Flashcards in Immuno Deck (176):
Loss smell, nasal itching and discharge, swollen and hyperemic nasal mucosa.
Tx with corticosteroid spray (fluticasone) +/- PO antihistamines
Laryngeal edema, abdo sxs (pain, D&V, constip, distension), ?swelling hands and feet.
Triggered by infections, stress, menstruation, ACEI
Ecchymoses and hyperpigmentation may occur in healing process
Biopsy for dx
Classic urticaria reaction
Which Ig is a dimer?
Which Ig is most abundant?
IL8, LTB4, C5a, bacterial products, kallikrein
Examples of Type II HSR
Type I DM
Examples Type III HSR
Oral polio (Sabin)
Inactivated bacterial preparation vaccine
Whole cell typhoid
Agent that produces predominantly Ab response through release IL-4 which primes naive B cells
Vaccination: active or passive immunity
Immune globulin: active or passive immunity
Innate immunity composed of?
Myeloid cells: granulocytes, macros, mast cells
On cells of innate immune system.
Recognize PAMPs, e.g. CD14 (on macros) is a TLR that recognizes LPS on gram neg bacteria
"On switch for acute inflamm response"
Which products of AA mediate vasodilation and increased vascular permeability?
PGI2, PGD2, PGE2
Mediate neutrophil chemotaxis
LTB4, IL8, C5a, bacterial products, kallikrein
Which AA products mediate vasoconstriction, bronchoconstriction, and increased vascular permeability?
LTC4, LTD4, LTE4
Activators or mast cells
Cross linking of IgE by antigen
Immediate response of mast cells
-increased vascular permeability at post-cap venule
Delayed response of mast cells
Production AA metabolites, esp LTs
Classical pathway complement
C1 bings IgG or IgM that is bound to an antigen
Alternative pathway complement
Microbial products directly activate
Mannose lectin binding pathway complement
MBL binds mannose on microorganisms
All complement pathways meet where
Production C3 convertase, C5 convertase
Complement proteins that trigger mast cell degranulation
Complement protein that acts as opsonin for phagocytosis
Inactive pro-inflamm protein produced by liver.
Activated on exposure to subendothelial or tissue collagen
Activates coag and fibrinolytic systems, complement, kinin system
IMPORTANT IN DIC!!!
Increased vascular permeability
Sensitize sensory nerve endings
Rubor and Calor
Due to vasodilation causing increased blood flow
HISTAMINE, PGs, bradykinin
Leakage fluid at post-cap venule into interstitial space
Histamine, tissue damage
Pyrogens cause release IL1, TNF which increase COX activity in perivascular cells of hypothalamus. Increased COX=increased PGE2 which increases temp set point
Steps of neutrophil arrival
6. Destruction phagocytosed material
Selectin speed bumps.
P selectin from Weibel Palade bodies, histamine mediated.
E selectin induced by TNF, IL1
Cellular adhesion molecules (CAMS) (on endothelium) and integrins (on neutrophils) bind
Leukocyte adhesion deficiency
AR defect in CD18 subunit of integrin
Thus no adhesion
Sxs/signs: delayed separation umbilical cord, neutrophilia, recurrent bacterial infections without pus
Chediak Higashi disease
Protein trafficking defect (microtubules)-phagosome can't bind with lysosome
Neutropenia (can't divide)
Giant granules by Golgi
Defective primary hemostasis
O2 dependent killing
Generates HOCl (O2 -> superoxide ->H2O2 ->HOCl
O2 independent killing
Via enzymes in leukocyte: lysozyme, major basic protein
NADPH oxidase defect
Infections and granulomas with catalase positive organisms
Nitro-blue tetrazolium test (NBT) remains colorless
Catalase positive organisms
MPO converts H2O2 to HOCl.
In theory similar to CGD but reality: only increased risk Candida
When in inflamm do macros peak
2-3 days after start inflamm
When in inflamm do neutrophils peak
24 hrs after start inflamm
How do macros get from blood into periphery
Same way neutrophils do (margination, rolling, adhesion, transmigration)
Method by which macrophages kill
O2 INdepedent, esp lysozyme
Outcomes acute inflamm
Resolution and healing (IL10, TGF-B)
Continued acute inflamm (macros call in more neuts via IL-8)
Chronic inflamm cells
Lymphos and plasma cels
Stimuli for chronic inflamm
Persistent infection (MCC)
Viruses, mycobacteria, parasites, fungi
T cell activation requirements
1. Binding antigen/MHC complex
2. Secondary signal
Types CD4+ cells
T cell growth factor
Express FasL which binds Fas on target cell
First Igs on B cell
Foreign material, e.g. leaking breast implant
Cat scratch (stellate shaped)
Developmental failure 3rd and 4th pharyngeal pouch
T cell deficiency, hypocalcemia, abnormalities great vessels, heart, and face
T cell deficiency symptoms
Viral and fungal infections
B cell deficiency symptoms
Bacterial, protozoal infections
3rd pharyngeal pouch
Inferior parathyroids, thymus
4th pharyngeal pouch
Defective cell-mediated and humoral immunity. All the infections, including opportunistic.
1. Cytokine receptor defects
2. Adenosine deaminase deficiency
3. MHC class II deficiency
Tx-sterile isolation, stem cell transplant
X linked agammaglobulinemia
Complete lack Igs due to disordered B cell maturation
Bruton tyrosine kinase (BTK) mutation
Infections with bacteria, enterovirus, Giardia
Avoid live vaccines
Common variable deficiency
Low Ig due to B cell or TH cell defects
(Exams: mutation MHC III)
Bacteria, enterovirus, Giardia infections
Increased risk AI disorders, lymphoma
Which two immunodeficiencies result in bacterial, enterovirus, and Giardia infections?
X linked (Bruton) agammaglobulinemia
Most common Ig deficiency
Mucosal infections, esp viral.
NB: celiacs tend to have this a lot
Mutation in CD40L or CD40R...problem with class switching-no 2nd signal.
Decreased IgA, IgG, IgE causes recurrent infections, esp mucosal
Wiskott Aldrich syndrome
Defect in WASP (Wiskott-Aldrich Syndrome Protein)
Thromboytopenia, eczema, recurrent infections (humoral and cell mediated)
C1 inhibitor deficiency
Hereditary angioedema (esp periorbital edema).
Excess activation complement (therefore vasodilation and increased vascular permeability)
Primary mech for autoimmunity
Loss of self tolerance: many self-reactive lymphos regularly generated but undergo TOLERANCE (central and peripheral). E.g. negative selection in thymus causes self-reactive lymphos to undergo apoptosis
AI polyendocrine syndrome (APECED): hypoparathyroidism, adrenal failure gonadal failure, alopecia, vitiligo, candida.
Failure of negative selection: no AIRE to express "self".
AIRE is also called "autoimmune regulator"
Central tolerance in bone marrow
Negative selection: if bind "self" too strongly, either undergo receptor editing or apoptosis
In blood. Anergy (no second signal) or apoptosis via Fas death receptor
Autoimmune Lymphoproliferative Syndrome
Mutation in Fas apoptotic pathway
Cytopenias, LAD, HSM (LAD and HSM due to proliferation lymphos....can lead to lymphoma)
Immune dysfn Polyendocrinopathy Enteropathy X linked
Associated with autoimmunity, e.g. MS, Type I diabetes
Environmental triggers for autoimmunity
Infection (self reactive activated)
Molecular mimicry (antigen resembles self-antigen)
Reason for female bias in autoimmunity
Esrogen decreases tolerance, therefore more self-reactive lymphocytes
Type III HSR
Decreased levels CH50, C3, C4
ANA, anti-dsDNA, anti-Sm
Drug induced lupus
Hydralazine, procainamide, isoniazid
CNS, renal involvement rare
Abs + hypercoagulable state
Lifeling anticoagulation--arterial and venous thromboses
Can occur with SLE but more commonly is primary disorder
AI destruction lacrimal, slaivary glands
Type IV HSR
Anti-SSA, SSB, ANA, RF
Increased risk B cell lymphoma (U/L enlargement parotid)
Fibroblast activation causing collagen deposition. Massive amounts fibrosis
Limited type (CREST) and diffuse type
CREST syndrome antibody
Diffuse systemic sclerosis Ab
Mixed connective tissue disease--Antibodies
Anti U1 RNP antibodies
Continuously cycle to regenerate tissue.
Small and large bowel
Quiescent but can re-enter cell cycle.
Heal by repair; no regenerative capacity
Initial phase repair
Formation of granulation tissue
Granulation tissue mediators
Fibroblasts, capillaries, myofibroblasts
Result of repair
Type III collagen replaced by Type I
Causes delayed wound healing
Vit C, Cu, Zn deficiency
Foreign body/continued inflamm, diabetes, ischemia, malnutrition
Excess production of Type I collagen
Excess production scar tissue out of proportion to wound
Type III collagen
Bare lymphocyte syndrome
Deficiency in MHC I or MCH II
Low IgA, IgG
Associated with sclerosing cholangitis (hepatomegaly, jaundice)
Can't form granulomas
And salmonella, for some reason
Monoclonal antibody (mAb) against CD3.
Treats rejection episodes in transplant pts, by clearing T cells from circulation.
Use when acute steroid-resistant rejection of heart, liver, kidney transplants
Inhibits calcineurin (therefore T cells)
SE: gum hypertrophy
Metabolized to 6MP. Prevents DNA synthesis, esp lymphocytes
Inhibits T cell prolif by binding FK-binding protein 1A (FKBP-1a)
Anti-glutamic acid decarboxylase
Against Type IV collagen.
Pulm, renal sxs (bleeding)
Myelin basic protein, proteolipid protein
Implicated in MS
Associated with oral allergy syndrome
SLE treatment when steroids fail
CTLA4-Ig fusion protein
Used in RA
Inhibits IMP DH (guanine synthesis).
Transplant alternative to cyclophosphamide
Also used in AI diseases, vasculitides
used in osteoporosis
mAb against IL-2alpha
mAb against CD11a
mAb to p40 subunit IL-12, IL-23.
Tests for sarcoidosis.
Not used in UK due to infection risk (involves placing sample of sarcoid pt's spleen intradermally into pt and biopsying in 4-6 weeks to see if caseating granulomas)
Latex fixation test
Used for rheumatoid factor
Acute or chronic inflamm
Graves, MG, SLE
Serum tryptase levels
Useful in diagnosing anaphylaxis
Minutes to hours.
Type IV HSR
Binds CXCR4 on surface CD4+ cell to gain entry
Initial step in HIV infection
Penetrates CD4+ wall
Tx for myasthenic crisis
mAb against alpha4 integrin (T cell migration)
mAb against IL-6
Fully humanized mAb to TNF-a
Speckled immunofluroescence pattern
Nucleolar immunofluorescence pattern
anti-RNA polym (systemic sclerosis)
Peripheral immunofluorescence pattern
anti-1A-2 and anti-phogrin antibodies
Against tyrosine phosphatase
Initially eye stuff (ptosis, difficulties with eye movement, pigmentation retina), then prox muscle weakness, cardiac conduction defects, hearing loss, cerebellar ataxia
Hypoparathyroidism, primary gonadal failure, DM, hypopituitarism