Adaptive immunity, cells & functions - T-cells and Dendritic cells Flashcards
What is an antigen?
Substance capable of stimulating an immune response and activating lymphocytes (proteins, peptides and polysaccharides)
What is an epitope?
antigenic determinant, part of a foreign protein, or antigen, that is capable of stimulating an immune response (epitopes can be common to different antigens)
How do CD4+ T-cells recognize antigen?
Through an antigen presenting cell (dendritic cell, B-cell or macrophage) presenting an antigen via its MHC (Major Histocompatibility Complex) class 2 For example used in bacteria infections
How do CD8+ T-cells recognize antigen?
Through an infected cell presenting an antigen via its MHC (Major Histocompatibility Complex) class 1 For example used in virus infections
Where is the primary lymphoid organ and what cell type matures in it?
The organ is the thymus, and T-cells mature in it (T-hymus like T-cell)
The vast majority of T-cells die in the thymus while going through the selection processes
In the TCR gene segments recombination, what is the CDR3 useful?
It is a variable junction where random nucleotides can be added => this helps TCR diversity, allows to recognize a multitude of antigens
What enzyme allows VDJ recombination?
RAG: Recombination Activating Genes
Non-homologous end joining (NHEJ) machinery
What is the selection process of T-cells in the thymus?
They first go through a positive selection where they must have a functional TCR, they can either die or continue with the selection process
Than, after becoming either CD4 or CD8, they go through a negative selection where the AIRE (AutoImmune REgulator) enzyme tests for T-cells that are too reactive to self proteins, they can either die or become regulatory T-cells
If AIRE is defected then T-cells will head to secondary lymphoid organs without going through a negative selection => this will lead to autoimmune diseases
Where is the MHC class 1 expressed?
It is expressed on all nucleated cells
Where is the MHC class 2 expressed?
It is expressed on antigen presenting cells: dendritic cells, macrophages and B-cells
What does MHC polymorphism imply?
MHC genes are highly polymorphic: many different alleles are present among the different individuals in the population
We get a combination of MHC from our parents, this increase the presentation possibilities
How are antigens presented in MHC class 1?
The infected cell degrades the proteins of the antigen (via the proteasome), binds to the MHC1 protein in the endoplasmic reticulum, goes to the membrane via an exocytic vesicle
How are antigens presented in MHC class 2?
The pathogen gets up-taken by an antigen presenting cell, it gets degraded in a lysosome, meanwhile the MHC2 in the endoplasmic reticulum goes into an exocytic vesicle, fusses with the lysosome where the antigen is, goes to the membrane
What co-stimulation does a T-cell need in order to proliferate and differentiate?
His CD28 receptors needs to bind to the antigen presenting cell
What is the use of memory T-cells?
Memory T-cells respond quickly compare to naïve T-cells
Increases the number of antigen specific T-cells
What is DISC?
How is it activated?
What happens?
Why is it useful?
DISC: Death-Inducing Signaling Complex in T-cells
It is activated when T-cells binds their FAS receptors (CD95)
It activates the induction of cell death
It is useful for T-cell homeostasis and go back to a normal state
Where is T-cell activation taking place?
- Naïve T cells constantly recirculate between the blood and peripheral organs (lymph nodes or spleen)
- Get activated in peripheral lymphoid organs
- Effector lymphocytes migrate to the sites of infection
How do T-cells migrate?
Effector T-cells express high levels of adhesion molecules and chemokine receptors (ligands expressed at the site of infection)
What are dendritic cells?
Which immune system are they part of?
What do they activate?
- Dendritic cells represent uniquely well-equipped antigen-presenting cells (APCs): they capture antigens (phagocytosis) and process these antigens into peptides
- They are part of the innate immune system
- They activate CD4+ T-cells: the represent the link between the innate and adaptive immune system
What are the stimuli of dendritic cells?
- Whole bacteria or bacterial-derived antigens (lipopolysaccharide, LPS, etc.)
- Inflammatory cytokines
- Ligation of selected cell surface receptors (Toll-Like Receptors, etc.)
- Viral products
How do dendritic cells mature?
- Dendritic cells maturate by recognizing and responding to pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs)
- They react through pathogen recognition receptors (PRRs)
What is a cross-presentation CDc1?
It follows the same MHC class 1 presentation pathway and presents the antigen to CD8 T-cells, but the antigen is exogenous like the MHC class 2 pathway This is vey important for tumor killing CD8 T-cells
What do Th1 cells do?
They activate macrophages (starts killing phagocytosed bacteria and secretes cytokines)
They allow IgG switching for B-cells
How do Th1 cells differentiate?
Via cytokine IL-12 (secreted by activated antigen presenting cells) and IFN-∂ (secreted by T-cells and NK-cells)
What do Th2 cells do?
Secrete IL-4 (antibody production for mast cell degranulation, intestinal mucus secretion and peristalsis, alternative macrophage activation for tissue repair), IL-13 (same as IL-4 for intestine and macrophage) and IL-5 (eosinophil activation)
What do Th17 cells do?
Secrete IL-17 (inflammation neutrophil response, anti-microbial peptides) and IL-22 (anti-microbial peptides, increased barrier integrity on the skin)
What is Immune tolerance?
The capacity of the immune system to NOT react to self-antigens
- Central tolerance (thymus): deletion of auto-reactive T-cell in the thymus
- Peripheral tolerance: T-cell anergy (lack of co- stimulation) and regulatory T-cells production
What is the FOXP3 gene and why is it important?
It is a gene active in regulatory CD4+ T-cells
It has a suppressive function on T-cells, dendritic cells, B-cells, macrophages, etc.
Important to avoid auto-immune diseases
Where is the CD40 receptor expressed, what does it bind to, and what does it do?
- CD40L is expressed by activated CD4+ T-cells
- Binds to CD40 (B-cells, macrophages, dendritic cells and endothelial cells) and
activate these cells - Stimulation of B-cells to produce antibodies and activation of macrophages
& dendritic cells
What is X-linked hyper IgM syndrome?
It’s a rare disorder that increases the susceptibility to infections because the CD40 receptor is defected
What does the CTLA-4 receptor do and where is it expressed?
• It is an inhibitory receptor, important to terminate immune responses
• It is up-regulated on activated T-cells
Expressed by tumor cells to not get killed (therapy for this is checkpoint inhibitor drugs)
What does the PD1 receptor do and where is it expressed?
• It is an inhibitory receptor, important to terminate immune responses
• It is up-regulated on activated T-cells
Expressed by tumor cells to not get killed (therapy for this is checkpoint inhibitor drugs)
What is an autoimmune disease?
• Immune reaction against self (autologous antigens)
• Affect 5-10% of the population in developed countries
=> for example: rheumatoid arthritis, psoriasis, etc.
