Immunology 5 Flashcards
What is involved with the adaptive immune response?
Dendritic cells are the communication between innate and adaptive systems B cells + antibodies T cells
This response can take days-weeks to occur
What are the stages of T and B cells recognising and responding?
Be able to recognise the pathogen
Find the pathogen
Activate
Respond
Difference between innate and adaptive immune systems?
Innate - rapid, non-specific response in minutes-hours; same general response to many different pathogen species with PRRs on innate cells and PAMPs on pathogens (non-specific recognition)
Adaptive - slow, specific response (days) that is unique to each individual antigen (B and T cells do not have PRRs but do have antigen receptors for the antigens on pathogens). Responsible for generating immunological memory
What are antigens?
Adaptive immune responses are induced by antigens - any substance which can cause an adaptive immune response by activating B and T cells
Describe movement of T and B cells
Constantly circulate through the blood, lymph and secondary lymphoid tissues Inactive until meeting with antigen
Functions of B and T cells?
Some are very long-lived (memory cells)
B cells - key role in defense against intracellular pathogens via ANTIBODY PRODUCTION
T cells - key role in defense against intracellular pathogens, (VIRUSES, mycobacteria):
Helper T cells - key regulators of entire immune system
Cytotoxic T cells - kill virally infected body cells
PAMPs vs antigens?
PAMPs:
Non specific recognition - limited no. of PAMPs which are common to many different pathogens
Only a small no. of different PRRs are required to stimulate innate immune cells
Antigens:
Specific recognition - millions of different antigens; individual T and B cells only express one specific antigen receptor, which binds to only one specific antigenic epitope
How do T cells and B cells recognise antigens?
T cell antigen receptor (TCR) - membrane-bound heterodimer that has an α chain and a β chain
B cells antigen receptor (BCRs) - membrane-bound antibody (IgM or IgD); BCRs have 4 chains (2 heavy chains and 2 light)
What are antibodies?
AKA immunoglobulins - proteins produced by B cells in response to an antigen and which bind SPECIFICALLY to that particular antigen:
Expressed on B cell surfaces
Secreted as soluble proteins into extracellular fluids
Function of antibodies?
Provide defense against extracellular pathogens (most bacteria, viruses and toxins)
What are the regions of an antibody?
Each heavy and light chain contains a VARIABLE REGION (forms antigen binding site) and a CONSTANT DOMAIN
Different types of antibodies exist with same basic structure but DIFFERENT HEAVY CHAIN CONSTANT REGIONS
Examples of differing heavy chain constant regions?
IgM - µ heavy chain
IgG - γ heavy chain
IgA - α heavy chain
IgE - ε heavy chain
IgD - δ heavy chain
Describe specificity of antibodies and what advantage does this give the adaptive immune system
Individual antibodies have unique, differently shaped antigen-binding sites, so they bind specifically to one particular antigenic epitope
Adaptive immune system able to recognise and respond to millions of different, highly diverse antigens
How can the adaptive immune system recognise millions of different antigens, when there are less genes than antibodies?
Antibody heavy and light chain proteins are encoded for by SEGMENTED GENES in the germ-line genome of HAEMATOPOIETIC STEM CELLS
RANDOM REARRANGEMENT of these gene segments occurs in individual B cells as they mature - produces a huge no. of antigen receptors and antibodies without having a lot of genes
Similar process of rearrangement of TCR α and β chain gene segments in developing T cells
Process of gene rearrangement is entirely RANDOM - giving rise to hugely diverse B and T cell populations and also to potential for AUTO-REACTIVE cells
Where do adaptive immune responses occur?
In SECONDARY LYMPHOID TISSUES:
- Mature antigen-specific T and B cells constantly re-circulate between different secondary lymphoid tissues, blood and lymphatic vessels
- Mature dendritic cells, pathogens, antigens, debris, etc are trapped in secondary lymphoid tissues:
Lymph - lymph nodes
Blood - spleen
How do T and B cells enter lymph nodes?
Use transendothelial migration
After several days, if they do not encounter specific antigen, B and T cells return to blood system via efferent lymphatics
How do antigens enter a lymph node?
- Particle and antigens derived from pathogens are released by phagocytes
- Inflammatory TNFα stimulates immature tissue-resident dendritic cells, leading to B7 expression (on activated antigen-presenting cells) and dendritic cells also begin to PRRs
- Dendritic cells phagocytose pathogen-derived particles and antigens
- Dendritic cells digest pathogen-derived proteins and display small peptides on surface in complex with MHC proteins (Major Histocompatibility Complex)
- Pathogen-derived particles, antigens and mature dendritic cells travel to local draining lymph nodes
Function of dendritic cells?
“Professional” antigen-presenting cells that are:
Present in peripheral tissues in a “immature” state PHAGOCYTOSE antigens, cell debris and particles
Mature and migrate into secondary lymphoid tissues where they play a key role in ANTIGEN PRESENTATION
Lymph node structure?
Tissue fluid (lymph) enters via afferent lymphatics and exits via efferent lymphatics Inside lymph nodes:
T cell zone
B cell zone with stromal cells
High Endothelial Venules (HEV) - express selectins allowing wbcs to bind and move down vessel
Function of stromal cells in B cell zones?
“Trap” opsonised antigens, e.g: C3b on opsonised antigen and C3b receptor on stromal cells
How are B cells activated?
Activation requires TWO SIGNALS
Protein antigens:
Signal 1: BCR + antigen
Signal 2: T cell help
Any antigen:
Signal 1 - BCR + antigen
Signal 2: PRR + PAMP
Antigens with repetitive antigenic receptors:
Signal 1 + 2: Multiple BCRs and antigens engagedw
Function of Major Histocompatibility Complex (MHC)?
Bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells
T cells can only recognise peptide antigens presented by MHC, AKA HLA (HUman Leucocyte Antigens) - able to present many different peptides, encoded by highly polymorphic genes; first identified in early transplantation procedures
Two classes of MHC proteins?
Class I MHC - expressed on ALL nucleated cells and present peptide antigens to cytotoxic T cells
Class II MHC - expressed ONLY on professional antigen-presenting cells, like dendritic cells, also macrophages and B cells; function is to present antigen to helper T cells
Fate of antigen activated B and T cells?
Resting cells can become activated by specific antigen and co-stimulation
Activated cells:
Entry into cell cycle/mitosis
Differentiation to form EFFECTOR cells and MEMORY cells
Over 7-10 days
