Which cells go under a clonal immune response?
B cells and T cells
What do T helper cells do?
They secrete cytokimes that help B cells to produce better antibodies, activate CTL, and further activate macrophages
When do antibodies enter the serum?
Whenever B cells are activated
What are naive lymphocytes?
lymphocytes that have never seen the antigen and that don't have an effector function
What do effector cells do once the infection is waning?
They become memory cells and retain some activity
When are you "immune"?
When you have memory cells against a certain antigen
Which response is faster and more elevated: the primary response or the secondary response?
The secondary response
What happens if you take a yellow graft and put it on a blue mouse?
It recognizes the yellow as foreign and rejects the graft
A second graft rejection will be _________ than the first.
faster, because of memory cells
What are the two functions of MHC molecules?
they display peptide antigens for recognition by T-cells and determine the acceptance or rejection of tissue grafts between individuals
What do MHC molecules do to display antigens?
MHC molecules put a peptide in their groove that can be recognized by a T cell receptor
What is the cause of specificity in transplants?
While MHC molecules can bind several different peptides, there is only one T cell receptor that can recognize the whole complex
How do T cells recognize a foreign graft?
The T cell recognizes allogeneic MHC molecule whose structure resembles the self MHC- foreign peptide complex
Explain gene expression for MHC class I.
There three different types of molecules (A,B,C) that are on each cell, and one individual has the same combination of HLAs (MHCs) on all cells, both alleles are coexpressed
What does beta-2-m do?
It combines with the HLA class I molecules
How do humans express HLA class II genes differently?
Three different combinations of dimeric molecules are on the cells, one individual has the same combination dimers on all his cells. Class II genes are especially expressed on hemapoeitic cells and antigen-presenting cells.
genes exist in a variety of versions each of which is used by a different individual. MHC/HLA comprises the most polymorphic gene cluster in humans. All alleles are inherited.
How are MHC alleles inherited and expressed?
We receive one allele from our mother and one allele for our father for each A, B, and C. Codominant expression o both MHC alleles.
How many different class I MHC molecules are on one cell?
What is the best possible organ donor?
What is the purpose of polymorphic genes in evolutionary terms?
It ensures that different individual are able to present and respond to different microbial peptides, so we can respond differently
What is important about MHC for a specie's survival?
1. a sufficiently large pool of MHC molecules and 2. they are spread out among individuals
T/F: All of us respond differently to a pathogen
What could a really bad pathogen do to the MHC molecule?
Affect the synthesis of MHC molecules or their ability to chop antigens into smaller pieces, so the infected cell could not be recognized by a T cell
Class I MHC molecules, Class II MHC, T cell receptors and Immunoglobulin (antibody ) all share a common __________.
The simplest antibody is made up of two _________ chains and two _________ chains
An antibody has two identical receptors that see...
a small portion of a natively folded protein
There are ____ distinct polymorphic genes for MHC II
There are ____ distinct polymorphic genes for MHC I
There are millions of different T cell receptors and B cell receptors/antibodies (diversity) because of ________ ________.
Why can't diversity of immunoglobulin and T-cell receptor genes be inherited?
There is not enough genetic material to pass it on
Immunoglobulin has ___ variable region(s) and T-cell receptors have ____ variable region(s).
Of what three pieces are variable regions made
Variable regions are made up of three different pieces-V,D, and J (variability, diversity, and joining)
What are the two parts of TCR?
TCR-alpha (from alpha gene locus) and TCR-beta (from beta gene locus)
What are the parts of a BCR?
Two heavy-chain and light-chain complexes linked by a disulfide bridge
How many V,D,and J alleles are there?
There are about 50 of each; about 125,000 genes possible
How does VDJ recombination work?
randomly cleaving D with J, then the D-J segment combines with a V segment
What are the mechanisms of VDJ recombination?
Rag-1 and Rag-2 proteins are the critical lymphocyte-specific components of the VDJ recombinase. These molecules are expressed in developing B and T-cells and bind to highly conserved recognition sequences that flank each gene segment. Other non-lymphocyte specific enzymes are also participating in the cutting and joining of the ends.
How many times does VDJ recombination take place?
What happens if cleaving goes wrong?
You can fuse a B-cell promoter to an oncogene
What can antibodies do that T-cell receptors cannot?
Isotype switching: Antibodies can change their constant regions after the cell has been activated making them specific to the same antigen but have different functions such as complement fixation and phagocyte binding
The constant (Fc) region is what determines the whether an antibody is one of which kinds?
IgM, IgG, IgA, or IgE
A different Fc region on an antibody can change what functions?
localization in the body, complement activation, and phagocyte receptor binding (which can be recognized by macrophages causing them to engulf the pathogen)
a proteolytic fragment of an antibody that contains the disulfide-linked carboxy-terminal regions of the two heavy chains.It promotes different biological distributions and effector functions by binding to different receptors on cells or complement. Thus antibodies have two biologically critical regions: The antigen recognition site and the Fc region
What determines the isotype of an antibody?
The constant region of the heavy chain
Where are IgG and IgA found?
IgG-serum, IgA-enters into the gut or lung tissues
Every antibody starts out as which isotype?
What is isotype switching?
A kind of recombination that involves looping out and
Function of IgG
neutralization, opsonization, activation of complement, a) IgG is the major Ig in serum - 75% of serum Ig is IgG
b) IgG is the major Ig in extra vascular spaces
c) Placental transfer - IgG is the only class of Ig that crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG. Not all subclasses cross equally well; IgG2 does not cross well.
d) Fixes complement - Not all subclasses fix equally well; IgG4 does not fix complement
e) Binding to cells - Macrophages, monocytes, PMNs and some lymphocytes have Fc receptors for the Fc region of IgG. Not all subclasses bind equally well; IgG2 and IgG4 do not bind to Fc receptors. A consequence of binding to the Fc receptors on PMNs, monocytes and macrophages is that the cell can now internalize the antigen better. The antibody has prepared the antigen for eating by the phagocytic cells. The term opsonin is used to describe substances that enhance phagocytosis. IgG is a good opsonin. Binding of IgG to Fc receptors on other types of cells results in the activation of other functions.
Function of IgM
a) IgM is the third most common serum Ig.
b) IgM is the first Ig to be made by the fetus and the first Ig to be made by a virgin B cells when it is stimulated by antigen.
c) As a consequence of its pentameric structure, IgM is a good complement fixing Ig. Thus, IgM antibodies are very efficient in leading to the lysis of microorganisms.
d) As a consequence of its structure, IgM is also a good agglutinating Ig . Thus, IgM antibodies are very good in clumping microorganisms for eventual elimination from the body.
e) IgM binds to some cells via Fc receptors.
f) B cell surface Ig
Surface IgM exists as a monomer and lacks J chain but it has an extra 20 amino acids at the C-terminus to anchor it into the membrane (figure 9). Cell surface IgM functions as a receptor for antigen on B cells. Surface IgM is noncovalently associated with two additional proteins in the membrane of the B cell called Ig-alpha and Ig-beta as indicated in figure 10. These additional proteins act as signal transducing molecules since the cytoplasmic tail of the Ig molecule itself is too short to transduce a signal. Contact between surface immunoglobulin and an antigen is required before a signal can be transduced by the Ig-alpha and Ig-beta chains. In the case of T-independent antigens, contact between the antigen and surface immunoglobulin is sufficient to activate B cells to differentiate into antibody secreting plasma cells. However, for T-dependent antigens, a second signal provided by helper T cells is required before B cells are activated.
Function of IgA
a) IgA is the 2nd most common serum Ig.
b) IgA is the major class of Ig in secretions - tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity.
c) Normally IgA does not fix complement, unless aggregated.
d) IgA can binding to some cells - PMN's and some lymphocytes.
Function of IgE
crosslinking on mast cells, causing the release of granule contents (histamine) a) IgE is the least common serum Ig since it binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen.
b) Involved in allergic reactions - As a consequence of its binding to basophils an mast cells, IgE is involved in allergic reactions. Binding of the allergen to the IgE on the cells results in the release of various pharmacological mediators that result in allergic symptoms.
c) IgE also plays a role in parasitic helminth diseases. Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.
d) IgE does not fix complement.
the process of attaching opsonins such as IgG (or complement) to microbial surfaces to target the microbes for phagocytosis by macrophages via their Fc receptors, (or NK cells or complement receptor)
antibody-dependent cellular cytotoxicity
NK cell sees infected cell because it has IgG on it surface
T/F: Isotype switching does not entail DNA rearrangements
T/F: Gene segments that reside of different chromosomes are joined
Rearrangements of the T-cell receptor generate different isotypes during an immune response
Intervening gene segments within a gene locus are removed and the ends are rejoined
What does the Fc portion of the antibody do?
When bound to an antigen, the Fc portion can attract complement and phagocytes.