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Immunology

Terms in this set (113)

what is made in the cortex, paracortex, medulla of LNs
cortex: follicles B cells
paracortex (t tubules): T cells
medulla sinus: macrophages
medulla cords: plasma cells
describe MALT
70% of immune system in GI tract
in lamina propria of intestine =GALT
describe Peyers patches
lamina propria of ileum
extending into submucosa of ileum
plasma cells at germinal center

follicle associated epithelium (flattened out vs normal columnar)
microfilm cells (M cell)- accepts antigen
what drains into right lymphatic duct
Right upper extremity, right hemicranium, and the heart and lobes of the lung (except the left upper lobe).
what drains into the axillary lymph nodes
UE, breast, skin above umbilicus
what drains into the popliteal nodes
DL foot, posterior calf
what drains into the superficial inguinal nodes
skin below umbilicus, thigh, anal lower than pectinate line, scrotum
what drains into the internal iliac nodes
lower rectum above pectinate line
(versus below is super inguinal) (versus above is IMA nodes)
bladder
prostate
vagina (upper and middle)
what lymph nodes drain the lower 1/3rd of the vagina
sacral LNs
what drains into the paraaortic lymph nodes
testes, ovaries, uterus, kidneys
what are the surface markers on T helper cells and T cytotoxic cells
All T cells: CD3, TCR

Th= "h"= 4 = CD4

Tc= CD8
where are MHC located, what do they do
on APC and dendritic cells

bind TCRs
describe MHC 1
bind TCRs of CD8+ Tc cells

HLA- A,B,C ("1" letter)

found on all nucleated cells and platelets

present endogenous antigens (viral or cytosolic proteins) broken down proteosome
delivered to RER by TAP (transported associated with antigen processing), antigen to MHC directly

loaded: in RER

1 long chain (alpha 2,3)
+
1 short chain (alpha 1 + "beta2 microglobulin")
describe MHC 2
bind TCRs of CD4+ Th cells

HLA DR,DP,DQ ("2" letters)

expressed on APCs
present exogenous (bacterial) antigens

loaded: following release of invariant chain in acidified endoscope, added to invariant chain

2 equal length chains (alpha 1,2 and beta 1,2)
+
invariant chain
what are some specific MHC 1 subtypes to know
A3- hemochromatosis
B8- Eightddison's disease, G8ve's disease, Myasthenia G8vis
B27- PAIR of B27s
what are some MHC class 2 subtypes to know
DQ- celiac disease

DR2- MS, SLE, good pasture, hay fever
DR3- DM1, graves and hashimoto, SLE (3 letters)
DR4- "4 walls in a rheum"- RA, DM1
DR5- pernicious anemia
what is the most important APC
dendritic cell

present class 1 and 2 MHC

B7 proteins (either CD80 or CD 86) binds cell to increase or decrease associated signal

CD40 to activate the APC when with t cell (CD40 is also on other APC, b cells, and macrophages)
what are the types of dendritic cells
langerhans in the epidermis of skin (CALT)
interstitium of nearly all other organs (except brain)
what is langerhans histio cytosis
express S100 marker and CD1a

EM shows birbecks granules (tennis rackets or rods)

child with lytic bone lesion or recurrent OM with mastoid bone mass
what is the origin or the thymus
epithelium of 3rd branchial pouch
describe t cell selection process in the thymus
cortex: CD4 and CD8 form Th and Tc respectively in the medulla

positive selection: thymic cortex, T cells with TCRs capable of binding surface self MHC survive

negative selection: C-M junction, T cells with TCRs with high affinity for self antigens -> apoptosis
what is the function, differentiating signal, association, and secretory factors of Th1 cells
IL-12 and IFN gamma cause differentiation to Th1

secrete IL-2 (co activate factor for Tc cells) and IFN gamma (IFN alpha would decrease Th2 cells)

promote cell based immunity
increase Th1, Tc cells, and macrophages

a/w T. leprosy and granuloma formation
what is the function, differentiating signal, association, and secretory factors of Th2 cells
IL-2 and IL-4 cause differential to Th2

secrete IL-4, IL- 5, IL-13

promote humoral immunity and eosinophils for parasite defense

a/w L leprosy and IgE production by B cells
what is the function, differentiating signal, association, and secretory factors of Th17 cells
IL-6, TGF- B cause differentiation

secrete IL-17, IL-21

activate neutrophils

a/w chronic inflammatory conditions
what is the function of IL-10
decrease production of Th1

secreted by Th2
which IL causes class switching from IgM to IgG and IgE
IL-4
what receptor on T cells bind the B7 protein (CD80,CD86) on APCs?
CD28
what IL do Tc cells release after activation with APC?
IL-2 (clonal expansion and coactivation factor)
which T cells interact with B cells to activate them to produce antibodies and promote humoral immunity, how are they activated
Th2 cells

CD40 on B cell interacts with CD40L on Th2 cell
MHC 2 on B cell with CD4 on Th2

TH2 releases:
IL-4 -> plasma B cell to make IgG and IgE
IL-5 -> plasma B cell to make IgA
what markers are on NK cells, what is their function, what increases them, what do they secrete
CD16, CD56

use perforin and granzyme like Tc cells (apoptosis for cells without MHC class I)

also use ab-dependent cell mediated cytotoxicity (CD16 on their surface binds to Fc region of bound Ig)

are not Tc cell because they are innate

increased by Il-2, IL-12, IFN alpha and beta

secrete IFN gamma to activate macrophages
what is the Fc portion of the antibody
carboxy terminal
carbohydrates side chains
constant for isotype
complement binding
CD16 on NK cells
what determines Ig isotype
heavy chain
what are the light chains
kappa and lambda
normal ratio is 2:1
Describe V(D)J recombination
rearrangement of DNA segments name V,D,J

compose coding regions for each specific antigen-R on T and B cells

breaks in dsDNA at recombinant signal sequences (RSSs) flanking VDJ

initiated by recomb activating gene complex (RAG1 and RAG 2) which recognize the RSSs
Describe the IgG antibody
delayed immune response
most abundant isotope in serum
fixes C', crosses placenta, opsonizes bacteria, neutralizes toxins and viruses

t1/2 21 days
Describe the IgA antibody
primary as MALT, most produced isotope, not high in serum

monomer in circulation, dimer when secreted (saliva, tears, mucus)

trancytosis thru epithelial cells, gains secretory component

DOES NOT FIX C'
Describe the IgE anitbody
mast cells and basophils with allergen, type I hypersensitivity -> HIs, parasites with eosinophils

low concentration
Describe the IgM antibody
"M"ade first
primary (immediate)
fixes C' but does not cross placenta

on B cells as monomer, pentad in serum
which bugs are fought with passive preformed antibodies
To Be Healed Very Rapidly

tetanus
botulinism
HBV
varicella
rabies
which vaccines are inactivated/killed
confer just humoral not cellular immunity

RIP Always

Rabies
Influ (IM)
Polio (SALK IM)
hAv
what is the only live vaccine given to HIV+ patients with CD4 <200
MMR
what are the bacterial vaccines
toxins
PS capsules (H influ, S pneumo)
killed (V cholera)
LA (typhoid, BCG)
what type of amyloid is associated with immunologic amyloidosis, secondary (inflammatory), T2DM, medullary thyroid CA, alzheimers, dialysis associated
immunologic:
MM, IgA light chains, AL

secondary:
inflammatory, RA, serum amyloid associated protein (SAA), AA

T2DM:
amylin (secreted with insulin), AIAPP

medullary thyroid:
calcitonin, A-CAL

alzheimer:
beta amyloid, APP

dialysis assoc:
beta2 microglobulin, AB2M
what auto antibody is associated with RA
anti IgG (RF)
what auto antibody is associated with PV
anti desmoglein
what auto antibody is associated with T1DM
anti glutamate decarboxylase
what are the antibodies associated with graves and hashimoto
graves:
thyroglobulin
thyrotropin-R

hashimoto:
thyroid peroxidase
thyroglobulin
what diseases are associated with p-ANCA
microscopic polyangiitis
churg strauss
pauci immune cresenteric GM
What is Anti-Jo-1?
anti-histidyl-tRNA synthetase
polymyositis and dermatopolymyositis
Describe type 1 hypersensitivity, dx
-Immediate Hypersensitivity
-free antigen cross links IgE bound to presensitized mast cells
-Histamine Response (H1 and H2 receptors) and bradykinin
-Allergic reactions to allergens
-allergy and atopy

dx: scratch test
Describe type 2 hypersensitivity, dx
antibodies against FIXED antigens ON CELLS
auto antibodies
C' mediated damage
macrophages, NK cells

dx: coombs test
Describe type 3 hypersensitivity, examples
vasculitis and systemic rxns
antibodies against SOLUBLE antigens IN BLOOD
antibody-antigen complexes are deposited in tissue
activation of C' and recruiting PMNs

resume sickness (rx rxns)- days
arghus reactions (vaccination swelling/inflammation)- hours
SLE, PAN, RA, PSGN
Describe type 4 hypersensitivity, examples
aka "delayed" or "cell-mediated"
no antibodies
-sensitized T-lymphocytes encounter an antigen
=> release leukokinin
=> mac activation.

TB skin test, contact dermatitis, corneal transplant rejection, GVHD, hashimoto, GBS, MS
describe the classic complement activation
"GM makes classic cars"

stimulation by antibody-antigen complexes
IgG or IgM antigen

initiating: C1q, r, s
C3 convertase: c4b, c2b
describe alternative complement activation
detects surfaces not protected by c' inhibitors
activated spontaneously

initiating: C3 factor turnover, factor D
c3 convertase: c3b, Bb
Describe the lectin pathway of complement activation
detects surfaces with mannose

initiating: mannose binding lectin and associated proteases
c3 convertase; c4b, c2b
what are the most important opsonins
c3b and IgG
what are the components of complement involved in anaphylaxis
c3a: increase mast cells and basophils
c5a: PMN chemotaxis
which part of complement binds bacteria
c3b
what are the inhibitors or the complement pathway
C1 esterase inh (c1 inh)
CD55 (decay accelerating factor)
Describe C1 esterase inhibitor deficiency
hereditary angioedema
unregulated activation of kallikrein, increased bradykinin
do not give ACEI
Describe C3 deficiency
recurrent pyogenic sinus and respiratory tract infections

S pneumonia, H influenza
increased type 3 hyper-sensitive (GN)
describe c5b or c6-9 def
increased Neisseria bacteremia (gonococcal or meningococcal) infections
describe a deficiency in DAF/CD55 (GPI anchor enzyme, CD59), tx
increased C' mediated RBC lysis
PNH

chronic intravascular hemolysis
hemosiderinuria
thrombosis

dx: ham's test (positive if RBCs lyse in acid)
flow cyotmetry to look for CD55 or CD59

tx:
transfusions
warfarin
eculizumab
describe the white pulp of the spleen
follicles: b cells
marginal zone at edge: APCs (macrophages)
periarterial lymphatic sheath (PALS): t cells
describe the life span of monocytes
leave marrow -> circulate 8 hrs to mature -> tissues and become macrophages
what are the names of various macrophages
blood, lungs, intestine: macrophages
joints: A cells
skin and CT: dendritic cells/histiocytes
liver: kupffer cells
kidney: mesangial cells
brain: microglia
bone: osteoclasts
what activates macrophages, what receptors do they have
IFN gamma by Th1 and NK cells

CD40, CD14: bind LPS of gram negative -> induces macrophages to make acute phase cytokines (IL1, IL6, IFN gamma)
what do macrophages do in a chronic infection
form multinucleate giant cells in granulomas and secrete vitamin D

generate oxygen radical s with NADPH oxidase
what causes increase in eosinophils
DNAAACP

drugs (NSAIDS, PCNs, Cephalosporins)
neoplasm
atopic/allergies
addisons
AIN
collagen vascular disease (PAN, dermatomyositis)
parasites
where are mast cells found, what prevents degranulation
in tissue (versis Basophils in Blood)
cromolyn
what is the purpose of IL1-6
Hot T-bone stEAK

IL1- fever
IL2- t cells
IL3- bone marrow
IL4- class switching to IgE and IgG
IL5- IgA, eosinophils
IL6- aKute phase protein production
which cytokines are secreted by t cells, what is their function
IL-2: proliferation of Th and Tc, NK cells

IL-3: bone marrow stem cell growth

IL-4: (from TH2): B cell differentiation, increase IgE and IgG, Th0 to Th2 cells

IL-5: (from Th2): IgA production, eosinophils, B cell differentiation

IL-10: (from Tr): stop macrophages and Th1 cells, decrease MHC 2, at"ten"uate immune cells (also TGF-beta)

IFN gamma: (from NK cells in response to IL-12 from macrophages): activates macrophages, increases MHC expression
what are IFNs
antiviral cytokines

alpha and beta: help cells around avoid virus, block cell protein synthesis, activation of ribonuclease to degrade viral mRNA

activate NK cells
which cytokines are secretes by macrophages and their function
IL-1: fever
IL-6: fever
TNF alpha: septic shock, leaky vessels, leukocyte recruitment
IL-8: chemotactic for PMNs
IL-12: activates NK cells, induces Th0 to Th1 cells
what are the PMN chemotactic cytokines
IL-8
c5a
LT-B4
what is aldeleukin and what is its use
recombinant IL-2

RCC
metastatic melanoma
what is oprelvekin and what is its use
recombinant IL-11
thombrocytopenia
what is recombinant IFN alpha used for
choleric hep B and C
capos sarcoma
malignant melanoma
genital warts
hairy cell leukemia
What is IFN-beta used to treat?
multiple sclerosis
What is IFN-gamma used to treat?
Chronic granulomatous disease
describe hyper acute transplant rejection
mins to hours (could see in OR)
type 2 hypersensitivity (antibody mediated)
preventable
describe acute transplant rejection
weeks to months
cell mediated
Tc recognize foreign MHC 1
describe chronic transplant rejection
months to years
T cells and antibodies
Tc treat transplant cells as self presenting non self
vascular damage and fibrosis
irreversible
describe GVHD
usually in marrow or liver transplant
grafted T cells proliferate and attack host as foreign
rash on neck, shoulder, ears, palms
hemolysis and jaundice
abdominal pain, NVD
hepatosplenomegaly
what is the MOA, SE and use of cyclosporine
binds cyclopholins -> inh calcineurin -> decrease IL-2

nephrotoxic (constrict afferent and efferent)

SLE
what is the MOA, SE of tacrolimus and pimecrolimus
bind to FK binding protein enzymes -> inh calcineurin -> decrease IL-2

nephrotox and HTN
neurotic and HA, parasthesias
what is the MOA, SE of Sirolimus (rapamycin)
binds FKBP-12 intracell protein -> binds MTOR -> inhibit T cell proliferation and response to IL-2

kidney "sir"vives
what is the MOA, SE, and use of azathioprine
precursor of 6-MP (mercaptopurine) "azathio"purine" to decrease synthesis of nucleic acids

bone marrow suppression, degraded by xanthine oxidase so too increases with allopurinol use
What is the MOA of mycophenolate mofetil?
inhibits IMP dehydrogenase -> blocks synthesis of guanine
prevents rapid proliferation of B and T cells
what is the MOA of muromonab
binds CD3 on all T cells and blocks T cell signal transduction
What is the MOA of Daclizumab?
binds CD25 (IL-2 receptor) on activated T cells
what is the use, MOA and toxicity warning of thalidomide
I/S in SLE and transplants, antiangiogenic

affects TNF alpha

phocomelia
what are the mabs that target TNF alpha and their use
infliximab
adalimumab

(etanerept binds receptor, not a -mab)

for HLA B27 PAIR and RA
what is the target and use of abciximab
glycoprotein IIb/IIIa (ab"six"imab= 2x3=6)
what is the target of trastuzmab
trast "2" zumab= HER2/neu + breast cancer
what is the target and use of rituximab
CD20

NHL
what is the target and use for omalizumab
IgE- prevents IgE binding to FcER1

asthma
Describe Bruton's agammaglobulinemia
Brutons= B

"B"oys= XR
defect in "B"TK (tyrosine kinase) -> no "B" cells maturing (absent CD19, 20, 21)
recurrence after 6 months (decrease maternal IgG), increased pyogenic (encapsulated) bacterial infections and enteroviral and giardiasis
describe selective IgA def
IgA

MCC of primary immunodef
majority are "A"sx
"A"irway and GI infxns
"A"utoimmune dz,
"A"topy, "A"naphylaxis to Ig"A" pdts (transfusion and blood products)

normal IgM and IgG
Describe DiGeorge Syndrome
no 3rd/4th much develops -> Thymus and Parathyroid Aplasia

No T Cells, SCID-like
Hypocalcemia (Tetany)
Particular Facial Appearance
Chromosome 22q11.2 Deletion

Dx: Few to No T Cells, B Cells normal
-> DON'T IMMUNIZE w/ LIVE VIRUSES (Fatal)

-> Also suffer from Heart (set of fallot) and Kidney Problems
describe chronic mucocutaneous candidiasis
T cell disorder
recurrent candida infections
tx with ketoconazole
Describe Hyper IgM syndrome
Inability to switch from IgM to Other Classes

X-HIGM: T-Cell Defect. Increased Infection Risk.
-> CD40L on T Cell is Defective

Autosomal Rec: no CD40 on B cells

Dx: Reduced levels of IgG (100%)
Reduced levels of IgA (75%)
IgM may be normal or elevated

Tx: Abx and IVIG or SCIG
Describe IL-12 receptor deficiency
T cell problem
recurrent mycobacterial infections
low IFN gamma
describe SCID
ADA def (AR)
NK cells intact
B and T cell problem

train: severe recurrent infections (RSSV, VZV, HSV, measles, flu, PCP)
chronic diarrhea
FTT

no thymus
Describe Wiskott-Aldrich syndrome
X linked

WAITER
wiskott aldrich
immunodeficiency (B and T cell)
thrombocytopenic purpura
eczema (truncal)
recurrent pyogenic infections

T cells can't reorganize actin
no IgM against capsular PS of bacteria
increased IgA
what are the X linked immunodeficiency syndromes
WACH

WAS
agammaglobulinemia
chronic granulomatous disease
hyper IgM
Describe Ataxia-Telangiectasia:
"A"

def in "A"TM -> no repair DNA ds breaks
"A"taxia
Ig"A" def
spider "A"ngiomas over 5 yo
high "A"FP
high leukemia and lymphoma risk
describe CGD
X linked
def NADPH oxidase (no reactive oxygen species)

susceptible to catalase positive bugs

Dx: nitro blue tetrazolium test negative
do not oxidize dye to turn it blue

tx: ppx bacterium, IFN gamma
What are the catalase positive organisms?
PLACESS for your CATs
Pseudomonas, listeria, aspergillus, Candida, E. coli, S. aureus, Serratia
Describe Chediak-Higashi syndrome
defect in LYST gene (lysosome trafficking), microtubules dysfunction
eosinophilic peroxidase-positive giant granules in neutrophils and PLTs
pancytopenia

triad:
partial albinism (blue eyes or white hair)
recurrent skin and RT infections
neuro disorders (peripheral neuropathy, seizures)
describe job syndrome
def Th17 and PMN chemotaxis due to STAT3 mutation
decreased IFN gamma -> phagocytes

FATED:
Facies
staph Abscesses
Teeth retained, Two rows
IgE increased
Derm sx (eczema)
describe LAD type 1
type 2= rolling
type 3= activation
type 1= adhesion

absent of defective LFA-1 integrin (CD18) on phagocytes
cannot integrate into tissues
delayed separation of umbilical cord, absent pus formation, gingivostomatitis
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