Clonal Selection and Soluble Mediators Flashcards
What is clonal selection?
During B and T cell development, random genetic recombinations occur within each cell among multiple copies of immunoglobulin gene segments (B cells) or TCR gene segments (T cells). = strategy 2.
Why is random genetic recombination important in clonal selection?
These processes generate the diversity of clones of lymphocytes: each clone is specific to a different antigen.
What does each lymphocyte carry?
Each lymphocyte carries a single, unique antigen receptor.Lymphocytes that meet an antigen they recognize will proliferate and survive. The huge majority of lymphocyte clones will die out
Clonal Selection summary?
Antigen binds to surface receptor on the B cell or T cell and causes selective expansion of that clone.
What are cytokines?
Small secreted proteins, involved in cell to cell communication, messengers of the immune system that acts locally and can have powerful biological effects at very low concentrations. They are short-lived.
Different families of cytokines?
- Interleukins - between leukocytes
- Interferons - antiviral effects
- Chemokines - chemotaxis (cell movement)
- Growth factors - proliferation and differentiations of cells
- Cytotoxic - tumor necrosis factor
What’s an Inducing Stimulus?
leads to cytokine producing cell releasing cytokines, which binds to receptor on target cell, activating/downregulating the gene(s) and producing biological effects. Cytokines can affect hundreds of genes each.
What are the 3 ways cytokines can work?
autocrine (self), paracrine (nearby), endocrine (circulate in blood to distant cell)
What are dendritic cells?
(antigen presenting cells) recognise pathogens and secrete cytokines -
network of cells located at likely sites of infection, these recognise microbial patterns and secrete cytokines →
capture pathogens and take them to local lymph node to present antigens to adaptive immune system (APC)
What’s complement?
Plays major role in complementing the activity of the specific antibody in lysing bacteria.
mixture of 30 proteins and glycoproteins that has a high concentration in the serum 3-4mg/ml. Triggered enzyme cascade system → rapid and amplified response, mainly produced in the liver as inactive enzyme precursors?
How is complement synthesized and activated?
when activated the substrate for enzyme is next component in the pathway and cleaves (activating) substrate (becoming active enzymes themselves) → substrate is component 3 which is cleaved and activated.
What are the 3 complement activation pathways?
Classical Pathway - activation through antibody binding to antigen (immune complex). The sections of the complement enzymes that are cleaved are pro-inflammatory molecules - binding to receptors on mast cells causing them to degranulate and release histamine.
Lectin Pathway- (lectin = protein bound to carbohydrate) Mannin Binding Lectin C Reactive Protein binds to carbohydrates only found on bacteria and triggers activation of complement
Alternative Pathway - Bacterial surfaces directly activate complement
Where do the 3 complement pathways converge?
These pathways converge on C3b - is a molecule that opsonines pathogens (coats them in antibody for phagocytes to more easily recognise them).
This then leads to the final common pathway - formation of the Membrane Attack Complex - inserts into membranes of pathogens leading to their lysis.
What are the functions of complement?
Lysis, Opsonization, activation of inflammatory response, clearance of immune complexes.
What is the acute-phase response?
Acute-phase response = systemic, after a local inflammatory response (+1-2 days), fever, increased production of white blood cells (leukocytosis), production of acute-phase proteins in the liver, induced by cytokines.
Acute phase proteins - produces a lot more of these proteins to help fight infection:
C-reactive protein - C polysaccharide of pneumococcus, activates complement, can increase x1000.
Mannan binding lectin - activates complement
Complement
Fibrinogen - clotting