Foundations

Question 1

Blood volume and percent body weight?

Answer 1

5 Liters, 5 % BW

Question 2

ECM for blood?

Answer 2

Plasma

Question 3

Peripheral Blood is…

Answer 3

All blood that’s not in the bone marrow

Question 4

plasma componenets

Answer 4

90% water, 10% protein

Question 5

Plasma is made how

Answer 5

Fluid phase after centrifugation in the presence of heparin to prevent clotting

Question 6

Serum

Answer 6

The fluid portion after coagulation and centrifugation. It is done to remove the clotting factors and cells

Question 7

Most clinical blood work is done on which fraction of blood?

Answer 7

Serum

Question 8

normal RBC range

Answer 8

4.6 to 6.1 million per mcL men, 4.2-5.4 mil per mcL women

Question 9

normal WBC range

Answer 9

4 to 10 thousand per mcL

Question 10

Differential count

Answer 10

A count that tells the wbc distribution

Question 11

Neutrophil

Answer 11

34-71%

Question 12

Eosinophils

Answer 12

0-7%

Question 13

Basophils

Answer 13

0-1%

Question 14

Monocytes

Answer 14

5-12%

Question 15

Lymphocytes

Answer 15

19-53%

Question 16

RBC diameter

Answer 16

7.5 microns

Question 17

HbF

Answer 17

2 alpha, 2 chi

Question 18

band-3

Answer 18

pumps bicarbonate out of the RBC… also binds ankyrin, which binds spectrins, to maintain biconcavity

Question 19

What is normal hematocrit

Answer 19

40-51%

Question 20

Hemoglobin is..

Answer 20

33% of RBC

Question 21

Chronic Granulomatous Disease (CGD)

Answer 21

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

Question 22

Leukocyte Adhesion Deficiency-1

Answer 22

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

Question 23

Leukocyte Adhesion Deficiency-2

Answer 23

Deficiency is fucosylation (Fuct1) a fructose transporter. also called CD15. Tested using flow cytometry with an anti-FUCT1 fluorescent antibody.

Question 24

MyD88/IRAK-4 Deficiency

Answer 24

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

Question 25

TLR3/4? or TLR3 Signaling defect

Answer 25

Defect in TRIF or in TLR 3 directly Causes herpes virus encephalitis, recurrent Not 100% penetrance

Question 26

Late Complement Deficiency

Answer 26

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)

Question 27

Early Complement Deficiency

Answer 27

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.

Question 28

Sever Combined Immunodeficiency

Answer 28

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!

Question 29

TRECs are a marker for

Answer 29

NORMAL, NAIVE T cells! Measured using real time PCR

Question 30

DiGeorge Syndrome (22qDS deletion syndrome)

Answer 30

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

Question 31

X-Linked Agammaglobulinemia

Answer 31

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.

Question 32

Common Variable Immunodeficiency

Answer 32

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

Question 33

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)

Answer 33

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

Question 34

Autoimmune lymphoproliferative syndrome (ALPS)

Answer 34

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

Question 35

Factor that allows T cell self antigens survive neg selection

Answer 35

Foxp3

Question 36

Immune Dysregulation Polyendocrinopathy, X-linked (IPEX)

Answer 36

Infant boys affected, IBD, eczema, very high IgE, foxp3 is busted with no Tregs functioning

Question 37

CD25 Deficiency

Answer 37

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

Question 38

Acute Rheumatic Fever

Answer 38

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

Question 39

Systemic Lupis Erythematousous

Answer 39

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)

Question 40

rheumatoid arthritis

Answer 40

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

Question 41

Ehlers Danlos Syndrome

Answer 41

Hyperextensible skin, easily traumatized Joints and ligaments hypermobile Rupture of internal organs, especially colon and large arteries Collagen with very low tensile strength

Question 42

Five reasons for elevated eosinophil count

Answer 42

``` Neoplasia Asthma Allergy Connective Tissue Disease Parasitic Disease ```

Question 43

Senstivity for farmer's lung

Answer 43

Alveolitis, Type III against spores or dust

Question 44

Systemic antigen excess

Answer 44

Type III if it is against viral hepatitis or bacterial endocarditis antigen in sera

Question 45

Pernicious anemia sensitivity

Answer 45

Megaloblastic anemia is a Type II specificity... intrinsic factor bound to gastric parietal cells

Question 46

Goodpasture syndrome

Answer 46

Causes nephritis. Type II sens. Type IV collagen binds basement membrane in lung and glomeruli attack

Question 47

Acute rheumatic fever

Answer 47

Type II cross reaction with M protein from strep and heart

Question 48

Bullous pemphigoid

Answer 48

Skin vesicles as epidermal basement membrane gets attacked. This is a type 2 sensitivity

Question 49

Vasculitides

Answer 49

Neutrophil cytoplasmic antibodies

Question 50

Antiphospholipid antibodies

Answer 50

These thrombotic phenomena are Type II

Question 51

What cells involved in type iv hypersensitivity?

Answer 51

CD4 TH1 and CD8 T cells

Question 52

Tuberculin response

Answer 52

Th1 mediated response causes swelling at site in 48-72 hours. Hypersensitive skin reactions same deal. Rhus dermatitis/poison ivy

Question 53

Which hypersensitive reactions are soluble and which aren't

Answer 53

Th1 mediated ones are soluble, but CD8 mediated ones are cell associated

Question 54

IL-4 and IL-13 purpose

Answer 54

Th2 release these to stimulate isotype switching of B cells

Question 55

IL-3, IL-5, GM-CSF

Answer 55

promote survival and eosinophilia

Question 56

RANTES and Eotaxin

Answer 56

Chemokines for T cells and eosinophils. CCR3 on eosinophils bind it. Eotaxin is always found at allergic inflammatory sites

Question 57

MIP-1alpha

Answer 57

chemtaxis for macrophages and everything else

Question 58

Platelet activating factor

Answer 58

Actives mononuclear and polymorphonuclear cells, attracting agent

Question 59

Steroids do what to IL-5

Answer 59

Decrease its release

Question 60

Effector mechanisms for allergy

Answer 60

Type !: mast cell activation 2: FcR regions 3: FcR regions and complement 4: Macrophage activation (for Th1), but directly cytotoxic for CD8