Usmle Immuno-3 Flashcards
How can you tell Brutons agammaglobulinemia apart from other humoral defect conditions?
It is the only one that does not give you ANY B-cells…they are all stuck in the Pre-B-cell stage
What is the usual defect leading to MHC class I deficiency?
Failure of TAP molecules to transport peptides to the ER for attachment to an MHC I molecule
What are the clinical manifestations of an MHC class I defect?
No CD 8+ T-cells but normal Cd4+ cells.
Recurrent viral infections
Normal delayed type hypersensitivity
What are the clinical manifestations of an MHC II deficiency? (AKA Bare lymphocyte deficiency)
Deficient CD4+ T-cells looking like an AIDS patient.
No GVHD
No Delayed type hypersensitivity.
Decreased Igs
What is the main receptor that HIV binds to on cells, and what are two co-receptors?
CD4 is the main receptor
CCR5 on macrophages
CXCR4 on T-cells
What is the gene from HIV that is responsible for virulence?
nef Gene… down regulates class I MHC expression
In what cells does HIV replicate?
Lymphocytes and macrophages
Macrophages are the reservoir for the virus
What does the TAT gene product of HIV do?
Inhibits cytokine synthesis in both infected and uninfected cells
What is the function of the gp120 glycoprotein on HIV?
It binds the CD4 receptor and the coreceptors…
What type of individual may be exposed to HIV over and over and never get infected?
One who is homozygous for a mutated CCR5 receptor….Heterozygotes CAN get it but just takes many many exposures and there is a much slower clinical progression
The presence of what protein on CD4+ T cells might facilitate ADCC via NK cells in HIV patients?
p24, one of the first HIV proteins to peak
What is the major mechanism of damage that occurs during a type I hypersensitivity reaction?
IgE present on mast cells or basophils is crosslinked by an antigen and initiates degranulation of vasoactive mediators, esp histamine….Leads to cellular swelling and itching
Which type of hypersensitivities are antibody mediated?
I, II and III
What are the two tests used to check for type I hypersensitivities?
The scratch test
or
The immunosorbant assay
What cell type is responsible for damage in type IV hypersensitivities and what are the two ways damage occurs?
Cell type is Th1 cells leading to a delayed type hypersensitivity.
Macrophages can get activated by then and release inflammatory cytokines OR
Cytotoxic killer cells can get activated an carry out cellular damage.
What are the 4 T’s of type IV hypersensitivity?
T-cells
TB
Touch (contact dermatitis)
Transplant rejections
What is the acronym ACID supposed to help you remember?
Hypersensitivities! I: Allergic and Atopic II: Cytotoxic antibody mediated III: Immune complex IV: Delayed celllular type
Why are type II hypersensitivities considered Antibody Mediated?
Because IgG or IgM binds to fixed antigen on enemy cell and causes lysis or phagocytosis…
What are the three mechanisms via which cellular damage occurs in a type II hypersensitivity?
Opsonization of cells or complement activation
Abs recruit neutrophils and macrophages that cause damage
The Abs can bind normal cellular receptors and interfere with functioning.
What are the tests used to check for type II hypersensitivity reactions?
Coombs, either direct or indirect.
What besides histamine is released from granules during a type I hypersensitivity?
Eosinophil chemotactic factor, which draws eosinophils that causes tissue damage via release of Major basic protein
and
Heparin, which acts as anticoagulant
What are the two major changes brought about by histamine?
Increased SM contraction (bronchoconstriction)
and
Increased vascular permeability
What are the main secondary mediators of a type I hypersensitivity?
PGs and LTs made after arachadonic acid is cleaved from damaged cellular membranes (damaged by histamines effects..) These cause much more prolonged damage than histamine via the same mechanisms
What type of hypersensitivity is occurring in a blood transfusion mismatch?
Type II….antibodies bind the ABO blood groups
What is important to remember about Erythroblastosis Fetalis?
It occurs in an Rh - mother with an Rh + fetus… The first pregnancy sensitizes BUT MISCARRIAGES COUNT so if the mom has had a few abortions her first viable child can still get hemolytic disease of the newborn
What type of antibodies are seen in RA?
Rheumatoid factor, which is IgM against the Fc portion of IgG. Anti IgG IgM
What is specifically targeted by T-cells in MS (type 4 hypersensitivity?)
Myelin Basic Protein… To differentiate this from MG, MG is a WEAKNESS…MS is a spastic paralysis.
What is the specific target of T-cells in Guillain Barre, type 4 hypersensitivity?
Peripheral nerve myelin or ganglionsides (think Campylobacter)
What is the clinical use of Abciximab?
Anti-platelet…antagonist of IIb/IIIa receptor
What is the clinical use of Infliximab?
RA and Crohn’s disease…Binds TNF
What is the clinical use of Trastuzumab?
Breast cancer…Antagonist to ERB-B2
What is the clinical use of Dacliximab?
Kidney transplants…Blocks IL-2 receptors
What is the clinical use of Muronomab?
Kidney Transplants–blocks CD3
What is the clinical use of Palivizumab?
RSV—blocks the fusion protein
What is the clinical use of Rituximab?
Non-Hodgekin Lymphoma…Binds CD20 on B cells
Who are 4 individuals who will NOT cause Gv Host disease if their BM is donated?
DiGeorges
HIV
SCID
Class II MHC deficiency…none of these have CD4+ T cells
What is the Microcytotoxicity test used for?
To test MHC I compatibility between donor and recipient.. .. .. Uses complement to determine the MHC haplotype. Mix donor cells with antibodies to a specific HLA A B or C subtypes, then spin them down. If antibodies bound they will be in the pellet..add complement and if it lyses the cell you can see it by incorporation of an added dye into the cells.
What is the Mixed Lymphocyte Reaction used to test?
Class II MHC compatibility… Irradiate donor cells so they cannot proliferate…give to recipient cells, and if the recipient cells proliferate (detected via radioactive assays) there is not a match.
Which type of test is more specific in a direct or indirect Coombs test?
Indirect is more specific for any kind of laboratory test.
What type of cells does Epstein Barr virus infect?
B-cells
What does a Positive Heterophile antibody tell you?
The pathogen is EBV
What is an immune complex comprised of?
Antigen
Antibody
Complement
What are the symptoms of serum sickness?
Fever, urticaria, arthralgias, proteinuria and lymphadenopathy..occurs in reaction to foreign proteins, esp of drugs
What is the test to determine a type III hypersensitivity?
Immunostaining to look for deposition in tissues
What is an Arthus reaction?
A subacute reaction after intradermal injection of antigen induces antibodies, which form complexes in the skin….Edema, necrosis and activation of complement occurs.
What are the major cells responsible for the damage done in Type III hypersensitivities?
Neutrophils, which secrete lysosomal enzymes after being attracted to an area via complement activation.
What are 8 classic granulomatous diseases?
TB Fungal like Histoplasmosis Syphilis Leprosy Cat Scratch Fever Sarcoidosis Crohn's Disease Berylliosis
How does a granuloma form?
An APC cell presents antigen to a Th cell via MHC II… this stimulates IFN-Gamma release which triggers monocytes to become macrophages, macrophages to become epitheliod cells and these cells to coalesce to form a giant cell
What is Anergy?
When Self-reactive T-cells become non-reactive in the absence of a costimulatory signal…..Can occur in B cells as well.
To Be Healed Rapidly stands for…
The diseases to which PASSIVE antibodies can be given..
Tetanus
Botulism
HBV
Rabies…Preformed antibodies with rapid onset and short half life
What is the main Ig in the secondary response to an antigen?
IgG
What is the most abundant Ig?
IgG
What Ig can cross the placenta?
IgG
What Ig can fix complement AND opsonize bacteria?
IgG
What is the Ig of the primary response to an antigen?
IgM
What Ig can fix complement but cannot cross the placenta?
IgM
Which Ig is found as a pentamer?
IgM
What Ig has the lowest concentration in serum?
IgE
Which Igs are found on mature but naive lymphocytes?
IgM and IgD
What is an allotype?
An Ig epitope that differs among members of the same species and can be present on the heavy or light chain…Represent different ALLeles
What are thymus independent antigens?
Those lacking a peptide component…cannot be presented by MHC to T cells because they cannot be attached to the MHC in the ER.
How are thymus independent antigens different from thymus dependent ones?
They can stimulate release of IgM only and to not result in immunologic memory
What is an example of a thymus-independent antige?
Lipopolysaccharides from the cell envelope of gram negative bacteria
or
Polysaccharide capsular antigens
What are thymus dependent antigens?
Those that contain a protein component (peptide) that can be linked to an MHC I and presented…can lead to class switching and immunologic memory. (Conjugated H.Influenza vaccine is an example, even tho the capsule of the organism is a polysaccharide)
What is the function of the B2 Microglobulin?
Is paired with MHC I molecules in the RER and aids in transport to the cell surface
How is the antigen loaded onto a MHC II molecule?
From an exogenous source… Loading occurs following release of invariant chain in an acidified endosome.
Which two cytokines released by Th cells can determine if Th1 cells or Th2 cells become activated?
IL-4 leads to the activation of Th2 cells which Make IL4, IL5, IL6, IL10 and help make antibodies…Humoral response.
IL-12 leads to the activation of Th1 cells, which make IL-2 and IFN-gamma to activate macrophages and CD8+ T-cells…Cellular response.
What cytokine inhibits Th1 cellular activation?
IL-10
What cytokine inhibits Th2 cellular activation?
IFN-gamma
What cytokines activate NK cells?
IL-12, IFN alpha and beta
What is the only lymphocyte of the innate immune system?
NK cells
What chemicals are used by NK cells to induce apoptosis of virally infected cells and tumor cells?
Perforin and Granzymes
When are NK cells induced to kill a target cell?
In the absence of MHC I on the cells surface
or
When exposed to a nonspecific activation signal on the target cell
Explain the macrophage-lymphcyte interaction…
Activated lymphocytes release IFN-gamma…This activates macrophages to release IL-1 and TNF-;alpha…Which stimulate lymphocytes
What bacteria contain superantigens?
S aureus and S pyogenes
What is the effect of superantigens?
They crosslink the Beta region of a TCR to the MHC II on APCs…Leads to uncoordinated release of IFN-gamma from Th1 cells and thus IL-1 IL6 and TNF-alpha from macrophages
Are Th cells involved in the reaction to endotoxins or lipolysaccharides in gram negative bacteria?
No…These directly stimulate macrophages by binding to endotoxin receptor CD 14
What type of complement changes are seen in Serum Sickness?
Low C3 in serum
What are two causes of angioedema?
ACE inhibitor use
or
C1 esterase inhibitor deficiency… Both lead to increased bradykinin levels
What are two things C1 esterase inhibitor blocks?
Activation of the complement cascade by preventing splitting of C1
AND
It inhibits Kallekrein activity
What are two functions of Kallekrein?
Cleaves plasminogen to plasmin
and
Cleaves Kininogen to Bradykinin… Deficiency here can lead to angioedema.
What is Omalizumab?
A monoclonal Ab against IgE….used to treat asthma
What type of Ig is RhoGam?
An IgG against RhD because this has the highest affinity and binds low levels of antibodies in the blood.
What is one major difference seen in Ig response months after a live versus a killed vaccine?
The live will have lead to increased IgA production, as the mucosal surfaces are directly stimulated by live vaccines.
What is an important unrelated clinical finding of MG patients?
Thymoma or Thymic hyperplasia
What type of hypersensitivity reaction is Sarcoidosis?
Type IV
Clinical findings of Polymyositis?
Proximal muscle WEAKNESS
Muscle biopsy show inflammation and necrosis of muscle fibers
MHC I is overexpressed on the sacrolemma leading to infiltration of CD8+ T cells
Associated with ANA and anti-Jo antibodies
What is the Invariant chain?
It is associated with MHC II in the RER…when this travels to an acidified lysosome it interacts with exogenous peptides and the chain gets degraded so the peptides can bind MHC II.
What two cytokines lead to the activation of NK cells?
IFN-2 and IL-12
Clinical signs of Henoch Schoenlein Purpura?
PALPABLE purpura
Abd pain
Arthalgias
Renal involvement….Caused by increased IgA in response to antigen trigger
What is the best way to prevent neonatal tetanus?
Tetanus toxin to pregnant mum.
What is the underlying cause of decreased phagocytic activity of macrophages in pts with silicosis?
Silica particles disrupt the phagolysosome mycobacterium have been ingested by macrophages.
What do T-cells interact with in the cortex to determine positive selection?
Cortical epithelial thymic cells
What do T-cells interact with in the medulla to determine negative selection?
Medullary epithelial and Dendritic cells
Where does affinity maturation via somatic hypermutation occur?
In germinal centers after antigen exposure
What are two antiinflammatory cytokines?
IL-10
and
TGF-Beta
What is the major way protection is conferred against influenza infection?
IgA or IgG against hemagluttinin of the influenza virus
What type of reaction is seen in the tissues of patients with hyperacute rejection?
Vascular fibrinoid necrosis and neutrophil infiltration
Where on the Ig molecules does complement protein C1 bind the Fc portion to cause complement activation?
Near the hinge region by the disulfide bond NOT at the tip of the Fc portion
What is Nikolsky’s sign?
Sloughing of the skin with gentle pressure…seen in pemphigus vulgaris and SSSS
What is the structure of MHC I?
A Heavy chain and Beta 2 microglobulin
What is the structure of MHC II?
Alpha and Beta polypeptide chains
What is the gene responsible for Ataxia Telangiectasia?
ATM gene—think Ataxia Telangiectasia Mutated
Where does recombination of VDJ chains occur?
Bone marrow
What type of organism of PCP?
Fungus
What type of immunity is conferred by killed or viral component vaccines?
HUMORAL response
What is the typical appearance of a tissue undergoing chronic rejection?
Scanty inflammatory cells
Interstitial fibrosis
Obliterative Smooth Muscle hypertrophy
What is the triad of Anti-Phospholipid Ab syndrome due to Lupus Anticoagulant?
Venous thromboembolism
Arterial thromboembolism
Increased fetal loss… Also seen are increased PTT and
High anti-phospholipid Abs, duh.
What are Birbeck granules ?
Intracytoplasmic granules seen in Langerhans cells that are shaped like a tennis racquet….These cells are also stellate.
What is IL-22 often a marker for?
ALL causing cells
What cell type is found increased intraalveolarly and interstitially in Sarcoidosis?
CD4+ T-cells….This leads to an increased CD4+:CD8+ ratio that can differentiate this from AIDS pts.
What is the UWORLD timeframe for acute rejection?
1-4 weeks with dense mononuclear infiltration
What can be the cause of a Positive VDRL test in the absence of treponemal antibodies?
Circulating Antiphospholipid antibodies indicative of Lupus Anticoagulant….
Leads to increased PTT and false VDRL positives.
Who is at risk for superficial candidal infections including esophagitis?
AIDS pts, due to lack of CD4+ cells
Who is at risk for disseminated candidal infections, including heart and liver abscesses or Candidemia?
Neutropenic patients, as neutrophils prevent the dissemination.
What is a major function of TGF-B?
Tissue regeneration and Repair
What is CD-15 a marker for?
Neutrophils and Reed_Sternberg cells in Hodgkins lymphoma.
What is the function of cytochrome c WRT the apoptosis pathway?
It activates caspases that activate the intrinsis or mitochondrial apoptosis pathway. .. Mitochondria become more permeable to pro-apoptotic substances… Anti-apoptotic genes Bcl-2 and Bcl-x turn off Pro apoptotic genes Bak, Bax and Bim turn on…these bring about the release of cytochrome c..WTF.
