Immuno Flashcards
DiGeorge syndrome
cause, embryo, sx/signs
22q11.2 microdeletion
failure of NC cell migration to THIRD + FOURTH phar. pouch > failed PT and thymic development
HYPOCALCEMIA > tetany, carpopedal spasm, seizure
T cell deficiency > VIRAL/FUNGAL/PROTOZOAL infections
CONOTRUNCAL abn.(interrupted aortic arch / truncus arteriosus)
Chvostek (CN VII tap) and Trousseau (bp cuff) signs + less thymic shadow on CXR
IFN types, where they’re made + effects
Type I- alpha/beta; from virus infected cells; paracrine signal to other infected cells > increased RNAse L andprotein kinase R(inhibits eIF-2 + thus translation initiation) in presences ofdsRNA
Type II- gamma; from T/NK cells; stim Th1 diff, incr MHC-II expression, improves intracellular killing by macros
Immune cell receptors which can be blocked by new mAb drugs for cancer therapy
PD-1andCTLA-4
stimulation of these receptors lead to T-cell inactivation
What isChediak Higashi syndrome?
triad
AR disorder of lysosomal function
triad of…
NEURO ISSUES(nystagmus, periph/cranial neuropathy)
ALBINISM (partial oculocutaneous)
IMMUNODEFICIENCY(defect in neutro phago-lysosome fusion >giant lysosomal inclusionson LM of periph blood + recurrent pyogenic infections by Staph/Strep)
Hematological issues in SLE?
Mechanisms?
Can have RBC, PLT and WBC deficits
RBCs - T2 HS rxn with WARM IgG Abs against RBCs causes SPHEROCYTOSIS, positive direct Coombs and extravascular hemolysis
PLTs - same as in ITP (anti-plt Abs)
Leukopenia - Ab-mediate neutrophil destruction (rarer)
Leukocyte Adhesion Deficiency
inheritance? gene? s/s?
AR disorder of CD18 needed for INTEGRIN formation > leukocyte adhesion
- recurrent skin/mucosal infection - Staph, gram-neg rods, periodontal infections
- NO PUS - neutrophils cant extravasate
- Poor wound healing
- DELAYED UMBILICAL SEPARATION (>21 days)
labs show peripheral LEUKOCYTOSIS with NEUTROPHILIA
IL-12
produced by MACROPHAGES to stimulate Th1 differentiation
IL-4
produced by non-macrophage APCs to stimulate Th2 differentiation
Hereditary Angioedema
cause? mech of edema?
C1 inhibitor deficiency > uninhibited cleavage of C2/C4 by C1
also uninhibited conversion of KININOGEN to BRADYKININ > increased permeability + edema
serum levels of what are used to support clinical dx of anaphylaxis?
TRYPTASE, a relatively mast cell-specific enzyme
anaphylaxis tx (3 things, most important first)
IM epinephrine
airway management + volume resuscitation
supportive drugs - anti-HA and steroids
NK cells
surface molecules
how are they activated? (molecules, organs)
antigen specificity?
CD16 or CD56
activated by IFN-y or IL-12 (do NOT require thymus for activation, present in athymic pts; innate immunity)
NOT antigen specific
Graft Versus Host Disease
MCC?
other causes?
allogeneic bone marrow transplant
lymphocyte rich organ transplant (LIVER)
NON-IRRADIATED transfusions
Mechanism of GVHD
donor T cells migrate into tissues and recognize host MHC antigens as foreign + become sensitized
CD4 and CD8 cells destroy host cells
main organs affected in GVHD
SKIN - early sign is diffuse maculopapular rash (PALMS/SOLES) that may DESQUAMATE
GI tract - diarrhea, bleeding, pain
Liver - abnormal LFTs
what are is the preferred dx method for chronic granulomatous disease (CGD)?
(preferred over what?)
DHR FLOW CYTOMETRY - measures conversion of dihydrorhodamine (DHR) to rhodamine, a fluorescent green compound > low fluorescence = positive
(Nitroblue tetrazolium testing - add NBT to pt neutros > functioning neutros make ros that changes yellow NBT to dark blue formazan)
Organs most involved in CGD?
infection manifestations most common in CGD?
lungs, skin, nodes + liver
Pneumonia
Skin/organ abscesses
suppurative adenitis
osteomyelitis
all via CATALASE-POSITIVE organisms
2nd most common cause of SCID?
inheritance and cellular changes?
Adenosine Deaminase deficiency
AR inheritance
major decrease in T and B cells; variable immunoglobulin deficiency
IL-8 function
released by MACROPHAGES and ENDOTHELIUM in infections…
acts as a NEUTROPHIL CHEMOATTRACTANT and induces phagocytosis via neutrophils
C3a, 4a and 5a are all “anaphylatoxins” that trigger HA release > vasodilation + permeability…
what else do they do? (individually)
C3a - recruits + activates EOSINOPHILS + BASOPHILS
C5a - also recruits eos/basos, plus NEUTROPHILS + MONOCYTES
(C4a idk… wasnt mentioned)
IL-3 function
made by activated T cells
stimulates growth/diff of BM stem cells
LTC4 / D4 / E4 do what?
trigger vasoconstriction, permeability and BRONCHOCONSTRICTION
LTB4 (plus LT precursor 5-HETE) does what?
stimulates neutrophil migration
myeloperoxidase deficiency
common manifestations? differential for CGD? what can MPO defic neutrophils not produce?
often asymptomatic
CANDIDA infections are most common
diff dx - MPO defic pt has a NORMAL (“positive” - turns blue) NBT test, whereas CGD has a “negative” test that stays yellow
can’t produce “hydroxy-halide” (H-Cl-O, “bleach”)
cytokines released by virally infected cells that induce synthesis of antiviral proteins in nearby cells
interferon alpha and beta
limit viral spread by suppressing REPLICATION and ASSEMBLY
Selective IgA Deficiency
Epidemiology?
S/S + comorbidities (3)?
Labs (2)?
1 primary immunodeficiency
usually asymptomatic
- recurrent SINOPULMONARY + GI INFECTIONS
- AUTOIMMUNITY (Celiac, etc.)
- TRANSFUSION ANAPHYLAXIS - react against donor IgA
- Low/absent serum IgA
- Normal IgG + IgM
Receptor for IL-8
what is it? on what cell?
CXCR1/2
on neutrophils
(IL-8 is neutrophil chemoattractant “cleanup on aisle 8”)
What causes induration at the site of a bee sting after the development of urticaria?
MACROPHAGES are attracted to the area and produce IL-1, IL-6 and TNF-a
Chediak-Higashi
inheritance, gene + affected process
AR defect of LYST lysosomal trafficking regulator
microtubule dysfunction in phagolysosome fusion
Chediak-Higashi
sx mnemonic (5)
PLAIN
Progressive neurodegen Lymphohistiocytosis Albinism (partial oculocutaneous) Infections - recurrent pyogenic Neuropathy
Chediak Higashi
clinical findings (3)
GIANT GRANULES in plts/granulocytes
Pancytopenia
Mild coagulation abnormalities
Early Complement Deficiency (C1, C2 and C4 defic.) can predispose to what AI disease?
SLE
Where on immunoglobulins does complement bind?
on the HEAVY CHAIN just proximal (closer to Fc end) of the hinge region / disulfide bonds
On IgM / IgA what structure enables formation of pentamers / dimers?
Where does it bind?
J chain
binds in the FcR binding region
What is IPEX?
gene? inheritance?
Immune dysregulation Polyendocrinopathy Enteropathy X-linked syndrome
defic. of FOXP3
IPEX
presentation?
3 main issues (+examples)
diabetes in a male infant, plus…
- Enteropathy
- AI derma issues - nail dystrophy, dermatitis, etc.
- Other Endocrinopathies
What are the live, attenuated vaccines?
mnemonic
“Attention! Please Vaccinate Small, Beautiful Young Infants with MMR Regularly!”
- Adenovirus (actually non-attenuated, for military)
- Polio (sabin)
- Varicella
- Smallpox
- BCG
- Yellow fever
- Influenza (intranasal form)
- MMR
- Rotavirus
When can MMR and varicella vaccines be given to HIV pts?
if they do not have evidence of immunity to these microbes and…
CD4 of AT LEAST 200/mm3
Diff btwn immune responses evoked by live vs. killed vaccines
live - humoral and cellular
killed - mainly humoral
What are the killed/inactivated vaccines?
“RIP Always”
- Rabies
- Influenza (injection form)
- Polio (Salk)
- Hepatitis A
(SalK = Killed)
What are the subunit vaccines?
(a mnemonic for 3, plus two others)
pros + cons?
the SHiN organisms:
- S. pneumo
- H. flu
- Neisseria meningitidis
- HBsAg
- HPV 6, 11, 16, 18
Pro - fewer adverse rxns
Cons - more expensive + weaker immune responses
What are the 2 toxoid vaccines?
Clostridium tetani
C. diphtheriae
T2 HS rxns involved Abs binding cell surface antigens…
What are 4 examples of T2 HS rxns in which the Ab binding results in CELLULAR DESTRUCTION?
(via opsonization > phagocytosis, complement activation, or ADCC via NK cells)
- Autoimmune Hemolytic Anemia
- Immune thrombocytopenia (Gp IIb/IIIa)
- Transfusion reactions
- Hemolytic newborn diseases
What are 3 examples of T2 HS rxns in which the Ab binding results in INFLAMMATION via complement activation + Fc-receptor mediated inflammation?
(as opposed to total cellular destruction)
- Goodpasture syndrome
- Rheumatic fever (M protein cross reactivity)
- HYPERACUTE transplant rejection
What are 3 examples of when T2 HS rxns result in CELLULAR DYSFUNCTION?
- Myasthenia Gravis
- Graves
- Pemphigus vulgaris
T3 HS rxns are mediated by Ag-Ab-complement complexes…
what cell type then mediates most of the damage?
Neutrophils
attracted by complexes and release lysosomal enzymes
What are 3 examples of T3 HS rxns?
think systemic, vascular and renal
- SLE
- Polyarteritis nodosa
- PSGN
What is the “prototype” immune complex disease (ie, T3 HS rxn)?
How does it occur?
What triggers is it associated with (2 categories + examples)?
Serum Sickness
Abs to foreign proteins produced and ONE TO TWO WEEKS LATER, complexes form and DEPOSIT in tissues > complement activation, inflamm. + damage
- Drugs - act as haptens, ex: PENICILLINS
- Infections - ex: HEP B
1-2 weeks after Ag exposure…
what are the sx that occur in serum sickness (5)?
- Fever
- Urticaria
- Arthralgia
- Proteinuria
- LAP
What is a local, dermal form of T3 HS rxn?
What is required for it to occur?
what 2 things happen locally?
Arthus reaction
intradermal injection of Ag into a PRESENSITIZED (pt already has IgG against it) causes INTRADERMAL COMPLEX FORMATION
edema, necrosis + complement activation
what are the 2 mechs in T4 HS rxn?
Both involve T cells
- CD8 cytotoxicity
- CD4 release inflammatory cytokines
Is the only of the 3 HS rxns that does NOT involve antibodies!
What type of transplant issue is a T4 HS rxn?
Graft versus host disease
What are the 4 types of BLOOD TRANSFUSION REACTIONS in order of how early/late they would happen post transfusion?
- Allergic/Anaphylactic - from minutes to 3 hours
- Acute hemolytic - within 1 hour
- Febrile nonhemolytic - btwn 1-6 hours
- Acute Lung Injury - within 6 hours
WHAT ANTIGEN (general) in the transfused blood is bound by IgE in an ANAPHYLACTIC/ALLERGIC transfusion rxn?
What consequence does this have for transfusions in patients with a certain humoral immune deficiency?
Donor PLASMA PROTEINS (as opposed to cell surface antigens)
IgA deficient pts must receive IgA-FREE BLOOD PRODUCTS or they would react to the IgA
What is the mechanism for FEBRILE NONHEMOLYTIC transfusion reactions? (2 parts)
Within 1-6 hrs pt has fever, headache, chills + flushing via…
- T2 HS rxn of host Abs against donor HLA or WBC
- CYTOKINES that are created + accumulate in blood during storage
What are the 2 possible mechanisms in ACUTE HEMOLYTIC transfusion reactions?
How do symptoms differ depending on the mechanism?
Within 1 hour, pt will have fever, hypotension, tachypnea/-cardia with…
- INTRAVASCULAR lysis - via ABO incompatibility; also includes sx of FLANK PAIN and HEMOGLOBINURIA
- EXTRAVASCULAR lysis - via host Ab against donor rbc surface Ag; includes JAUNDICE
What is the mechanism of TRANSFUSION-RELATED ACUTE LUNG INJURY?
DONOR ANTIBODIES against RECIPIENT NEUTROs and PULMONARY ENDOTHELIUM
resp distress and non-CV pulmonary edema within 6 hrs
X-linked agammaglobulinemia
defect? chromosome?
general presentation?
an X-linked defect in BTK (Bruton tyrosine kinase)
no B-cell maturation (Bruton, B cells, Boys)
recurrent BACTERIAL and ENTEROVIRAL infections after 6 months when maternal IgG is gone
X-linked agammaglobulinemia
blood findings (2)? anatomical findings?
preventative tx contraindications?
Low Ig (all classes) No B cells
Small/no lymph nodes or tonsils
LIVE vaccines are CI
Common variable immunodef.
what is the general defect?
when does it present?
defect in B-CELL DIFFERENTIATION
presents AFTER 2 YEARS but may be delayed
Common variable immunodef.
Increases risk of what 4 things?
Blood findings?
(if you think of the defect in B-CELL differentiation, the TYPE of infections is hinted at, and the type of infection hints at another risk… and if you consider that it’s DIFFERENTIATION, a 3rd risk is hinted at)
- SINOPULMONARY infections
- Bronchiectasis
- Lymphoma
- Autoimmunity
decreased PLASMA CELLS and Ig
Deletion and developmental failure in DiGeorge
22q11 deletion
failed dev. of THIRD and FOURTH pharyngeal POUCH
(parathyroid and thymus affected)
3 main signs/sx in DiGeorge
think serum, immunity and CV
- hypocalcemia with TETANY
- VIRAL + FUNGAL infections - T-cell def.
- “conotruncal” issues such as FALLOT or TRUNCUS ARTERIOSUS
If other pharyngeal pouches are involved in DiGeorge, what MORPHOLOGICAL sx might you see?
if 1st/2nd phar. pouch involved…
hypertelorism - eyes far apart short palpebral fissures micrognathia - small jaw bifid uvula cleft palate
What immune deficiency is specifically a Th1 response deficiency?
Inheritance? Types of infections? Serum?
IL-12 receptor deficiency - with AR inheritance
severe FUNGAL and MYCOBACTERIAL infections that MAY PRESENT AFTER BCG vaccine
low IFN-y
What T-cell disorder presents with high IgE?
Inheritance, gene + defect?
“Autosomal Dominant Hyper-IgE Syndrome” or Job syndrome
deficient TH17 response due to STAT3 mutation causes…
IMPAIRED NEUTROPHIL RECRUITMENT
what are the features of Job syndrome / autosomal dominant hyper-IgE syndrome?
(mnemonic with 6 items)
Be FATED to do your Job
Bone - fractures via minor trauma
- Face - coarse features
- Abscesses - “cold” uninflamed Staph (no neutros)
- Teeth - primary teeth retained
- Eosinophils and IgE - elevated
- Derma - eczema etc.
Aside from HIV and immunosuppressant tx…
what immune deficiency can cause Candida infections of the skin and mucosa?
what is the congenital defect? diagnostic tests (2)?
“Chronic Mucocutaneous Candidiasis”
a T-cell defect due to IL-17 or IL-17R defect
NONINVASIVE Candida infections of skin/mucosa
- IN VITRO T cell response to Candida is low
- CANDIDA SKIN TEST is negative (similar to PPD)
SCID
2 common types/defects and their inheritance
- IL-2R gamma chain defect - most common, XR
- Adenosine deaminase defic. - AR
(Guys have Gamma chain issue
Adenosine deaminase is Autosomal)
SCID presentation
3 items (systemic, GI and oral)
- Failure to thrive
- Chronic diarrhea
- Thrush
recurrent infections with EVERYTHING - fungi, protozoa, viruses, bacteria
SCID treatment
curative (1) vs. preventative (2)
contraindications
BM transplant is curative (no rejection!)
Abx prophylaxis + IVIG
LIVE vaccines are CI
Lab (2), imaging (1) and biopsy (1) findings in SCID
- Low TCR “excision circles” - small DNA circles in t cells as they pass thru thymus + rearrange DNA
- No T cells on FCT
- Absent thymic shadow
- Nodes have NO GERMINAL CENTERS
What is the immune deficiency in Ataxia Telangiectasia?
the name, gene, SERUM FINDING, immune def. and other symptoms all follow a memory hook!
Autosomal recessive ATM gene issue > Ataxia, spider Angiomas and…
IgA deficiency (also IgG and IgE, apparently…)
high AFP in serum
remember the As
what cancers are Ataxia Telangiectasia pts at increased risk of?
Leukemias and lymphomas
Hyper-IgM syndrome
what is the defect? inheritance?
defective CD40L on Th cells causes CLASS SWITCHING issues
XR
Hyper-IgM syndrome
presentation?
3 specific organisms
SEVERE PYOGENIC infections EARLY in life
- Pneumocystis jirovecii
- Cryptosporidium parvum
- CMV
NO GERMINAL CENTERS; IgM is high, all other Igs low
Which immune deficiency is specifically an ANTIGEN PRESENTATION defect?
Specific defect + inheritance?
Wiskott-Aldrich syndrome
WASp gene defect via XR
WBCs and PLTs can’t detect actin cytoskeleton > Ag presentation issues
Wiskott-Aldrich syndrome
mnemonic for 3 issues
increased risks?
WATER = Wiskott-Aldrich +
- Thrombocytopenia - with bloody diarrhea!
- Eczema
- Recurrent pyogenic infection
incr. risk of AI disease and cancer
Wiskott-Aldrich
Ig abnormalities (some high, some low)? cell counts?
low-to-normal IgG/M
HIGH IgE and IgA
fewer + smaller PLTs
Leukocyte Adhesion Deficiency (type 1)
defect + inheritance?
LFA-1 integrin (CD18) on phagocytes
impairs migration + chemotaxis
AR inheritance
Leukocyte Adhesion Deficiency
presentation (infection type + special characteristic of infection; special birth-related sign)
Recurrent SKIN + MUCOSA BACTERIAL infections with NO PUS!
Impaired wound healing
LATE CORD SEPARATION (>30 days)
high neutros in blood, low neutros at infection sites
How does IkB regulate NF-kB?
binds it and prevents its translocation to nucleus
then IKK (IkB kinase) will P-ate IkB when an extracellular signal (eg, IL-1 binding IL-1R) activates it…. IkB releases NF-kB and it can translocate to nucleus
T-cells within thymic cortex express…
2 things (note: not asking about CD molecules)
Class I MHC
Rearranged D and J segments of the TCR beta chain
Unique AA in bacterial peptides that can act as a PAMP?
how?
N-formyl-methionine
activates WBCs by binding their “formyl peptide receptors” which are GPCRs
an infant with SCID has severe anemia
what transfusion product should he be given?
IRRADIATED PACKED RBCs
not whole blood!
2 types of pneumococcal vaccines
PPSV23 - polysaccharide 23-valent
PCV13 - conjugate 13-valent with diphth toxoid
Who gets the polysacch-23 vs. the conjugate-13 valent pneumococcal vaccines?
polysacch-23 is given to ADULTS > 65 and anyone 2-64 with DM, or chronic LUNG/CV disease
conjugate-13 is given to KIDS < 2, anyone who is IMMUNOCOMPROMISED and ADULTS > 65
Functional differences between…
23-valent polysaccharide
vs.
13-valent conjugate pneumococcal vaccines
Polysacch - wider serotype range; titers decline over 5 years; not immunogenic in kids <2 due to immature humoral immunity; overall MODERATE AMOUNT of INTERMEDIATE-AFFINITY Abs
Conjugate - diphtheria toxoid > T AND B-CELL recruitment > higher levels of higher affinity Abs with LESS MUCOSAL CARRIAGE (herd immunity)
