adaptive immune system B cells Flashcards
(32 cards)
what is the Innate immune system?
→Rapid response
→Non-specific (generic anti-bacterial or anti-viral mechanisms)
→Most often fails to completely eliminate the infection
what is the Adaptive immune system?
→Delayed response →Highly specific →Usually eliminates infection →Memory →Long term immunity, but specific to that particular pathogen
what are the branches of adaptive immunity and what are they regulated by?
Humoral immunity
→Mediated by B-lymphocytes
Cellular immunity
→Mediated by CD8+ cytotoxic T- lymphocytes
→Both branches regulated by CD4+ helper T-lymphocytes (T-helper cells)
what is Humoral immunity?
→Humor = fluid
→Following an infection
→Plasma contains substances- “antibody (Ab)”
→which neutralise that specific infectious agent
→Demonstrate in vitro Or in vivo, e.g. treatment of rabies by infusion of antibody “adoptive immunotherapy”
what is an antibody?
→Protein- “immunoglobulin (Ig)”
→Migrates in the γ-globulin fraction on serum electrophoresis
→Each antibody binds to a specific antigen (most often a protein) on the infectious agent
→But plasma contains many different Abs
what is the structure of an antibody?
→Immunoglobulin protein
→Y-shaped
→Tetrameric
→2 identical heavy chains
→2 identical light chains
→Held together by non-covalent interactions
→and by –S-S- crosslinks between cysteine a.a. residues
→Each Ig molecule has two antigen binding sites
→flexible hinge region
describe light chains
→There are two types of light chain Kappa (κ) and lambda (λ)
→But any B-cell will only make one type
→Any Ig molecule will contain either kappa or lambda, never both.
→This phenomenon is called “light chain restriction”
how many regions do antibodies have and describe them
variable region
→Amino acid sequence varies from one Ig molecule to another
→Binds antigen
→constant region
→Responsible for effector functions E.g. activating complement, binding to phagocytes
what is Ig?
Ig is a glycoprotein (Carbohydrate added in the Golgi)
what happens if you treat Ig with protease?
→Cuts molecule at hinge region
→Fab- fraction Antigen binding
→Fc- fraction crystallisable
what are the three ways in which antibodies fight infection?
COATING AND NEUTRALIZING
→if a virus is coated with Ab it cannot bind to its receptors
ACTIVATING THE COMPLEMENT
→which can blow holes in a bacterial cell membrane
OPSONIZATION
phagocytes have Fc receptors on their cell membrane
→bind to pathogens coated in Ab and phagocytose them
How does an Ab bind to an antigen?
→Non-covalent interactions →Electrostatic →hydrophobic →van der Waals forces →hydrogen bonds
→ Depends on the antibody binding site being exactly complementary, sterically and chemically, with a site on the surface of the antigen
→ The binding site on the antigen for one specific Ab is called an epitope
what are different types of B cells?
→The body generates over 100,000,000 different B-cells each making a different “random” Ig
→Each B-cell only makes one specific Ig
→These naïve B-cells sit around in lymph nodes doing not very much
what happens to the B cells in lymph nodes during an infection?
→During an infection, a small number of B-cells will, by chance, be making an Ig that binds one of the foreign antigens
→These B-cells are activated and begin to multiply- “clonal selection”
why are B cells called clones?
→Descendants of the original activated B-cell make the same Ig
→therefore they are a clone
how does Lymphocyte Development happen in the Bone Marrow?
→ Haematopoietic stem cells differentiate into either
→common myeloid progenitor (neutrophils,red cells, platelets)
→ common lymphoid progenitor ( either pre-T or pre-B)
what are Primary and Secondary Lymphoid Organs?
→ HSC into Pre-B
→ imm B-cells
→ Imm B-cells into follicles containing resting B-cells
→ (secondary lymphoid organs, lymph nodes, spleen, gut etc)
how are B cells activated?
→Functional Ig is first expressed as IgM on the cell surface (sIgM)
→this acts as a “B-cell receptor” in a similar way to a growth factor receptor.
→The IgM does not have intrinsic tyrosine kinase activity, but associates with other tyrosine kinases
→Binding of antigen to IgM activates the tyrosine kinases and their signal transduction pathways
what does B cell activation require?
→Antigen binding to the B-cell receptor (sIgM), resulting in stimulation of signal transduction pathways
→Co-stimulation by T-cells
→The activated B-cell begins to secrete soluble IgM
what happens to activated B cells?
→B cells activated
→Multiply rapidly
→Differentiate to become Ig secreting cells
→First make IgM
→Then undergo class switching to make Igs with the same Ag specificity but different heavy chain constant regions
what do memory B-cells do?
→Memory B-cells allow a very rapid response to a second exposure
→Immediate production of IgG rather than IgM
why are natural immune responses described as polyclonal?
→More than one clone of B-cells is generated
→More than one Ig is synthesised
→ Multiple antigens on organism
→Multiple epitopes on each antigen
→More than one Ig may recognise the same epitope
what is class (or isotype) Switching?
→The body can make different classes of Ig IgG, IgM, IgA, IgD, IgE differ slightly in heavy chain constant region amino acid sequence
→Have different functions note: there are actually 4 types of IgG (subclass IgG1 – IgG4) →And 2 types of IgA (subclass IgA1 and IgA2)
what are the heavy chain isotypes?
γ = IgG μ = IgM α = IgA δ = IgD ε = IgE
