Adaptive Immunity Flashcards
What are the phases of adaptive immune response (4)
Establishment of infection
Induction of adaptive response
Adaptive immune response
Immunological memory
What are the two key cells of the adaptive immune response? (2)
B and T lymphocytes
How do B and T lymphocytes recognise antigens? (2)
Express unique receptors for antigens
T-cells and B-cells have antigen receptors
T-cell receptor (TCR) and B-cell receptor(BCR) – both specific for only one antigenic determinant
What are the functions of B-lymphocytes? (4)
Produce antibodies (Humoral immunity)
10-15% of lymphocytes
Triggered by antigen to differentiate into plasma cells and memory B-cell
Combat bacterial and some viral infections
What are the functions of T-lymphocytes? (3)
Cell mediated immunity
75-80% of lymphocytes
Combat viruses, fungi, intracellular bacteria and cancerous cells
How do B and T lymphocytes produce a response? (5)
Receptors recognise antigens
T and B cells selected as they can recognise the antigens
B and T cells expand to produce larger numbers (clonal expansion)
This produces effector cells which directly deal with the antigen
Also produces memory cells - long-lived cells that recognise antigen and more rapid response if encounter same antigen again
What is immunological memory and why is it important? (3)
Ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously
This reflects the clonal expansion lymphocytes with specificity for the antigen
Harnessed in vaccination in which pathogen antigens are administered in a less harmful form, thus priming a response against the pathogen
Why are vaccines important? (1)
Harnesses the adaptive immune response to protect against pathogens
How does immunological memory confer long lasting protection? (5)
More responder cells available
More efficient antigen recognition/activation: may not require costimulatory signals for activation
Rapid and effective migration to tissues and lymph nodes
More effective function: produce more cytokines (T-cells) or antibodies (B-cells)
Longer lasting: naïve cells live for few days/months; memory cells persist for years
Where are lymphocytes present? (1)
In specialised lymphoid tissues
What are primary and secondary lymphoid organs? (2)
Primary organs - where the lymphocytes develop and undergo maturation steps
Secondary - where they complete maturation and, encounter antigens and differentiate
What are the primary organs of the lymphoid system? (4)
Bone marrow
Thymus
Initial sites for production of lymphocytes
Lymphocytes 1st express antigen receptors
What are the secondary organs of the lymphoid system? (4)
Lymph nodes
Spleen
Mucosal-associated lymphoid tissue (MALT)
Sites where lymphocytes first encounter antigens
Where do T cells originate? (1)
Thymus
Where do B cells originate? (1)
Bone marrow
What is antigen-independent differentiation and where does it occur? (1)
Cells differentiate into B and T cells
Secondary lymphoid organs
Where is the adaptive immune response initiated? (1)
In secondary lymphoid tissues
How do lymphocytes continually survey secondary lymphoid organs for evidence of infection? (3)
Movement of cells out of the lymph into the blood ensures that populations of cells in the nodes are in a state of flux
This ensures that should a pathogen be present there is an increased likelihood that it will be encountered by a lymphocyte in a lymph node
Allows lymphocytes to continually survey secondary lymphoid organs for evidence of infection.
What are lymph nodes? (1)
A secondary lymphoid tissue that provides a site for resting B-cells and T-cells to reside
What is the function of lymph nodes? (4)
Filter lymph of cells and foreign material
Where B-cells and T-cells can first recognise and respond to antigen
Antigen recognition can drive antigen-dependent differentiation
Tissues where products of the adaptive immune response (antibodies, effector T-cells) are generated
How does T cell development take place in the thymus? (4)
Progenitor cells from sites of haematopoiesis (bone marrow) begin to migrate to the thymus in the eight or ninth week of gestation in humans.
Developing T-cells in the thymus are known as thymocytes.
Thymocytes proliferate and differentiate into distinct sub-populations of mature T-cells.
Mature T-cells can then migrate to the secondary lymphoid tissues
What is the thymus? (1)
A lobular organ that is functionally separated
Where do immature thymocytes proliferate? (1)
In the outer layer of the cortex and undergo selection in the inner layer of the cortex
What is DiGeorge syndrome? (2)
A developmental defect in which the thymus does not form
Subjects with this disorder have B-cells, but few T-cells
What are T cell receptors (TCR) and why are they important? (2)
During T-cell development cells must first express a TCR
Only once it expresses a TCR can it be considered a T-cell
How does T cell development occur? (3)
Involves rearrangements of the germ-line TCR genes to produce TCR proteins that recognise antigens
T-cells can then be selected for those T-cells that have TCRs that can bind to MHC molecules: positive selection
T-cells are then eliminated when their TCRs recognise self-antigens: negative selection
What is positive selection? (2)
It is MHC restriction i.e. are compatible with the MHC molecules made by that individual
What is negative selection? (2)
It is is deletion of autoreactive cells i.e. recognise self-antigens
98% of the thymocytes die via apoptosis (programmed cell death)
What is immunological tolerance? (2)
Tolerance is a state of unresponsiveness to a particular antigen
Prevents immune system from attacking self-tissues or cells under normal conditions
Why is tolerance to self-antigens important during T cell development in the thymus? (2)
To prevent autoimmunity: this is termed central tolerance
How does the number of cells that recognise self-antigens decrease? (1)
Negative selection of autoreactive T-cells in the thymus reduces the number of cells that recognise self-antigens
What are naive T-cells? (1)
T-cells that have not yet encountered antigen
How does a naive T cell participate in an adaptive immune response? (2)
A naïve T cell must encounter its antigen to allow activation and antigen–dependent differentiation
Upon antigen recognition, naïve T cells differentiate into effector cells and long-lived memory cells
What are dendritic cells? (2)
Cells that present antigens to naive T-cells
Act as a link between innate and adaptive immunity
Where do naive T-cells encounter antigens? (2)
In the secondary lymphoid tissues
Naïve T-cells that encounter an antigen remain in the lymph tissue and proliferate
Efficiency of T-cell sampling (2)
Very high – required as only 1 in 10^4 to 10^6 cells likely to recognise a particular antigen
How are antigens presented to T cells? (3)
Antigen presenting cells (APC) has MHC molecule on the surface
Antigenic peptides are displayed by MHC molecules
These are recognised by T cell receptor (TCR)
Where are dendritic cells found? (2)
Found in the tissues and concentrated in the skin and mucosa
How do dendritic cells initiate adaptive immunity? (3)
Constantly sampling their environment for antigens to present to T-cells
Microbial molecules recognised by the dendritic cell induce its migration to secondary lymphoid organs
Present captured antigens on MHC molecules to T-cells in the secondary lymphoid tissues
What does activation of naive T cell require? (2)
Both antigen and co-stimulation
How do mature dendritic cells deliver co-stimulation? (2)
B7 on dendritic cell binds to CD28 on T-cells
B7 binding provides a second signal that is required to activate naïve T-cells
What is B7? (1)
B7 is co-stimulatory molecule expressed on mature, but not immature dendritic cell
What are CD4+ effector cells? (2)
Important for coordination of adaptive immune responses
CD4+ T-cells act via cellular interactions and via the secretion cytokines
How are CD4+ effector cells important for coordination of adaptive immune responses? (3)
In the activation of B-cells in secondary lymphoid tissues
In mycobacterial infection
In immunity to intestinal parasites
What are cytokines? (1)
Small proteins that modulate the function of other cells
What are the different CD4+ subsets and what are they involved in? (10)
TH1 cells - compact intracellular infection caused by viruses/bacteria and B cell help
TH2 cells - Extracellular worm infections and B-cell help
TH17 cells - Inflammatory response/bacteria
TFH cells - B-cell help
Treg cells - Tolerance
How do CD4+ help regulate production of antibody? (2)
The majority of antibodies produced by B-cells are T-cell dependent i.e. need T-cell help
A B-cell requires help from a CD4 T-cell specific for the same antigen before it can proliferate and differentiate
How are CD4+ involved in activation of B cells? (4)
B cells capture antigens and present these on MHC class 2 molecules
This will present antigen to T helper cell which will recognise by TCR and via cell interaction and via cytokine production
Combination of CD40 ligand and interaction and cytokine production will lead to activation of B cell
This will proliferate and produce effector cells and plasma cells
How are TH1 cells involved in macrophage activation? (5)
Enhance macrophage function
against intracellular pathogens
Important with Mycobacteria
Involves recognition of antigenic peptides presented by MHC class II molecules
Activation of macrophages requires 2
signals provided by TH1 cells:
- Priming signal such as the cytokine Interferon-gamma
- Second signal such as CD40 ligand (CD40L) which binds CD40 on the macrophage surface
What are TH2 effector cell functions? (5)
Produce IL-13 which induces epithelial cell repair and mucus
IL-5 produced by TH2 cell recruits and activate eosinophils
Drive B cells to produce IgE
Drive mast cell recruitment via IL-3, IL-9
Also participate in type 1 hypersensitivity reactions
What are CD8+ effector T-cells termed? (1)
Cytotoxic T-lymphocytes (CTLs)
Function of CTLs (4)
Kill host cells that are infected with intracellular pathogens or which are cancerous
They recognise antigenic peptides displayed by MHC class I molecules
They cause cell presenting the antigen (target cell) to die via apoptosis
Killing is via the secretion of cytotoxic molecules (perforin and granzymes) released from CTL granules
What is perforin? (2)
Forms pores in the target cell’s plasma membrane through which granzymes enter the cytoplasm
What do granzymes do? (1)
Induce apoptosis
Where does antigen dependent differentiation ofT T-lymphocytes take place? (1)
Secondary lymphoid tissues
What do lymph nodes respond to? (1)
Antigens from tissues
What does the spleen respond to? (1)
Bloodborne antigens
What does mucosal-associated lymphoid (MAL) tissue respond to? (1)
Mucosal antigens
Where does antigen independent development take place? (1)
Thymus
How is clonal expansion of antigen-specific T and B cells stimulated? (1)
By detection of antigen
How do macrophages take up
microorganisms? (1)
Via phagocytosis
Give an example of a bacteria that can survive
inside macrophages (1)
Mycobacterium
tuberculosis which causes
tuberculosis (TB)
TB is a common cause of death in which disease? (1)
AIDS
