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Chapter 16 Lecture 2 Preparation for Adaptive Immunity Response (The…
Chapter 16 Lecture 2
Preparation for Adaptive Immunity Response
The Roles of the Major Histocompatibility Complex and Antigen-Presenting Cells
Skin Grafting- type of surgery that is the transplantation of skin and tissue.
Scientists took skin from one animal and had attached it to another animal, to try and treat burns, they had discovered that the animals were not closely related and the skin had very quickly been rejected by the recipient.
The graft recipient had a very strong immune response to a specific protein that had been found on the other animals skin, resulting in it being rejected.
This helped scientists understand how the body is able to distinguish “self from nonself”.
Major histocompatibility complex (MHC)
“MHC protein” is the genes. “MHC” is used to describe both protein product and gene Histo meaning tissue
In humans, MHC is located on each copy of Chromosome 6.
MHC must have some natural function
Immunologists have determined that each MHC molecule has an antigen-binding groove, that lies between two polypeptides that make up an MHC.
Inherited Variations in the amino acid sequences of the polypeptides which modifies the shapes of MHC binding sites, and that determines which epitopes that can bound and presented.
Cells of adaptive immunity recognize epitopes that are bound to MHC molecules.
There are two classes of MHC proteins
Class I
Class II
Class I
Molecules are found on the cytoplasmic membrane of all human cells except red blood cells.
Professional antigen- presenting cells (APC) regularly present antigens.
Class I and II
includes macrophages, B cells, and Dendritic cells (named because they have many long, and thin cytoplasmic processes called dendrites.)
Phagocytic dendritic cells are found under the skin and mucous membranes.
Some dendritic cells extend dendrites between skin cells or through a mucus surface to sample antigens.
Example- Submarine extending periscope to get a view of surface activity.
Dendritic cells collect antigens and then move to the lymph nodes in order to interact with the cells of adaptive immunity.
Phagocytes in the brain, microglia, and stellate macrophages in the liver called Kupffer cells, may also present antigens in certain conditions.
These cells are called non professional antigen presenting cells
Professional APC
The cytoplasmic membrane of a professional apc had around 100,000 MHC II molecule, but has both class I and II.
These molecules can bind many thousands of different epitopes because they are not specific like enzymes.
Their binding diversity depends on genes.
Some epitopes won't be bound to a particular person meaning they won't usually cause an immune response.
MHC molecules determine which epitopes might trigger responses, and that explains why some people are allergic to peanuts and others are not.
Antigen Processing
Before MHC proteins can display epitopes, antigens must be processed to isotate epitopes.
Can occur via 2 different processes
Endogenous: come from cells cytoplasm or from pathogens living within the cell.
Exogenous: have extracellular sources, such as pathogens in the lymph.
Processing endogenous antigens
Include epitopes of the polypeptides, move into the ER and bind onto complementary antigen-binding grooves of MHC class I molecules
The ER membrane now loaded, is packaged by a golgi body to form vesicles
Each vesicles membrane fuses with the cytoplasmic membrane
Cell displays the MHC I protein-epitope complex on cell surface
Every nucleated cell in the body makes MHC class I, which allows immune cells to detect all the antigens inside cells
Processing Exogenous antigens
In contrast only dendritic cells process exogenous antigens
A lysosome, which contains MHC class II molecules in its membrane, and fuses with the Phagosome, binding complementary epitopes.
Vesicles fuses with the cytoplasmic membrane.
Leads to leaving MHC class II-epitope complexes on the cells surface.
Empty (not bound to epitopes) MHC II molecules are not stable on a cells surface.
Degrades as a result
T Lymphocytes (T Cells)
Often act against body cells that harbor intracellular pathogens, like a virus, and act against body cells that produce abnormal antigens such as cancer cells
T cells act directly against antigens, immune activities called cell-mediated immune response
Adult red bone marrow produces T cells, which get released into the blood.
Chemotactic molecules attract T lymph from blood vessels to the thymus, where they adhere under the influence of sticky adhesive chemicals and molecular signals from the thymus.
T cells account for 70-80% of all lymph in blood
T cell maturation involves the production of about half a million copies of a protein called T cell receptor, (TCR)
Each T cell randomly chooses and combines segments of DNA from TCR genes to create a new genetic combination specific to that cell which codes for a cells unique and specific TCR.
Specificity of the T Cell Receptor (TCR)
In the body there is at least 10^9 different TCR’s--each specific to a different T cell.
Each T cell expresses one TCR.
TCR binds with only one unique epitope.
EX- Imagine a locksmith who has a copy of every possible key, to fit every possible lock. If a customer at the shop arrives with a lock needing a key, then the locksmith can provide it (sometimes this could take a while to find the right key).
Similarly you have a TCR complementary to every possible epitope in the environment, though you will only encounter some of them.
EX- you have lymphocytes complementary to epitopes of stingray venom, though its very unlikely that you will be stabbed by a stingray.
Types of Lymphocytes
Immunologists recognize three main types of T cells based on surface molecules and characteristics functions.
Cytotoxic T cells
Distinguished by copies of its own unique TCR.
Presence of CD8 cell-surface glycoproteins.
These lymphocytes directly kill other cells, such as those infected with viruses or other intracellular pathogens.
They also kill abnormal cells such as cancer cells.
Helper T cells
Are distinguished by the presence of CD4 glycoproteins, which are found in the cells cytoplasmic membranes.
Th cells are also called CD4 positive cells
These cell are called helpers because their function is to help regulate the activity of b cells and cytotoxic T cells during immune responses.
They provide necessary signals and growth factors.
During an immune response there are two main subpopulations of helper T cells.
Type I helper T cells
assist cytotoxic t cells, stimulate and regulate innate immunity.
Type II helper T cells
function in conjunction with B cells.
Immunologists distinguish these two cells on the basis of their secretions, and by characteristic cell-surface proteins.
Helper T cells secrete cytokines that regulate the entire immune system
Both adaptive and innate portions.
Regulatory T cells
Also known as suppressor T cells.
Identified by the presence of CD4 and CD25 glycoproteins.
Not completely known how they work, but is known that they are activated by contact with other immune cells.
They secrete cytokines different from those secreted by helper T cells.
Generally suppress immune responses and promote tolerance of certain antigens.
Clonal Deletion of B cells
Occurs in bone marrow
Prevents B cells from attacking autoantigens by destroying those with BCRs that complement autoantigens
Some self-reactive B cells become inactive or change their BCR instead
Cells that survive are sent to the spleen where they further mature
Steps of clonal deletion of B cells:
1)Stem cells in red bone marrow generate a host of B cells.
2)These B cells randomly generate a BCR with a particular unique shape.
3)Cells with BCR that’s complementary to an autoantigen bind with it and this stimulates apoptosis (cell suicide)
4)Cells with a non-complementary BCR are released into the blood
Immune Response Cytokines
Cytokines: Soluble proteins secreted by certain cells to act as intracellular messengers
Many immune system cytokines have nearly identical functions
Cytokine network: complex web of signals among all cell types in the immune system
Interleukins (ILs):
Send signals among leukocytes
However, can sometimes be used by other cells
37 ILs discovered in the human body
Interferons (IFNs):
Inhibit the spread of viral infections
Can also function as cytokines
The most important interferon that functions this way is the gamma interferon
Growth Factors:
Stimulate leukocyte stem cells to divide
Ensure the body is supplied with all types of WBCs
The body can control adaptive immune response by limiting production of growth factors
Tumor Necrosis Factor (TNF):
Secreted by macrophages and T cells
Kills tumor cells
Regulates immune response and inflammation
Chemokines:
Signal leukocytes to move (Chemotaxis)
Usually call leukocytes to a site of infection or inflammation