
Lymph Node- Paracortex
|
T-cells. Contains high endothelial venules. Not well developed in DiGeorge syndrome.
|
|
|
High endothelial venule.
|
Where T and B cells enter lymph node from blood. Located in the paracortex.
|
|
|
Lymph Drainage: Upper limb, lateral breast.
|
Axillary
|
|
|
Lymph Drainage: stomach
|
Celiac
|
|
|
Lymph Drainage: duodenum, jejunum
|
Superior mesenteric
|
|
|
Lymph Drainage: sigmoid colon
|
colic --> inferior mesenteric
|
|
|
Lymph Drainage: lower rectum, anal canal above pectinate line
|
Internal iliac
|
|
|
Lymph Drainage: anal canal below pectinate line
|
Superficial inguinal
|
|
|
Lymph Drainage: Testes
|
Superficial and deep plexuses --> para-aortic
|
|
|
Lymph Drainage: scrotum
|
Supericial inguinal
|
|
|
Lymph Drainage: thigh (superficial)
|
Superficial inguinal
|
|
|
Lymph Drainage: Lateral side of dorsum of foot
|
Popliteal
|
|
|
What drains through the right lymphatic duct?
|
right arm and right half of head
|
|
|
What does the Thoracic duct drain?
|
Everything but right arm and right half of head.
|
|
|
Location of T-cells in spleen?
|
periarterial lymphatic sheath (PALS) and red pulp
|
|
|
Location of B-cells in spleen?
|
follicles in the white pulp
|
|
|
Fnx of macrophages in spleen
|
remove encapsulated bacteria
|
|
|
Mechanism of increased susceptibility to encapsulated organisms in splenic dysfunction?
|
decreased IgM --> decreased complement activation -->decreased C3b opsonization
|
|
|
Post-splenectomy RBC morphology?
|
Howell-Jolly bodies (nuclear remnants), Target cells, Thrombocytopenia
|
|
|
Thymus- embryologic derivation
|
Epithelium of 3rd branchial pouch
|
|
|
Thymus: anatomy
|
Encapsulated. Cortex (dense with immature T-cells). Medulla (pale with mature T-cells and epithelial reticular cells. Also contains Hassall's corpuscles.)
|
|
|
Thymus: Corticomedullary Junction
|
Location where positive selection (MHC restriction) and negative selection (nonreactive to self) occur.
|
|
|
Innate Immunity
|
Receptors recognizing pathogens are germline encoded. Response fast and nonspecific. No memory. Consists of neutrophils, macrophages, dendritic cells, natural killer cells, and complement.
|
|
|
Adaptive Immunity
|
Receptors recognizing pathogens undergo V(D)J recombination. Response slow on first exposure, memory response faster and more robust. T cells, B cells, and circulating antibody.
|
|
|
Cytotoxic T cell functions?
|
kills virus-infected, neoplastic, and donor graft cells
|
|
|
Cytokine promoting helper T cell differentiation into Th1 cell (cell-mediated response)?
|
IL-12
|
|
|
Cytokine promoting differentiation from helper T cell into Th2 cell (humoral response)?
|
IL-4
|
|
|
Th1 cells are inhibited by which cytokine?
|
IL-10
|
|
|
Th2 cells are inhibited by which cytokine?
|
IFN-gamma
|
|
|
Cytokines/ function of Th1 cell?
|
IL-2, IFN-gamma. Activated macrophages and CD8+ T-cell.
|
|
|
Cytokines and functions of Th2 cell?
|
IL-4, IL-5, IL-10. Help B cells make antibody (IgE>IgG).
|
|
|
MHC functions?
|
present antigen fragments to T cells and bind TCR
|
|
|
HLA's encoding MHC I
|
HLA-A, HLA-B, HLA-C
|
|
|
HLA's encoding MHC II
|
HLA-DR, HLA-DP, HLA-DQ
|
|
|
What cells express MHC I?
|
Almost all nucleated cells.
|
|
|
What cells express MHC II?
|
Antigen presenting cells (Macrophage, B cell, Dendritic cell)
|
|
|
Key feature of MHC II antigen presentation?
|
antigen loaded following release of invariant chain in acidified endosome
|
|
|
Disease: HLA-A3
|
Hemochromatosis
|
|
|
Disease: HLA-B27
|
Psoriasis, Ankylosing spondylitis, Inflammatory bowel disease, Reiter's syndrome (PAIR)
|
|
|
Disease: HLA-B8
|
Graves' Disease
|
|
|
Disease: HLA-DR2
|
Multiple sclerosis, hay fever, SLE, Goodpasture's
|
|
|
Disease: HLA-DR3
|
Diabetes mellitus type 1
|
|
|
Disease: HLA-DR4
|
Rheumatoid arthritis, diabetes mellitus type 1
|
|
|
Disease: HLA-DR5
|
pernicious anemia -->B12 deficiency, Hashimoto's thyroiditis
|
|
|
Disease: HLA-DR7
|
Steroid-responsive nephrotic syndrome
|
|
|
Major B-cell functions?
|
1. Make antibody
2. IgG antibodies opsonize bacteria, neutralize viruses 3. Allergy (type I hypersensitivity): IgE 4. Cytotoxic (type II) and immune complex (type III) hypersensitivity: IgG 5. Ab cause organ rejection (hyperacute) |
|
|
Major T-cell functions?
|
1. CD4+ cells help B cells make Ab and produce IFN-gamma (activates macrophages)
2. Kill virus-infected cells (CD8+) 3. Delayed cell-mediated hypersensitivity (type IV) 4. Organ (allograft) rejection (acute and chronic) |
|
|
Natural killer cells: function/ mechanism of action?
|
Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells. Induced to kill when exposed to non-specific activation signal on target cell and/or absence of class I MHC on target cell surface.
|
|
|
Cytokines enhancing natural killer cell activity
|
IL-12, IFN-beta, IFN-alpha
|
|
|
What T-cell glycoprotein binds MHC II?
|
CD4
|
|
|
What T-cell glycoprotein binds MHC I?
|
CD8
|
|
|
CD3 complex
|
cluster of polypeptides associated with T-cell receptor; important in signal transduction
|
|
|
Cytokines involved in macrophage-lymphocyte interaction?
|
Activated lymphocytes release IFN-gamma and activated macrophages release IL-1 and TNF-alpha to stimulate one another.
|
|
|
Mechanism of superantigens?
|
Cross-link beta-region of T-cell receptor to MHC class II on APCs --> uncoordinated release of IFN-gamma from Th1 cells and subsequent release of IL-1, IL-6, TNF-alpha from macrophages.
|
|
|
Mechanism of LPS (endotoxin)?
|
Directly stimulate macrophages by binding endotoxin receptor (CD14). Th cells NOT involved.
|
|
|
Mechanism of Th cell activation?
|
1. Foreign body phagocytosed by APC
2. Foreign antigen presented on MHC II and recognized by TCR on Th cell (signal 1) 3. "Costimulatory signal" given by interaction of B7 on APC and CD28 on Th cell (signal 2). 4. Th cell activated to produce cytokines. |
|
|
Mechanism of cytoxic T-cell activation.
|
1. Endogenously synthesized (viral or self) proteins presented on MHC I and recognized by Tc cell (signal 1).
2. IL-2 from Th cell activates Tc cell to kill virus infected cell (signal 2). |
|
|
Mechanism of B-cell class switching. What are signal 1 and 2?
|
1. IL-4, IL-5, IL-6 from Th2 cells
2. CD40 receptor activation by CD40 ligand on Th cell |
|
|
The Fc portion of which Ig's fix complement?
|
IgM and IgG
|
|
|
Fc portion of antibody
|
Constant.
Carboxy terminal. Complement binding at CH2 (IgG, IgM) Carbohydrate side chains. Determines isotype. |
|
|
Fb portion of antibody.
|
Binds antigen. Only recognizes one epitope.
|
|
|
Functions of antibodies
|
Opsonization
Neutralization Complement activation |
|
|
How is antibody diversity generated?
|
1. Random "recombination" of V(D)J chain genes
2. Random combination of heavy/ light chains 3. Somatic hypermutation (following antigen stim.) 4. Addition of nucleotides to DNA during "recombination" by terminal deoxynucleotidyl transferase |
|
|
What immunoglobulin isotypes do mature B cells express on their surfaces?
|
IgM, IgD
|
|
|
What Ig(s) cross the placenta?
|
IgG
|
|
|
What Ig is most involved in delayed response (secondary) to an antigen?
|
IgG
|
|
|
What is the most abundant Ig?
|
IgG
|
|
|
Ig that prevents attachment of bacteria an viruses to mucous membranes?
|
IgA
|
|
|
When is IgA a monomer? Dimer?
|
Monomer- circulation
Dimer- when secreted |
|
|
Ig found in breast milk?
|
IgA
|
|
|
Ig produced in immediate response to an antigen?
|
IgM
|
|
|
Why is the shape of IgM important?
|
Pentamer allows it to trap free antigens out of tissue while humoral response evolves.
|
|
|
What are thymus independent antigens?
|
Antigens lacking peoptide component; cannot be presented by MHC to T cells (e.g., LPS and polysaccharide capsular antigen). Only stimulate release of IgM (no memory).
|
|
|
What are thymus-independent antigens?
|
Antigens containing a protein component. Class switching and immulogic memory occur as a result of CD40-CD40L interaction and release of IL-4, IL-5, and IL-6.
|
|
|
Ig Allotype
|
Ig epitope that differs among members of the same species (can be light or heavy chain). ALLotypes represent different ALLeles.
|
|
|
Ig Isotype
|
Ig epitope common to a single class of Ig (determined by heavy chain).
|
|
|
Ig Idiotype
|
Ig epitope determined by antigen-binding sites. Hypervariable region is unique (idio)
|
|
|
IL-1
|
1. Secreted by macrophages
2. Causes acute inflammation 3. Induces chemokine production to recruit leukocytes 4. activates endothelium 5. Endogenous pyrogen |
|
|
IL-1 through IL-5
"Hot T-Bone stEAK" |
IL-1: fever (hot)
IL-2: stimulates T cells IL-3: stimulates Bone marrow IL-4: stimulates IgE production IL-5: stimulates IgA production |
|
|
IL-2
|
1. Secreted by Th cells
2. Stimulates growth of Th and Tc cells |
|
|
IL-3
|
1. Secreted by activated T cells
2. Supports growth/ differentiation of bone marrow stem cells 3. Functions similar to GM-CSF |
|
|
IL-4
|
1. Secreted by Th2 cells
2. Promotes growth of B cells 3. Enhances class switching to IgE and IgG (IgE>IgG) |
|
|
IL-5
|
1. Secreted by Th2 cells
2. Promotes differentiation of B cells 3. Enhances class switching to IgA 4. Stimulates production and activation of eosinophils |
|
|
IL-6
|
1. Secreted by Th cells and macrophages
2. Stimulates production of acute-phase reactants and immunoglobulins |
|
|
IL-8
|
1. Secreted by macrophages
2. Major chemotactic factor for NEUTROPHILS |
|
|
IL-10
|
1. Secreted by regulatory T cells
2. Inhibits actions of activated T cells 3. Inhibits Th1, activates Th2 |
|
|
IL-12
|
1. Secreted by B cells and macrophages
2. Activates NK cells and Th1 cells |
|
|
gamma-interferon
|
1. Secreted by Th1 cells
2. Stimulates macrophages 3. Activates Th1, Inhibits Th2 |
|
|
TNF
|
1. Secreted by macrophages
2. Mediates septic shock 3. Causes leukocyte recruitment/ vascular leak |
|
|
What cell surface receptors are on Helper T cells?
|
CD4, TCR, CD3, CD28, CD40L
|
|
|
What cell surface receptors are on cytotoxic T cells?
|
CD8, TCR, CD3
|
|
|
What cell surface receptors are on B cells?
|
IgM, CD19, CD20, CD21 (receptor for EBV), CD40, MHC II, B7
|
|
|
What cell surface markers are on macrophages?
|
MHC II, B7, CD40, CD14.
Receptors for Fc and C3b. |
|
|
What cell surface markers are on NK cells?
|
Receptors for MHC I
CD16 (binds Fc of IgG), CD56 |
|
|
What are the two primary opsonins in bacterial defense?
|
C3b and IgG
|
|
|
What prevents complement activation on self-cells?
|
1. Decay-accelerating factor (DAF)
2. C1 esterase inhibitor |
|
|
What stimulates activation of the Classic complement pathway?
|
Antigen-antibody complexes (IgM or IgG)
|
|
|
What activates the alternative complement pathway?
|
Microbial surfaces (nonspecific activators like endotoxin)
|
|
|
Complement components involved in viral neutralization?
|
C1, C2, C3, C4
|
|
|
What causes hereditary angioedema?
|
C1 esterase inhibitor deficiency
|
|
|
C3 deficiency
|
Severe, recurrent pyogenic sinus and respiratory tract infections.
Increased susceptibility to type III hypersensitivity reactions. |
|
|
Components of the alternative complement pathway
|
C3b --> C3 (via C3 convertase) --> C5 (via C5 convertase) --> MAC
|
|
|
DAF (decay-accelerating factor) deficiency
|
Complement mediated lysis of RBC's and paroxysmal nocturnal hemoglobinuria (PNH).
|
|
|
Mechanism of Interferons (alpha, beta, gamma)
|
Induce production of a ribonuclease that inhibits viral protein synthesis by degrading viral mRNA.
|
|
|
Mechanism of gamma-interferons
|
Increase expression of MHC I and II.
Increase antigen presenting in all cells. |
|
|
What are some infections for which part of the treatment involves giving preformed antibodies? What is this called?
|
Passive immunity.
Tetanus toxin, Botulinum toxin, Rabies, HBV "To Be Healed Rapidly" |
|
|
What bacteria use antigen variation?
|
Salmonella (flagella), Borrelia (relapsing fever), Neisseria gonorrhoeae (pili)
|
|
|
What parasite uses programmed rearrangement as a mechanism for antigenic variation?
|
Trypanosomes
|
|
|
What is the half-life of passive immunity?
|
3 weeks
|
|
|
What is anergy?
|
Self-reactive T cells become nonreactive without costimulatory molecule. B cells also become anergic but tolerance is less complete.
|
|
|
What are the components of a granuloma?
|
1. Epithelioid cells
2. Giant cells 3. Fibroblasts. 4. Lymphocytes |
|
|
Name 8 granulomatous diseases
|
1. Tuberculosis
2. Fungal infections (e.g., Histo) 3. Syphilis 4. Leprosy 5. Cat scratch fever 6. Sarcoidosis 7. Crohn's disease 8. Berylliosis |
|
|
What cytokine is important in every step in granuloma formation?
|
IFN-gamma
|
|
|
Type I hypersensitivity
|
-Anaphylactic and atopic.
-Free antigen cross-links IgE on mast cells and basophils, triggering release of vasoactive amines that act at postcapillary venules. -Rapid due to preformed antibody. |
|
|
Type II Hypersensitivity
|
-Antibody mediated.
-IgM and IgG bind to fixed antigen on "enemy" cell, leading to lysis or phagocytosis. -3 mechanisms 1. opsonize cells or activate complement 2. recruit PMNs/macros that cause tissue damage 3. bind normal cell receptors and interfere with functioning |
|
|
Immune Complex Hypersensitivity
|
Type III.
-Ag-Ab (IgG) complexes activate complement, which attracts neutrophils -> release of lysosomal enzymes. -antigen-antibody-complement stuck together |
|
|
Serum Sickness
|
-Immune complex disease (Type III)
-antibodies to foreign proteins produced (takes 5 days) -immune complexes form and deposit in membranes where they fix complement ->tissue damage |
|
|
Arthus reaction
|
-local, subacute type III hypersensitivity rxn
-intradermal injection of antigen induces Abs -complexes form in skin -> edema, necrosis, and activation of complement |
|
|
Presentation of serum sickness
|
-caused by drugs usually
-fever, urticaria, arthralgias, proteinuria, lymphadenopathy 5-10 days after antigen exposure |
|
|
Delayed type (type IV) hypersensitivity
|
-sensitized T lymphocytes encounter antigen and then release lymphokines -> macrophage activation.
-No Ab involved (not transferable by serum) -4 T's (T lymphocytes, Transplant rejections, TB skin tests, Touching (contact dermatitis)) |
|
|
ACID pnemonic for hypersensitivity
|
Anaphylactic and Atopic (type I)
Cytotoxic (type II) Immune complex (type III) Delayed (cell mediated) (type IV) |
|
|
Test for Type I hypersensitivity
|
scratch test and radioimmunosorbent assay
|
|
|
Test for type II hypersensitivity
|
direct/ indirect Coombs
|
|
|
Test for type III hypersensitivity
|
immunofluorescent staining
|
|
|
Test for type IV hypersensitivity
|
patch test (e.g., PPD)
|
|
|
Type I hypersensitivity disorders
|
Anaphylaxis (bee sting/ food, etc)
Allergic and atopic (rhinitis, hay fever, eczema, hives, asthma) |
|
|
Type II hypersensitivity disorders
|
-Hemolytic anemia
-Pernicious anemia -ITP -Erythroblastosis fetalis -Acute hemolytic transfusion rxns -Rheumatic fever -Goodpasture's syndrome -Bullous pemphigoid -Pemphigus vulgaris -Graves' disease -Myasthenia gravis |
|
|
Type III hypersensitivity disorders
|
-SLE
-Rheumatoid arthritis -Polyarteritis nodosa -Post-strep glomerulonephritis -Serum sickness -Arthus reaction (following tetanus vaccine) -Hypersensitivity pneumonitis (farmer's lung) |
|
|
Type IV hypersensitivity disorders
|
-Type I DM
-MS -Guillain-Barre syndrome -Hashimoto's thyroiditis -Graft-versus-host disease -PPD (TB test) -Contact dermatitis (poison ivy, nickel allergy) |
|
|
Anti-nuclear antibodies
|
SLE
|
|
|
Anti-dsDNA
|
SLE
|
|
|
Anti-Smith
|
SLE
|
|
|
Antihistone
|
Drug-induced lupus
|
|
|
Anti-IgG (Rheumatoid factor)
|
Rheumatoid arthritis
|
|
|
Anti-centromere
|
Scleroderma (CREST)
|
|
|
Anti-Scl-70 (anti-DNA topoisomerase I)
|
Scleroderma (diffuse)
|
|
|
Anti-mitochondrial Ab
|
primary biliary cirrhosis
|
|
|
Antigliadin, antiendomysial
|
Celiac disease
|
|
|
Anti-basement membrane
|
Goodpasture's syndrome
|
|
|
Anti-desmoglein
|
Pemphigus vulgaris
|
|
|
Anti-microsomal, antithyroglobulin
|
Hashimoto's thyroiditis
|
|
|
Anti-Jo-1
|
Polymyositis, dermatomyositis
|
|
|
Anti-SS-A (anti-Ro)
|
Sjogren's syndrome
|
|
|
Anti-SS-B (anti-La)
|
Sjogren's syndrome
|
|
|
Anti-U1 RNP
|
Mixed connective tissue disease
|
|
|
Anti-smooth muscle
|
autoimmune hepatitis
|
|
|
Anti-glutamate decarboxylase
|
Type I DM
|
|
|
c-ANCA
|
Wegener's granulomatosis
|
|
|
p-ANCA
|
-Microscopic polyangiitis
-Churg-Strauss |
|
|
Bruton's agammaglobulinemia: defect
|
BTK (tyrosine kinase).
Blocks B-cell differentiation/ maturation. X-linked recessive (more in boys). |
|
|
Bruton's agammaglobulinemia: Presentation
|
Recurrent bacterial infections after 6 months (lose mother's IgG) because they cannot opsonize.
|
|
|
Bruton's agammaglobulinemia: Labs
|
Normal pro-B.
Dec. maturation/number of B cells. Dec. immunoglobulins of all classes. |
|
|
Hyper-IgM syndrome: Defect
|
Defective CD40L on helper T cells.
Cannot class switch -> only IgM. |
|
|
Hyper-IgM syndrome: Presentation
|
Severe pyogenic infections early in life.
|
|
|
Hyper-IgM syndrome: Labs
|
Increased IgM.
Significantly decreased IgG, IgA, IgE |
|
|
Selective Ig deficiency
|
Defect in isotype switching
|
|
|
Selective Ig deficiency: Presentation
|
Sinus and lung infections.
Milk allergies and diarrhea. Anaphylaxis to blood products with IgA. |
|
|
Selective Ig deficiency: Labs
|
IgA deficiency most common.
Failure to mature into plasma cells. |
|
|
Common variable immunodeficiency (CVID): Defect
|
B-cell maturation; many causes
|
|
|
CVID: Presentation
|
Can be acquired in 20s-30s.
Increased risk of autoimmune disease, lymphoma, sinopulmonary infections. |
|
|
CVID: Labs
|
Normal number of B cells.
Decreased plasma cells. Decreased immunoglobulins. |
|
|
Thymic aplasia (DiGeorge syndrome): Defect
|
22q11 deletion.
Failure to develop 3rd and 4th pharyngeal pouches. |
|
|
DiGeorge syndrome: Presentation
|
-Tetany (hypocalcemia)
-Recurrent viral/fungal infections (T-cell deficiency) -congenital heart and great vessel defects |
|
|
DiGeorge syndrome: Labs
|
Thymus & Parathyroids fail to develop:
-Decreased T cells -Decreased PTH -Decreased calcium -Absent thymic shadow on CXR |
|
|
IL-12 receptor deficiency: Defect
|
Decreaesd Th1 response
|
|
|
IL-12 receptor deficiency: Presentation
|
Disseminated mycobacterial infections
|
|
|
IL-12 receptor deficiency: Labs
|
Decreased IFN-gamma
|
|
|
Hyper-IgE syndrome (Job's syndrome): Defect
|
Th cells do not produce IFN-gamma -> inability of neutrophils to respond to chemotactic stimuli
|
|
|
Job's syndrome: Presentation
|
"FATED"
-coarse Facies -non-inflamed staph. Abcesses -retained primary Teeth -increased IgE -Dermatologic problems (eczema) |
|
|
Job's syndrome: Labs
|
Increased IgE
|
|
|
Chronic mucocutaneous candidiasis
|
T-cell dysfunction.
Candida albicans infections of skin and mucous membranes. |
|
|
SCID: defect
|
-defective IL-2 receptor (X-linked, most common)
-ADA (adenosine deaminase deficiency) -failure to synthesize MHC II antigens |
|
|
SCID: Presentation
|
Recurrent viral, bacterial, fungal, and protozoal infections due to both B and T cell deficiency.
|
|
|
SCID: Treatment
|
bone marrow transplant (no allograft rejection)
|
|
|
SCID: Labs
|
Decreased IL-2R
Increased adenine (toxic to B/T cells) Decreased dNTPs, decreased DNA synthesis |
|
|
Ataxia-telangiectasia: Defect
|
Defect in DNA repair enzymes
|
|
|
Ataxia-telangiectasia: Presentation
|
Triad:
Cerebellar defects (ataxia) Spider angiomas (telangiectasia) IgA deficiency |
|
|
Wiskott-Aldrich syndrome: defect
|
X-linked recessive.
Progressive deletion of B/T cells. |
|
|
Wiskott-Aldrich syndrome: Presentation
|
Triad:
Thrombocytopenic purpura Infections Eczema |
|
|
Wiskott-Aldrich syndrome: Labs
|
Increased IgE, IgA
Decreased IgM |
|
|
Leukocyte adehesion deficiency (type I): defect
|
LFA-1 integrin (CD18) protein on phagocytes
|
|
|
Leukocyte adhesion deficiency (type I): Presentation
|
Recurrent bacterial infections.
Absent pus formation. Delayed separation of umbilicus. Neutrophilia |
|
|
Chediak-Higashi syndrome: defect
|
Autosomal recessive.
Defect in microtubular function with decreased phagocytosis. |
|
|
Chediak-Higashi syndrome: Presentation
|
Recurrent pyogenic infections by staph and strep.
Partial albinism. Peripheral neuropathy. |
|
|
Chronic granulomatous disease: defect
|
Lack of NADPH oxidase.
Results in decreased ROS and absent respiratory burst in neutrophils. |
|
|
Chronic granulomatous disease: Presentation
|
Increased susceptibility to catalase-positive organisms (staph aureus, E. coli, aspergillus)
|
|
|
Chronic granulomatous disease: test
|
Negative Nitroblue tetrazolium dye reduction test
|
|
|
Autograft
|
from self
|
|
|
Syngeneic graft
|
from identical twin or clone
|
|
|
Allograft
|
from nonidentical individual of same species
|
|
|
xenograft
|
from different species
|
|
|
Hyperacute rejection
|
-Antibody mediated (type II) due to preformed antidonor Abs in transplant recipient.
-occurs within minutes |
|
|
Acute rejection
|
-cell mediated (cytotoxic T lymphocytes against foreign MHCs)
-occurs weeks after transplantation -reversible with immunosuppressants (cyclosporin and OKT3) |
|
|
Chronic rejection
|
T-cell and Ab-mediated vascular damage (obliterative vascular fibrosis)
-months to years after transplant -irreversible -class I MHC (nonself) perceived by CTLs as class-I MHC self presenting non-self antigen |
|
|
Graft-versus-host disease
|
-grafted immunocompetent T cells proliferate in irradiated immunocompromised host
-reject cells with "foreign" proteins -severe organ dysfunction -symptoms: maculopapular rash, jaundice, hepatosplenomegaly, diarrhea |
|
|
Cyclosporin: Mechanism
|
-binds cyclophilins
-inhibits calcineurin, preventing production of IL-2 and its receptor |
|
|
Cyclosporin: Clinical use
|
-suppress organ rejection after transplantation
-select autoimmune disorders |
|
|
Cyclosporin: Toxicity
|
-predisposes to viral infections and lymphoma
-nephrotoxic (preventable with mannitol diuresis) |
|
|
Tacrolimus (FK506): Mechanism
|
-similar to cyclosporin
-binds FK-binding protein, inhibiting secretion of IL-2 and other cytokines |
|
|
Tacrolimus (FK506): Clinical use
|
potent immunosuppressive used in organ transplants
|
|
|
Tacrolimus (FK506): Toxicity
|
Significant:
-nephrotoxicity -peripheral neuropathy -HTN -pleural effusion -hyperglycemia |
|
|
Azathioprine: Mechanism
|
-Antimetabolite precursor of 6-mercaptopurine.
-Interferes with metabolism and synthesis of nucleic acids. |
|
|
Azathioprine: Clinical use
|
Kidney transplant.
Autoimmune disorders (glomerulonephritis and hemolytic anemia) |
|
|
Azathioprine: Toxicity
|
-bone marrow suppression
-mercaptopurine (active metabolite) metabolized by xanthine oxidase -> increased toxic effects with allopurinol |
|
|
Muromonab-CD3 (OKT3): Mechanism
|
Monoclonal Ab against CD3 (epsilon chain).
Blocks T cell signal transduction. |
|
|
Muromonab-CD3 (OKT3): Clinical use
|
Immunosuppression after kidney transplant.
|
|
|
Muromonab-CD3 (OKT3): Toxicity
|
Cytokine release syndrome.
Hypersensitivity rxn. |
|
|
Mycophenolate mofetil: Mechanism
|
-inhibits de novo guanine sythesis
-blocks lymphocyte production |
|
|
Sirolimus (rapamycin): Mechanism
|
-binds mTOR
-inhibits T-cell proliferation in response to IL-2 -immunosuppression after kidney transplant in combination with cyclosporine and corticosteroids |
|
|
Sirolimus (rapamycin): Toxicity
|
-hyperlipidemia
-thrombocytopenia -leukopenia |
|
|
Daclizumab
|
Monoclonal Ab with high affinity for IL-2R on activated T cells
|
|
|
Aldesleukin (IL-2) uses
|
Renal cell carcinoma, metastatic melanoma
|
|
|
Erythropoietin (epoetin) uses
|
Anemias (especially in renal failure)
|
|
|
Figrastim (GC-SF) use
|
recovery of bone marrow
|
|
|
Sargramostim (GM-CSF)
|
Recovery of bone marrow
|
|
|
recombinant alpha-interferon uses
|
Hepatitis B, C, Kaposi's sarcoma, leukemias, malignant melanoma
|
|
|
recombinant beta-interferon uses
|
Multiple sclerosis
|
|
|
recombinant gamma-interferon uses
|
chronic granulomatous disease
|
|
|
Oprelvekin (IL-11) uses
|
thrombocytopenia
|
|
|
Thrombopoietin uses
|
thrombocytopenia
|
