Antigen presentation and cytokines Flashcards
What are the different functional classes of T-cells?
-CD8⁺ cytotoxic T cells
-CD4⁺ T cells (Th - T helper cells) > Th1, Th2, Th17, Tfh (follicular helper cells)
-CD4⁺ T regulatory cells
What is the main function of CD8 cytotoxic T cells?
What pathogens do they target?
-Kill virus-infected cells
-Target viruses (eg. influenza, rabies) & some intracellular bacteria
What is the main function of CD4 Th1 T cells?
What pathogens do they target?
-Activate infected macrophages
-Provide help to B cells for antibody production
-Target microbes that persist in macrophage vesicles & extracellular bacteria
What is the main function of CD4 Th2 T cells?
What pathogens do they target?
-Provide help to B cells for antibody production, esp. switching to IgE
-Target helminth parasites
What is the main function of CD4 Th17 T cells?
What pathogens do they target?
-Enhance neutrophil response
-Promote barrier integrity (skin, intestine)
-Target fungi
What is the main function of CD4 Tfh cells?
What pathogens do they target?
-B cell help
-Isotype switching
-Antibody production
-Target all types of pathogens
What is the main function of CD4 regulatory T cells?
Suppress T cell responses
What do T cells recognise?
-Small peptide fragments bound to MHC molecules which are expressed at the cell surface
-T cells express T cell receptors which are responsible for recognising cell-surface-peptide-MHC complex
How is antigen processing achieved?
- Antigen uptake
- Antigen processing
- Antigen presentation at cell surface
Where is MHC Class 1 found?
surface of most nucleated cells
Describe the MHC1 processing pathway
-Antigens found in the cytoplasm are referred to as endogenous or cytosolic antigens
-Endogenous antigens are processed & presented with MHC class 1 molecules
-Presented peptide fragments
How do MHC1 molecules come to present antigens derived from proteins in the cytosol?
- Virus infects cell
- Viral proteins are synthesised in cytosol
- Peptide fragments of viral proteins are transported into endoplasmic reticulum (ER)
- Peptide fragments bound by MHC1 in ER & delivered to cell surface
Where is MHC class II found?
(APCs)
-Dendritic cells
-Macrophages
-B cells
Describe the MHCII processing pathway
-Antigens taken up from outside the APC (extracellular pathogens & toxins) are referred to as exogenous antigens
-Exogenous antigens are processed & presented by MHC class II molecules at the cell surface
-MHCII molecules are found on specialised antigen presenting cells > dendritic cells (DCs), macrophages & B lymphocytes
-Presented peptide fragments are usually 15-24 amino acids long
How do MHCII molecules come to present extracellular antigens at the cell surface?
-Antigen is taken up from the extracellular space into intracellular vesicles
-In early endosomes of neutral pH, endosomal proteases are inactive
-Acidification of vesicles activates proteases to degrade antigen into peptide fragments
-Vesicles containing peptides fuse with vesicles containing MHCII molecules
How do cDCs (conventional dendritic cells) work?
-Important in stimulating immune response (most potent APC)
-Present antigens from virtually any pathogen (fungi, parasites, bacteria, etc)
-Activate naive T cells
-Multiple membrane outgrowths = dendrites
-Large surface area to increase efficiency of antigen uptake
-Widespread distribution (in most epithelia & solid organs, eg heart, kidneys)
-Mediate phagocytosis: actively ingest antigens using cell surface complement receptors & Fc receptors (enhance phagocytosis)
-Mediate macropinocytosis: engulf large amounts of surrounding fluid non-specifically
-Use PRRs (pattern recognition receptors) to recognise pathogen (eg. TLRs (toll-like receptors) & respond by secreting cytokines (stimulate immune response) that link innate & adaptive immunity)
What are the different roles cytokines can play in the immune system?
-Haemopoietic
-Regulatory
-Cytotoxic
-Autocrine
What are chemokines?
-Chemotactic cytokines
-Soluble messengers
-Helps cells communicate within immune system
-Chemotactic attraction & recruitment of cells fro, blood into tissues at sites of inflammation & infection
