Integration of innate and adaptive branches of the immune system Flashcards
What are included in phagocytes
neutrophils, macrophages and dendritic cells
Characteristics of phagocytes
express PRR that detect PAMPs and complement receptors and Fc receptors to detect complement or antibodies that facilitate phagocytosis
what chemicals do basophils produce and their functions
Histamine • Vasodilator that increase blood vessel permeability and smooth muscle contraction
• Responsible for many symptoms during allergic reactions
Serotonin • Stimulates monocyte and lymphocyte
• Modulate which cytokines get produced during a given immune response
Heparin • Anti-coagulant that prevents blood clotting
Action and characteristic of cytotoxic T cells
it express CD8+ TCR that recognise MHC I and kills intracellular pathogen infected cells or tumour cells directly by releasing toxins and also release cytokine that activate macrophages
Role and characteristics of Helper T cells
It express Cd4+ receptors that binds to antigens presented on MHC Class II .
It stimulates B cells to secrete antibodies and activate macrophages to destroy ingested microbes and trigger cytotoxic T cells to kill infected target cells
what are the types of helper T cell and their function
• helper T cells 1(TH1) - activate macrophages and cytotoxic T cells to kill more effectively
○ Function : produce cytokine that activate T cells to produce the cell-mediated response
• helper T cells 2(TH2) - activate B cells
○ Function: Produce cytokine that activate T cells to produce the humoral response
what determines the Th1 or Th2
types of antigen (extracellular and eintracellular), • Type of co-stimulatory molecules
• Dominant cytokine environment
Describe the initiation of TH1 response
- An intracellular pathogen such as a virus will be detected by a PRR such as TLR-3
- This triggers a signalling cascade which starts with a DC producing cytokines such as IL-12
- IL-12 then binds to its receptors on T cells and activates kinases such as JAKs and the signal transducer and activator of transcription STAT4
- STAT4 binds to the DNA and induces the transcription of the master regulator T-bet
• leading to the production of IFN-γ - an effector cytokine that defines a TH1 response.
Describe the initiation of TH2 response
- Extracellular pathogens such as a parasitic worm will be detected by PRRs such as TLR-2 and TLR-4
- This triggers a signalling cascade which starts with an immune cell such as mast cells, basophils or germinal centre B cells producing cytokines such as IL-4
- IL-4 then binds to its receptors on T cells and activates kinases such as JAKs and the signal transducer and activator of transcription STAT6
- STAT6 binds to the DNA and upregulates the expression the transcriptional regulator GATA-3
- This leads to the production of effector cytokines such as IL-4, IL-4 and IL-13, which define a TH2 response.
Role of Dendritic cells
- They serve as sentinel cells and activateinnate defenceswhen needed
* They process and present antigens, and therefore, initiateadaptive immuneresponses
* They regulate adaptive immunity by determining whether an antigen will trigger an antibody (TH2) or a cell-mediated (TH1) response.
What happens when Dendritic cells detect a pathogen
- they phagocytose it, degrade its proteins into pieces and present them at the cell surface associated with MHC Class II molecules.
- they upregulate cell-surface receptors that act as co-receptors in T cell activation (such as CD80, CD86 and CD40).
- Makes up the second signal - required to activate T cells
• First signal - recognition of antigen loaded onto MHC Class II molecule by TCR
• Second signal - co-stimulatory signal provided by CD80/86 binding to CD28 - Dendritic cells (DCs) also upregulatechemotactic receptors, such as the chemokine CCR7
• induce them to travel to the spleen or to the lymph nodes where T cells reside and they act as antigen-presenting cells (APCs). - Then, they activate helper T cells (TH) by presenting them with antigens derived from the pathogen
- Finally, DCs can secrete a diversified panel ofcytokines (IL-12, IL-10 and TNF-a)that provide a third signal that allows helper T cell to differentiate to the appropriate subtype (i.e. TH1, TH2)
Innate and adaptive system respond to viral and bacterial infection
check notes IMI4
- Which other signal from the APCs can be used by T cells to ‘figure out’ the type of infection that Patrick is suffering from?
- 1st signal:
* antigen presentation- 2nd signal:
- costimulatory signal (i.e. CD28 on T cells interacts with CD80 and CD86 on DCs)
- 3rd signal (outcome of 1st and 2nd signals):
- release of specific cytokines
- 2nd signal:
- How do Patrick’s CD4+ T cells help resolve his infection?
• CD4+ T polarise into TH2 T cells, which promote the humoral response
• This results in plasma cells producing antibodies
• APCs release signals in the form of cytokines (e.g. IL-4,IL-6) which act as messages that let CD4+ T cells know what type of extracellular pathogen they are dealing with
• T helper (TH) cells respond by polarising the immune response into a TH2 response
• TH2 response involves the release of cytokines that act on B cells inducing their maturation into plasma and memory B cells
• Plasma cells then release antibodies against P. aeruginos
Lead to neutralisation, agglutination, immobilization, phagocytosis by opsonisation
- What is the function of TH1 response
- TH1 cells release INF-y and IL-12 which activate macrophages and cytotoxic T cells (CD8+) to kill more effectively and potently infected or tumour cells
- TH1 polarisation leads to the activation of cell-mediated responses against the intracellular pathogen
