Flashcards in Immunology Deck (79)
How do B-cell markers change from the stem cell phase to maturity?
Early: CD34+, TdT+, HLADR+
During maturation, CD34 and TdT are lost. Gain expression of CD10, CD19, CD20, and Ig.
Plasma cell: Loss of B-cell markers and cytoplasmic (not surface) Ig
How do T-cell markers change from the stem cell phase to maturity?
Early: CD34+, TdT+, HLADR+
During maturation, lose CD34. Gain CD1, CD2, CD3 (cytoplasmic), 4+8 double, CD5, CD7.
Mature: Lose CD1 and TdT. CD3 becomes surface expressed. Become either CD4 or CD8.
What is the structure of immunoglobulin?
Consists of 2 light chains (1 variable + 1 constant domain) and 2 heavy chains (1 variable + 3-4 constant domains).
On what chromosomes are light and heavy chains expressed?
Light: Chr2 (kappa) and chr22 (lambda)
Heavy: Chr14 (all; gamma, alpha, mu, epsilon, delta)
What does the "VDJ region" refer to?
The variable region of heavy chains (or light chains, just "VJ", or TCR) which undergoes rearrangement during lymphocyte development to confer increased antigen recognition diversity.
What immunoglobulins are expressed by mature and activated B-cells?
Mature B-cells express surface IgM and IgD. After activation, they proliferate and undergo isotype switching by expressing a different heavy chain gene.
What heavy chain genes define each antibody isotype?
Gamma - IgG
Delta - IgD
Alpha - IgA
Mu - IgM
Epsilon - IgE
What is the normal ratio of T and B lymphocytes in circulation? What is the normal CD4:CD8 ratio?
2:1 (twice as many T as B)
2:1 (twice as many CD4+ as CD8+)
What is the structure of TCR?
A heterodimer (alpha+beta > gamma+delta) which is analogous to immunoglobulin but can only recognize antigens presented on MHC molecules.
Usually expressed in noncovalent association with the CD3 molecule.
Where are gamma-delta T cells most often found?
In mucosal surfaces and skin
What features distinguish NK cells from T cells?
NK cells have neither TCR nor CD3. They express CD16 (FcyR), CD56, and CD57. They are morphologically recognizable as LGLs
What properties are common to all antigen presenting cells?
MHC Class II
S100, CD1a (except monocyte macrophages)
What chemical signals attract each of the granulocytes lineages?
Basophils/mast cells: IgE
What are the primary endpoints of complement activation?
Opsonization by C3b
Formation of MAC by C5-9
Activation of basophils by C3a/C5a
Classical pathway of complement activation
Activated by IgG (not IgG4) and IgM.
Fc interacts with C1q, which when activated to C1 generates the C3 convertase, which then becomes the C5 convertase (C14b2a3b).
Alternative pathway of complement activation
Activated by bacterial antigens or complexed IgA
C3b deposits and forms a different C5 convertase (C3bBbP).
Mannose binding pathway of complement activation
Activated by mannose on microbial surface
Binding lectins undergo a conformational change which generate the C3 convertase as in the classical pathway.
What is the structure of MHC-I?
Heterodimer of heavy chain (3 alpha domains) and a light chain (alpha-2-microglobulin)
What is the structure of MHC-II?
Heterodimer of alpha and beta chains each very similar to Ig.
What genes are encoded in the "MHC III" region?
Complement proteins, NOTCH4, 21-hydroxylase, HFE
What are the odds of having an HLA-identical sibling given N siblings?
1 - 0.75^N
What are the clinical manifestations of immunodeficiencies relating to B-cells, T-cells, phagocytes, and complement?
B-cells: Impaired mucosal immunity >> diarrhea, bronchiectasis
T-cells: Viral and fungal infections
Phagocyte defects: Staph and other catalase+ organisms
Complement: Encapsulated organisms (pneumococcus, meningococcus)
RAST (radioallergosorbent test)
An allergen-specific IgE measurement. NOT the skin test used for allergy determination.
How are the function of B-cells, T-cells, NK cells, and neutrophils tested?
B-cells: Antibody levels and responses
T-cells: Flow, skin tests, proliferation assays
NK cells: Chromium release
Neutrophils: Nitroblue tetrazolium, flow, MPO staining
What are the most common complement assays?
CH50 - Functional assay of classical complement (dilutions until serum causes 50% lysis of coated sheep red cells
Specific antigens: C3 (classic pathway), C4 (alternative)
What are CREGs and public antigens?
CREGs are alleles with known serologic crossreactivity
Public antigens are nonvariable regions which confer very high crossreactivity (HLA-Bw4, HLA-Bw6)
How is HLA crossmatching performed?
Flow cytometric crossmatch (more sensitive? eg. Luminex)
Luminex serology (>5000 MFI is positive T or B crossmatch, >10000 MFI predicts hyperacute rejection)).
What HLA and ABO compatibility is required for renal transplantation? Heart/Liver/Lung? HSCT?
Renal: ABO compatible, HLA-A/B/DR matched?
Other solid organ: ABO compatible, HLA optional
HSCT: ABO optional, HLA stringently required (10/10 best)
What IgG subtype does not cross the placenta?