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147 Cards in this Set
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- 3rd side (hint)
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Site of B cell localization/proliferation within a lymph node
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Follicle
germinal center (active) Outer cortex |
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Site of T-cells in lymph node
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paracortex
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Medullary sinus/cords of lymph nodes
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where macrophages and plasma cells hang out
communicates with efferents |
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High endothelial venules
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post-capillary in LN where B and T cells enter from blood
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Thoracic duct drainage
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everything except the right arm and right half of the head
drains into the left subclavian vein |
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Rectum (above pectinate line) drains to
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internal iliac
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Anal canal (below pectinate line)
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superficial inguinal
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Testes/ovaries drain to
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superficial and deep plexuses ==> para-aortic
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Scrotum/labia drain to
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superficial inguinal
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White pulp of spleen contains
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T cells (PALS) centrally
Bcells (in follicles) more peripherally |
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Red pulp of spleen contains
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Blood
APC's macrophages |
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In which region of the thymus are the mature T cells found?
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medulla
also contains Hassall's corpuscles and reticular cells |
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Where does positive and negative selection occur within the thymus?
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corticomedullary junction
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Which genes code for MHCI?
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HLA-A/B/C
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Which genes code for MCHII?
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HLA-DR/DP/DQ
*two letters for class 2 |
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What is the HLA-B27 subtype associated with?
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PAIR:
psoriasis Ankylosing spondylitis IBD Reiter's syndrome |
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What is the HLA-A3 subtype associated with?
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Hemochromatosis
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What is the HLA-B8 subtype associated with?
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Grave's disease
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What is the HLA-DR2 subtype associated with?
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MS,
hay fever, SLE, Goodpasture's |
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What is the HLA-DR3 subtype associated with?
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DM1
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What is the HLA-DR4 subtype associated with?
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RA
DM1 |
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What is the HLA-DR5 subtype associated with?
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pernicious anemia
Hashimoto's thyroiditis |
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What do NK cells use to kill?
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perforins and granzymes induce apopotosis of virally infected cells and tumor cells
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What activates NK cells killing?
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virally infected cells release IFN-alpha/beta
IL-12 absence of MHCI on a cell |
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What is the costimulatory signal for T-helper cell activation?
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B7 from APC binds with CD28 on CD4+ Th cell
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What is the costimulatory signal for Tc cell activation?
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Th1 cell releases IL-2 which binds with IL-2 receptor on CD8+ Tc cell
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What is the costimulatory signal to induce Bcell activation and class-switching?
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CD40L on Th2 cell binds with CD40 receptor on B cells
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Which cytokines induce Bcell activation/class-switching?
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IL-4, IL-5 and IL-6 coming from Th2 cells
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What do Th2 cells do?
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regulate humoral response
Helps B cells make antibody (IgE>IgG) |
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What inhibits Th2 cells?
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IFN-gamma from Th1 cells
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What do Th1 cells do?
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Reculate cell-mediated response
Activates macrophages and CD8+ T cells |
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What inhibits Th1 cells?
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IL-10 from Th2 cells
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What does IL-2 do?
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cytokine releases by Th1 cells that induces CB+ Tc cells to proliferate and do their killing
also stimulates proliferation of more Th cells |
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What does IFN-gamma do?
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inhibits Th2
activates macrophages, Th1 cells and NK cells inc. MHC I and II expression and antigen presentation in all cells |
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What do macrophages secrete in order to activate Th1 cells?
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TNF-alpha and IL-1
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Which immunoglobulins cross the placenta?
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IgG only
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Which immunoglobulins are secreted in breast milk?
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IgA only
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Which immunoglobulins fix complement?
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IgG and IgM
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What activates complement in the classic pathway?
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IgG or IgM
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What activates complement in the alternate pathway?
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molecules on the surface of microbes (e.g. endotoxin)
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Which are the primary opsonins in bacterial defense?
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IgG and C3b
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What do DAF and C1 esterase inhibitor do?
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help prevent complement activation on self-cells (eg RBCs)
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Where are complement proteins made?
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The liver
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What do C1, C2, C3, and C4 do?
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viral neutralization
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what do C3a and C5a do?
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anaphylaxis
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what allows for neutrophil chemotaxis?
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C5a
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What comprises MAC and what does it do?
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C5b-9
cytolisis by membrane attack |
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What does C1 esterase inhibitor deficiency cause?
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hereditary angioedema (overactive airway constriction)
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What does C3 deficiency cause?
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severe, recurrent pyogenic sinus and respiratory tract infections
inc. susceptibility to type III hypersensitivity rxn |
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What does deficiency of C5-C8 cause?
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Neisseria bacteremia
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What does deficiency of DAF cause?
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leads to complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)
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What does IL-1 do?
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causes fever
acute inflammation activates endothelium to express adhesion molecules induces chemokine secretion to recruit leukocytes |
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Which cytokines are secreted by macrophages?
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IL-1
IL-6 IL-8 IL-12 TNF-alpha |
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What does IL-6 do?
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causes fever
stimulates production of acute-phase proteins (also secreted by Th cells) |
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What does IL-8 do?
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major chemotactic factor for neutrophils
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What does IL-12 do?
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induces differentiation of T cells into Th1 cells
Activates NK cells (also secreted by B cells) |
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What does TNF-alpha do?
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Mediates septic shock
Activates endothelium Causes leukocyte recruitment, vascular leak |
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Which cytokines are secreted by T cells?
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IL-3
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What does IL-3 do?
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Supports growth and differentionation of bone marrow stem cells
Functions like GM-CSF |
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What do Th1 cells secrete?
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IL-2 and INF-gamma
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What do Th2 cells secrete?
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IL-4, IL-5 and IL-10
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What does IL-4 do?
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Induction of more Th2 cells
Promotes growth of B cells Enhances class switching to IgE and IgG |
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What does IL-5 do?
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Promotes differentiation of B cells
Enhances IgA class switching Stimulates growth and differentiation of eosinophils |
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What does IL-10 do?
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Modulates inflammatory response
Inhibits actions of activated T cells and Th1 Activates Th2 (Also secreted by Treg cells) |
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What do IFN-alpha/beta do?
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inhibit viral protein synthesis by inducing the production of a ribonuclease that degrades viral but not host mRNA
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CD3
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associated with TCR for signal transduction
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CD19/20/21
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Found on B cells (receptor for EBV)
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What cell surface receptors are found on T cells?
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CD4
CD8 CD3 CD40L TCR CD28 |
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What cell surface receptors are found on B cells?
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CD19/20/21
B7 CD40 MHC II |
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What cell surface receptors are found on macrophages?
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MHC II
B7 CD40 CD14 (endotoxin receptor) receptor fo Fc receptor for C3b |
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WWhat cell surface receptors are found on NK cells?
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MHC I
CD16 (binds Fc of IgG) CD56 |
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Which microorgansims exhibit antigenic variation
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shigella
neisseria borrelia influenza trypanosomes |
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What is an immune complex?
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antigen-antibody-complement
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What is an Arthus reaction?
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intradermal injection of antigen causing local edema, necrosis and activation of complement induces type III hypersensitivity rxn
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What is serum sickness?
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type III hypersensitivity rxn leading to tissue damage 5-10 days after exposure (to drugs or foreign stuff)
fever urticaria arthralgias proteinuria lymphadenopath |
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Antihistone antibodies indicate?
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drug-induced SLE
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Anti-IgG is?
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aka rheumatoid factor
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anticentromere
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Scleroderma (CREST)
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Anti-Scl-70
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aka anti-DNA topoisomerase-1
Scleroderma (diffuse) |
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Antimitochondrial antibodies
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Primary biliary sclerosis
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Anti-Jo-1
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Polymyositis, dermatomyositis
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Anti-SS-A
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aka anti-Ro
Sjogren;s syndrome |
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Anti-SS-B
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aka anti-La
Sjogren's |
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Anti-U1 RNP
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mixed connective tissue disease
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anti-smooth muscle
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autoimmune hepatitis
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anti-glutamate decarboxylase
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DM1
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Bruton's aggamaglobulinemia presentation
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recurrent bacterial infections due to opsonization defect
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Bruton's aggamaglobulinemia
defect |
defect in BTK, a tyrosine kinase
blocks Bcell differentiation and maturation so dec. total number of bcells (except pro-B) and all types of Ig |
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Hyper IgM syndrome presentation
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Sever pyogenic infections early in life
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Hyper IgM syndrome defect
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defective CD40L on Th cells so can't class switch
IgM is elevated but all other classes are dec./absent |
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Selective Ig deficiency presentation
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sinus and lung infections
milk allergies and diarrhea anaphylaxis on exposure to IgA |
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Selective Ig deficiency defect
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defect in isotype switching so deficiency of a certain subset of Ig occurs (IgA is most common)
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Common variable immune deficiency presentation
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can be acquired in 20s-30s
inc. risk of autoimmune disease, lymphoma inc. risk sinopulmonary infections |
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Common variable immune deficiency defect
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B cells can't mature properly so you get a dec. number of plasma cells and Ig even though your B cell count is normal
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IL-12 receptor deficiency presentation
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disseminated mycobacterial infections
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IL-12 receptor deficiency defect
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dec. Th1 response ==> dec. IFN-gamma ==> dec. macrophage activation
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Hyper-IgE syndrome presentation
(Job's syndrome) |
FATED:
Facies (coarse) Abcesses (cold (noninflamed) staph) Teeth (baby) IgE inc. Dermatologic probs (eczema) |
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Hyper-IgE syndrome defect
(Job's syndrome) |
Th cells fail to produce IFN-gamma ==> inability of neutrophils to respond to chemotactic stimuli
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Chronic mucocutaneous candidiasis
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T-cell dysfunction
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Severe combined immunodeficiency disorder (SCID) presentation
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Recurrent infections (all kinds)
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Severe combined immunodeficiency disorder (SCID) defect
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1) defective IL-2 receptor ==> dec. T-cell activation
2) adenosine deaminase deficiency ==> inc. adenosine which is toxic to B and T cells 3) failure to synthesize MHCII (dec. dNTPs ==> dec. DNA synthesis) |
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Ataxia-telangiectasia defect
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faulty DNA repair enzymes leads to IgA deficiency
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Ataxia-telangiectasia presentation
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ataxia
telangiectasia (spider angiomas) IgA deficiency |
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Wiskott-Aldrich syndrome presentation
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TIE:
Thrombocytopenic purpura Infections Eczema |
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Wiskott-Aldrich syndrome defect
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progressive deletion of B and T cells due to faulty intracellular signaling protein (WASP)
Inc. IgE and IgA Dec. IgM |
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Leukocyte adhesion deficiency (type I) presentation
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recurrent bacterial infections
absent pus formation delayed separation of umbilicus |
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Leukocyte adhesion deficiency (type I) defect
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defective LFA-1 integrin (CD18) protein on phagocytes
neutrophilia for some reason? |
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Chediak-Higashi syndrome defect
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Defect in microtubular function ==> dec. phago
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Chediak-Higashi syndrome presentation
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recurrent pyogenic infections by staph and strep
partial albinism peripheral neuropathy |
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Chronic granulomatous disease defect
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lack of NADPH oxidase ==> dec. ROS ==> absent respiratory burst in neutrophils
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Chronic granulomatous disease presentation
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inc. susceptibility to catalase-positive organisms (e.g. S. aureus, E. coli, Aspergillus)
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Nitroblue tetrazolium dye test
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if negative, indicates chronic granulomatous disease
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cyclosporine MOA
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binds to cyclophilns ==> inhibits calcineurin ==> dec. T cell maturation ==> dec. IL-2 and IL-2R production
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cyclosporine clinical use
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suppresses organ rejection after transplant
(some auto-immune disorder) |
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cyclosporine toxicity
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predisposes to viral infections and lymphoma
nephrotoxic |
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What do you give with cyclosporine to dec. nephrotoxicity?
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mannitol diuretic
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Tacrolimus MOA
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similar to cyclosporine:
inhibits calcineurin by binding to FK binding protein ==> dec. secretion of IL-2 and other cytokines |
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Tacrolimus clinical use
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organ transplant
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Tacrolimus toxicity
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nephrotoxicity
hyperglycemia pleural effusion peripheral neuropathy HTN |
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Sirolimus MOA
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aka rapamycin
binds to mTOR inhibits T-cell proliferation in response to IL-2 |
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Sirolimus clinical use
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used in combo with cyclosporine and corticosteroids for kidney transplant
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Sirolimus toxicity
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hyperlipidemia
thrombocytopenia leukopenia |
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Daclizumab MOA
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monoclonal Ab with high affinity for the IL-2 receptor on activated T-cells so IL-2 can stimulate more T-cell proliferation/activation
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Azathioprine MOA
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blocks de novo purine synthesis
(antimetabolite precursor of 6-MP) |
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Azathioprine clinical use
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kidney transplant
autoimmune hemolytic anemia and glomerulonephritis |
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Azathioprine toxicity
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bone marrow suppression
don't give with allopurinol!! |
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Muromonab-CD3 (OKT3) MOA
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binds and inhibits CD3 on surface of Tcells ==> blocks signal transduction ==> T-cell activation
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Muromonab-CD3 (OKT3) clinical use
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kidney transplant
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Muromonab-CD3 (OKT3) toxicity
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cytokine release syndrome
hypersensitivity reaction |
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Aldesleukin (IL-2) clinical use
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renal cell carcinoma
metastatic melanoma |
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Filgrastim clinical use
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granulocyte colony-stimulating factor
recovery of bone marro |
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Sargramostim
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granulocyte-macrophage colony-stimulating factor (GM-CSF)
recovery of bone marrow |
clinical use
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alpha-interferon clinical use
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Hep B and C
Kaposi's sarcoma leukemias malignant melanoma |
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beta -interferon clinical use
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MS
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gamma-interferon clinical use
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chronic granulomatous disease
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Oprelvekin (IL-11) clinical use
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Thrombocytopenia
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Thrombopoetin clinical use
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Thrombocytopenia
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Infliximad MOA
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anti-TNF-alpha
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Infliximab clinical use
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Crohn's
RA Psoriatic arthritis |
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Adalimumab MOA
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anti-TNF-alpha
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Adalimumab clinical use
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Crohn's
RA Psoriatic arthritis |
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Abciximab MOA
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anit-glycoprotein IIb/IIIa
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Abciximab clinical use
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prevent cardiac ischemia in unstable angina and percutaneous coronary intervention
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Trastuzumab MOA
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aka Herceptin
binds erb-B2 |
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Trastuzumab clinical use
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HER-2-overexpressing breast cancer
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Rituximab MOA
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Binds CD20
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Rituximab clinical use
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B-cell non-Hodgkin's lymphoma
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