Lecture 5: adaptive immunity-lymphoid organs Flashcards
Three major group of receptors
Pattern Recognition Receptors
Recognize molecules common to groups of pathogens (or damaged tissue)
Discussed previously
Major Histocompatibility (MHC) Receptors
Recognize normal cell surface MHC proteins
Lymphocyte antigen receptors
Recognize antigens (proteins and sugar chains) that are NOT normally present
How was MHC discovered
Tissue grafts with mice
Could transfer tumor tissue successfully between closely related mice
Not between mice of different strains
Unless you first killed their immune system
So tissues carry antigens unique to that individual
MHC type I are found in and do what
Marks cells as self
Found on the cell surface of most nucleated cells within the host tissues
Genetically the same in a given individual
Used by NK lymphocytes to identify cells as normal
MHC I work by
Binds to internal proteins and displays them on cell surface
Have a binding site for lymphocytes so they can check out the internal proteins
Helps T lymphocytes recognize viruses, tumors and foreign grafts
Most nucleated cell types within the body display some MHC antigens
Except?
Red blood cells (+/- neurons, sperm and ova,cells forming the placenta)
Blood transfusions between animals is relatively easy, tissue grafts between animals is almost impossible
MHC II is
MHC type II is found on professional phagocytes and antigen presenting cells
Fragments of pathogen or damaged tissue are broken down into antigen and attached to antigen presenting receptors
The antigen presenting receptors are type II MHC molecules
Antigen presentation is required to generate an adaptive immune response
MHC III function
Pattern Recognition Receptors
Signaling molecules
Complement components
Lymphocyte antigen receptors are found on
Found on T and B cells
Lymphocyte Antigen Receptors work by
Receptors on B cells are released→Antibodies
T cells have antibody-like receptors
Genetic material is randomly re-arranged and modified
Allows for diversity and an increased likelihood of Ag binding
On each lymphocyte the lymphocyte antigen receptor binds to only one specific antigen
Millions of lymphocytes with different antigen receptors
Only cells with receptors for non-self are allowed to survive
If the cells are going to attack host cells, they are destroyed by apoptosis
T-lymphocytes are produced in and found in
Produced in the bone marrow, mature in thymus, reside in lymph nodes and spleen
Circulate in blood and through the tissues
The predominant lymphocyte found in blood
T cell education occurs in
Thymus
T cell education is
Initially T cells are selected for cells that will:
Recognize MHC receptors (self) so that they can communicate with other cells
Further selected for lymphocyte antigen receptors that:
Are not activated by self antigens
Function of T cells
adaptive immune response
Effector cell line for cell mediated immunity
Specific– the receptors on the cells are randomly generated
One cell is only able to recognize one antigen
Types of receptors on t cells
Lymphocyte antigen receptor
Receptors for MHC antigens (self)
T cells do what
The lymphocyte antigen receptors and MHC receptors are next to each other
T cells bind to other cells using MHC and test the displayed antigens using their lymphocyte antigen receptors
Tolerance in the immune system is
“Tolerance”
Failure of the immune system to respond to an antigen at a second or subsequent presentation.
An important method of telling self from non-self.
Normal T lymphocytes are tolerant of normal tissue.
T cell activation occurs by
Occurs when a T cell lymphocyte antigen receptor binds its specific antigen.
Requires Ag presentation
Activate the appropriate, specific, T cell
T Cell with a receptor for that antigen
Initial activation is called priming.
Multiply and differentiate.
New cells are clones of the original cell- all recognize the same antigen.
Why are dendritic cells important for T cell activation
Reside in tissues
Use pattern recognition receptors to identify pathogens and damaged cells
Phagocytose pathogens and damaged cells.
Degrade ingested material.
Take components of this material and display them on the surface with MHC antigen – Ag presentation.
Dendritic cells move to lymph nodes.
What happens to T cells when activated by an antigen
Concentrate at sites of inflammation and draining lymph nodes.
Activation of T cells typically occur when
Typically, an abnormal protein displayed on a MHC molecule
Virus infected cell with virus antigen on its surface
Dendritic macrophage displaying on its surface bits of material it has phagocytosed.
Different types of t cells
Helper T cells (stimulates the immune response)
Suppressor T cells (tone down the immune response)
Cytotoxic T Cells (kill infected/abnormal cells)
Recognize non-self antigens (bound to MHC complex)
Destroy these cells by releasing.
Interferon (shuts down virus production)
Perforin which punches holes in the cell
Memory T Cells
Similar appearance but different functions
Memory t cells are and good for
Some move to areas of inflammation, others to lymph nodes
More rapid response when the same antigen is seen again
More cells, better cells
Long lived – this is why vaccines work
T cell mediated immunity is
Takes time to develop (days to months)
Specific for a particular antigen
Involves memory so more rapid and efficient at a second presentation.
An example of ADAPTIVE IMMUNITY
Importance of T cell immunity
Viral infections
Graft rejection
Essential for B cells to work (part of the “second signal”)
Identifying self from non-self
Self does not have surface molecules that react with pattern recognition receptors.
Self has APPROPRIATE MHC antigen
Some lymphocytes are checked specifically for this.
Lymphocytes are tolerant to self antigens normally displayed on the cell surface
No lymphocyte antigen receptor for self-molecules
B lymphocytes are produced in
Produced in the bone marrow
Mature in bone marrow or in lymphoid tissue within the gut.
B lymphocytes are found in
Travel through the blood to populate:
Lymph nodes
Spleen
All other lymphoid tissue
B lymphocytes do what
Humoral Immunity: produce immunoglobulin.
Some is bound to cell surface to act as a receptor (lymphocyte antigen receptor)
Some is released from the cell as antibody.
Adaptive immune response
Specific: a B lymphocyte only recognizes one antigen
B cell activation is caused by
B Cell binds antigen using its surface antigen receptor
Antigen can by soluble or cell bound.
MHC is not required
Usually needs a second signal to complete activation.
B cell activation second signal is
Often by helper T cells
The activated T cell secretes molecules (cytokines) and express surface molecules that activate the B cell.
Binding of Ag to pattern recognition receptors
Typically, parts of bacterial cell wall
Lipopolysaccharide
Useful in:
Inflammation
Vaccination
B lymphocytes when activated do what
Clone themselves
All respond to the same antigen
The strength of binding may improve
Some become plasma cells→ make antibodies
Some become memory cells
Plasma cells do what
Antibody Factories
Secrete immunoglobulin
Release into the circulation
Binds antigen and inactivate it (more about this later)
memory B cells are
Persist for years
Respond rapidly when antigen is seen for a second time
Numbers increase with subsequent exposure
Efficiency of binding increases with time
More effective
Benefits of memory B cells
Rapid production of effective antibody
Called an anamnestic or secondary response (as opposed to a primary response)
Same thing for memory T cells and cell mediated immunity
Basis for vaccination
Organs of the immune system are organized into
Lymphocyte production
Primary lymphoid organs – lymphocyte development and differentiation
Secondary lymphoid organs – lymphocytes interact with antigen
NIH: Great resource
The big four organs of the immune system
Bone marrow
Thymus
Spleen
Lymph nodes
Bone marrow is the site of
Formation of white and red blood cells
Maturation of red cells and many white blood cells
Site where lymphocytes are produced
The thymus does what
Largest in early life
T lymphocytes migrate from the bone marrow to the thymus
A primary lymphoid organ
T Lymphocytes divide within the thymus
Randomly generate new antigen receptors
About 98% of T cells die in the thymus because they react to normal tissue or they don’t recognize host MHC
Only useful mature T lymphocytes are released.
They move to the secondary lymphoid organs.
Tonsils, spleen, lymph nodes, peyer’s patches +/- bone marrow
Lymph nodes do what
A secondary lymphoid organ
Contain many T and B lymphocytes
A connective tissue support structure
Contain many antigen presenting cells (dendritic cells and macrophages)
Plasma cells
Lymph is filtered through the lymph nodes.
It brings immune cells and antigens with it
What is lymph
Starts as tissue fluid (from blood capillaries)
Added proteins and fats
The spleen is
What cavity is it found in?
Abdomen
Some similarities with lymph nodes
It filters blood not lymph
Has red and white pulp
Red pulp in the spleen has
Macrophages remove old red blood cells (iron recycling)
Contains many monocytes.
White pulp in the spleen is
Rich in T and B cells
Lymph nodes increase in size when
In response to inflammation
Infiltrated by tumor
We palpate lymph nodes to
Detect disease
Localize disease
