What are antigens and what are they usually made up of?
What molecules are present with a large amount?
- molecules that are recognised by B-cell receptor (antibody) and T-cell receptor
- mostly proteins, carbohydrates and lipids
- with many epitopes
What are immunogens?
- substances that induce an immune response
- not all antigens are immunogens as recognise is not the same as trigger (eg. self-antigen)
What is B-cell receptor and what is its function?
- membrane-bound antibody or immunoglobin (Ig) molecules (IgM and IgD isotopes)
- recognise the 3D structure (conformation) of unprocessed antigens
What is the structure of B-cell receptor?
- Y-shaped with 2 heavy and 2 light chains (include constant Fc and variable Fab regions) joined together by disulphide bonds
- variable heavy and variable light chain –> antigen-binding sites
Where can T-cell receptor be found and what is its function?
- only found on the surface of T-cell receptor membrane
- only recognise processed peptide antigen fragments displayed on MHC molecules, which bind to CD4 or CD8 co-receptors (CD4 on helper T cells bind to MHC II and CD8 ono cytotoxic T cells bind to MHC I)
Why can our immune cells specifically recognise so many different types of antigens?
- millions of harmful pathogens –> millions of antigen-binding sites on B-cell and T-cell receptors are required
- diversity is achieved by the rearrangement of gene segments coding for variable domains of B-cell and T-cell receptors during lymphocyte maturation
- heavy chain: V (variable), D (diversity) and J (joining) genes
- λ and κ light chain: V and J genes
What is the structure of T-cell receptor?
- with 2 polypeptide chains: α and β (with constant and variable regions)
- variable regions of α and β chains –> antigen-binding sites
What is the process of acute inflammation?
- tissue injury triggers the release of histamine from mast cells –> vasodilation (redness and heat) and increased permeability of blood vessels (swelling and pain)
- blood clotting proteins move from the blood to the tissue –> clotting begins
- increased migration of phagocytes from blood to the injury site
- phagocytes eliminate invading pathogens and cell debris by phagocytosis –> tissue heals
What is the role of B cells in antibody production?
- B cells circulate in blood and lymph or reside in lymphoid tissues
- respond to T-dependent and T-independent antigens
What are T-dependent antigens?
- mainly peptide Ag/ protein Ag so most antigens are T-dependent
- require helper T cells which secrete cytokines (eg. interleukin-2) –> stimulate B cells differentiate into plasma cells and memory B –> production of antibody
What are T-independent antigens?
- mainly polysaccharide or lipopolysaccharide Ag with long repeating units
- bind to many B-cell receptors at the same time –> strong stimulus for B cell to proliferate and differentiate into plasma cells –> Ab production
- no memory B cells –> no secondary immune response
What are the functions of antibodies?
- Ab bind to and enhance elimination of Ag
- variable regions Fab of Ab –> Ag binding sites
- constant regions of heavy chain –> Ag elimination (as Ab receptor will bind to Fc region)
Through what mechanisms can antibodies eliminate Ag?
- neutralisation –> Ab attach to microbes –> coat and inactivate bacterial toxins
- agglutination –> Ag are clumped together by antibodies as each Ab has at least 2 Ag-binding sites
- opsonisation –> antibody-bound Ag are more susceptible to phagocytosis as phagocytes have Fc receptor to recognise antibody –> enhance phagocytosis
- complement activation –> complement bind to antibody-coated antigen –> efficient cell lysis –> cells become leaky
- antibody-dependent cell-mediated cytotoxicity (ADCC) –> non-specific cytotoxic cells (eg. neutrophils, macrophages, natural killer cells and eosinophils) bind to Ab-coated Ag via Fc region of Ab –> destroy target cells by lytic enzymes (lysozyme), perforins (pore-forming enzymes) and granzymes (digestive enzymes)
What is primary response? What is the process and result of this response?
- first exposure to Ag (T-dependent)
- B and T cells are activated and differentiate into plasma cells, helper and cytotoxic T cells and memory B and T cells
- Ab level increases from 10-14 days after exposure to Ag
- IgM predominates over IgG
What is secondary response? What cells are involved? What is the process and comparison between primary and secondary response? What is the result of the response?
- second exposure to the same Ag –> involves memory B and T cells
- faster (2-7 days), higher titres, more prolonged than primary response
- IgG predominates over IgM
What is the role of helper T cells (CD4+) in cell-mediated immune response?
- primary regulators of immune response
- operate indirectly by secreting cytokines that enhance the activity of macrophages and NK cells (innate immune response) and B cells, cytotoxic T cells and helper T cells themselves (adaptive immune response)
What is the role of cytotoxic T cells (CD8+) in cell-mediated immune response?
- responsible for killing virus-infected cells, abnormal cells and cancer cells
How do T cells recognise Ag?
T cells use T-cell receptors to recognise only processed Ag presented with self MHC proteins
What is the function of MHC molecules? Why do they have this function?
- to discriminate self from non-self
- in thymus, T cells are educated to respond only to foreign Ag presented by self MHC
What are the characteristics of the two types of MHC class?
MHC I
- 3α + 1β domains
- located on the surface of all nucleated cells
- presents peptides from intracellular Ag
- recognised by CD8+ cytotoxic T cells
MHC II
-2α + 2β domains
- located on antigen-presenting cells
- presents peptides from extracellular Ag
- recognised by CD4+ helper T cells
How are antigen being presented through the endogenous pathway?
- intracellular Ag are cut into small peptides in the cytosol by proteasome (with proteases)
- peptides move into endoplasmic reticulum and combine with MHC I
- form peptide-MHC I complexes –> released from the ER and transport to Golgi apparatus –> plasma membrane for presentation to CD8+ T cells
How do activated cytotoxic T cells kill virus-infected and cancer cells?
- release their granules (perforins and granzymes) onto the surface of the infected cells
- perforins create pores on cell membrane to create passage for granzymes (proteolytic enzymes) into the cells –> killing (digested/ lysed)
How are antigens being presented through the exogenous pathway?
- extracellular Ag internalised by antigen-presenting cells
- exogenous Ag are digested within endosome or MHC II compartment (MIIC) –> become small peptide fragments
- In ER, MHC II combines with invariant chain (Ii) –> form Ii-MHC II complex –> transport to Golgi apparatus and MIIC endosome
- In MIIC, Ii is degraded by proteases –> peptide Ag fragments combine with MHC II –> transported to plasma membrane for presentation to CD4+ helper T cells
