Antigen-presenting Cell (APC),T & B Cell Activation
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What is the adaptive immune system also known as?
Aquired/specific immune system
What is the function of adaptive immune system?
- Eliminates foreign substances & abnormal body cells
- Cleans up dead cells
- Magnifies inflammatory responses
- Shuts down inflammatory responses
- Activates complement
- Regulates itself
What is the initial exposure to a specific substance?
Reaction time of adaptive immune system?
What are the stages of acquired immunity?
- 1. Establishment of infection
- 2. Induction of adaptive response
- 3. Adaptive immune response
- 4. Immunological memory
What are the two branches of adaptive immunity?
- Humoral immunity
- Cellular immunity
What happens in humoral immunity?
- Extracellular microbes e.g. bacteria activate B cells to secrete antibody
- Antibody attach to bacteria
- Neutralisation occurs --> lysis (complement)
- Leads to phagocytosis by macrophage
What happens in cellular immunity?
- Intracellular microbes e.g. virues activate APC and Th cells to produce cytokines
- Cytokines attach to cytokine receptors --> proliferation and activation of effector cells (cytotoxic T cells, NK cells, macrophages)
- Lysis of infected cell
What are the adaptive effector responses of B cells?
Antibodies - eliminate extracellular pathogens
What are the adaptive effector responses of T cells?
- CD4+ Helper T cells - Th1, Th2, Th3, Th17 and even Th100
- CD8+ Cytotoxic cells
What is the function of Th1?
help CD8+ T via cytokines
What is the function of Th2?
Help B cells via cytokines
What is the function of CD8+ cytotoxic T cells?
destroy infected & altered cells
What is an antigen?
Any substance that can trigger an immune response
5 examples of antigens.
- Pathogens: bacteria, fungi, viruses, worms
- Foreign proteins: pollen, insect venom, transplantation antigens, antibiotics etc
- Mainly proteinsLipids & carbohydrateDNA
T cells can only bind to processed (chopped up)...
What are processed antigens?
- Small chemical subunits made up of amino acids
- Known as epitopes
B cells recognise epitopes within intact...
What are B Cell Receptors (BCR) or T Cell Receptors (TCR)?
- Expressed on lymphocyte surfaces
- Bind to antigen
- Beginning of B & T cell activation
What plays a key role in B & T cell activation?
Cytokines - act as signalling molecules between immune cells
What is T cell activation initiated by?
Interactions between antigen-presenting cells (APCs) & T cells APCs process (chop up) intact antigen into small fragments (epitopes)
What are the 3 things epitopes must be?
- 1. Inside major histocompatibility complex (MHC) molecules
- 2. On the APC cell surface
- 3. Presented to the TCR on T cells
What are the MCH I restriction & T cell activation?
Present intracellular antigens to CD8+ cytotoxic T cells only
What are the MCH II restriction & T cell activation?
Present extracellular antigens to CD4+ T cells only
What are the professional APCs?
- Dentritic cells
- B cells
What dendritic cells, macrophages and b cells do in cell activation?
Express MHC class I & II molecules
Which of the professional APCs are the best at priming naive T cells?
Where is the T cell first activated (primed)?
- Antigen capture in tissue site by DCs
- DCs activated & start to mature
- DCs migrate towards lymph nodes
- Migrating DCs mature into APC
- DCs in lymph nodes present antigen to T cells
In lymph nodes T cells "stick" to DCs using what?
Cell Adhesion Molecules (CAMs)
How are immunological synapse formed?
- Numerous receptor-ligand interactions bing T cells to APCs
- TCR bind to peptide in MHC
- CD4/8 bind to MHC
- Co-stimulatory molecules B7 (on APC) bind to CD28 (on T cells)
- Group together to form synapses
How are APC activated?
- Pattern recognition receptors (PRRs) detect pathogens
- Toll-like receptors (TLR) recognise specific pathogen structures
- Activate APC
- Co-stimulatory molecules (B7 molecules) up-regulated
Professional APC's express TLRs to...
- ensure immune system responds to pathogens & not to harmless substances
- Activates APCs = upregulation of co-stimulatory molecules
What are the two signal model of T cell activation for a full activation?
- Signal 1: Antigen recognition
- Signal 2: Co-stimulatory molecules on APCs
What is the first signal (antigen recognition) in T cell activation for?
Ensure that response is Ag-specific
What is involved in the second signal (co-stimulatory molecules on APCs) in T cell activation?
- B7 family = CD80 & CD86 = bind to CD28 on T cells
- CD40 = binds to CD40L on T cells
What is the key cytokine the T cell needs to make and why?
- Key cytokine is IL-2
- Proliferation dependent on IL-2 through autocrine pathway
What are the Steps to T cell activation?
- Pathogen activates APC
- APC expresses co-stimulatory molecules
- Pathogen phagocytosed
- Pathogen processed
- APC presents peptide in MHC to naive T cells
- T cell activated
- T cells leave the lymph node
What happens after T cell leaves lymph node?
- Travel to site of infection/mutated cells
- CD8+ cytotoxic T cells seek target cells
- Target cell must present same epitope in MHC class I molecule --> killing occurs = effector cells
B cell is activation is required to initiate antibody production. What are the (3) steps?
- B cell responds to intact antigens via the B cell receptors (BCR)
- BCR = antibody on the B cell surface
- B cell proliferate & differentiate into: clone of antibody-secreting plasma cells
What are the (3) steps in B cells process antigens for the presentation to CD4 Th2 cells?
- Antigen bound by B cell surface receptor
- Antigen internalized and degraded to peptide fragments
- Fragments bind to MHC class II & transported to cell surface
B cells require 2 signals for activation what are they?
- Signal 1: B cell binding to peptide. B cells present peptide in MHC class II molecules to CD4+ T cells
- Signal 2: Activate CD4+ T cells --> secrete cytokines (IL-4, IL-5)
further activate B cells --> fully differentiate antibody-secreting B cells = plasma cells
What is the priming phase of T cells?
- APC present antigenic fragments in MHC molecules to TCR
- T cells require 2 signals for full activation
- 1. Antigen in MHC molecules binding to the TCR
- 2. Activated APC express co-stimulatory molecules
Where is the effector stage of T cells?
Somewhere in the body
What is the priming phase of B cells?
- BCR attaches to epitopes still in a whole antigen
- Process antigen for presentation to CD4+ Th cells
- B cells require 2 signals for full activation (different to T cells)
- 1. Epitope bind to BCR
- 2. Cytokine secreted by activated T cells
Where is the effector stage for B cells?
Somewhere in the body
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