Adaptive immunity Flashcards
Large Glycoproteins that recognize a specific Antigen
Immunoglobulin
Types of immunoglobin
Membrane bound-b cell receptors
Non-membrane bound-antibody
Parts of an antibody
Heavy(long) and light(short) chain
how heavy and light chain connect
Disulfide bond
How many different types of heavy and light chains can a b cell produce
one type of each
Papain turns an antibody into
2 Fab fragments and one Fc fragment
Where anitgen binds
Fab fragments
The Fc area of an antibody binds wehre
Fc receptors on innate immune cells
Where antigen binding occures
Variable region(different between antibodies) contain and light and heavy chain part
Are Immunoglobulins flexible
Yes, needs to move a bit to bind to antigens
Amino acid sequence that demonstrate extreme variability between different lg molecules
Hypervariable regions
Where the Hypervariable region is found
at least 3 areas of the variable region
length of the hypervariable region
5-7 amino acids longs
Role of the hypervariable regions
give rise to the enormous antigenic diversity associated with Ig molecules
Region of antigen with little variation
Constant region
changes in the Constant region leads to
change in size, charge, solubility, and structure of an Ig molecule
Different structures of Ig molecules
isotypes
Light chain isotypes
Kappa and Lambda
Role of Light Chain Isotypes
Contribute to diversity but not function
different heavy chain isotypes
Mu, Delta, Gamma, Epsilon, and alpha in addition to subclasses within
What is produced when a naive b cell first encounters an antigen
It will produce IgM
what can lead to class switching of isotypes
Genetic Rearrangements of the constant region
Structural Isoforms
Membrane-bound Ig
Secreted Ig
Secretory Ig
Where Secretory and Secreted Isoforms are found
Secretory- secretions (tears mucus)
Secreted-found in blood
Domain found on membrane-bound Ig
Cytoplasmic and Transmembrane domain
Secreted Ig lacks
Transmembrane and cytoplasmic donmains
Roll of Secretory component of Ig
Protection
Packages the Heavy and light chain Immunoglobins
the Smooth ER
When membrane bound immunoglobin binds to the membrane
In the ER and allways until it binds to cell membrane
Multiple immunoglobulins together
Polymeric Immunoglobulins
Most common Polymeric Immunoglobulins
igM=5
igA=2
Holds together Polymeric Immunoglobulins
J chain
How Secretory Immunoglobenulins enter the lumen
Bind to receptor, enter transport vesicle then enter the lumen of body tract
Because B Cell receptors don’t go far into the cytoplasm, what do they complex with to induce a response
Ig-alpha and Ig-beta and they use ITAM to induce a response
Exons vs introns
Coding
Non coding
What makes up the variable region of Immunoglobulin genes
Small DNA fragments call gene segements
Types of Gene segments
Variable, Diversity, Joining
What gene segment does the light chain not have
D segment
What is Somatic recombination
Random rearangement of the V, D, and J segments of the variable region
Where V, D, J recombination occures
in every naive B cell
Changing V, D, J recombination
Perminant
V, D, J Recombination allows for
Large antigenic diversity of Ig
Relation between V, D, J recombination and the Ig Isotype
NO relation
The Antigenic Determinant is also called an
Epitope
Do antigens always bind to the entire Ag site
No, tend to make most contact with CDR3 of Ig H chain
how the anti body can change to for to the antigen
conformational changes
The strength of the non-covalent association between one antigen-binding site and one antigenic epitope
Affinity
The overall strength of the bond between a multivalent Ab and Multivalent Ag
Avidity
Occurs when one epitope is shared by two Ag, or when two epitopes on separate Ag are similar in structure
Cross Reactivity
Stages of B Cell development
Maturation and Differentiation
B Cell Development that begins in the bone marrow and ends in the periphery
Maturation
What stage is the B cell still naive
Maturation
B cell Development that begins once a B cell recognizes its sepcific Ag, ends with the generation of Ag-specific plasma cells and memory B cells
Differentiation
Stages of B cell Maturation
Hematopoietic stem cell Mutlipotent progenitor cell Common Lymphoid progenitor Progenitor B cell Precursor B cell Immature Naive B cell Mature Naive B cell
Roll of Stromal cells in B cell maturation
Bind to B cell and help it stay in place and feed it, then secrete shit to make it change and mature
The first Hematopoietic cells that are recognizable as B cells
Pro-B cells
Configuration of Immunoglobulin genes of Pro-B Cells
Germline configuration
What separates Pro-B and Pre-B Cells
Pre-B cells have their V(D)J recombinations of both chains complete
Late pre-B cells produce
Membrane bound IgM plus Ig-alpha and Beta
What do Immature B cells develop
Central Tolerance
What do Immatre B cells get to do to their Ig loci
Can rearrange in the process of receptor editing
how many Immauter B cells survive positive/negative selection
2-5%
Process of Central tolerance
Immauter B cells bind to bond marrow stromal cells, self react, edit and if still self react, they pop(negative selection)
Travel of Transitional Type 1 B cells
Red pulp then PALS
Transition Type 2 B cells express
Both Igm and IgD
How a B Cell can have 2 different receptors
Excise different exons
Mature B cells express
IgM and IgD
V(D)J rearrangements of Mature B cells
Cannot do it
What are Mature B cells considered to be
Naive
Types of B cell antigens
T-dependent and T-independent
T dependent B cell antigens are usually
Follicular B cells
T-independent B cell antigens are usually
Marginal zone B cells
B cell antigen that are Isotype-switched, High affinity antibodies, memory b cells and long lived plasma cells
T-dependent
B Cell antigens with mainly Igm, low affininty antibodies, short lived plasma cells
T-independent
T-independent antigen TI-2 binds to
only the B cell receptor
T-Indepenent Antigen TI-1 binds to
B cell receptor plus others
Process of T-dependent antigens
Dendritic cell recognizes the Protein antigen. Presents it to Helper T cell and this then goes and gives it to the B cell
Zones for T-dependent antigens
T cell zone and B cell zone(Primary follicle)
Steps of B cell activation
Antigen Binding, Costimulation, Cytokine help, and B cell clonal expansion and differentiation
Where B cell acivation occurs
Secondary lymphoid tissues
Signal 1 of B cell activation
Binding of Multiple Ag to B cell receptor. Isgnal tranmitted via Ig-alpha/Ig-beta
Result of Signal 1 of B cell activation
Internalization of Ag, processes Ag for presentation via MHC II
B cell expands in size and gets ready for interaction with T cell
Signal 2 of B cell acitvation
Interaction with activated, Ag-specific T helper cell
T cell receptor for B cell Activation
Peptide-MHC II
CD40L binds to:
CD40 on B cell
Signal 3 for B cell activation
Cytokine stimulation by activated, Ag-specific T helper Cell. Also receive cytokines from nearby activated macrophages and dendritic cells
Pimary follicle does what to become a secondary follicle
Th effector cell from paracortex binds to receptive B cell. Forms a Mantle of Naive B cells
What occures in the Geminal centers
Somatic Hypermutation, Affinity maturation, Isotype switching
Types of Plasma cells
Short lived and Long Lived
Short lived Plasma cells secrete
Low affinity IgM
Short lived Plasma cells can be made way
Ti and Td Antigens
Long lived Plasma cells arise from
Germinal centers then mirgrate tot he bone marrow, lymph node medulla or red pulp of spleen to secrete IgG, IgA, IgE
Role of antibodies
Aid with clearance/ destruction of antigen
Neutralization, classical complement activation, opsonization, antibody-dependent cell mediated cytotoxicity
How to block attachment of antibodies
Steric interference, Capsid Stabilization, strucural changes
Ways to neutralize antibodies
Block attachment or uncoating
How to block uncoating of antibodies
Capsid stabilization, and fusion interference
Coating of an antigen with host protein to trigger phagocytosis
Opsonization
Immunoglobulins involved in Opsonization
IgG1 and IgG3
What helps to destroy Ab-coated substance that is too large to be ingested by phagocytosis
Natural Killer T cells baring FcRs
Roll of Memory B cells
Aid in the time and overal effectiveness of the seoncdary response to an attack