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147 Cards in this Set

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Site of B cell localization/proliferation within a lymph node
Follicle
germinal center (active)
Outer cortex
Site of T-cells in lymph node
paracortex
Medullary sinus/cords of lymph nodes
where macrophages and plasma cells hang out
communicates with efferents
High endothelial venules
post-capillary in LN where B and T cells enter from blood
Thoracic duct drainage
everything except the right arm and right half of the head

drains into the left subclavian vein
Rectum (above pectinate line) drains to
internal iliac
Anal canal (below pectinate line)
superficial inguinal
Testes/ovaries drain to
superficial and deep plexuses ==> para-aortic
Scrotum/labia drain to
superficial inguinal
White pulp of spleen contains
T cells (PALS) centrally
Bcells (in follicles) more peripherally
Red pulp of spleen contains
Blood
APC's
macrophages
In which region of the thymus are the mature T cells found?
medulla

also contains Hassall's corpuscles and reticular cells
Where does positive and negative selection occur within the thymus?
corticomedullary junction
Which genes code for MHCI?
HLA-A/B/C
Which genes code for MCHII?
HLA-DR/DP/DQ

*two letters for class 2
What is the HLA-B27 subtype associated with?
PAIR:
psoriasis
Ankylosing spondylitis
IBD
Reiter's syndrome
What is the HLA-A3 subtype associated with?
Hemochromatosis
What is the HLA-B8 subtype associated with?
Grave's disease
What is the HLA-DR2 subtype associated with?
MS,
hay fever,
SLE,
Goodpasture's
What is the HLA-DR3 subtype associated with?
DM1
What is the HLA-DR4 subtype associated with?
RA
DM1
What is the HLA-DR5 subtype associated with?
pernicious anemia
Hashimoto's thyroiditis
What do NK cells use to kill?
perforins and granzymes induce apopotosis of virally infected cells and tumor cells
What activates NK cells killing?
virally infected cells release IFN-alpha/beta

IL-12

absence of MHCI on a cell
What is the costimulatory signal for T-helper cell activation?
B7 from APC binds with CD28 on CD4+ Th cell
What is the costimulatory signal for Tc cell activation?
Th1 cell releases IL-2 which binds with IL-2 receptor on CD8+ Tc cell
What is the costimulatory signal to induce Bcell activation and class-switching?
CD40L on Th2 cell binds with CD40 receptor on B cells
Which cytokines induce Bcell activation/class-switching?
IL-4, IL-5 and IL-6 coming from Th2 cells
What do Th2 cells do?
regulate humoral response

Helps B cells make antibody (IgE>IgG)
What inhibits Th2 cells?
IFN-gamma from Th1 cells
What do Th1 cells do?
Reculate cell-mediated response

Activates macrophages and CD8+ T cells
What inhibits Th1 cells?
IL-10 from Th2 cells
What does IL-2 do?
cytokine releases by Th1 cells that induces CB+ Tc cells to proliferate and do their killing

also stimulates proliferation of more Th cells
What does IFN-gamma do?
inhibits Th2

activates macrophages, Th1 cells and NK cells

inc. MHC I and II expression and antigen presentation in all cells
What do macrophages secrete in order to activate Th1 cells?
TNF-alpha and IL-1
Which immunoglobulins cross the placenta?
IgG only
Which immunoglobulins are secreted in breast milk?
IgA only
Which immunoglobulins fix complement?
IgG and IgM
What activates complement in the classic pathway?
IgG or IgM
What activates complement in the alternate pathway?
molecules on the surface of microbes (e.g. endotoxin)
Which are the primary opsonins in bacterial defense?
IgG and C3b
What do DAF and C1 esterase inhibitor do?
help prevent complement activation on self-cells (eg RBCs)
Where are complement proteins made?
The liver
What do C1, C2, C3, and C4 do?
viral neutralization
what do C3a and C5a do?
anaphylaxis
what allows for neutrophil chemotaxis?
C5a
What comprises MAC and what does it do?
C5b-9

cytolisis by membrane attack
What does C1 esterase inhibitor deficiency cause?
hereditary angioedema (overactive airway constriction)
What does C3 deficiency cause?
severe, recurrent pyogenic sinus and respiratory tract infections

inc. susceptibility to type III hypersensitivity rxn
What does deficiency of C5-C8 cause?
Neisseria bacteremia
What does deficiency of DAF cause?
leads to complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria (PNH)
What does IL-1 do?
causes fever

acute inflammation

activates endothelium to express adhesion molecules

induces chemokine secretion to recruit leukocytes
Which cytokines are secreted by macrophages?
IL-1
IL-6
IL-8
IL-12
TNF-alpha
What does IL-6 do?
causes fever

stimulates production of acute-phase proteins

(also secreted by Th cells)
What does IL-8 do?
major chemotactic factor for neutrophils
What does IL-12 do?
induces differentiation of T cells into Th1 cells

Activates NK cells

(also secreted by B cells)
What does TNF-alpha do?
Mediates septic shock

Activates endothelium

Causes leukocyte recruitment, vascular leak
Which cytokines are secreted by T cells?
IL-3
What does IL-3 do?
Supports growth and differentionation of bone marrow stem cells

Functions like GM-CSF
What do Th1 cells secrete?
IL-2 and INF-gamma
What do Th2 cells secrete?
IL-4, IL-5 and IL-10
What does IL-4 do?
Induction of more Th2 cells

Promotes growth of B cells

Enhances class switching to IgE and IgG
What does IL-5 do?
Promotes differentiation of B cells

Enhances IgA class switching

Stimulates growth and differentiation of eosinophils
What does IL-10 do?
Modulates inflammatory response

Inhibits actions of activated T cells and Th1

Activates Th2

(Also secreted by Treg cells)
What do IFN-alpha/beta do?
inhibit viral protein synthesis by inducing the production of a ribonuclease that degrades viral but not host mRNA
CD3
associated with TCR for signal transduction
CD19/20/21
Found on B cells (receptor for EBV)
What cell surface receptors are found on T cells?
CD4
CD8
CD3
CD40L
TCR
CD28
What cell surface receptors are found on B cells?
CD19/20/21
B7
CD40
MHC II
What cell surface receptors are found on macrophages?
MHC II
B7
CD40
CD14 (endotoxin receptor)
receptor fo Fc
receptor for C3b
WWhat cell surface receptors are found on NK cells?
MHC I
CD16 (binds Fc of IgG)
CD56
Which microorgansims exhibit antigenic variation
shigella
neisseria
borrelia
influenza
trypanosomes
What is an immune complex?
antigen-antibody-complement
What is an Arthus reaction?
intradermal injection of antigen causing local edema, necrosis and activation of complement induces type III hypersensitivity rxn
What is serum sickness?
type III hypersensitivity rxn leading to tissue damage 5-10 days after exposure (to drugs or foreign stuff)
fever
urticaria
arthralgias
proteinuria
lymphadenopath
Antihistone antibodies indicate?
drug-induced SLE
Anti-IgG is?
aka rheumatoid factor
anticentromere
Scleroderma (CREST)
Anti-Scl-70
aka anti-DNA topoisomerase-1

Scleroderma (diffuse)
Antimitochondrial antibodies
Primary biliary sclerosis
Anti-Jo-1
Polymyositis, dermatomyositis
Anti-SS-A
aka anti-Ro

Sjogren;s syndrome
Anti-SS-B
aka anti-La

Sjogren's
Anti-U1 RNP
mixed connective tissue disease
anti-smooth muscle
autoimmune hepatitis
anti-glutamate decarboxylase
DM1
Bruton's aggamaglobulinemia presentation
recurrent bacterial infections due to opsonization defect
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
Hyper IgM syndrome presentation
Sever pyogenic infections early in life
Hyper IgM syndrome defect
defective CD40L on Th cells so can't class switch

IgM is elevated but all other classes are dec./absent
Selective Ig deficiency presentation
sinus and lung infections
milk allergies and diarrhea
anaphylaxis on exposure to IgA
Selective Ig deficiency defect
defect in isotype switching so deficiency of a certain subset of Ig occurs (IgA is most common)
Common variable immune deficiency presentation
can be acquired in 20s-30s

inc. risk of autoimmune disease, lymphoma

inc. risk sinopulmonary infections
Common variable immune deficiency defect
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
IL-12 receptor deficiency presentation
disseminated mycobacterial infections
IL-12 receptor deficiency defect
dec. Th1 response ==> dec. IFN-gamma ==> dec. macrophage activation
Hyper-IgE syndrome presentation
(Job's syndrome)
FATED:
Facies (coarse)
Abcesses (cold (noninflamed) staph)
Teeth (baby)
IgE inc.
Dermatologic probs (eczema)
Hyper-IgE syndrome defect
(Job's syndrome)
Th cells fail to produce IFN-gamma ==> inability of neutrophils to respond to chemotactic stimuli
Chronic mucocutaneous candidiasis
T-cell dysfunction
Severe combined immunodeficiency disorder (SCID) presentation
Recurrent infections (all kinds)
Severe combined immunodeficiency disorder (SCID) defect
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)
Ataxia-telangiectasia defect
faulty DNA repair enzymes leads to IgA deficiency
Ataxia-telangiectasia presentation
ataxia
telangiectasia (spider angiomas)
IgA deficiency
Wiskott-Aldrich syndrome presentation
TIE:

Thrombocytopenic purpura
Infections
Eczema
Wiskott-Aldrich syndrome defect
progressive deletion of B and T cells due to faulty intracellular signaling protein (WASP)

Inc. IgE and IgA
Dec. IgM
Leukocyte adhesion deficiency (type I) presentation
recurrent bacterial infections
absent pus formation
delayed separation of umbilicus
Leukocyte adhesion deficiency (type I) defect
defective LFA-1 integrin (CD18) protein on phagocytes

neutrophilia for some reason?
Chediak-Higashi syndrome defect
Defect in microtubular function ==> dec. phago
Chediak-Higashi syndrome presentation
recurrent pyogenic infections by staph and strep

partial albinism

peripheral neuropathy
Chronic granulomatous disease defect
lack of NADPH oxidase ==> dec. ROS ==> absent respiratory burst in neutrophils
Chronic granulomatous disease presentation
inc. susceptibility to catalase-positive organisms (e.g. S. aureus, E. coli, Aspergillus)
Nitroblue tetrazolium dye test
if negative, indicates chronic granulomatous disease
cyclosporine MOA
binds to cyclophilns ==> inhibits calcineurin ==> dec. T cell maturation ==> dec. IL-2 and IL-2R production
cyclosporine clinical use
suppresses organ rejection after transplant

(some auto-immune disorder)
cyclosporine toxicity
predisposes to viral infections and lymphoma

nephrotoxic
What do you give with cyclosporine to dec. nephrotoxicity?
mannitol diuretic
Tacrolimus MOA
similar to cyclosporine:

inhibits calcineurin by binding to FK binding protein ==> dec. secretion of IL-2 and other cytokines
Tacrolimus clinical use
organ transplant
Tacrolimus toxicity
nephrotoxicity
hyperglycemia
pleural effusion
peripheral neuropathy
HTN
Sirolimus MOA
aka rapamycin

binds to mTOR
inhibits T-cell proliferation in response to IL-2
Sirolimus clinical use
used in combo with cyclosporine and corticosteroids for kidney transplant
Sirolimus toxicity
hyperlipidemia
thrombocytopenia
leukopenia
Daclizumab MOA
monoclonal Ab with high affinity for the IL-2 receptor on activated T-cells so IL-2 can stimulate more T-cell proliferation/activation
Azathioprine MOA
blocks de novo purine synthesis

(antimetabolite precursor of 6-MP)
Azathioprine clinical use
kidney transplant

autoimmune hemolytic anemia and glomerulonephritis
Azathioprine toxicity
bone marrow suppression

don't give with allopurinol!!
Muromonab-CD3 (OKT3) MOA
binds and inhibits CD3 on surface of Tcells ==> blocks signal transduction ==> T-cell activation
Muromonab-CD3 (OKT3) clinical use
kidney transplant
Muromonab-CD3 (OKT3) toxicity
cytokine release syndrome

hypersensitivity reaction
Aldesleukin (IL-2) clinical use
renal cell carcinoma

metastatic melanoma
Filgrastim clinical use
granulocyte colony-stimulating factor

recovery of bone marro
Sargramostim
granulocyte-macrophage colony-stimulating factor (GM-CSF)

recovery of bone marrow
clinical use
alpha-interferon clinical use
Hep B and C

Kaposi's sarcoma

leukemias

malignant melanoma
beta -interferon clinical use
MS
gamma-interferon clinical use
chronic granulomatous disease
Oprelvekin (IL-11) clinical use
Thrombocytopenia
Thrombopoetin clinical use
Thrombocytopenia
Infliximad MOA
anti-TNF-alpha
Infliximab clinical use
Crohn's

RA

Psoriatic arthritis
Adalimumab MOA
anti-TNF-alpha
Adalimumab clinical use
Crohn's

RA

Psoriatic arthritis
Abciximab MOA
anit-glycoprotein IIb/IIIa
Abciximab clinical use
prevent cardiac ischemia in unstable angina and percutaneous coronary intervention
Trastuzumab MOA
aka Herceptin

binds erb-B2
Trastuzumab clinical use
HER-2-overexpressing breast cancer
Rituximab MOA
Binds CD20
Rituximab clinical use
B-cell non-Hodgkin's lymphoma