Foundations Flashcards
Blood volume and percent body weight?
5 Liters, 5 % BW
ECM for blood?
Plasma
Peripheral Blood is…
All blood that’s not in the bone marrow
plasma componenets
90% water, 10% protein
Plasma is made how
Fluid phase after centrifugation in the presence of heparin to prevent clotting
Serum
The fluid portion after coagulation and centrifugation. It is done to remove the clotting factors and cells
Most clinical blood work is done on which fraction of blood?
Serum
normal RBC range
4.6 to 6.1 million per mcL men, 4.2-5.4 mil per mcL women
normal WBC range
4 to 10 thousand per mcL
Differential count
A count that tells the wbc distribution
Neutrophil
34-71%
Eosinophils
0-7%
Basophils
0-1%
Monocytes
5-12%
Lymphocytes
19-53%
RBC diameter
7.5 microns
HbF
2 alpha, 2 chi
band-3
pumps bicarbonate out of the RBC… also binds ankyrin, which binds spectrins, to maintain biconcavity
What is normal hematocrit
40-51%
Hemoglobin is..
33% of RBC
Chronic Granulomatous Disease (CGD)
Young person, liver abscess with low virulence bacteria. Caused by no NADH oxidase in PMNs… x linked or recessive autosomal.
Treat with TM-Sulfa prophylaxis and itraconazola (for bacteria and fungi). Give prednisone for granulomas that will form. Hepatosplenomegaly and pneumonia common.
Cured with BMT
Diagnosed by testing for respiratory burst with fluorescent DHR… also detects carries, who have two populations which is visible upon stimulation
Leukocyte Adhesion Deficiency-1
Loss of beta unit of CD18, which binds… needed to adhere to integrins on epithelium.
BMT for sever cases, otherwise aggressive antibiotic treatment
Present with pyogenic infections, delayed umbilical cord detachment… Cannot form pus, and have leukocytosis during infection
Tested with flow cytometry with anti-CD18 fluorsenet antibody… ULCERS without PUS
Leukocyte Adhesion Deficiency-2
Deficiency is fucosylation (Fuct1) a fructose transporter. also called CD15. Tested using flow cytometry with an anti-FUCT1 fluorescent antibody.
MyD88/IRAK-4 Deficiency
All TLRs that use common pathway will be busted. TLR3/4 can still work via TRIF, a separate activator. Phenotype is the same for both MyD88 and irak-4. Manifest with similar PID.
high mortality until age of 8, at which point they can fend off infection on their own. Very susceptible to strep, staph, pseudomonas… meningitis, sepsis, and arthritis. ALL BACTERIAL
Susceptiblity not predicted based on mice models
IVIG and Abx prophylaxis until 8.
Bad infections but with no elevation in white counts or c reactive protein? suspect this
TLR3/4? or TLR3 Signaling defect
Defect in TRIF or in TLR 3 directly
Causes herpes virus encephalitis, recurrent
Not 100% penetrance
Late Complement Deficiency
Onset later in life, with variable penetrance. Usually adolescent. Must be homozygous, and susceptible to adolescent-onsite mengococcal disease, which becomes recurrent through adulthood. Homozygous null C5-C9, which form the membrane attack complex (MAC)
Early Complement Deficiency
C2 deficiency is the most common. Autosomal recessive. Causes collagen vascular diseases (SLE), recurrent bacteria. Best screening test CH50. A CH50 of 0 suggests individual complement deficiency. A low, but non-zero, CH50 score suggests consumption.
Sever Combined Immunodeficiency
SCID. Profound cellular and humoral immunity defects. P. jirovecii, otitis media, thrust, diarrhea, failure to thrive
100% mortality unless BMT. Need to do a genetic screening test using CBC, and detect a lymphopenia less than 1500 per mcl
Definitive Testing: is with TRECs!
TRECs are a marker for
NORMAL, NAIVE T cells! Measured using real time PCR
DiGeorge Syndrome (22qDS deletion syndrome)
CATCH22… Cardiac Defects; Abnormal face; Thymic hypoplasia; Cleft palate; Hypocalcemia; 22nd chromosome.
Low set ears, chin inward, fish shaped mouth, chola brow. Issues with swallowing, liquid comes back out of nose. Heart issues were common during childhood. Recurrent infections (thrust, otitis media, pneumonia)
Up to 30% have low T cell counts, with many abnormal. Need monthly IVIG supplementation, since B cells are dysfunctional without T cells. Autoimmunity, likely due to abnormal thymus (incomplete negative selection)
Test chromosome microarray or RT PCR for haploinsufficiency of TBX1
X-Linked Agammaglobulinemia
No B cells. Very low immunoglobulins IgG/A/M. Frequent recurrent respiratory sickness, otitis media, pneumonia as early as first year.
Treat with gamma globulin in order to prevent bronchiectasis…
Also able to get vaccine- related polio, and other enteroviral infections and encapsulated bacteria infections (mycoplasma, h. influenzae)
Screen all Ig’s (will be pan-hypogammaglobulinemia) in newborns is best.
Btk or BLNK in cell signaling is abolished. This is what mediate survival signals in B cells after cross linking.
Common Variable Immunodeficiency
Often presents with Bronchiectasis and interstitial lung disease
Leads to abnormal function of bronchi and cilia, making them susceptible to bronchitis and pneumonia. Progresses even with IVIG treatment
Similar therapy to CF. Physiotherapy, vests, chest pumping, hypertonic saline, hospitalizations with Abx for severe cases. Prophylaxis with Ab? possible
Very low IgG, with lower IgA and IgM also
Onset is greater than 4 years old
Exclude primary Ab deficiency (Ab), and secondary Ab deficiency, such as BCL, corticiosteroids, rituximab
Increases risk for B cell lymphomas
Later onset common, low FEV1/FVC (less than 50%)
Diffuse parenchymal disease, including GLILD… 10% of patients, with hepatomegaly and lung disease, due to multisystemic lymphoproliferative disorder
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)
Adrenal, parathyroid disease, and other endocrine dysfunction. Autoimmune disease, hypogonadism, vitiligo, pernicious anemia… all because AIRE is missing. Central negative selection fails.
Central tolerance failure
Autoimmune lymphoproliferative syndrome (ALPS)
Widespread lymphadenopathy and splenomegaly, with autoimmune cytopenias (anemia, thrombocytopenia)
FAs or Fas ligand busted, very high gamma globulin titers, many double negative T cells, leading to peripheral tolerance failure
Factor that allows T cell self antigens survive neg selection
Foxp3
Immune Dysregulation Polyendocrinopathy, X-linked (IPEX)
Infant boys affected, IBD, eczema, very high IgE, foxp3 is busted with no Tregs functioning
CD25 Deficiency
IPEX-like disease, with eczema, hypothyroidism, anemia, neutropenia, diarrhea, hepatosplenomegaly, lymphadenopathy, respiratory illness
Excessive amounts of gabba globulins. CD25 is a receptor Tregulatory cells that binds IL-2, leading to T cell reg dysfunction
Acute Rheumatic Fever
Joints, heart, nodules, erythema marginatum, sydeham’s chorea are major
Fever, arthralgia, elevated acute phase reactants and prolong PR interval are minor
two major or 1 major with two minor for diagonsis.
Give PCN prophylaxis for life once one bout of rheumatic fever occurs to prevent another strep infection
5 year prophylaxis or til 21 if carditis
10 year prophylaxis or til 21 if valvular disease
IF both… then 10 year prophylaxis or til 40, whichever longer
M protein in strep has mimicry with cardio cells
Example of Type II, with disease breaking self-tolerance
Systemic Lupis Erythematousous
Fatigue, fevers, rash, butterfly rash, high ANAs, low complement levels
Arthritis, serositis, cerebritis, nephritis, pleuritis, carditis
Early onset SLE can be caused by early complement defects, especially C2 (also C1q and C4)
rheumatoid arthritis
Proximal joint
Synovial fibroblasts activated by T cells, released IL1 IL6, TNF, all are inflammatory cytokines
B cells aggregated in synovium, and autoantibodies such as ANAs present in many
Both cell and humoral mediated immunity, but this is generally thought of as a type IV hypersensitivity
Treat with NSAIDs
Ehlers Danlos Syndrome
Hyperextensible skin, easily traumatized
Joints and ligaments hypermobile
Rupture of internal organs, especially colon and large arteries
Collagen with very low tensile strength
Five reasons for elevated eosinophil count
Neoplasia Asthma Allergy Connective Tissue Disease Parasitic Disease
Senstivity for farmer’s lung
Alveolitis, Type III against spores or dust
Systemic antigen excess
Type III if it is against viral hepatitis or bacterial endocarditis antigen in sera
Pernicious anemia sensitivity
Megaloblastic anemia is a Type II specificity… intrinsic factor bound to gastric parietal cells
Goodpasture syndrome
Causes nephritis. Type II sens. Type IV collagen binds basement membrane in lung and glomeruli attack
Acute rheumatic fever
Type II cross reaction with M protein from strep and heart
Bullous pemphigoid
Skin vesicles as epidermal basement membrane gets attacked. This is a type 2 sensitivity
Vasculitides
Neutrophil cytoplasmic antibodies
Antiphospholipid antibodies
These thrombotic phenomena are Type II
What cells involved in type iv hypersensitivity?
CD4 TH1 and CD8 T cells
Tuberculin response
Th1 mediated response causes swelling at site in 48-72 hours. Hypersensitive skin reactions same deal. Rhus dermatitis/poison ivy
Which hypersensitive reactions are soluble and which aren’t
Th1 mediated ones are soluble, but CD8 mediated ones are cell associated
IL-4 and IL-13 purpose
Th2 release these to stimulate isotype switching of B cells
IL-3, IL-5, GM-CSF
promote survival and eosinophilia
RANTES and Eotaxin
Chemokines for T cells and eosinophils. CCR3 on eosinophils bind it. Eotaxin is always found at allergic inflammatory sites
MIP-1alpha
chemtaxis for macrophages and everything else
Platelet activating factor
Actives mononuclear and polymorphonuclear cells, attracting agent
Steroids do what to IL-5
Decrease its release
Effector mechanisms for allergy
Type !: mast cell activation
2: FcR regions
3: FcR regions and complement
4: Macrophage activation (for Th1), but directly cytotoxic for CD8
