Immunology and Complement Flashcards
CD5
found on B-1 cells, predominant cells present in Chronic Lymphocytic Leukemia
CD27
found on memory B cells
Bcell corecepter
made up of CD21 CD81(TAPA1) and CD19, helps to encourage activation.
CD1
molecules that present lipids and glycolipids expressed by macrophages and dendritic cells . Similar to MHC1 molecule. structure with deep grooves that lipid tails are kept in and polar head faces outside. separate molecule and b-2-microglobulin added onto the structure
CD22
negatively regulates Coreceptor for B cell (CD21, CD81, CD19)
CD32
low affinity receptor for the Fc portion of IgG, expressed on virtually all mature Bcells, feedback loop when bound to IgG- halts production of antibody
CLL
Chronic lymphocytic leukemia- CD5 is the primary cell marker in this type of leukemia
TAP-1 and TAP-2 genes
gene makes protein products that help transport peptides into the endoplasmic reticulum for binding to the MHC class 1 molecule
B cell receptor
The total structure is made up of an antibody on the cell surface (either IgM monomer or IgD) and the IgAlpha (CD79alpha) and IgBeta (CD79Beta)
ITAM
immunoreceptor tyrosine-based activation motifs
CD40
on Bcell binds to CD40L (CD154) on Tcell, involces the isotype switching of antibodies class of B cells
CD28
on T cell surface, reacts with B7 on Bcells surface, important for Tcell synthesis of IL-2 a T cell growth factor, needed for T cell proliferation
CTLA-4
CD152 has a similar structure to CD28 so it binds to B7, however it is a negative feeback loop that then terminates the response
CD4:CD8 ratio
2:1
Tcell receptor
made from a structure similar to an Ig molecule, within the Ig superfamily. it has variable and constant regions. Its a noncovalently associated with another structure that contains two domains (CD3) and this is paired with two identical zeta units (CD247) that are ITAMs. CD3 and CD247 come together to initiate signal transduction
Digeorge Syndrome
Deletion of a small segment of chromosome number 22. Autosommal dominant. Among other things, thymic aplasia- lack of mature T cells affecting ability to amount appropriate immune response
X-linked agammaglobulinemia
lack of bruton’s tyrosine kinase. enzyme involved in intracellular signaling for pre-B cell transition. With lack of BTK cells are susupended in the pre-B cells stage.
NK cells
CD16 CD56
NK T cells
CD161c. REACTS TO c1d as opposed to MHC molecules
T reg cells
type of CD4 cell that regulates the actions of other T cells, CD25
TH17
proinflammatory cytokine
Hyper IgM syndrome
Dysfunctional CD154 (CD40L) which binds to CD40 on B cell and stimulates the isotype or class switching of antibodies from the B cell
CD8
cytotoxic T cells, interact with MHC class I molecules, along with Fas-Fas ligand binding induces apoptosis of infected cell.
IFN-Gamma
interferon gamma- activates macrophages and regulates cells
GM-CSF
granulocyte-macrophage colony stimulating factor. activates macrophages
TNF-alpha
Tumor necrosis factor alpha activates macrophages
IL-3
interleuken 3 involved in hematopoiesis
TNF-beta
Tumor necrosis factor-Beta involved in imflammatory responses
IL-4 IL-5
activates B cells
IL-10
involved in hematopoiesis
TGF-beta
Transforming growth factor-beta, inhibits monocyte activation
IFN-gamma
Promotes synthesis of IgG3
Antibodies that are the best activators of compliment
IgG3 and IgM: In order IgM>IgG3>IgG1>IgG2
Where and when does C1 bind
It binds to the Fc portion of the antibody when bound to corresponding antigen. Binds to one IgM molecule and 2 IgG molecules
Where is MBL found
in circulation in conjuction with proteases (MASPs) Manose associates serine proteases
In MBL pathway what cleaves C2 and C4
MASP-2
Explain C3b process in alternative pathway
C3b binds to the cell surface accompanied by Factor B, Factor D cleaves Factor B into Bb. C3bBb form complex together, increases opsonization of pathogen
Factor P
properdin, stabilizes C3bBb
C1 esterase inhibitor
Binds to C1r and C1s, causes them to unbind from C1q, also inhibits MASP-1 and 2 in MBL
CD55 role
DAF- dissociates C4bC2a complex as well as (MCP and CR1) also disrupts the C3bBb complex
CD59 role
prevents C9 binding and formation of MAC by binding to C5b-C8 complex
Opsonins
Makes something more likely for pathogen removal by tagging it, C3b, C4b, iC3b
C-reactive protein
an acute phase reactant, binds to polysaccharide phosphocoline express on surface of many bacteria (strep pneumoniae) and also activates the complement pathway
complement anaphylatoxins
C3a C5a
Half life of IgG
25 days
GM
genetic marker only present on IgG antibodies that is specific to the person the IgG came from (think mitochondrial DNA) think of this as an ‘antigen’ that is present on the antibody. antibodies against these specific GM’s can be made.
Function of antibodies 2 fold
- opsonization making the antibody more easily digestible for phagocytosis 2. neutralization for example Ig binds to Viruses blocking the virus from attachment to target cell.
Heavy chains
alpha, beta, gamma, delta and epsilon
Light chains
kappa, lambda
Which antibodies have J chains
IgM and IgA, only secreted polymers
enzyme affect on antibodies
papain- splits into three parts, two Fab portions and one Fc portion. pepsin, splits into two parts (peppy le pu makes two) one connectd Fab unit +Fc fragments
Ig supergene family
makes up IgG, MHC, CD4 and Tcell receptor
In electrophoresis of immunoglobulin what moves fastes towards the anode?
albumin
what move slowest towards anode in IG electrophoresis
IgG
Polyclonal gammopathy
chronic infection or inflammation, immune mediated disease, liver disease, occult hearworm disease, manifests with stead and gradual increase in gamma (right most quadrant of graph)
Monoclonal gammopathy
narrow spike of alpha2, beta, or gamma, light chains-bence jones proteins. 1. multiple myeloma 2. waldenstrom’s macroglobinlinemia, 3. lymphoma 4. CLL
Half life of IgG antibody
23 days
Half life of IgM antibody
5 days
Staph protein A
has very high affinity for IgG except IgG3 (test read and performed similar to solid phase- positive is monolayer of red cells, negative is a cell button)
IgG antibody subclasses, not bound to macrophages
IgG2 and weakly IgG4, do not bind to Fc receptors on phagocytes therefore if antibody is on cell it will not be phagocytosed by macrophages.
How can it be used clinically to know subclass if IGg
If IgG2 anti-yta will bind transfused red cells but will not be destroyed because phagocytes cannot ingest without being able to bind Fc receptor on antibody. RBCs will circulate normally with antibody bound.
Kappa gene chromosome
2
Lambda gene chromosome
22
Heavy chain gene chromosome
14
How do we get multiple antibodies with different specificities
gene rearrangement. Genes for antibodies are present in pieces that can be combined into many different combinations to form a large number of unique antibodies
Ig Diversity what type of recombination
V(D)J recombination, one gene segment recombines with other gene segments to form a single unique gene, this occurs at birth.
best IgG at activating complement biding c1q
IgG 3
best IgG at activating alternate pathway binding C1q
IgG2
GM and AM
genetic marker on IgG, AM marker on IgA. this are allotypes or parts of antibody that are common to host
Isotype
Heavy chain classification, A, M, G D, E
idiotype
specific to the antigen stimulating the response, all antibodies that react with same antigen have same idiotype, regardless of class!
GM applications
- monitoring Bone Marrow grafts (monitor allotype of the graft) 2. forensic medicine, detectable in blood and semen 3. parentage testing (previously)
