Humoral Immunity Flashcards
Which immunoglobulin isotypes can cross the placenta?
IgG
What complement protein subunit initiates the formation of the membrane attack complex?
C5b
What are the polypeptide chains that make an antibody?
2 identical heavy chains
2 identical light chains
What chromosome are the heavy chain genes on?
14
What chromosome are the light chain genes on?
2 (kappa) and 22 (lambda)
In early B-cell differentiation what are the bone marrow genes rearranged to generate?
Immunologlobulins
Which comes first; the Ig heavy or light chain?
The heavy chain comes first
What are the protective mechanisms of binding antibodies to anitgens?
Agglutination Opsonization Neutralization Activation of complement Inflammation Antibody-dependent cell-mediated cytotoxicity
What does agglutination do?
Enhances phagocytosis and reduces the number of infectious units to be dealt with
What does neutralization do?
Blocks adhesion of bacteria and viruses to mucosa and blocks active site of toxin
What are the characteristics of follicular B cells??
T-dependent isotype-switched high affinity; long lived plasma cells
What are the characteristics of marginal zone B cells?
T-independent (IgM); short lived plasma cells
What are the characteristics of B-1 B cells?
T-independent (IgM); short lived plasma cells
CD5 positive
What are T-independent antigens?
Polysaccharides, nucleic acids, lipids
What are T-dependent antigens?
Protein antigens
What are the secondary immune organs?
The lymph nodes and the spleen
What is somatic hypermutation (SHM)?
Introduction of a single nucleotide substitution (point mutation)
Follows B-cell activation by an antigen
More common in the V chain of heavy chain (results in higher affinity)
What is class switching?
Process by which an Ig changes class or isotype The antigenecity is preserved
Where does class switches occur?
On the heavy chain
When does class switching occur and what happens during it?
It occurs during the immune response and invovles the deletion of the C segment
What are some of the factors in immunoglobulin diversity?
V(D)J recombination Somatic hypermutation Class switching RAG1/RAG2 Base excision and repair
What is hyper IgM syndrome?
Results from mutations affecting class switching which is rare Decreases the IgG, IgA, IgE
How do you treat hyper IgM syndrome?
IVIG, BMT
Describe to me IgM;
A pentamer which is the first Ig made by a fetus and B cells
Expressed as membrane bound Ig
Opsonization (Fc receptor - phagocytes)
Where is IgM present in the mother?
In colostrum (momma milk) to protect newly born
Is IgM produced in secondary immune response?
Sometimes
Tell me about IgG;
Major serum Ig and most abundant
Major immunoglobulin of secondary immune response and in the extravascular spaces
Involved in opsonization
Which Igs fix complements;
IgM, IgG
Explain the IgA;
Found in serum and body secretions, major secretory Ig on mucous surfaces
Where is IgA present in the mom?
Colostrum and momma milk
What about IgE?
Least common serum Ig which binds to basophils and mast cells
What is IgE active in?
Allergic and hypersensitivity rxns Parasitic infection (helminths) and binds to Fc receptors on eosinophils
Tell me about those IgD;
Found on membrane of mature B-cells and have a small presence in serum
B cell surface Ig
What does IgD do biologically?
Who knows
Describe IgA1;
Monomeric and found in the blood and extracellular spaces
Describe IgA2;
Dimeric and found in mucous and secretions
What are the characteristics of the primary antibody response?
Usually 5-10 days, has a small peak response has more IgM than IgG and has a lower average antibody affinity yet more variable
What are the characteristics of the second antibody response?
1-3 days, has a large peak response, relatively increases IgG and sometimes IgA and IgE when there is heavy chain isotype switching
Higher average antibody affinity
What is the process of opsonization and phagocytosis?
The C3b (C4b) binds to the microbe
The C3b is recognized by a phagocyte C3b receptor
Phagocytosis and microbe killing occurs
What is the process of compliment-mediated cytolysis?
The C3b binds to a microbe activating the late components of complement
There is a formation of the membrane attack complex (MAC)
Osmotic lysis of microbe occurs
What is the process of stimulation of inflammatory reactions?
Proteolysis of C3, C4 and C5 to release C3a, C4a and C5a
Recruitment and activation of leukocytes by C5a, C3a and C4a
Destruction of microbes by leukocytes
What is the function of C2b?
Prokinin: Cleaved by plasmin -> Kinin -> Edema
What is the function of C3a?
Anaphylotoxin: Activate basophils and mast cells to degranulate -> inc vascular permeability and contraction of smooth muscle cells -> anaphylaxis
What is the function of C3b?
Opsonin: promotes phagocytosis by binding to complement receptors -> activation of phagocytic cells
What is the function of C4a?
Anaphylotoxin: weaker than C3a
What is the function of C4b:
Opsonin: promotes phagocytosis by binding complement receptor
What are the ligand for complement receptor CR1 (CD35)?
C3b > iC3b
C4b
Where is compliment receptor CR1 (CD35) distributed?
B-cells
Phagocytes
RBC
Follicular dendritic cells
What are the ligands for CR2 (CD21)?
iC3b
C3dg
Where is CD2 (CDdg) found?
B cells and epithelial cells
What are the ligands for Cr3 (CD18/11b)?
iC3b
Zymosan
ICAM-1
Where is CR3 (CD18/11b) found?
Phagocytes
NK cells
Follicular dendritic cells
What are the ligands for CR4 (CD18/11c)?
iC3b
Where is CR4 found?
Phagocytes
What does C5a and b do?
C5b initiates assembly of the MAC
C5a stimulates inflammation
What are the three compliment pathways?
Classical, lectin, alternative
Where to all the compliment pathways lead?
To the formation of the membrane attack complex
What are three mechanism of humoral immune evasion?
Antigenic variation
Inhibition of complement activation
Resistance to phagocytosis
If there is a defective FasL on a T-cell what syndrome does it cause?
Lymphoproliferative syndrome
IL4 stimulates IL4R to do ___ while CD40L stimulates CD40 to ___.
Enter mitosis
Class switch
What organisms are splenectomy patients vulnerable to?
Encapsulated organisms because you need marginal zone B cells to react but these reside in the white pulp of spleens. Thus these pts have normal reactions to protein antigens but not the lipids and polysaccharides
so vaccinate these pts against organisms like S. pneumo
What is the cause of Hyper IgM syndrome?
if T cells do not express the CD40L when activating B cells then no class switching is induced
so then pt is only able to produce IgM when mounting an immune response
Leaves pt susceptible to repeated chronic infections
What are the three types of evasion from the humoral system?
Antigenic variation
Inhibition of complement activation
Resistance to phagocytosis
