L14 CD4 II Flashcards
Th1 immune response
Targeting things inside your cells e.g: viruses
I.e: intracellular pathogens bacteria voruses and fungi.
Strong TCR
Information captured by dendritic cell and express mhc class 2 and secrete il-12: acting as signal 3 to direct differentiation into th1. So il-12 will be recognised by the il-12 receptor (signal 3) in the presence of a strong tcr signal and costimulation. Then sarc proteins will move and then the master transcription factor for th1 which is T-bet will be in promoters for genes that encode effector function proteins for the cell which are: IFN-Y (Macrophage activation
and antigen presentation
Activate NK and T cells
Class switch to IgG2a)
IL-2 (T and NK cell proliferation)
TNF-ALPHA - a very potent inflammatory cytokine (Macrophage activation from monocytes)
These are all soluble mediators (cytokines).
This happens in tertiary and secondary lymphoid organs.
Th2 immune responses
IgA- most abundant immunoglobulin in the body. Characteristic: secreted. Immunoglobulin of the gut, keeps your microbiome ? and IgE bind and activate macrophages and complement?
EXTRACELLULAR
PATHOGENS
Helmints
Weak TCR
secrete IL-4 - signal 3 recognised by IL4R
Master TF- Gata-3 is activated
Effector mechanism:
IL-5
B cell proliferation
Class switch IgA
Eos+Bas activation
IL-13
B cell proliferation
Class switch IgA
Mucus production
Muscle contractility
IL-4
B cell proliferation
Class switch IgE
Mast cell activation
M2 macrophage activation
Immunity Effector cells &
mechanisms
Eosinophils
Basophils
Mast cells
IgA/E production
Th17 immune responses
Immunity against: EXTRACELLULAR
PATHOGENS
Bacteria
Fungi
Molecular
programme
In the presence Strong TCR and co stimulatory signal in the lymph node, nascent naive t cell will differentiate to th17 by expressing il-6 receptor.
Dc in lymph node screte IL-6
(TGF)
Have IL6R
Master TF: RORc2
Migration: CCR6
Effector
mechanism
Neutrophil recruitment
NK cell activation
Antimicrobial peptides
IL-17
IL-22
Proliferation epithelia
CCL20
Th17 cell recruitment
Effector cells and mechanisms:
Neutrophils
Macrophages
Fibroblast/epithelia
NK cells
Tfh (follicular helper) immune responses
Immunity: B cell help
in the GC
NO CD28
ICOS-ICOSL
Secrete IL-6 , IL-27
Have IL6R
Master TF: Bcl6
Migration: CXCR5
Effector mechanism: IL-21
B cell memory, plasma cell differentiation
Effector cells and mechanisms: interactions with B cells
Regulation and Tolerance
dual roles of immune regulation and tolerance in determining the outcome of immune responses. Effective regulation ensures a balanced immune response, facilitating clearance of infections or tumors while preventing excessive inflammation. Dysregulation, however, can lead to chronic inflammation and autoimmunity, where the immune system mistakenly attacks healthy tissues. On the other hand, immune tolerance mechanisms, which suppress overactive immune responses, are essential for preventing allergies, maintaining tolerance to self-antigens, and ensuring graft tolerance in organ transplantation. However, excessive tolerance can also allow undesirable outcomes, such as chronic infections persisting due to immune evasion or tumor growth due to insufficient immune responses. Thus, the balance between regulation and tolerance is critical for both protective immunity and preventing immune-mediated damage.
In autoimmunity: there is a high ratio of inflammatory immune cells to treg cells.
In healthy there is a balance between them.
In cancer there is a high ratio of treg to inflammatory immune cells.
central tolerance?
Central tolerance (thymus) is not effective 100%
(Self-Ag specific cells are detectable in healthy and diseased individuals’ peripheral
blood)
Cells in the periphery (blood, tissues) can control the activation of the immune system:
peripheral tolerance.
populations of tregs?
Depending on their origin:
- Thymus derived – natural Tregs (nTregs)
- Upon differentiation in periphery – induced Tregs (iTreg)
iTregs?
Immunity: Regulation of
the immune
response
Molecular programme:tolerogenic DC (in situations where antigen is ours like microbiota which is foreign but do not want to fight as required for living) secrete (TGF beta)
IL-2
Treg has IL2R
Master TF: FoxP3
Constitutive CD25 and CTLA-4
(CD25 allows compeittion for IL-2 with effector T cells) deplete effector cells from signal 2 by expressing ctla-4 which binds to b7 with high affinity.
Effector mechanism:
Cytokine production:
IL-10 - block effector mechanisms
Inhibits macrophage
activation
Inhibit DC function
IL-35
Promotes Breg and
Treg function
TGF-B
Other suppressive mechanisms:
Competition for IL-2
- Competition for B7
so effector t cells do not have enough to grow and their effector functions are blocked.
- Metabolic disruption:
Hydrolysis of ATP into
adenosine (CD39, CD79)
- Direct killing (perforin,
granzymes)
Other regulatory t cells:
Transforming effector cells to regulator cells
** don’t understand this slide one bit
