Immunology 2 Flashcards
what determines T helper cell differentiation
- Cytokines in the environment at the time of naïve T cell activation define the differentiation pathway of the T helper cells.
○ Cytokines present in environment are dependent on the danger signals PAMPS that bind to the neutrophils - The cytokines produced by the T helper cells affect their other cells and is the basis of the T helper cell effector function
Dendritic cells, macrophages and B cells what proteins present
Dendritic cells
- Peptides, viral antigens, allergens
- Able to class switch in terms of activation of both CD4 and CD8 cells from outside antigens
Macrophages
- Particulate antigens (larger)
- Intracellular and extracellular phagocytosis
B cells
- Only good at presenting antigens if the antigen is specific to the B cell receptor
- Soluble antigens, toxins and viruses
Steps in activation of Cytotoxic CD8 T cells
1) 3 signal activation of naive T cell
2) IL-2 released allowing differentiation into CD8 T cells
3) effector T cell doesn’t require co-stimulation signal just recognition of Ag + MHC -> T cell receptor has already gone through selection to ensure doesn’t recognize self
4) CTL recognised and binds to virus-infected cell
5) Programs target for death inducing DNA fragmentation
6) CTl migrates to new target as the cell just targeted dies via apoptosis
List 3 molecules that are released by CD8 cells and their functions
1) cytotoxins - perforins, granzymes -> apoptosis
2) FAS ligand - binds to FAS molecule on target cells -> apoptosis
3) cytokine IFN-γ - directly inhibits viral replication
What are the 2 types of antigens and what can they be recognised by
1) TI-1 antigen
- Large antigens that can be recognised by B cells directly
○ Don’t need TH2 cells to activate
2) TD antigen
Needed to be processed by T cell first before can activate B cell
Can T cell receptors recognize MHC molecules from other individuals
Need to be from the same individual as T cell receptor also recognises the MCH molecule (self) which varies between individuals
List the 4 steps and the 3 signals that are involved with TH2 activation of B cells
1) Antibody (only IgM as haven’t been activated by TH2 cell yet) binds to antigen and brings the antigen in to be processed via MCH class II
2) Activation TH2 cells (previous lecture) then recognises and binds to the MCH class II molecule + antigen complex with accompanying CD4 molecule to stabilise
○ This could also occur via memory T cells - secondary infection mainly occurs
- SIGNAL 1
3) CD40L-CD40 interaction between B cell and Activated TH cell
- SINGAL 2
4) Cytokines released from TH2 cell act on the B cell resulting in differentiation
- SIGNAL 3 - different isotypes produced by the B cell ○ Also clonal expansion
What cytokines leads to the production of IgE, IgG and IgA
IL-4 - IgE
IFN-γ > IgG1 & IgG3
TGF β > IgA
What are the 2 types of macrophages, how activated and function
1) M1
- Classically activated macrophages - via TH1 cells and DAMPS as described above
- Pro-inflammatory with microbicidal actions such as phagocytosis and killing of bacteria
2) M2
- Alternatively activated macrophages
○ TH2 cytokines IL-13 and IL-4 activate these macrophages
- Function is to terminate inflammation and produce growth factors and enzymes that start the process of tissue repair
○ Can be an issue due to increase fibrous tissue - chronic infections may lead to blockage of airways
- Release anti-inflammatory cytokines such as IL-10 and TGF-β
Describe the 3 main functions of TH1 cells
1) Macrophage activation (classic macrophages M1)
- Signals from CD40L and IFN-ƴ activate macrophages
- Macrophages can then
1. kill phagocytosed microbes with substances such as reactive oxygen species, nirtric oxide, lysosomal enzymes
2. secrete TNF, IL-1,2 - pro-inflammatory cytokines
3. increased MCH and costimulatory to activate naïve T cells
2) B cell opsonizing Ab via complement
- IFN-ƴ (as present in environment lead to IgG production in presence of TH2 therefore better at opsonisation)
3) Neutrophil recruitment and activation
- Release TNF to recruit and activate
What are the 4 functions of TH17 cells in inflammation
- Neutrophil accumulation
- Monocyte accumulation
- Increased mucus secretion
- Release of pro-inflammatory mediators
Where is activation of T and B cells occurring
1) Primary activation of T cells within the loose lymphatic tissue - dendritic cells and T cells
○ Usually occurs in secondary lymphoid tissues such as lymph nodes, spleen and Peyer’s patches
2) Germinal centres - B cell activation
What cell presents antigens to activate T cells
Dendritic - engulf pathogens within tissues, other proteins and cells then migrate to the lymph node
- Present to the T cells - generally nothing occurs if no infection
1. If infection - activation of T cells to the dendritic cells resulting in differentiation into different types of T cells
2. Proliferation and differentiation of T cells
3. Migration into the efferent lymph through the lymphatics
4. Eventually into blood stream as activated T cells
5. Will move into the tissues where needed as inflammation is occurring at site of infection resulting in innate response producing cytokines that upregulate adhesions molecules on endothelial cells at that point of the circulatory system
Define tolerance and its significance in the immune system
- Specific immune unresponsiveness to an antigen that is induced by previous exposure of lymphocytes to that antigen
• Significance: - Self/non-self-discrimination
○ Failure of self-tolerance —-> autoimmunity
What are the 2 main mechanisms of immunological tolerance and features
• Central tolerance
- T cell education
• Peripheral tolerance
- Anergy
○ Lymphocytes recognize Ag without adequate co-stimulation (B7/CD28)
- Regulatory lymphocytes (T-cells)
Suppression of lymphocyte activation & effector functions
What is anergy and how used in the immune system
- T cells that are rejected initially during the activation of naive T cells due to the lack of co-stimulatory molecules (B7) on the dendritic cell
- Cannot be activated again
Regulatory T cells what are the 2 functions and what are the 2 forms
2 functions
1) Suppress immune response
2) Downregulate response after it has been occurring - once the pathogen has been cleared
○ Preventing inappropriate chronic inflammation
2 forms
1) Require contact with naïve T cells - contact-dependent inhibition of T cell responses
2) Mediated through suppressive cytokines - interleukin 10 and TGF- beta
What are the 3 requirements for the development for an autoimmune disease
1) Genes - genetic predisposition - specifically certain MCH molecules genes - high affinity for self-peptides so presenting
2) Immune regulation - problem with the 3 levels of defence - central and peripheral tolerance
3) Environment - new antigens expressed the same time as DAMPS present therefore recognise new antigens in the wrong context, bacterial protein could also look similar to antigen of self or cross-react - example below
List 2 drugs that that prevent auto-immunity and transplant rejection
Cyclosporine: blocks cytokine (IL-2) production by T cells
Corticosteroids: inhibit cytokine secretion by macrophages and reduces inflammation
List 4 targets on tumors that the immune system can respond to
1) Mutate own proteins that lead to uncontrolled proliferation
- Mutation can be detected by immune system
2) Oncogene -encode for proteins that lead to increase proliferation
- Generally not produced by normal cells
3) Over-express self-proteins
- If express too much can be detected by the immune system
4) Oncogenic viruses - Viruses that create tumours
- Proteins from the viruses that
What are 3 ways tumours evade the immune system
1) Failure to produce the tumour antigen
- Can no longer be seen by
2) Mutate to not produce MCH class 1 molecule therefore avoid recognition by T cells
- However NK cells can still kill as activated when MCH molecules are missing
3) Secrete cytokines resulting in downregulation of immune response - immunosuppressive proteins
List one way vaccination against tumours work
Take plasmid that expresses peptide from tumour and place within dendritic cell, that dendritic cell is then injected into the patient and acts on naïve T cells to activate then against the tumour ○ As the peptide is being created within the dendritic cell it will be expressed on MCH class I which activates CD8 which are the cytotoxic T cell that have the ability to destroy the tumours
What are the 6 features of ideal vaccines
1) Affordable worldwide
2) • Heat stable
3) • Effective after a single dose
4) • Applicable to a number of diseases
5) • Administered by mucosal route
6) Suitable for administration early in life
what do most vaccines induce
immune memory
- increases speed, magnitude, persistence and avidity
