BL3 Flashcards by Nebuchadnezzer II

What is the serum concentration of:
IgG
IgA
IgM

IgG: 1000 mg/dL -> most abundant in plasma remember?
IgA: 200 mg/dL
IgM: 100 mg/dl

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What is the combining site on the antibody?

where antibody binds to the antigen
○ Made up of V domains of both the H and L chain
○ 6 total

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What is the difference between antigen precipitation and agglutination?
Which is easier to detect? (more sensitive?)

When the antigen is a molecule → called precipitation.

When antigen is cell/cell sized → called agglutination

agglutination easier to detect

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What is the only class of antibody (Ig) that can pass the placenta?

IgG via active transport

bc placenta is gross

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What is the only class of antibody (Ig) that is opsonizing?

IgG

phagocytic cells have receptors that recognize the Fc of bound IgG→ clearance of extracellular bacteria
- Helps other cells Gobble up bacteria (opsonizing)

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What is the only antibody made by the fetus?

IgM

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What is the first immunoglobulin seen in blood after immunization

IgM

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Which Immunoglobulin is the most efficient complement activator? Why?

IgM

-always has 2 adjacent Fc’s to begin complement cascade.

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Do phagocytes have IgM or IgG receptors?

IgG

(IgG is only class that is opsonizing for phagocyte, which have receptors for Fc of IgG)
Helps other cells Gobble up bacteria (opsonizing)

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The most common immunodeficient disease is being able to not make enough of which Ig?

IgA

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In mature B cells, the antigen receptor normally consists of which two isotypes?

IgM and IgD

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Which part of IgE adheres to mast cells and basophils?

Fc of IgE

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main inflammatory mediator of the humoral immune system.

Complement

- remember, Humoral is an antibody mediated response

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Three ways to activate complement © cascade, C3.

And whether it is part of innate or adaptive immunity.

§ Classical: adaptive
§ Alternative: innate
§ Lectin: innate

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In adaptive immune system what triggers complement

antibodies

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Innate immune system what triggers complement

Substances on surfaces of pathogens (not antibody)

-remember: PAMPs and DAMPs

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Which way is complement activated by IgG and IgM?

via classical pathway (adaptive)

require antibodies → trigger complement

Classical complement activation pathway

Bacteria invaders identified → antibodies trigger
classical pathway activated by complexes of IgG or IgM antibody with antigen →
C1q must interact with the 2 Fcs simultaneously →
C1 activates C4 then C2 → C4b2a together activate C3 →C4b2a3b together activate C5-C6-C7-C8-C9

Alternative complement activation pathway

Bacteria cell wall structures →
activate complement (absent of antibody) →
C3 break down to C3a and C3b →
C3b binds to cell wall anchor, properdin (P), located on bacteria cell wall structure →
Normal rapid degradation of C3b halted and stabilized →
Anchor allows for assembly of C3b, factor B, and Factor D →
C3bDbC3b (trimer of Db and 2 C3b units) → activates C5 → C6-7-8-9

What bacterial infect may indicate a defect in the C3b-C8 pathway?

Neisseria(ie gonorrhea, a Gram-negative coccus):

resistant to lysis by C9 (which is necessary for their clearance)

Two mechanisms for red cell destruction (hemolysis)

Intravascular hemolysis

Extravascular hemolysis

Intravascular hemolysis

RBC basically explodes in vessel → Releases Hb into circulation → dissociate into αβ dimer → bind to haptoglobin →circulated haptoglobin/Hb removed by liver

How can methemoglobin result from intravascular hemolysis?

RBC basically explodes in vessel → Releases Hb into circulation → Iron can be oxidized (Fe3+) → methemoglobin (cannot bind O2)

What does the presence of metheme and Hb in your urine indicate? What does free metheme bind to?

intravascular hemolysis

Metheme binds to albumin → taken to liver

Extravascular hemolysis (90% of all hemolysis)

RBC trapped in spleen is ingested by macrophages of RE system → releases blood components → Heme (w/ porphyrin ring) separate from globin → iron removed → stored in ferritin → porphyrin ring converted to bilirubin → released from cell → conjugated in liver via glucuronide conjugation→ excreted into bile duct → Small intestine → converted to urobilinogen → excreted in feces or filtered and excreted by kidneys

Will you expect to see high or low levels of bilirubin with intravascular hemolysis?

High that free porphyrin ring man!

Would you expect to see high or low levels of haptoglobin with intravascular hemolysis?

Low

What are the clinical symptoms and signs of Hereditary spherocytosis?

Anemia, jaundice, splenomegaly, hyperbilirubinemia as neonates can lead to aplastic crisis and biliary stones

Would you expect to see high or low levels of bilirubin in hereditary spherocytosis? Why?

High - RBC rupturing->released hb converted to unconjugated bili-> high bili can lead to gallstones

How does G6P Deficiency → hemolysis?

Premature loss of G-6-PD activity → oxidation of hemoglobin → denatured globin attaches to membrane (Heinz bodies) → spectrin gets oxidized → RBC less deformable → trapping in spleen →extravascular hemolysis

Major foods, drugs, or other chemicals which can induce hemolytic anemia in patients with G6PD deficiency.

* Aspirin * Fava beans * Legumes * Methylene blue (for methemoglobinemia- remember?), * Vitamins C and K.

Direct Coombs test / Direct antiglobulin test (DAT):

Evaluates presence of IgG or complements on surface of Pt's RBCs (not serum) • Autoimmune hemolytic anemia = (+) DAT

Indirect Coombs test / Indirect antiglobulin test:

Evaluates if Pt's serum (not RBCs) can bind IgG or complement

Cold antibodies: 1. Which Ig? 2. Intravascular or extravascular?

1. IgM 2. Intravascular I M COLD so i want to be INside

Warm antibodies: 1. Which Ig? 2. Intravascular or extravascular?

1. IgG | 2. Extravascular

Cells of adaptive immunity

B and T lymphocytes | APCs

Innate immunity

Toll like receptors recognize PAMPs and DAMPs Absence of normal cell surface molecules recognized by NK cells

Which Immunoglobulins are involved in classical complement activation

IgM and IgG General Motors make Classical cars

which immunoglobulin is most abundant in plasma?

IgG - present in Great amounts

Distinguish between actions of Cold and Warm antibodies and how they can induce AIHA

Cold: Transiently bind RBCs → activates complements to lyse them Warm: Bind strongly to RBC →Spleen → activate macrophages → destroy bounded RBCs