1.5.2 Humoral Effector Mechanisms Flashcards
What is an antigenic shift?
Mutation of epitopes so that antibodies can no longer bind
What are characteristics of immunogens?
These are greater than 10kDa, able to elicit an immune response w/o help
What is a hapten?
A small antigen that must be bound to a large molecule to elicit an immune response
Where are plasma cells concentrated?
These are concentrated in the bone marrow and medulla of lymph nodes
How are antibodies transported?
By blood
What antibody classes areinvolved in neutralization of toxins?
IgM, IgG and IgA
What is the mechanism by which antibodies neutralize viruses and toxins?
Bind viruses and prevent attachment to cells and bind toxins and prevent it from binding receptors on cells
What antibody classes are involved in opsonophagocytosis?
IgM and IgG
What is the mechanism by which antibodies carry out opsonophagocytosis?
These coat the microbe with antibody. IgG-Ag complexes or complement bind macrophages and neutrophils via Fc-gamma-R or complement receptors and induce phagocytosis; induces ROS, NO, and proteolytic enzymes
What is the major site for phagocytosis?
Spleen
Phagocytosis is the major mechanism against what foreign pathogen?
Encapsulated bacteria
What is the class of antibody that is involved in antibody-dependent cellular toxicity?
IgG
What is the mechanism of antibody-dependent cellular toxicity?
IgG-Ag complexes bind to Fc-gamma-R on NK cells. The NK cells release perforin and granzyme B
What antibody class is most involved with eosinophils and mast cells?
IgE
What is the role of IgE and eosinophils?
These bind to Fc-epsilon-R and work against helminths and have a role in asthma
What antibodies classes are involved in mucosal immunity?
IgA and IgM - IgA production is induced by TGF-beta produced in mucosal-associated lymph tissue
What are some mechanisms of the immune system in the gut?
The villi drain into the mesenteric lymph node
M cell - transports antigens across intestinal wall and brings it to the peyers patch
What are the characteristics of parenteral polio vaccines?
Intermuscular; Induces serum IgG; Neutralizes virus in blood; Protective no CNS infection; does not block viral entry and replication; permits carrier state
What are the characteristics of oral polio vaccines?
Oral; Induces secretory IgA; neutralizes virus in GI tract; blocks viral entry and replication in gut; does not permit carrier state
What is the mechanism of fetal and neonatal immunity?
FcRn binds free IgG and transports it across the placenta
Is hypogammagloblinemia normal during infancy
Yes
What are the major characteristics of the complement system?
effector system of Innate and Adaptive immunity; more than 25 serum proteins with biological activity; effects are mediated directly by peptides or through complement receptors
What is the key step in the activation of the complement system?
formation of a C3 convertase
What are the characteristics of the classical pathway?
IgM or IgG bound to antigen recruits C1q; C1q binds the Fc region of IgM or IgG; C1q recruits C1r and C1s to form the active enzyme that cleaves C2 and C4 (C3 convertase)
What are the characteristics of the alternative pathway?
Spontaneous C3 hydrolysis leading to C3b on microbial charged surface; recruiting of factor B; Cleavage of Factor B by factor D; C3bB = C3 convertase; Factor P creates C3bBbP which is a very stable convertase leading to cleavage of C3 to C3a and C3b aids in amplification of all pathways
What is the defining characteristic associated with the lectin pathway?
triggered by mannose-containing microbial carbohydrates
What are the components of the C5 convertase?
C3 convertase and C3b
What is the reaction the C5 convertase helps carry out?
Leads to conversion of C5 to C5a and C5b
What is the role of C5a?
will be a key component in inflammation
What is the role of C5b?
aids in the formation of the MAC complex
What is the function of the MAC complex?
poly C-9 puts physical holes in the plasma membrane leading to cell lysis
C3b and C4b carry out what function of the complement?
opsonization
C5a carries out what function of the complement?
Inflammation - chemotaxis of neutrophils relies on C5a
C3b and iC3b have what functions of the complement?
Solubilizing and clearance of immune complexes from circulation
C3d is a co-activator for what cells?
B cells
Mast cells, basophils, and SMCs have what receptor to work in anaphylaxis?
C5aR
Phagocytes have what receptors for complement to aid in phagocytosis?
CR3 and CR4
What is the receptor on erythrocytes what aids in clearance of soluble immune complexes?
CR1
What are the characteristics of LAD-1?
CD18 deficiency leading to poor cell adhesion proteins. This leads to poor neutrophil adhesion and poor opsonophagocytosis using C3b or C4b
C3 complement deficiency usually leads to?
Fatal susceptibility to infection
C2 and C4 complement deficiency usually leads to?
Increased immune complex disease
C9 deficiency leads to?
Neisseria
When measuring complement what does ELISA do?
It measures the level of function for each protein in the pathway
When measuring complement what does total hemolytic complement measure?
CH50 units. Measures the overall production of the complement
What does an opsonophagocytic activity test do?
measuring the uptake of antibody-coated bacteria by neutrophils in the presence of fresh nonimmune serum
The C1 inhibitor has what role?
a serine protease that dissociates C1qrs, which is involved in the classical pathway. This regulates the complement pathway
What is hereditary angioedema?
unabated classical pathway activation leading to production of anaphylatoxins and resulting edema. Result from a loss of the C1 inhibitor
What is the role of decay accelerating factor?
Preventing factor B from binding to C3b - blocking the formation of the C3 convertase (alternative pathway)
What is the role of complement receptor 1?
Prevents Factor B from binding C3b - blocking the formation of the C3 convertase alternative pathway
What is the role of Factor I?
degradation of C3b and C4b to iC3b and iC4b - blocking the formation of the C3 convertase
What is the role of Factor H?
Binds C3b and acts as a co-factor for Factor I - blocking the formation of the C3 convertase
What is the role of C4b binding protein?
Binds C4b - blocking the formation of the C3 converstase
What is paroxysmal nocturnal hemaglobinuria?
Deficiency in enzyme that creates the glycolipid anchor that tethers DAF and MCP to membrane. Sporadic hemolysis due to spontaneous C3 activation on membranes of RBCs
Homologous restriction factor does what?
Blocks MAC
What is the role of anaphylatoxin inhibitor?
Cleaves and inactivates C3a, C4a and C5a
What is the role of the S protein?
blocks MAC by attaching C5b678 to C9
What is a reason the xenotransplantation is difficult?
Transplanting organs from pigs has problems because pig complement reg proteins do not regulate human complement