Adaptive immunity Flashcards
Characteristics of adaptive immunity
Takes a longer time period to be activated
Specific
Highly specialised
Functions of adaptive immune system
Recognises non-self antigens
Generates specific response
Immunological memory
What are the three main cells in the adaptive immune system?
B cells
T cells
NK cell
What are cytokines?
Cell signalling molecules
Function of interleukins
Target leukocytes
Function of interferons
Antiviral response
Function of chemokines
Mediate chemotaxis
What are the 4 different ways in which cytokines can act?
Individually - autocrine
Individually - paracrine
Individually - endocrine
Together
What is an autocrine chemical?
Acts on cell releasing chemical
What is a paracrine chemical?
Targets nearby cell
What is an endocrine chemical?
Released into blood stream to target distant cells
Which cytokines activate t-cells?
IL-12
IL-2
IFN-gamma
TNF- alpha
Which cytokines stimulate antibody production?
IL-4
IL-5
IL-13
Which cytokines are anti-inflammatory?
IL-10
TGF-beta
Where are T cells produced?
Bone marrow
Where do T-cells mature?
Thymus
Where are T-cells activated?
Lymph node
What are CD4 cells?
Helper cells
What are CD8 cells?
Cytotoxic cells
Which three cells can activate helper T cells and why?
Dendritic cells, macrophages and B cells
They all have MCH II
How are T-helper cell activated?
- CD4 t-cells activated by antigen presentation
- Antigen presented to helper T cell by MHC II molecule on dendritic cell in lymph node
- Second signal - co-stimulation
- Third signal - cytokines released
- All 3 signals = activated CD4 T-cell that specifically targets this pathogen
- CD4 cell proliferates and clonally expands
What will MHC II bind to always?
CD4 helper cells
What is produced when a helper T cell is exposed to IL-12?
TH1
What is produced when a helper T cell is exposed to IL-4?
TH2
What is produced when a helper T cell is exposed to IL-1 beta and IL-6?
TH17
What is produced when a helper T cell is exposed to IL-10 and TGF-beta?
T reg cells
What do TH1 cells do?
Fight intracellular pathogens by releasing IFN-gamma and IL-2
Cell-mediated response
What are the two outcomes when TH1 cells are exposed to IFN-gamma?
B - cell and the plasma cell
Macrophage - activated macrophage
What are the two outcomes when TH1 cells are exposed to IFN-gamma and IL-2?
NK cell - activated NK cell
CD8 cell - cytotoxic T cell
What do TH2 cells do?
Defend against extracellular bacteria and parasites
Humoral response
What is produced when Th2 cells are exposed to Il-4?
Plasma cells
What is produced when TH2 cells are exposed to IL-4 and Il-13?
Alternatively activated macrophage
What is produced when TH2 cells are exposed to Il-3 and IL-5?
Eosinophils
What is produced when TH2 cells are exposed to IL-3 and IL-9?
Basophils
What do TH17 cells do?
Defend against some bacteria and fungi
Pro-inflammatory response
What is produced when TH17 cells are exposed to Il-17?
Cytokines and chemokines lead to increased neutrophil production
What do T-reg cells do?
‘Turn off’ immune system to return to normal state
Releases anti-inflammatory cytokines like IL-10 and tif-beta
What do CD8 cells do?
Release perforin and granzymes to puncture holes in infected cell
Kill by Fas
How do CD8 cells kill?
- When activated, travels through blood to infection via chemotaxis
- Infected cell has MHC I on surface to present to cytotoxic t-cell which kills cell
- Can kill by Fas on viral cell binding to Fas ligand portion of CD8 cell - connection triggers cascade to cause apoptosis (death receptor signaling)
How are CD8 cells activated?
Activated by dendritic cell entering lymph node and presenting antigen to MHC II to activate T-helper cells. This presents antigen via MHC I. CD8 requires MHC I signals, co-stimulatory molecule and IL-2 and IFN-gamma to be released from T-helper cells
How do NK cells recognise pathogens?
PRR on surface
What do NK cells do?
Activate macrophages
Kill pathogens similarly to CD8 cells
Where do B-cells develop and mature?
Bone marrow
What molecule are B-cell receptors made from?
Immunoglobins
Process of B-cell editing
Challenged with self-peptides
If they recognise peptides, receptor editing occurs
If this is successful the B cell matures in periphery
If unsuccessful the B cell is anergia
What does anergy mean?
Frozen - inactive
What is receptor editing?
Re-arranging B-cell receptor to stop it recognising self-tissue
What is isotope switching?
Cytokines from T-cells (TH2) tell B-cells which antibodies to produce
What will all antibodies initially be?
IgM
How is IgG produced?
TH2 exposed to Il-2/4/6 or IFN-gamma
How is IgE produced?
Th2 exposed to Il-4
How are B cells activated?
- Requires CD4 to be activated initially
- Antigen binds to B-cell receptor
- B cell processes antigen, presents on MHC II molecule which is recognized by T-helper cell
- T-helper cell recognizes that B-cell knows what infection is being fought and creates antibodies
- 3 signals and release of cytokines
- Activates B-cell
- Clonally expands (IL-2 and IL-5)
- Differentiates into plasma cell (antibody production) or memory B-cell
What are the 4 chains in an antibody?
2 heavy and 2 light
Where is the antibody binding region on an antibody and what is it called?
At the top of the Y and variable region
What is the constant region of an antibody?
The stalk
What does the constant region of an antibody do?
Binds to cell membranes and starts complement cascade
Starts phagocytosis
Initiates cytotoxicity
What are the 5 classes of antibodies?
IgD, IgM, IgG, IgA, IgE
Characteristics of IgM
First antibody produced
Bind up to 10 antigen
Lower affinity to antigen
Good at opposing/neutralising pathogens
Characteristics of IgG
Most abundant
High affinity to antigen
Neutralise pathogens/activate inflammation
Characteristics of IgA
Secretory antibody found in secretory surfaces
Neutralise pathogens
Characteristics of IgE
Largest antibody
causes mast cells to granulate
Fights parasitic infection and allergies
What is opsonisation?
Antibodies bind to pathogen to highlight it to phagocyte
How is the complement cascade activated?
Inflammation and activation of mast cells
Process of cytotoxicity
Cytotoxic T cells and NK cells bind to antibody
Release enzymes and perforating granzymes to cause apoptosis
Where is IgM found?
Blood
Where is IgG found?
Blood, from mother to fetes, extravascular tissues
Where is IgA found?
Milk
Lungs and airways
Intestines
Urogenital tract
Where is IgE found?
Connective tissue mast cells
What is the passive immune response?
Antibodies are given to us to fight pathogens
What is the active immune response?
Body is creating antibodies
What is natural passive response?
Placental transfer of antibodies
IgA in breast milk
What is artificial passive response?
Injection of immunoglobulin
What is natural active response?
Infection and resistance to re-infection
Where do memory cells wait until re-infection?
Lymph nodes
What are long-lived plasma cells?
Remaining after infection has been fought, continually secreting antibodies for quick response in future
What is sub-clinical re-infection?
Repeatedly getting infections and mounting immune response in clearing infection. We don’t get any symptoms because immune system is always getting topped up. Forms constant reservoir of antibodies
Why is it beneficial to test for t-cell tolerance?
Stops them attacking self tissue
What happens if a t-cell binds to self tissue?
Apoptosed
What happens to functioning t-cells?
Released in periphery to lymph node
Where does t-cell tolerance occur?
Thymus
When will T-cells undergo positive selection?
When they can’t bond to MHC
When are cytotoxic T cells produced?
Weak affinity to peptide and MHC I-CD8 cells
When are helper T cells produced?
Weak affinity to MHC II-CD4 cells
What is the aim of T-cell tolerance?
Turn them single positive
What is negative selection of T cells?
T-cells challenged by medullary epithelial cells. Medullary epithelial cells can produce proteins form any area of body. They produce lots of self peptides and display those to T-cells
Where does negative T-cell selection take place?
Medella
Process of T-cell tolerance
T-cells interact with DCs. They recognise peptide-MHC complexes with medium or high affinity undergo apoptosis (negative selection)
- Weak affinity to peptide and MHC I-CD8 cells - cytotoxic T cells
- Weak affinity to peptide and MHC II-CD4 cells = helper T cells
Initially double negative but converted to double positive (both CD4 and CD8 on surface)