Immunology

• vertebrates have the same immune system as humans
• Mammals have complex immune systems
• Why is immunolgoy important?

  Infectious diseases- vaccines

  Autoimmunity - diabetes I rheumatoid arthritis

  Allergy - anaphylactic shock, asthma

  Cancer - vaccination, (HPV CAR T cells)
• Innate immunity is the first line of defense against any foreign material, including microorganisms, encountered by the host. It includes general mecha nisms such as skin, mucus, and constitutively produced antimicrobial chemicals. Innate resistance mechanisms are always prepared to defend against foreign invaders to the same maximal extent each time a foreign invader is encountered.
• adaptive immune response must be activated (turned on) by cells and chemicals of innate immunity. Unlike innate immunity, each adaptive immune response is tailored to a particular foreign agent.Adaptive immune re- sponses coordinate and amplify a variety of cellular and chemi- cal responses that evolved to meet the challenge of each specific invader. The effectiveness of adaptive immune responses increases if the host encounters the specific foreign agent again
• innate immunity most plants and animals have some form of innate immunity. Examples are TLR, complement and lysozyme.

  • rapid response, but low -specificity
  • no requirements for MHC, B cell, t-cells but synergises with adaptive immunity in vertebrates.
• Toll-like receptor use innate sensing but also feed into adaptive
• Toll-like receptors recognise conserved structures i.e flagellum, endotoxin and lippopolysaccaharide in gram negative bacteria. they also transmit signals to the nucleus to alter gene transcription.
• Toll like receptors are always imbedded in the membrane of the cell and endosomes
• In an endosome nucleic acids are exposed. They are unwound by the acidic environment and increases recognition of TLR.
• Signalling domains on TLR in the plasma membrane initiate a transcriptional change when TLR sense something changing genes transcribed.
• TLR9 recognises bacterial DNA. This DNA is rich in C and G and C is undermethylated compared to compared to human DNA. Commonnbacteria motif.
• TLR produce a number of molecules for defence, by changing gene transcription.
• TLR2 recognises gram positive bacteria - lipoteichoic acid
• TLR4 recognises gram negative bacteria - lipopolysaccharide which is an endotoxin for toxic shock.
• TLR5 - motile bacteria - flagellin
• TLR 3 is in the endsome and recognises dsRNA viruses
• TLR7 in the edosome recognises ssRNA viruses
• TLR9 in the endosome recognises bacterial DNA (CpG)
• TLR signal via other adaptor proteins and activate transcription factors
• Gene transcription patterns are changed towards pro-inflammatory, e.g cytokines are secreted.
• Microbial invasion to regions rich in leukocytes and TLR (or other PRR) triggers inflamation and immune activation
• commensals and pathogens have PAMPs but commensals generally do not cause extensive inflammation and immune activation. (commensal only triggered when they invade.)
• The innate and adaptive system responds to both commensals and pathogens
• Pathogens are intrinsically invasive. Commensals are generally kept out by physical and chemical barriers.
• pathogens act to supress the immune system
• In the gut IgA is produced to contain both commensals and pathogens.
• Adaptive immunity

  • appeared abrubtely in jawed fish.
  • Slower initial responses , but memory response rapid. Highly specific.
  • MHC dependent and requires B and/or T cells with somatically rearranged DNA
• Mast cells are important in the immune repsonse
• Macrophages

  • differentiate from monocytes as they migrate into tissues
  • major role in phagocytosis
  • Express MHC-1 and MHC-II and act as antigen presenting cells.
• Dendritic cells

  • Most potent of all antigen-presenting cells.
  • mainly found in tissues as 'sentries'
  • carry antigen into lymph nodes for t-cell responses.
  • myeloid cell
• Dendritic cells go into the lymph node and present antigen on MHC to the T-cells, (mainly CD4)
• CD4 'helper' T cells help B cells to make antibody. They also help in the stimulation of CD8 T -cell responses.
• CD8 t-cells can become cytotoxic and kill virus- infected or cancer cells.
• Dendritic cells activate helper t-cells. CD4 T-cells then activate CD8 and B cells. CD8 becomes cytotoxic. secreting perforin and gramzyme to virus infected cell causing apoptosis. B-cells produce antibody that neutralise toxins or Tag microbed for destruction.
• Innate immunity demonstrates rapid response and low specificity.
• The adaptive immune systems evolved in vertebrates due to increased prey range, longer reproductive ages.
• Stem cell -> myeloid precursor -> monocyte -> macrophage
• The main opsonin produced during complement activation is C3b.
• Spontaneous hydrolysis of C3 results in complement actiation through the alternative pathway