MOD E2, Chp4-6 Flashcards
Where are CR2 and CD21 located? Fxn?
Located on B cells, receptors for complement.
EBV uses CR2 to get into the B cell
What contains the Fc receptor? What binds to Fcr?
FceR?
Fc Receptors: (phagocytes)
- Follicular dendritic
- NK cells
- Mast cells
- Macrophages
Fc is the main stem part of an Ab
IgG after it’s opsonized something
FeCR on Mast cells
For NK cells, what activates perforin/granzyme release and what inhibits it?
ACtivatino: NKG2D
Inhibiting: MHC1
NK cells, what activates them? What do NK cells release?
Activated by:
IL-2, 12, 15, IFN a & b
Secretes:
IFNy
What chromosome are MHC/HLA on?
Chromsome 6
What activates NFKb?
TLR’s
HIV uses this
What do the following sense? TLR? NOD? CLR? RIG? GPCR? MLR?
TLR -- bacteria NOD - Intracellular uric acid, nectroic cells, ion imbalance [uses inflammasome] CLR fungal RIG - viruses GPCR - n formylmethionine MLR - sugar
What does MHCI present? What part of the receptor binds to CD8? What genes?
MHCII same except CD4?
Intracellular viral or tumor proteins
A3 - CD8;
Genes: HLA-DP, DQ, DR
Present only on APCs,
Extracellular that’s been internalized
B2 binds CD4
Genes: HLA-DP, DQ, DR
How does a T cell become activated?
- MHC on APC binds to TCR on T cell
2. B7/CD80 on APC; CD28 on T cell
How does a B cell class switch?
B cell has CD40. T cell had CD40L. Once bound, T cell shoots out IFNy, IL4, IL5 to class switch
What uses ADCC?
Antibody dependent compliment cascade?
NK cells! They have Fc receptor for IgG, which opsonizes tumor or viral cells
What abs do what? IgG IgM Iga IgE IgD
IgG: opsonizes, C', crosses placenta IgM: C', but also on naive cells IgA: Mucosal IgE: parasites, allergens IgD: NKF
What is atopy?
atopy = prone to allergy bc you have high IgE, IL4, Th2
What is anergy?
Peripheral tolerance =
T cells latch onto self cells, but without the second signal of B7-CD28 (B7 is only on foreign) then it becomes anergic
What is the apoptosis mechanism in peripheral tolerance?
- T cell binds self cell, cell sticks out Bim, mitochondrial apoptosis
- Self cell sticks out FAS-L and apoptosis the T cell.
Ankylosing spondylitisl gene?
B27
There are genes that aren’t MHC that can cause autoimmune dx. What are they?
PTPN22 cause polymorphisms –> RA, DMI, Tyrosine kinase defects
NOD2 cause polymorphisms –> crohns
IL-2 or IL7 receptor defects –> MS
How do infection cause autoimmune diseases? (2 ways)
- infections upregulate expression of costimulators on APC so that T cells can get that 2nd signal
- Molecular mimicry
What is BAFF?
(B-cell Activating Factor)
Promotes survival and differentiation of B cells.
If there is a n abnormality, coudl be SLE or common variable immunodeficiency
Wha tis a n LE cell?
Lupus cell - any phagocytic leukocyte htat has engulfed the denatured nucleus of an injured cell.
Produced when a damaged cell reacts with ANAs.
A pt presents with edema, erythema, scaliness and follicular plugging on the face and scalp. They have malar rash and discoid rash, but lack renal involvement.
Chronic Discoid Lupus
On autopsy a pt presents with Libman sacks endocarditis. What other symptoms did the pt probably experience while alive?
With this disease, what are they at a huge increased risk for?
IM DAMN SHARP
Igs. Malar Rash Discoid Rash Mucositis Antinuclear Antibodies Serositis Hematologic Defects Arthritis Renal defects Photosensitivity
- rub on auscultation
- Pleuritis, Pleural effusion
- Splenomegaly,
- Pericarditis
SLE
MALT cell lymphoma
A pt has the HLA isotype DR6, what are they at risk for?
DR4?
Drug- induced SLE with procainamide
with drug hydralazine
A pt blood test shows anti- DNA topoisomerase I (SCI-70), what is the preliminary dx? What about anticentromere ab?
What is the characteristic presentation?
What is this pt at risk of?
SCI70 = Diffuse Sjogren Anticentromere = limited Scleroderma OR SCLERODERMA
CREST:
antiCentromere abs, Raynaud’s phenom, Esophageal, sclerodatyly, Telangiectasia
Risk of: - pulmonary hypertension and fibrosis (cause of death)
- Scleroderma Renal Crisis = malignant HTN
A dx of mixed connective tissue dx has symptoms from what 3 ds and how do you dx?
SLE, Scleroderma, polymositis
U1 ribonucleoprotein abs
A pt presents with Idiopathic retroperitoneal fibrosis and obliteraive phlebitis. WHat is causing this and what do you expect to see on gross inspection? What is the pt at risk for?
IgG4 related dx
Mikulicz (enlargement and fibrosis of salivary and lacrimal glands)
Autoimmune pancreatitis,
inflammatory pseudotumors of lungs
Pt presents in shock, unable to give PMH. Pt’s medical bracelet says he had received a liver transplant, but the date is indecipherable. A quick biopsy shows many NK, Complement and T cells. When did the pt most likely receive their transplant?
Just a few weeks ago.
A pt on long term immunosuppression is at risk for what?
how does immunosuppressive therapy work?
Polyoma virus.
Immunosuppressive: inhibits NFAT
Pt presents with maculopapular rash, jaundice, diarrhea, hepatosplenomegaly following an HSC transplant. What type of rejection is this most likely from?
Graft vshost
bone marrow and liver transplants HSC
A 30 yo Sephardic Jewish man comes in, complains of intermittent fever. You find liver inflammation. What is the MOA and name of Dx?
Familial Mediterranean Fever
AR.
SAA –> AA from liver inflammation.
A female pt presents with a PMH of a certain amyloidosis. The pt’s mother and half of her siblings also have the ds. what is the pt at risk for?
Autosomal dominant amyloidosis= amyloid in peripheral and autonomic nerves.
At risk of polyneuropathies.
What is a sago spleen?
Lardaceous spleen?
Amyloid in spleen.
Sago = tapioca like granules, gross inspectino
Lardaceous: amyloid in walls of sinuses
Defect in Leukocyte adhesion type 1?
Defect in leukocyte adhesion type 2
LFA-1 and Mac-1 integrin b2 chains
Fucosyl transferase
& Absence of sialyl Lewis X
A pt presents with recurrent viral infections of epstein-barr virus. What would be seen on biopsy? MOA?
Decrease in NK and T cells.
due to the SAP protein being defective
SAP = SLAM=-associated protein
X linked lymphoproliferative syndrome
What is the HIV core made of?
- Major capsid protein p24.
- Nucleocapsid protein p7/p9
What does a naive T cell have that doesn’t allow HIV to infect it?
APOBEC3G
what type of calcificaiton is Scleroderma?
Dystrophic - CREST syndromes always are.
CAG is deleted, what dz?
CAG is repeated too much, dz?
Deleted: Klinefelter
Repeated: Huntington
What are langerhans?
Dendritic cells in the epidermis
A patient has emphesema, what enzymatic disorder could ahve caused it?
a1-antitrypsin –> inhibits neutrophil elastase –>
A pt is given primaquine and goes into hemolytic anemia. What defect has caused this?
Glucose 6 phosphate deficiency presidsposes pt to RBC lysis
What is DAF?
Decay Accelerating Factor
- binds to GPI anchor on cells and prevents formation of C3 convertase to inhibit MAC. Deficiency = too much complement = paroxysmal nocturnal hemoglobinuria
What is the fxn of PGI2? PGE2? TXA2 Leukotriene lipoxin? Thrombomodulin fxn? platelet factor 4 ADP?
PGI2: Vasodilation, inhibits platelet aggregation
PGE2: Vasodilation, increase vascular permeability; fever and pain
TXA2: Vasoconstriction, platelet aggregation
Leukotrienes: bonchospasm, increase vascular permeability
Lipoxin: inhibit inflammation
Thrombodulin: inhibits coagulation by activating protein C
PF4: promotes platelet aggregation
ADP: released from platelets, sitmulates platelet aggregation
you find anti-dna topoisomerase in a pt. Dx?
Scleroderma diffused
Alheimers is caused by what type of amyloid?
familial amyloid polyneuropthy?
Senile?
Multiple Myloma?
Familial Mediterranean disease?
Ab
TTR
TTR
AL amyloid
Al –> Pyrin is mutated which regualtes proinfalmmatory IL 1; fever inflammatino of serosal surfaces
A pt presents with a PMH of pheochromocytoma and now presents with fibrosis of the kidney,
Amyloidosis
A pt has U1 ribonucleoprotein abs will have what syx
Mixed connective tissue dz
Sx:
- Synovitis, Raynaud, Mild Myositis, Pulmonary HTN, Lung dz, Renal
Mikulicz, pseudotumors of lungs is associated
IgG4
What is mixed chimerism?
Giving the recipient some other host cells to get them used to foreign stuff
A pt presents with bloody diarrhea, jaundice, maculopapular rash, what kind of transplant reaction are they having?
Acute GVH
What is Acute retroviral syndrome?
Flu symptoms
what is the seroconversion of HIV?
3-7 week, how long from getting it to seeing antibodies in blodo
How does aspirin work?
block COX pathway, inhibiting thromboxane A2, which does not allow vascoconstriction or platelet aggregation
Type III Hypersensitivity is seen in what organs?
nephritis, vasculitis, arthritis
T cells deal with what infections?
B cells deal with what infections?
T cells = virus fungi most of the time
B cells = bacteria
Cells take HIV places. what cells take HIV to what places?
Macrophages –> CNS
Langerhans –> Lymph nodes to T cells
A pt has a mRNA mutation that changes CTC for CAC, glutamic acid –> Valine; what is the dz?
Sickle Cell anemia
What dz is associated with a stop codon?
beta thalassemia
What is an example ofa dynamic disease?
Fragile X. more repeats
What is locus heterogeneity?
What is allelic heterogeneity?
What is pleiotropism?
Dominant negative?
Mutations at different loci can produce a similar phenotype, Such as albinism
Different mtations in the same locus produce teh same phenotype, exampe beta thalassemia
Single mutant gene with many effects
When the cra protein inhibits hte normal functionnig protein
What is an example of an accumulation in a minor pathway?
What is an exapme of a decrease in end product?
What about failure to inactivate a tissue damaging substrate?
Lysosomal storage diseases
Albinism, tyrosinase loss
A1 tryptase deficiency, can’t inactivate neutrophil elastsase in lungs = emphysema
acrocentric means what?
Risk for Robertsonian translations where acrocentric chromosomes lose the short arms
What is the morphological hallmark for a trinucleotide repeat?
Large intranuclear inclusions
A doc is checking for a genetic disease, he first uses PCR and then Soutehr blot. What was he testing for?
Fragile X
When does genomic imprinting occur?
When do trinucleotide repeats occur?
Imprinting: Ovum or sperm before fertilization
Trinucleotide: spermatogenesis/oogenesis
A deficiency in Rag will cause what?
B cells cannot express and amkea wide variety of receptor ptroteins, at risk for diseases that don’t already have receeptors
What are these T cell receptors and components in charge of: Ab- chain? yd- chain? CD3/zeta CD4/8: CD28 CD40
ab chain = MHC recognition
Yd = mucosa and GI for recognition wihtout MHC
CD3 and Zeta: transudce signals
CD4/8, first signals in t cella ctivation
28: bidns B7 and CTLA4, second signal for activation
CD40 L: activation signaling for B cells
B cell receptors and componnets fxns?
Ig-a, Ig-b?
CR2, CD21
CD40
Iga/b signal tranduction in T cells
CR2: recognize C’ (EBV gets in this way); second signal in T-independent activation
CD40: Class swithcing from Thelp; second signal in T-dependant
What presents to B cells with Fc receptors for IgG and C3b and takes them to Spleen or IgG?
Follicular dendritic cells
What are innate lymphoid cells?
Early defense, recognize and eliminate stressed ells and produce: IFNgam, IL5, IL 17, IL22
What does MHC I have for binding? What binds CD8? Genes?
MHCII binding for peptide? Binding for CD4? genes
Peptide = A1A2
CD8 = A3
Genes: HLA ABC
Peptide = A1,b1
CD4 = B2
Genes: HLA DP DQ DR
What is the ultimate culprit in HS1? What are the preformed mediateors?
Excessive TH2 cell response
Histamine
ENzymes (tryptase)
Proteoglycans (heparin)
What are examples of non atopic allergies?
Cold, Exercise.
If a patient experiences a fall in blood pressure and airway obstruction, what is this called? What causes it?
Systemic anaphylaxis
Fall in blood pressure via vascular dilation
Airway obstruction via laryngeal edema
non-MHC genes with autoimmune disesaes include Crohn’s, RA, DM1, MS.
Crohn’s = NOD2
RA/DM1 = PTPN22 Polymorphisms (Tyrosine kinase?)
MS = IL-2/IL7
How cna a pt with streptococcal infection cause myocarditis?
Streptococcal has similar antigen to heart self antigen -> rheumatic heart diseases –> myocarditis
Antihistone abs are from? What sx?
drug induced lupus
Fever, serositis, arhtralgia, NO CNS or Renal involvement
Pleuritis is heard upon chest auscultation. Dz?
SLE
What is the triad of scleroderma:
Sx?
-Autoimmunity
- noninflammatory vasculopathy
- collagen deposition with fibrosis
CREST:
Calcinosis, Raynaud, Esophageal dysmotiltiy, sclerodactyly, telangiectasia
How do people with scleroderma die?
Renal crisis from severe HTN and fibrosis of lungs
A pt presents with allorecognition syndromes, and has CD4+ and CD8s attacking. Is it direct or indirect?
Direct!!
Indirect is only CD4s and B cells
How can you increase graft survival?
INhibit NFAT with therapy, then give them IVIG, corticosteroids.
Prolonged immunosuppession can cause wht?
Polyoma virus
EBV
HPV
Kaposi Sarcoma
How can you die from a GvH disease?
Depletion of lymphocytes.
pneumonic for Chediak Hiashi syndrome?
PLAIN - Progressive neurodegeneration - lymphohistocytosis - albinism - pyogenicinfecions by staph and strp neuropathy
A pt presents with Failure to thrive, chronic diarrhea, thrush. What is the defect?
WHat if there is a big decrease in NK cells?
Life expectancy?
SCID
AR = adenosine deaminase
X linked = gamma chain, IL2 recepor and IL7 and IL15 sucks, which do T cell adn NK cells repsectively
Not good life expectancy. 3 yr?
Recurrent infections of haemophilus influenzae, giardia lamblia, streptococcus and staphylococcus is most likely? What is the pt most at risk for?
Bruton agammaglobulinemia
Enteroviruses disseminate to CNS [NO POLIO Vaccs]
poliomyelitis or fatal encephalitis
Giardia lamblia
2 syndromes where you will find undeveloped germinal centers. How do you tell them apart?
Agammaglobinunemia and X linked lymphoproliferative.
X linked lymphoproliferative = epstein barr virus
A pt’s labs show incresaed IgM and lowIgA, IgG, IgE, what could be the cause? What are they at risk for?
Xl inked: CD40L
AR: CD40
AR: AID (required for class switching and affinity maturation)
Pneumonia,
Excessive IgM reacts with blood cells = anemia, thrombocytopenia, neutropenia
A 3 yo pt presents with decreased plasma cell and immunoglobins.
What are they at risk for?
Common variable immunodeficiency
- At risk for lymphoma, sinopulmonary infections
- ## Arthritis
A pt with Celiac (including inflammation of intestines), Giardia lamblia infection and sinopulmonary infection could be what? What does this mean for your clinic?
Risk of?
Isolated IgA deficiency.
Cannot give transfusions with IgA in it becasue foreign
Risk for RA
What do these genes enode for?
gp120
gp41?
p24, p17?
gp120 and gp41 = env
gp120 = attachment to CD4
gp41 = fusion and entry
24and 17 = gag
capsid and matrix proteins
pol = reverse transcriptase, aspartate protease, integrase
What is the HIV core1 made from?
What different groups can they be divided into?
major capsid protein p24 - assay for testing HIV
Nucleocapsid protein p7/p9
2 copies of viral genomic RNA
Group M, O, and N
how might HIV use inflamasome to kill an infected cell?
Other ways to kill CD3?
pyroptosis
activation -induced cell death
Syncytia = one big cell kills a bunhc
How are mucosal and follicular dendritic cells associated with HIV?
Mucosal: Transport to lymph nodes so it can infect Cd4
Follicular: Reservoirs of HIV, in lymph nodes
B cell lymphoma is seen in HIV patients because why?
What about CNS diz?
Unchecked porliferaiton to B ecells infected with oncogenic herpesviruses
- Progressive encephalopathy
Bence Jones proteins are seen. Where do these come from? what does this put the pt at risk for?
Primary amyloidoss = AL
excessive Antibodies –> Multiple myeloma
A 46 yo Armenaian man presents with PMH of haemophilus influenza infection and now complains of attacks of fever, inflammation of serosal sufaces.. what is the defect?
Familial Mediterranean fever
Protein Pyrin is mutated. SAA Aggregates from excessive IL1
A deposition of amyloid in peripheral and autonomic nerves is genetically transferred via what? what isthe defect?
TTR mutations, AD
What Neimann Pick is teh most common? WHich is the worst?
Common: C, mutation in NPC1; can’t tranport lipids out of lysosymes
Type A is worst: die in 3 years bc neuro and visceral accumulations
TypeB: Organomegaly w/ no CNS
What are Klinefelter pts at risk for?
DM
MVP
Osteoporosis
Breast Cancer
Isochromosome is most likely to be found in what disease?
Turner syndrome
or ring or anything really
What is the triad of Ataxia telangiectasia?
Ataxia, Angiomas, IgA deficiency
What is mode of inheritance in Familial cholesterolemia?
AUtosomal dominant
