1 / 18

The Fascinating World of Immune Systems and Antibiotics in Bacteria and Vertebrates

Explore the intricate web of the immune systems in bacteria and vertebrates, including how antibodies work, the role of MHC proteins, and the impact of antibiotics in combating infections.

jbellanger
Download Presentation

The Fascinating World of Immune Systems and Antibiotics in Bacteria and Vertebrates

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Restriction-modification systems in bacteria Sites on bacterial chromosome protected by proteins/methylation G A A T T C C T T A A G EcoRI Sites on phage DNA/RNA unprotected and cut

  2. Penicillin and other antibiotics • Discovered by Fleming in 1929 and turned into a useful treatment by Florey and Chain (1940s) • Prevents the formation of the bacterial cell wall (by interfering with peptidoglycan cross-linking) • New cells subject to osmotic lysis • Only acts against Gram-positive bacteria • Other antibiotics • Streptomycin from bacterium Streptomyces acts on protein synthesis • Tetracycline, also from Streptomyces, also acts on protein synthesis on a wide range of bacteria

  3. The immune system of Drosophila • Body fluid of insects contains haemolin • a member of the immunoglobulin superfamily, which binds to microbes • Also several short peptides that play an unknown role in antibacterial action • Defensins – like scorpion venom taxins • Cecropins and attacins (disrupt cell membrane) • Drosomycin (antifungal) – similar to plant substances • Rapid evolution of some these proteins indicates an ongoing evolutionary arms race • Cellular immunity • Haemocytes secrete antimicrobial peptides and are involved in coagulation, phagocytosis and encapsulation

  4. Immune systems in vertebrates - overview • Mechanical barriers • Collagen/skin , mucous membranes, secretions • Non-specific defence (innate immunity) • Phagocytosis by neutrophils (70% WBC) • Macrophages (5% WBC) • The inflammatory response (histamine, chemokines, fever) • Antimicrobial proteins (complement, interferons) • Specific immune defence (adaptive immunity) • Humoral (antibodies, B cells) • Cell-mediated (Cytotoxic T cells, Helper T cells)

  5. Antigen (1st exposure) Engulfed by Free antigens directly activate Antigens displayed by infected cells activate Macrophage Stimulates B cell Helper T cell Cytotoxic T cell Stimulates Stimulates Gives rise to Gives rise to Memory helper T cell Stimulates Stimulates Antigen (2nd exposure) Memory B cells Stimulates Plasma cells Memory T cells Active cytotoxic T cells Antibodies

  6. B cells (made in bone marrow) • B cells secrete antibodies which recognise intact foreign particles outside cells and block their action/target them for destruction Infected cell B cell Antibody Antigenic determinant Each antigen can present many different antigenic determinants and be recognised by many different Antibodies Antigen

  7. The structure of antibodies

  8. The diversity of antibodies • Collectively referred to as immunoglobulins • IgM (pentamer) first to appear in response to infection • IgG (monomer) most abundant circulating form, confers maternal immunity • IgA (dimer) produced by mucous membranes • IgD (monomer) Differentiation of B cells • IgE (monomer) stimulate mast cells and histamine • Each has own heavy chain (a, d, e, g, m) • There are 2 types of light chain (k and l) • Both light and heavy chains are encoded by libraries of subunits which are shuffled to generate diversity

  9. Light-chain diversity Variable (40 units) Joining (5 units) Constant Somatic recombination with imprecise joining TGGCCAG TGGCTGGCAG TGGAG TGGCTGGAGCAGCC x ‘Fine-tuning’ by somatic hypermutation (error-prone DNA repair process) Possible diversity – (prior to mutation) about 1012

  10. Cell memory and clonal selection • Acquired immunity ensures that self-antigens are not attacked through • Clonal selection • Clonal deletion • Repeated editing • Absence of Helper T cells ensures that immune response is not mounted • Initially, B cells produce membrane bound antibodies • Cells stimulated by an antigenic response proliferate and differentiate into effector cells that secrete antibody • A fraction of the simulated cells differentiate instead into memory cells that are rapidly induced in subsequent antigenic challenges

  11. T cells (made in thymus) • Only respond when foreign antigen displayed on surface of self-cells in periperal lymphoid organs • Recognise fragments of foreign particles displayed by MHC proteins • Cytotoxic T cells recognise and destroy infected cells • Helper T cells stimulate other cells • Macrophages • B cells • Cytotoxic T cells • T cell receptors are very like antibodies, but are membrane bound ONLY and are less variable

  12. Cytotoxic killing • Cytotoxic cells release perforin (related to C9) which makes the infected cell permeable to secreted serine proteases • Activate apoptosis (cell death) through capsase family

  13. MHC proteins • Major histocompatibility complex (chromosome 6 in humans) • Class I MHC present to Cytotoxic T cells • Class II MHC present to Helper T cells • The most polymorphic loci in humans (some have >200 alleles) 6p21.3 4 Mbp c. 127 genes DP DQ DR C4 C2 TNFa,b HLA-B HLA-C HLA-A HLA-D 18 genes Class II Class III Class I

  14. Rapid evolution of MHC genes In both humans and house mice, the antigen-binding site (ABS) of class I and II MHC molecules (light blue) have a high rate of nonsynonymous versus synonymous nucleotide substitutions, which is the opposite pattern for genes under purifying selection, such as nonantigen-binding sites of MHC molecules (dark blue). Adapted from Potts WK and Wakeland EK (1990) Evolution of diversity at the major histocompatibility complex. Trends in Ecology and Evolution5: 181–187.

  15. Helper T cell activation • Two signals are required • MHC bound peptide • Costimulatory signal • Different costimulatory receptors occur in different cell types • CD3 complex on all T cells • CD4 on helper T cells • CD8 on cytotoxic T cells • Cytokines secreted by T cells (and B cells) provide communication between elements of the immune system inducing and suppressing reactions • Interleukins • Interferons • TNF-a

  16. The immunoglobulin superfamily

  17. How to evade the immune system • Once in, replicate really fast • Bacteria, viruses • Replicate within cells that are trying to destroy you • Mycobacterium tuberculosis replicates in macrophages • Trick normal cells into taking you in • Yersinia pseudotuberculosis expresses a protein that binds to E-cadherin and stimulates cells into forming a cell junction, through which the bacterium can enter • Present very diverse surface proteins which immune systems are unlikely to have experienced before • Trypanosomes somatic switching

More Related