Immunology Flashcards
Muromonab-CD3 (OKT3)
Target: CD3
Use: Prevent acute rejection
Digoxin immune Fab
Target: Digoxin
Use: Digoxin toxicity
Infliximab
Target: TNF-alpha
Use: Crohn’s, RA, psoriatic arthritis, ankylosing spondylitis
Adalimumab
Target: TNF-alpha
Use: Crohn’s, RA, psoriatic arthritis
Abciximab
Target: Gp2b/3a
Use: PCI; unstable angina
Trastuzumab (Herceptin)
Target: Her2
Use: Her2 overexpressing BRCA
Rituximab
Target: CD20
Use: B-cell non-Hodgkins lymphoma
Omalizumab
Target: IgE
Uses: Additional line treatment for severe asthma
Anti-nuclear Ab
Non-specific AI, SLE
Anti-dsDNA Ab
SLE
Anti-Smith Ab
SLE
Anti-histone Ab
Drug-induced SLE
Anti-CCP Ab
RA
Anti-centromere Ab
CREST
Anti-Scl-70 Ab
Scleroderma
Anti-DNA topoisomerase I Ab
Scleroderma
Anti-mitochondrial Ab
PBC
Anti-TTG
Celiac disease
Anti-GBM
Goodpasture’s
Anti-desmoglein Ab
Pemphigus vulgaris
Anti-microsomal Ab
Hashimoto’s
Anti-thyroglobulin Ab
Hashimoto’s
Anti-Jo-1 Ab, anti-SRP Ab
Polymyositis, dermatomyositis
Anti-SSA Ab (anti-Ro)
Sjogren’s
Anti-SSB Ab (anti-La)
Sjogren’s
Anti-smooth muscle Ab
AI hepatitis
Anti-glutamate decarboxylase Ab
DM1
c-ANCA (PR-3 ANCA)
Wegener’s (GWP)
p-ANCA (MPO-ANCA)
CS, Microscopic polyangiitis
HLA A3
Hemochromatosis
HLA B27
Psoriasis, AS, IBD, Reiter’s
HLA DQ2/DQ8
Celiac disease
HLA DR2
MS, SLE, Goodpasture’s, Hay Fever
HLA DR3
DM1, Grave’s
HLA DR4
DM1, RA
HLA DR5
Pernicious anemia, Hashimoto’s
Describe the different regions of a lymph node
Cortex = follicle (primary/secondary B cells)
Paracortex = T cells + HEV
Medullary cords = plasma cells + lymphocytes
Medullary sinuses = macrophages + reticular
Where in the lymph node are the high endothelial venules?
Post-capillary venules in the paracortex
What is the difference between a primary and secondary LN follicle?
Primary: inactive (dormant)
Secondary: Pale, germinal centers (active)
What is the difference between medullary cords and sinuses in a lymph node?
Cords: Plasma cells
Sinuses: Macrophages + reticular cells
Lymph drainage: upper limb + lateral breast
Axillary nodes
Lymph drainage: stomach
Celiac nodes
Lymph drainage: duodenum and jejunum
SM nodes
Lymph drainage: sigmoid colon
Colic / IM nodes
Lymph drainage: rectum (AP)
Internal iliac
Lymph drainage: anal canal (BP)
Superficial inguinal
Lymph drainage: scrotum
Superficial inguinal
Lymph drainage: superficial thigh
Superficial inguinal
Lymph drainage: testes
Para-aortic
Lymph drainage: lateral dorsum of foot
Popliteal
In what zone of the spleen are APC’s found?
Marginal zone (between red/white pulp)
What are the 2 major divisions of the spleen
Red pulp
White pulp w/ PALS & Follicles
What is the role of splenic macrophages?
Removal of encapsulated bacteria (i.e. SHiN SKiS)
Howell-Jolly bodies
Post-splenectomy
The thymus is derived from what branchial pouch?
3rd
Lymphocytes in the thymus are derived from what cell line?
Mesenchymal
Positive vs. Negative selection in the thymus
Positive: Cortex
Negative: Medulla
Where are Hassall’s corpuscles found?
Thymic medulla
NK cells are of myeloid or lymphoid origin
Lymphoid
NK cells use _________________ & __________________ to induce necrosis/apoptosis of virally infected and tumor cells.
Perforin & Granzyme
* Apoptosis
IL-2, IL-12, IFN-alpha & IFN-beta enhance the activity of…
NK cells
NK cells’ activity is enhanced by which cytokines?
IL-2, IL-12, IFN-alpha & IFN-beta
Which MHC pairs with beta-2 microglobulin?
MHC 1
Expressed on all nucleated cells: MHC1 or MHC2?
MHC-1
T/F MHC-1 expressed on RBC
False! No nuclei
MHC1 or MHC2: Antigen is loaded following release of invariant chain in an acidified endosome.
MHC2
HLA-A, B, C vs. HLA-DP, DQ, DR
Which is MHC-1 vs. 2?
ABC = MHC1
DP, DQ, DR = MHC2
In MHC1, Ag is loaded in what organelle?
RER
Cytotoxic hypersensitivity: T2 or T3 HSR?
T2
Hypersensitivity: IgM or IgG
IgG
Which Ig neutralizes virus: IgM or IgG?
IgG
Th1 vs. Th2 helper T cells: Il-12 vs. IL-4
Th1: Il-12
Th2: Il-4
Which are the only Ag presenting cells that have the ability to activate naive T cells?
Dendritic cells
The professional Ag presenting cells
- Dendritic cells
- B cells
- Macrophages
Co-stimulatory signals for T-cell vs. B-cell activation
T-cell: B7/CD28
B-cell: CD40L/CD40
Th1 cytokines are stimulated by… & inhibited by…
What do they secrete?
IL-12
Inhibited: IL-4, 10
Secrete: IFN-gamma
Th2 cytokines are stimulated by… & inhibited by…
IL-4
Inhibited: IFN-gamma
Secrete IL-4, 5, 10, 13
Activated lymphocytes release which cytokine?
IFN-gamma
Activated macrophages release which cytokines?
IL-1, TNF
Cytotoxic T cells release what 3 substances to induce apoptosis?
- Perforin
- Granzyme: serine protease / induce apoptosis
- Granulysin: antimicrobicidal / apoptosis
Anti-inflammatory cytokines, such as, _____ & _____ are released by activated T-regs.
IL-10 & TGF-beta
T-regs help maintain specific immune tolerance by suppressing CD4 & CD8 T-cell effector functions. They express which cell surface receptors?
CD3, 4, 25 (alpha-chain of IL-2 R)
CD25
Expressed on cell surface of T-regs
T/F In opsonization, Ab promotes phagocytosis
T
Antibody idiotype vs. isotype
Idiotype: Ag diversity
Isotype: IgG, IgM, etc.
Which chain contributes to both Fab & Fc component of Ab: heavy or light chain?
Heavy chain (Light chain only contributes Fab)
Complement and Macrophages bind to Fab or Fc portion of Ab?
Fc
Complement: CH2
Macrophage: CH2 & CH3
Mature lymphocytes express … on their surfaces
IgM & IgD
Mature lymphocytes may differentiate by isotype switching into plasma cells that secrete IgE, IgA, IgG. What interaction mediates this?
CD40/CD40L
Somatic hypermutation
Making the Ab’s even more specific for the Ag
Who crosses placenta: IgG or IgM
IgG
B cells have Ag receptor for IgG or IgM
Both!
Most abundant Ig
IgG
Least abundant Ig
IgE
Ig that is a monomer in circulation, but dimer when secreted
IgA
Ig that is pentameric when not bound to B cells
IgM
Ig that cross-links when bound to eosionphils
IgE
Ig part of colostrum
IgA
Role of tdt
Adds nucelotides for random recombination of VJ, VDJ chains during Ab maturation
Thymus independent Ag vs. Thymus dependent Ag
Independent: Ag lack peptide component; cannot be presented by MHC to T cells (i.e. LPS from cell envelope of GN bacteria and polysaccharide capsular Ag). No immunologic memory
Dependent: Protein component (i.e. diptheria vaccine / class switching occurs)
MAC of complement defends against G+ or G- bacteria
Gram negative
What activates classical complement pathway?
IgM or IgG
What activates alternative complement pathwat?
Microbe surface molecules
What activates lectin complement pathway?
Mannose or other sugar on microbe surface
The two primary opsonins.
C3b & IgG
Role of C3b
Opsonization
Role of C3a and C5a
Anaphylataxis
Which complement component is an anaphylataxin and promotes neutrophil chemotaxis?
C5a
What is the role of C5b-9?
Cytolysis by MAC
Two inhibitors of complement activation
- DAF (CD55)
2. C1 esterase inhibitor
C3 convertase: Classical pathway vs. Alternative pathway
Classical: C4b2a
Alternative: C3bBb
C5 convertase: Classical pathway vs. Alternative pathway
Classical: C4b2a3b
Alternative: C3bBb3b
ACE inhibitors are contraindicated in what disorder of complemenet?
Hereditary angioedema (C1 esterase inhibitor)
C3 deficiency results in…
Severe, recurrent pyogenic sinus and RT infections; increased susceptibility to type 3 HSR
C5-C9 deficiency results in recurrent…
Neisseria bacteremia
DAF (GPI enzyme) deficiency results in…
Complement-mediated lysis of RBC’s and PNH
What cytokines are secreted by macrophages? What are their roles?
IL-1 IL-6 IL-8 IL-12 TNF-alpha
What cytokines are secreted by all T cells? What are their roles?
IL-2
IL-3
What cytokines are secreted by Th1 cells? What are their roles?
IFN-gamma:
What cytokines are secreted by Th2 cells? What are their roles?
IL-4:
IL-5:
IL-10:
IL-13:
What is the mechanism of IFN?
Proteins that place uninfected cells in an antiviral state; unduce the production of ribonucease that inhibits viral protein synthesis by degrading viral mRNA, but no host mRNA.
Alpha, Beta: inhibit viral protein synthesis
Gamma: Increase MHC 1 & 2 expression
Activates NK cells
All cells except for mature _______ have MHC 1.
RBC
Major chemotactic factor for neutrophils
IL-8 (and C5a)
T cell cell surface proteins
TCR
CD3 (associated with TCR for signal transduction)
CD28 (binds B7 on APC)
B cell receptor for EBV
CD21
B cell surface markers
CD19, 20, 21, 40
MHC2, B7
Macrophage cell surface markers
CD14, CD40
MHC2, B7
Fc, C3b receptors
NK cell surface markers
CD16 (binds Fc of IgG), CD56
What are superantigens?
S. aureus, S. pyogenes; cross link beta-region of T cell receptor to the MHC Class 2 on APC’s. Can activate any T cell leading to massive cytokine storm
Endotoxins/LPS directly stimulate macrophages by binding to
CD14; Th1 cells are not involved
Several examples of Ag variation
Bacteria:
Salmonella: 2 flagellar variants
B. burgdorferi: Relapsing fever
N. gonorrohea: Pilus protein
Virus:
Influenza shift/drift
Parasite:
Trypanosomes - programmed rearrangement
Infuenza major shift
DNA rearrangement and RNA reassortment
Difference between antigenic drift and shift
Drift: minor over time
Shift: major over short period of time
Role of IL1-5
Hot T-Bone stEAk
IL-1: Fever IL-2: T cell IL-3: BM IL-4: IgE IL-5: IgA
IL-1
An endogenous pyrogen; causes fever and acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit WBC’s
An endogenous pyrogen; causes fever and acute inflammation. Activates endothelium to express adhesion molecules; induces chemokine secretion to recruit WBC’s
IL-1
Il-6
Endogenous pyorgen. Secreted by macrophages, Th2. Causes fever and stimulates production of acute phase proteins.
Endogenous pyorgen. Secreted by macrophages, Th2. Causes fever and stimulates production of acute phase proteins.
Il-6
IL-8
Major chemotactic factor for neutrophils.
IL-12
Induces differentiation into Th1 cells, activates NK cells.
Induces differentiation into Th1 cells, activates NK cells.
IL-12
TNF-alpha
Mediates septic shock; activates endothelium. Causes leukocyte recruitment, vascular leak
Mediates septic shock; activates endothelium. Causes leukocyte recruitment, vascular leak
TNF-alpha
Stimulates growth of helper, cytotoxic and regulatory T cells
IL-2
Cytokine that functions like GM-CSF
IL-3
This cytokine activates macrophages and Th1 cells; suppresses Th2 cells. Has antiviral and antitumor properties.
IFN-gamma
This cytokine induces differentiation into Th2 cells. Promotes growth of B cells and class switching of IgE & IgG.
IL-4
This cytokine enhances class switching to IgA. It stimulates the growth and differentiation of eosinophils
IL-5
________ has a similar action to IL-10 because it is involved in inhibiting inflammation.
TGF-beta
Modulates inflammatory response. Inhibits Th1 and T cells. Also secreted by Tregs.
IL-10
Passive immunity examples
To Be Healed Rapidly
- Tetanus, Botox, HBV, Rabies
This type of immunity involves receiving pre-formed Ab. Rapid onset of action; short life-span of Ab (3 weeks). Examples include IgA in breast milk, antitoxin, humanized mAb
Passive immunity
This type of immunity involves exposure to foreign Ag. It is slow and long lasting.
Active immunity
Live attenuated vaccines induce …. response
Cellular
Inactivated, or killed vaccines, induce … response
Humoral
Booster shots are required for live or killed vaccines?
Killed (aka inactivated)
Examples of vaccines inducing cellular response
- Live attenuated
MMR, Sabin-oral, VZV, Yellow fever
Examples of vaccines inducing humoral response
- Killed, inactivated
Cholera, HAV, Salk polio, rabies
3 mechanisms of cytotoxic hypersensitivity
- Opsonization
- Complement mediated
- ADCC
Test for type 2 hypersensitivity reaction
Coombs
Serum sickness & Arthus reaction are Type 2 or Type 3 HSR?
Type 3
Most serum sickness is now caused by ________ acting as ___________. P/W fever, urticaria, arthralgia, proteinuria, LAD 5-10 days 2/2 Ag exposure
Drugs; haptens.
Local, subacute T3 hypersensitivity reaction. Intradermal injection of Ag induces Ab, which form complexes in the skin
Arthus reaction
Any Ab involved in T4 HSR?
No
Contact dermatitis is what type of HSR reaction?
Type 4
Type of HSR: Anaphylaxis
1
Type of HSR: Allergic and atopic disorders
1
Type of HSR: AIHA
2
Type of HSR: Pernicious anemia
2
Type of HSR: ITP
2
Type of HSR: Erythroblastialis fetalis
2
Type of HSR: Acute hemolytic transfusion reaction
2
Type of HSR: Rheumatic fever
2
Type of HSR: Goodpasture’s syndrome
2
Type of HSR: Bullous pemphigold and pemphigus vulgaris
2
Type of HSR: SLE
3
Type of HSR: PAN
3
Type of HSR: PSGN
3
Type of HSR: Serum sickness
3
Type of HSR: Swelling/inflammation 2/2 tetanus rxn
3
Type of HSR: MS
4
Type of HSR: GBS
4
Type of HSR: GVHD
4
Type of HSR: PPD test
4
Type of HSR: Contact dermatitis, i.e. poison ivy, nickel allergy
4
Type 1 HSR against plasma proteins in transfused blood. What to treat with?
Allergic reaction; anti-histamine
Febrile non-hemolytic transfusion reaction
T2 HSR against donor HLA Ag on leukocytes
Acute hemolytic transfusion reaction
T2 HSR against ABO [IV or EV hemolysis]
Anti-glutamate DC Ab
DM1
Recombinant IL-2 is called ____________-
Can be used to treat….
- Aldesleukin
RCC, Metastatic melanoma
Which therapeutic Ab can be used to treat severe asthma?
Omalizumab (IgE)
IL-2 R antagonist
Basiliximab, Daclizumab
Recurrent bacterial infections after 6 months 2/2 opsoinization defect.
XLR/Bruton’s agammaglobulinemia
* Defect in BTK kinase (tyrosine kinase / no B cell maturation)
Most common primary immunodeficiency
Selective IgA deficiency
What immunodeficiency p/w false positive beta-HCG due to presence of heterophile Ab
IgA deficiency
Defect in B-cell maturation; acquired in 20-30s. Increased risk of AI disease, lymphoma, sinopulmonary infections.
CVID
22q11 deletion
DiGeorge; failure of 3rd and 4th pharyngeal pouches
IL-12 deficiency p/w
Disseminated mycobacterial infections; decreased IFN-gamma
Hyper-IgE syndrome also called … p/w
Job syndrome; Coarse facies, cold staph abscesses, retained primary teeth, increased IgE, eczema
Recurrent candida infections
Chronic mucocutaneous candidiasis
Several types of this disorder that p/w FTT, chronic diarrhea, thrush and pan-infections. Absence of thymic shadow, germinal centers and B cells
SCID
- ADA deficiency
- IL2 receptor deficiency
Defects in ATM gene, which codes for DNA repair enzymes. Serum marker?
Ataxia-telangiectasia
AFP, low IgA
Defective CD40L on helper T cells
Hyper IgM syndrome
T cells unable to reorganize actin cytoskeleton in this disorder. What is the inheritance?
Wiskott-Aldrich Syndrome (XLR)
* TBOpenia, infections, eczema [decreased IgM]
Defect in Cd18 (LFA-1) integrin on phagocytes
LAD Type 1
Recurrent bacterial infections, lack of pus, delayed separation of umbilical cord
LAD Type 1
AR defect in lysosomal trafficking regulator (LYST); aka microtubule dysfunction in phagosome-lysosome fusion
Chediak-Higashi Syndrome
Chediak-Higashi Syndrome p/w
Histology?
P/W: recurrent pyogenic infections, partial albinism and peripheral neuropathy; giant granules in PMN’s
Recurrent pyogenic infections, partial albinism and peripheral neuropathy; giant granules in PMN’s
Chediak-Higashi Syndrome
Absent didydrorhodamine flow cytometry
CGD (Nitroblue tetrazolium dye reduction test no longer preferred)
Patients with which disorder p/w increased frequency of catalase + infections, i.e. S. aureus, E. coli, Aspergillus
CGD (NADPH oxidase)
What is a syngeneic graft?
From identical twin or clone
What is the difference between an autograft and an allograft?
Auto: From self
Allo: From other
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
Acute graft rejection; cell-mediated 2/2 CTL reacting against foreign MHC. Reversible with IS
Maculopapular rash, jaundice, HSM, diarrhea
GVHD
No thymic shadow in…
DiGeorge & SCID
Treatment of Bruton’s X-linked agammaglobulinemia
IVIG
X-linked disorder of BTK kinase
XLA
Wiskott-Aldrich Syndrome has elevated levels of which Ig?
IgA
Cobalophilin is also referred to
R-binder
Anti-microsomal Ab are seen in…
Hashimoto’s thyroiditis
Symmetric priximal muscle weakness; characteristic heliotrope rash; elevated serum muscle enzymes; myopathic changes on EMG and muscle bx abnormalities
Polymyosititis, dermatomyositis
Anti-IgG Ab
RF/ Rheumatoid arthritis
NADPH oxidase deficiency results in…
CGD
T/F PNPP deficiency causes SCID with near normal levels of Ig
True
The most common paraneoplastic syndromes a/w thymoma
RBC aplasia, MG, hypogammaglobulinemia
Derivatives of neural crest cells
Adrenal medulla, Schwann cells, sensory and autonomic ganglia; melanocytes
Neuroectoderm gives rise to…
CNS, astrocytes, oligodendrocytes, pineal gland
T/F DPT vaccine is contraindicated in patients with a hx of seizure disorder
T
Eczema is a Type ___ HSR
Type 1
Anti-MPO Ab
P-ANCA (CA, Microscopic polyangiitis)
Anti-Proteinase 3 Ab
C-ANCA (Wegener’s)
CD59
MAC inhibitory factor (think PNH)
Genetic defect in ataxia telangiectasia? Associated with a deficiency of what Ig?
Defect in DNA repair enzymes; IgA
T/F Exposure to hydrocarbons in dry cleaning solvents has been associated with Goodpasture’s syndrome
T
Large lysosome vesicles in neutrophils are characteristic of
Chediak-Higashi disease
Low IgM with elevated IgE & IgE are characteristic of
Wiskott-Aldrich Syndrome
T/F In ITP, platelets can be larger than normal
True
Drepanocytes
Sickle cells
Pappenheimer bodies
Excess iron (siderosomes)
Mutation in fatty aldehyde DH gene
Sjogren-Larsson syndrome: a/w congenital ichthyosis and mental retardation/spastic paraplegia
A toxoid is a toxin that…
Has been modified to the extent that it is no longer toxic but still maintains some antigenic similarity; therefore toxoid cross-reacts with the toxin
What type of vaccine is diptheria vaccine?
Toxoid
T/F Rheumatic fever is an autoimmune disease.
True (T2 HSR)
T/F In DiGeorge’s syndrome, the patient’s BM contains a full assortment of immune system progenitors
True
