Defensin- can disrupt bacterial surface membranes, and defensin- , anti-HIV.
Monkey cells express Trim-5 protein, which confers resistance to HIV infection (human Trim-5a cannot resist to HIV) --species specific innate immunity
TLR in macrophages/DC; pattern recognition of microbial molecules; recognition results in phagocytosis, cytokine release, local inflammatory responses or facilitates innate and adaptive immune response
Toll-like receptors (TLR) & pattern recognition of microbial molecules
Toll-like receptors (TLR) are expressed in macrophages/DC.
TLR 1-10 are pattern recognition receptors recognizing a molecular pattern present on the surface of many microbes.
PAMPs (Pathogen-Associated Molecular Patterns)
TLR recognition results in phagocytosis, cytokine release, local inflammatory responses
TLR recognition induces cellular signaling and activates macrophages/DC to initiate innate & adaptive immune responses.
Over-activating can induce inflammation (LPS from Neisseria meningitides activate TLR-4 -> TNF IL-1 -> septic shock).
Adaptive (acquired) immunity Immunity established to adapt to infection • Learnt by experience • Confers pathogen-specific immunity • Enhanced by second exposure • Has memory • Uses cellular and humoral components • Innate immune components make it more effective Antibodies and microbe-specific T cells reflect infections to which an individual has been exposed - diagnostic for infection Immune memory is the basis for vaccine
CD4 T helper, produce various cytokines including interleukin-2, -4, -5 and interferon- (IL-2, IL-4, IL-5, IFN- ). IL-4 and IL-5 help B cells to produce antibodies) ; IL-2 help CD8 T killers, T cells to enhance T effector function for cell-mediated immunity; IFN- activates macrophages/dendritic cells.
CD8 T killer, produce cytotoxic granules (perforin, gramzyme A,B,K, granulysin), and kill virus-infected cells.
T cells, recognize nonpeptide antigen produced by many bacteria, produce cytokines, and exert cytotoxic activities.
Regulatory T cells (Treg), suppressive cells that are important for control of autoimmune diseases
NK T cells, express NK receptors, and T cell receptors
Features of innate and adaptive immunity yes n/a Relevance to anti-cancers or anti-autoimmune diseases yes no Utility for vaccine-induced prevention against infections/diseases n/a Yes, (monkeys resist to HIV but susceptible to SIV) Species-specific resistance to some pathogens/infections yes no Improve after the re-exposure Slow, days/weeks (but improve to act fast after 2 nd exposure) Fast, minutes Responding time after initial exposure to pathogens yes no Immune memory (faster, greater magnitude, longer lasting response after re-exposure) yes No (but TRL in macrophages show pattern recognition of some microbial molecules) Specific recognition of many different antigens adaptive immunity Innate immunity
Integrated question A 4-year old boy had a fever with skin rash, and quickly developed convulsions and signs of early shock. He was suspected to have Neisseria meningitides septicemia and meningitis. Which of the following is NOT TRUTH ?
The shock occurred because the immune system over-reacted to the endotoxin LPS from Neisseria meningitides.
LPS was recognized by TLR-4 expressed on monocytes/macrophages/DC.
TLR-4 recognition of LPS led to cell signaling and production of large amounts of IL-1 and TNF- , which contributed to the shock.
The boy would develop the Neisseria-specific T cell and antibody responses, which should confer him protective immunity against potential 2 nd Neisseria infection.
The boy would develop adaptive TLR/macrophage response, which can prevent from the over-reaction to LPS in subsequent Neisseria infection.