(I) Lecture 5: Intro to Adaptive Immunity Flashcards
Main Cells of Adaptive Immunity
From lymphoid progenitors
B cells: antibodies
- important against EXTRACELLULAR pathogens
T cells: helper T cells (Th cells, CD4+ T cells) and cytotoxic T cells (CTL; CD8+ T cells)
- important against INTRACELLULAR pathogens
Primary response
FIRST exposure to pathogen
Kicks in later
Secondary response
subsequent exposure to the SAME pathogen
- memory B & T cells respond
- later and faster due to immunological MEMORY
adaptive b/c immune response is more efficient w/ re-exposure to an identical pathogen (memory)
Primary Immune Response
- Establishment of infection
- Inductive phase (turns on adaptive immune cells)
- Effector phase (adaptive cells perform)
- Memory phase
most adaptive cells die but a few remain as memory cells
Naive B and T cells
never encountered a pathogen before
differentiate into effector cells
Effector cells
B cells = plasma cells
T cells = helper T cells and cytotoxic T cells
they die once pathogen is destroyed
Memory cells
remain after infection is resolved
Immunological memory
initial exposure either due to vaccination or natural exposure
- naive B & T cells respond and become effectors
- primary immune response: memory B & T cells form
secondary exposure
- memory B & T cells respond
- more effector cells form
- faster and stronger response
Basis of Vaccination
Basis of vaccination is immunological memory to bypass primary response
Lots of antibodies against pathogens years after vaccination
Primary Lymphoid Tissue
where lymphocytes are developed
- Thymus (T cells)
- Bone marrow (B and T cells start here)
Secondary Lymphoid Tissue
where naive lymphocytes are further differentiated
- lymph nodes
- spleen (filters blood)
- mucosa-associated lymphatic tissue (MALT)
Lymph
Interstitial tissue fluid that enters the lymphatic vessels to be transported back into the blood
Lymphatic system
network of tissues, vessels and organs that work in close proximity with the circulatory system
lymphatic capillaries run parallel to blood caplillaries
when lymph leaves tissues it carries wast products from tissues like dead cells, CO2 and pathogens
Lymph nodes
filters lymph that passes through
perfect spot for immune cells to “look for” pathogens
Vaccine injections
Typically intramuscular, on the arm
- good blood flow
- optimizes immune response
- vaccine components travel to closest lymph node (usually in armpits)
- other routes of admin: subcutaneous (infants), orally, nasally
Lymphoid tissue
B cells develop in bone marrow
T cells start to develop in bone marrow and finish developing in the THYMUS
T-Cell Development
Th Cell (CD4+) = double positive precursor loses CD8
CTL (CD8+) = double positive precursor loses CD4
Spleen
Not actually in lymphatic system (does NOT filter lymph)
Filters BLOOD
Shows similar B/T cell organization where they meet BLOOD-BORNE PATHOGENS
MALT
Mucosa-associated lymphoid tissue
- site where B and T cells meet pathogens in mucosal areas
- found in oral-pharyngeal cavity and gastrointestinal, respiratory, urogenital tracts
- MALT is located in tonsils, lungs, colon, appendix, etc
- Microfold cells (M cells) help transport antigens into the tissue
B-cell and T-cell receptors
Naive B and T cells migrate to secondary lymphoid tissues to find pathogens
B/T cells express SURFACE receptors that recognize and bind to a pathogen/antigen
both have a variable region, constant region, transmembrane region and cytoplasmic tail
Antigen
any macromolecule that the variable region of a BCR/TCR can bind to
can be microbes or our own cells
- ex. blood type is determined based on antigens on blood cells (A, B, Rh)
a microbe expresses many copies of its own unique antigens
Blood type with all 3 antigens
Type AB+
- has type A and B antigens and Rh factor
Blood type with no antigens
Type O
Epitope
a motif that is recognized by immune cells
- a given antigen may contain several motifs
Variable region of a BCR/TCR binds to one unique epitope based on STRUCTURAL FIT
Antigens vs PAMPs
A PAMP is expressed by a WIDE VARIETY of pathogens and is recognized by PRRs (innate)
An antigen is a molecular structure that is generally UNIQUE to a specific pathogen and is recognized by a specific antigen receptor (BCR/TCR adaptive response)
- ex. H1N1 influenza
Antigen Recognition
Shape and size of the antigen determines specificity of antigen binding site of receptor
Antibodies can recognize linear (exposed) or conformational derterminants in folded proteins
B- cell receptor and antibody
Can be membrane-bound form (BCR) or secreted form (antibody)
Membrane-bound form contains a spacer, hydrophobic segment and cytosolic segment
The transmembrane domain and cytosolic segments are lost from membrane-bound to antibody form
Both antibody and membrane-bound form
- have the same antigen specificity
- can bind pathogen directly
T-cell receptor
has a double chain (alpha and beta)
NOT secreted
need antigen to be PRESENTED to them in a MHC molecule (CANNOT bind directly)
BCR and TCR regions
BCRs and TCRs have two variable regions
BCR has a heavy-chain variable region and the light-chain variable region
TCR has an alpha and beta region
Variable regions
encoded in gene segments of only PART of the receptor domain
segments are rearranged through somatic DNA recombination (gene rearrangement) to form a UNIQUE variable region coding sequence
Diversity of B/T cell receptors
more unique TCRs than BCRs
B and T cells make surface receptors UNIQUE to each individual, which are NOT passed on to offspring
Both B and T cells express many exact copies of a receptor with a unique antigen binding site
Each B/T cell expresses a BCR/TCR with a variable region specific for one unique peptide
Clonal expansion
When a specific antigen is encountered, that cell proliferates to create an army of cells with the same specificity
Clonal Selection
Different clones of B/T cells go through a deletion process to weed out self-recognizing receptors
Remaining cells enter circulation to secondary lymphoid tissues where they can interact w/ antigens/pathogens
Can then undergo clonal expansion if a specific antigen is encountered
What properties do T cell receptors and antibodies have in common?
They both contain a variable region and a constant region
B cell receptor
has 2 heavy chains and 2 light chains
