LN follicles (general and primary vs secondary)
general - B cells are here, found in outer cortex
primary - dense and dormant
secondary - pale central germinal centers > active
where do T cells live in LNs?
paracortex
high endothelial venules - where and function
in paracortex of LN
where T and B cells enter from blood
LN drainage of rectum above pectinate line
internal iliac nodes
LN drainage of anal canal below pectinate line
superficial inguinal
LN drainage of testes
superficial and deep plexuses > para aortic
where are B and T cells found in spleen, respectively
B - follicles in white pulp
T - periarterial lymphatic sheath (PALS) in white pulp
3 postsplenectomy PBS findings
Howell Jolly Bodies
target cells
thrombocytosis
embyro origin of thymus
3rd branchial pouches
Hassall’s corpuscles found where
medulla of thymus
where do pos and neg selection take place in thymus respectively?
pos - cortex
neg - medulla
MHC bind to
T cell receptor
MHC I vs MHC II types (ex HLA-__)
MHC I : A, B, C
MHC II: DR, DP, DQ
MHC I:
binds to? expressed by? antigen loading?
TCR and CD8
all nucleated cells
loaded in RER - intracellular peptides
MHC II:
binds to? expressed by? antigen loading?
TCR and CD4
APCs
loaded after release of invariant chain in acidified endosome
which MHC pairs w/ beta 2 microglobulin?
MHC I
HLA A3 assoc w/
hemochromatosis
HLA B27 assoc w/
psoriasis, ankylosing spondylitis, IBD, Reiter’s syndrome
HLA DQ2/DQ8 assoc w/
celiac dz
HLA DR2 assoc w/
MS, hay fever, SLE, Goodpasture’s
HLA DR3 assoc w/
DM type 1, Grave’s dz
HLA DR4 assoc w/
DM type 1, RA
HLA DR5 assoc w/
pernicious anemia, Hashimoto’s thyroiditis
fn of NK cells
use perforin and granzymes to indue apoptosis of virally infected or tumor cells
cytokines that inc NK activity (4)
IL2, IL12, IFN beta, IFN alpha
when do NK cells kill another cell?
cell expresses nonspecific activation signal and/or absence of self MHC I
4 types of hypersensitivity rxn
1 - allergy, IgE mediated
2 - cytotoxic (ab mediated)
3 - immune complex mediated
4 - delayed cell mediated
APCs
dendritic cell (*only one that can activate naive T cell)
macrophage
B cell
signal 1 and 2 for T cell activation
signal 1 - antigen on MHC
signal 2 - B7 and CD28 complex
signal 1 and 2 for B cell activation
1 - antigen on MHC II binds to TCR
2 - CD40L on T cell binds to CD40 on B cell
Th1 cells - secrete? main function? inhib by?
IFN gamma
activate macrophages
IL4 and IL10
Th2 cells - secrete? main function? inhib by?
IL4, IL5, IL10, IL13
recruits eosinophils, promotes IgE production
IFN gamma
3 components of CD8 cytotoxic granules
perforin, granzyme, granulysin
Tregs - secrete? main function? surface markers?
IL10, TGF beta
immune tolerance - suppress CD4/8 functions
CD3, CD4, CD25
function of Fc region of Ab
fixes complement
2 main processes that create antibody diversity
VDJ recombination
somatic hypermutation following antigen stimulation
IgD
found of surface of many B cells, unk function
thymus indepedent vs dependent antigens
independent - no protein component. stim release of abs, but no immunologic memory dependent - protein component. cause class switching and immunologic memory
3 pathways of complement activation
classic - IgG or IgM
alternative - microbe surface molecule
lectin - mannose or other sugars
functions of C3b, C3a, C5a, C5b-9
3b - opsonization (b for bind)
3a - anaphylaxis
5a - anaphylaxis and neutrophil chemotaxis
5b-9 - cytolysis by MAC
inhibitors of complement pathway
DAF (decay accelerating factor), C1 esterase inhibitor
C1 esterase inhibitor def
hereditary angioedema - cant use ACEIs
C3 def
severe recurrent sinus and resp tract infections, inc type 3 hypersensitivity reaction
C5-9 defs
recurrent Neisseria bacteremia
DAF (decay accelerating factor) def
complement mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
fn of IL1-5
Hot T-Bone stEAk 1 - hot (fever) 2 - stim T cells 3 - stim Bone marrow 4 - IgE production 5 - IgA production
IL6
pyrogen and acute phase reactants
IL8
major chemotactic agent for neutrophils
IL12
Th1 differentiation, activates NK cells
TNFalpha
mediates septic shock, activates endothelium, leukocyte recruitment, vascular leak
IFNgamma
activates macrophages and Th1, suppresses Th2
IL10
inhibits activated T cells and Th1. dec immune response
surface marker for macrophages
CD14
surface marker for NK cells
CD56
superantigens
cross link beta region of TCR to MHC II on APCs > activate any T cell > massive release of cytokines
endotoxin/LPS immune response
directly stimulates macrophages by binding to endotoxin receptor CD14 - no Th involvement
for what infxns are preformed abs indicated? (4)
tetanus, botulinum, HBV, rabies
2 examples of type 3 hypersensitivity
serum sickness, arthus reaction
pts w/ what condition are more likely to get an anaphylactic reaction to a transfusion?
IgA deficiency
Bruton’s agammaglobulinemia - inheritance, gene, presentation/findings
XLR
BTK gene
recurrent bacterial infxns after 6 mo, dec B cells and Igs of all classes
combined variable immunodeficiency (CVID)
defect in B cell maturation (many causes)
inc risk of autoimmune dz, lymphoma, sinopulmonary infxns
normal # b cells but dec plasma cells and Igs
thymic aplasia - aka, genetic cause, presentation/findings
DiGeorge syndrome
22q11 deletion (3rd and 4th pharyngeal pouches dont form)
tetany (hypoCa), recurrent viral/fungal infxns, congenital heart/great vessel defects
dec T cells, dec PTH, dec Ca
IL12 receptor def pts get
disseminated mycobacterial infxns
hyper IgE syndrome (Job’s) findings
coarse facies, cold staph abscesses, retained primary teeth, inc IgE, dermatologic problems
MCC SCID
defective IL2 receptor
hyper IgM syndrome - MCC and presentation
defective CD40L on Th cells > inability to class switch severe pyogenic infxns early in life
Wiskott Aldrich syndrome - inheritance, problem, presentation
XL
T cells can’t recognize actin
thrombocytopenic purpura, infections, eczema
Chediak Higashi syndrome - inheritance, problem, presentation
AR
defect in LYST - MT dysfunction in phagosome/lysosome fusion
Recurrent pyogenic infxns, partial albinism, peripheral neuropathy
chronic granulomatous dz - cause, presentation
lack of NADPH oxidase > dec ROS / respiratory burst
inc susceptibility to catalase pos organisms
sx of GvHD
maculopapular rash, jaundice, hepatosplenomegaly, diarrhea
cyclosporine - mech, use, tox
inhib calcineurin > prevent production of IL2/IL2R
suppress organ rejection, some autoimmune
nephrotox, HTN, hyperlipidemia, hyperglycemia, tremor, gingival hyperplasia, hirsutism
tacrolimus
similar to cyclosporine, but no gingival hyperplasia or hirsutism
Hamill - “AIDS in a bottle”
sirolimus - mech, use, tox
inhibits mTOR > inhib T cell prolif
after kidney transplants
hyperlipidemia, thrombocytopenia, leukopenia
azathioprine - mech, use, tox
precursor of 6MP, toxic to proliferating lymphocytes
kidney transplants, autoimmune disorders
bone marrow suppression, c/i w/ allopurinol
muromonab - mech, use, tox
anti-CD3, prevents T cell signal transduction
kidney transplants
cytokine release syndrome, hypersensitivity rxn
aldesleukin - what is it, use
synthetic IL2
RCC, metastatic melanoma
filgrastim and sargramostim are
synthetic GCSF and GMCSF
oprelvekin - what is it, use
synthetic IL11
thrombocytopenia
abciximab - what is it, use
anti GP 2b/3a
prevent cardiac ischemia in unstable angina and PCI pts
trastuzumab - what is it, use
anti HER2
some breast cancers
rituximab - what is it, use
anti CD20 (b cell) B cell NHL
omalizumab - what is it, use
anti IgE
severe asthma