Adaptive immunity Flashcards
What is adaptive immunity
Specific and acquired immunity
What is the adaptive immunity response
Occurs within 4-10 days
The adaptive immune response consists of cell-mediated responses and antibody responses
T cells drive cell-mediated immunity, it involves the activation of macrophages, natural killer (NK) cells
B cells produce antibodies driving humoral immunity
Each pathogen is “remembered” by a signature T cell and/or B cell receptor = immunological memory
Does adaptive immunity produce memory cells
Yes
How long is the adaptive response
4-10 days
What arwe the steps in adaptive immunity
Infection
Transport of antigen to lymphoid organs
Recognition by naive B and T cells
Clonal expansion and differentiation to effector cells
Removal of infectious agent
What receptors are present in adaptive immunity
T cell Receptor
B cell Receptor
Major Histocompatibility Complex
Why are adaptive immune receptors highly variable
Genes encoding each allows the development of a repertoire of receptors with wide specificity
What are some pattern recognition receptors
Toll like
Dectin
NOD-like
Where are T cells derived from
Bone marrow
Where do T cells mature
Thymus
Where are T cells found
Circulate in the blood and lymph and are found in large numbers in lymphoid organs
What is diversity in the TCR known as
T cell repertoire
How is it ensured T cells only respond to foreign antigens
Checkpoints are in place
What is the TCR
T cell receptor allows recognition of peptides presented by antigen presenting cells
What are the different sub sets of T cells
T helper cells (CD4+)
Cytotoxic T cells (CD8+)
Regulatory T cells (Tregs)
What do T cells start as
Naive T cells
What are T helper cells
Function to help support other immune cells t fight threats
-Can be TH1, TH2, TH17, TFH
What are cytotoxic T cells
Destory our own cells which have become infected (usually virus-related)
What are regulatory T cells
Regulate or suppress other cells in the immune system
How are T cells differentiated
Undergo ‘programming’ to determine which subset to become - driven through the DC-T cell interactions
What does CD8+ bind to
MHC 1
What does MHC 2 bing do
CD4+
What is the purpose of CD3
It is a co-receptor involved in activation of both CD4+ and CD8+ T cells
What do most T cell receptors consist of
alpha and beta chains
What do 5% of the populations T cells consist of
y and delta chains
What are the two regions of the receptors
Constant region
Variable region
What gene segments encode the variable region of a T cell receptor
V (variable) - alpha and beta chains
D (diversity) -beta chain only
J (joining) -alpha and beta chains
What drives somatic recombination
RAG (recombinase enzymes)
How are genes rearranged
Somatic recombination
How many combinations are there for V(D)J
Approx. 3x10^11
What are pre-thymic T cells
Undifferentiated lymphocytes
What do T cells interact with in the thymus
Thymic cortical epithelial cells
What is positive selection
No recognition = apoptosis
What is negative selection
The cells that DO NOT recognise the self antigen are selected
Recognition of self antigen = apoptosis
Which T cells leave the thymus
Positively and negatively selected T cells
Where do Pre-thymic T cells undergo education
Thymus by positive and negative selection
Are educated cells naive
Yes
What are B cell receptors
Immunoglobulins e.g. antibodies
How does T cell activation occur
Results from antigen presentation by dendritic cells
Where do DCs go when they take up antigens on the skin
Lymoh nodes/draining lymphatic vessels
Where do DCs mature
En route to lymph nodes after taking up antigens
What co-stimulatory molecules do DCs have
CD40, CD80/CD86
Where does T cell priming occur
In the lymph nodes
How many signals does T cell priming involve
3
What are the three signals involved in T cell priming
Signal 1 = activation of T cells
Signal 2 = survival and clonal expansion of T cells – signal 1 but no signal 2 is known as anergy
Signal 3 = differentiation into subsets OR effector function through production of cytokines
Does anergy arise from co-stimulation
NO only activation
What is the function of TH2 cells
Main role in supporting humoral responses and allergic reactions
Source of cytokines such as interleukin-4, 5 and 6 (IL-4, IL-5 and IL-6) which instruct B cells to produce antibodies
What is the function of regulatory T cells
Main role is to function in immune suppression
Release inhibitory cytokines (e.g., interleukin-10, [IL-10])
Inhibit T cell and dendritic cell activation
Whar is the function of Cytotoxic T cells
Activation arises from interactions between MHCI and TCR
Induce host cells to undergo apoptosis (programmed cell death)
Produces enzymes such as granzyme/perforin
Which signal prevents T cell anergy
Signal 2
Which cells are cytotoxic and drive cellular lysis
CD8+ T cells
What form of B cells leave the bone marrow
Immature B cells
Where do B cells originate
Bone marrow
Where do naive mature B cells arise
Periphery
What is the difference between mature and immature B cells
immature only expresses IGM receptor while mature cells express IGD also
What do B and T cell receptors have in common
Both have variable and constant receptors
Which receptors have light and heavy chains
B cell receptors
What is the heavy chain
Involves rearrangment of Variable, Diversity and Joining
How many segments are there of the J gene
5-6
What are the light chains
involves rearrangment of Variable and Joining genes
Where do B cells undergo negative selection
Bone marrow
What happens toB cells that react with self antigens
Retained within bone marrow and egulfed by macrophages to ensure no release into circulation
What is negative selection
Process of selection in which Bcells which react with self antigens are NOT selected hence negative selection
Which antibody produces the most effective immune response
IgG
What are the different types of immunoglobulins
IgG IgE IgM IgD IgA
What type of immunoglobulins are B cell receptors
IgM and IgD
What are the functions of antibodies
Neutralization
Opsonization
-Antibody-dependent cellular cytotoxicity (ADCC)
-Mast cell degranulation
Initiation of complement
How many pathways of complement production are there
3 pathways
Mature B cells are still antigen naïve,when are they not
After the have been activated
What are the types of B cell activation
Thymus-dependent
Thymus-independent
Where does B cell activation occur
Lymph nodes
What does activation of naive B cells cause
Rise in plasma cells
What cells are antibody factories
Plasma cells
What does a rise in plasma cells lead to
Class switching e.g. IgM to IgG
What does thymus-dependent B cell activation consist of
Requires co-stimulatory molecules (CD40-CD40L)
Requires cytokine responses from T helper cells (TH2 cells)
Leads to differentiation into memory B cells and plasma cells
How does class switching occur
Gene rearrangement
What is the main difference between thymus independent and dependent activation
Only generation of differentiation of plasma cells
How does Thymus independent B cell activation occur
Stimulation through microbial antigens (e.g., LPS)
Leads to differentiation into plasma cells
No memory cells
What class is most often switch
IgM as response is weak
Do B cellsundergo positive selection
no
What is the roe of B cells in adaptive immunity
Communicate with T cells
Have a specific B cell receptor for antigens
B cells produce antibodies
Clonal expansion leads to generation of two subsets
-Plasma cells are great big antibody factories
-Memory B cells are important to mount a quicker antibody response to any subsequent infections
B cells are also capable of antigen presentation (to T cells for T cell activation)
How do B cells recognise antigens
Through B cell receptors which is the actual antibody IgM or IgD
How can numerous antigens be fought with only B cells
Diversity in BCR (potential to respond to numerous antigens)
Where issecretory IgA produced
mucosal surfaces
Where is secretory IgA found
Saliva/GCF
What does secretory IgA do
Binds to flagella and can prevent motility (microorganisms)
Binds to and neutralizes bacterial toxins (microorganisms)
Prevents attachment of bacteria to mucosal surfaces
Which immunoglobulins are monomers
IgD IgE IgG
What immunoglobulins are dimers
IgA
What immunoglobulins are pentamers
IgM
What immunoglobulins have a high affinity
IgG, IgD, IgE
Which immunoglobulins have a high avidity
IgA IgM
What is the first antibody produced following B cell activation
IgM
On first antigen presentation, IgM switches to IgG which also produces memory cells at the time which are then specific to that particular antigen which allows for what
Rapid production of IgG on secondary expossure allowing for quicker immune response as no switching has to occur
What is central immunological tolerance
Active response to a particular antigen in the primary lymphoid organs
What can failure in tolerance mechanisms result in
Autoimmune diseases
What is peripheral tolerance
Involves an active response to a particular antigen outside the primary lymphoid organs e.g. lymph nodes
What is an example of central tolerance
B cell negative selection in the bone marrow
What does a breach of tolerance lead to
Reactivity against self antigens (autoimmune disease)
Where does Class Switching occur
mature B cells
How does the body prevent autoimmune disease
Checkpoint to test central and peripheral tolerance
Why can anergic T cells be problematic
They can activate self reactive B cells
If self reactive T cells survive how can they be activated
3 signals result in activation
-2nd results in anergy
-3rd results in cytokine production
How can T regulatory cells block activity
By binding to antigens
What is anergy
Absence of the normal immune response to a particular antigen or allergen
