Immunology: Principles Flashcards
What are the two types of lumped tissue and what do they do?
Primary (central) - where lymphocytes are generated/matured
Secondary - Where lymphocytes interact with antigen presenting cells (APC’s) and immune responses are generated
Where can you find primary lymphoid tissue?
Bone marrow, thymus, bursa of fabricius
Illegal payers patches (in cattle, horses, dogs)
Appendix/caecal patch in rabbits
Where can you find secondary lymphoid tissue?
– Lymph nodes
– Mucosal-associated lymphoid tissue (MALT, e.g. BALT)
– Spleen
What do naive lymphocytes do until they are activated?
Naïve lymphocytes recirculate through blood and lymph continuously until they encounter their specific Ag in the LN
When lymphocytes encounter their antigen what happens?
This stimulates cell activation, division, lymph node enlarges, activated Lymphocytes leave LN in lymph, enter blood via thoracic duct then enter tissues at site of infection.
Part of this response is to form memory cells
What do memory cells do when they encounter their specific antigen?
When memory cells are established and encounter their specific antigen again, they leave blood at site of infection to enter tissues, become effectors and some then travel back to LN. Memory cells can live years, dividing infrequently.
What are the two subsets of lymphocytes?
T and B
Where do B cells mature?
Bone marrow or the bursa of fabricius
Where do T cells mature?
In the thymus
What do B cells do when they encounter their antigen?
Antibody secreting cells (plasma cells)
Memory cells
What do T cells do when they encounter their antigen?
memory cells
Cytotoxic T lymphocyte (CD8+ Tc)
Helper T lymphocyte (CD4+ Th)
T regulatory cells
What MHC class are CD8+ Tc ?
MHC class 1 restricted
What MHC class are Th CD4+ cells?
MHC 2 restricted
What are the subtypes of Th CD4+?
Th1, Th2 and Th17
What cytokines do Th1 produce?
Th1 cytokines include IFNg and TNFa to activate macrophages and mediate delayed type hypersensitivity
What cytokines do Th2 produce?
Th2 cytokines promote the differentiation of B cells into antibody secreting plasma cells, include IL-4, IL-5
What cytokines do Th17 produce?
TH17 cells secrete IL-17 which is important in neutrophil recruitment, fungal infection and autoimmunity (identified in mammals)
What is the role of Th1 cells?
Activate effectors (CTL) to kill intracellular pathogens
What is the role of Th2 cells?
Stimulate B cells antibody production and class switching
What do Tregs express on their surface?
CD25+ and FoxP3+ transcription factor
What cytokines do Tregs produce and what is their role?
IL-10 and TGFbeta
Regulate the immune response and crucial in developing tolerance
What type of response does TB generate?
A cellular response, so in TB IFNg can be detected in the blood
What is an epitope?
A localized region on the surface of an antigen capable of eliciting an immune response and of combining with a specific antibody to counter that response.
Each T or B lymphocyte is specific for…
a single antigenic epitope
Each T or B lymphocyte is specific for…
a single antigenic epitope
The diversity of antigens which T or B cells can recognize is explained by
T cell receptor (TCR) or BCR (surface membrane immunoglobulin). The diversity of the TCR and BCR can alter through mutations in the genes encoding these receptors.
How can TCR on T cells recognise antigens?
TCRs on T cells must have antigen presented to them by MHC class I or II molecules on other cells
How can BCR on B cells recognise antigens?
BCRs or surface immunoglobulin on B cells can bind antigen directly
If pathogens infect a cell how is this recognised on the surface of the cell?
Peptides from the pathogen will be presented on the surface within the groove of the MHC class I molecule.
How does endogenous antigen processing occur within the host cell?
Endogenous processing involves antigen entering cytoplasm where it is tagged with ubiquitin, enters proteasome where proteins are degraded into peptides. These are transported to the endoplasmic reticulum where they associate with MHC class I. This complex then moves through the Golgi to be expressed on the cell surface.
What will happen when a CTL recognises an endogenously presented peptide/MCH complex?
Engagement will occur between the CTL’s TCR and CD8 molecules. As a result the infected cell will be lysed. The CTL will also secrete cytokines (IFNg) which enhance activation and recruitment of other CTL. The CTL will only recognize the peptide if it is presented by MHC class I. As a result the T cell is described as being MHC class I restricted.
Which cells possess MCH 1, what does this mean?
MHC class I is present on virtually all nucleated cells in the body, so virtually any cell can present peptide antigen to CTL.
How are pathogen peptides presented with MHC2?
Exogenous antigen processing Antigen presenting cells (macrophage, dendritic cell, B lymphocyte) which endocytose pathogens will process the antigen and present peptides on the cell surface within the groove of the MHC class II molecule
What types of pathogen have exogenous antigen processing?
Infectious (bacteria, viruses, fungi, protozoa, helminths)
Environmental (pollen, dust mites, food)
What does MHC class 1 present its antigen complex to?
T Cytotoxic cells
What does MHC class 2 present its antigen complex to?
T helper cells
B cells can bind soluble antigen with high affinity, what happens when this occurs?
Binding of antigen to the B cell stimulates proliferation of B cells. Ultimately B cells differentiate into lymphoblast and plasma cells. Plasma cells secrete immunoglobulin, which can also bind antigen directly
How can activated B cells act as APC’s?
Activated B cells can also act as antigen presenting cells to MHC class II restricted T helper lymphocytes, especially Th2 lymphocytes.
What are the stages of clonal expansion?
Co-stimulation (multiple signals)
Lymphocyte activation then division
Multiple “clones” of identical antigen specific T or B lymphocytes
What do you get if there is a lack of the complete clonal expansion cascade?
tolerance to the antigen
How does co-stimulation in T cells occur?
Signal 1: Engagement of TCR with MHC and antigen. TCR can only recognise cognate peptide antigen in conjunction with MHC presented by APC
Signal 2: Co-stimulation to stabilise contact between the APC & T cell e.g. CD4-MHC II or CD8-MHC 1
Signal 3: APC cytokines bind to T cell receptors
Outcome: This induces intracellular signalling which drives the T cell to activation
How does co-stimulation occur in B cells?
Signal 1: antigen binds to BCR (surface immunoglobulin) on B cells. The B cell processes the antigen and presents it on the surface with MHC class II
Signal 2: The peptide-MHC complex is recognised by circulating, antigen specific T helper cells. These then co-stimulation the B lymphocyte via secretion of cytokines
How is immunodeficiency different to tolerance?
Whole immune system is damaged & unresponsive Non specific (i.e. not restricted to one antigen)
What is secreted by T cells that promotes proliferation?
IL-2
What are the main outcomes of antigen presentation?
» antigen recognition by lymphocyte (>2 signals)
» cytokine synthesis
» lymphocyte activation
» clonal expansion
» development of effector T or B cells
» development of T or B memory cells specific for that
