Immune Response to Infectious Diseases - Bacteria PDF

Immune Response to Infectious Diseases - Bacteria Learning Objectives On completion of this session you should be able to 1) Describe how the immune system recognises and responds to bacterial pathogens. 2) Identify various strategies employed by bacterial pathogens to evade detection an...

Immune Response to Infectious Diseases - Bacteria Learning Objectives On completion of this session you should be able to 1) Describe how the immune system recognises and responds to bacterial pathogens. 2) Identify various strategies employed by bacterial pathogens to evade detection and elimination by the immune system. 3) Describe what bacterial superantigens are and comprehend the immunological consequences of superantigen activation. Learning aims and objectives The different immune responses tailored to differing threats to health Bacteria, viruses and parasites How the body responds and how pathogens use natural abilities for advantage Introduction 1) Innate and adaptive (humoral and cell mediated) are involved 2) Extent of involvement depends on infectious agent 3) Three types of infectious agent: 1. Bacteria 2. Viruses 3. Eukaryotic parasites Bacteria 1) Prokaryotic cells - do not need host cell ‘machinery’ to replicate. 2) Bacterial Surface Structures: 3) Gram positive and gram negative bacteria 4) All bacteria have a cell wall surrounding plasma membrane which contains peptidoglycan 5) Gram negative bacteria have an additional outer lipid membrane containing lipopolysaccharide (LPS) anchored to the peptidoglycan cell wall by lipoproteins 6) LPS is an endotoxin and causes antigenic variation Bacteria 1) LPS can trigger inflammation and fever by activating phagocytic cells. Also directly activate B1 and mantle zone B cells (IgM predominant response) 2) Gram positive bacteria comprise peptidoglycan cell walls combined with teichoic acids which are antigenic structures 3) Gram positive and gram negative bacteria may also have a capsule 4) Capsules are saccharide residues that mask underlying antigenic structures Bacteria Immune Response to Bacterial Infection 1) Physical barriers e.g. skin, mucosa 2) Commensal organisms - prevent colonisation of pathogenic bacteria 3) Lysozyme – found in secretions and digests peptidoglycan wall (especially Gram positive bacteria) 4) Complement - activated via classical and alternative pathways 5) Phagocytosis – direct or mediated by opsonisation with antibody or complement 6) Antibodies - neutralisation; opsonisation; activation of complement 7) Th1 cells – activate phagocytes and mediate inflammatory response Immune Response to Bacterial Infection 1) Immune responses depend on the bacterium 2) Gram + bacteria are resistant to lysis by the MAC 3) Activation of complement leads to destruction of Gram+ bacteria via opsonisation 4) Encapsulated bacteria are resistant to direct phagocytosis 5) Encapsulated bacteria require opsonisation to stimulate phagocytic uptake Mechanisms of Evading Immune Detection 1. Capsule - saccharide coating of some bacteria e.g. Streptococcus pneumoniae Protects against phagocytosis and complement activation (MAC) Associated with virulence 2. Alteration of antigenic structures e.g. LPS of Gram negative bacteria 3. Localising within cells e.g. Listeria monocytogenes Antibody Responses to Bacterial Antigens 1) Most protein antigens induce T cell dependent responses (TD response) 2) Some bacterial polysaccharides, nucleic acids, polymeric proteins and LPS can stimulate B cells in the absence of T cell help – TI responses 3) 2 classes of TI antigen 1. TI-1: Stimulate B cell division (mitogens) via binding TLRs Bind to BCR and TLR -> specific Ab response Predominantly IgM, occurs early Poor inducers of class switching and memory cell formation as no germinal centre reaction Antibody Responses to Bacterial Antigens 2. TI-2: Do not have mitogenic activity Stimulate B1 and marginal zone B cells Cross link BCR Generate specific IgM response early in anti-bacterial response Important in the response to encapsulated bacteria IgM -> complement activation -> opsonisation -> uptake and destruction Intracellular Bacteria 1) Bacteria promote uptake by phagocytes 2) They either remain within the phagosome e.g. Mycobacterium or escape to cytosol e.g. Listeria monocytogenes 3) L. monocytogenes Produces a pore forming toxin to disintegrate the phagosome membrane In initial extracellular phase, antibodies mediate immunity to L. monocytogenes In intraphagosomal stage, Listeria antigens are presented to Th1 cells via MHC Class II proteins In cytosolic phase, Listeria antigens are presented to Tc cells in association with MHC Class I proteins L. monocytogenes life cycle  Host immune system against infection of Mycobacterium tuberculosis (Mtb) Yuk et al. (2014). Clinical and experimental vaccine research, 3(2), 155-167. Bacterial superantigens 1) Stimulate T cell responses (similar to allogeneic MHC response) 2) Recognised by T cells without being processed into peptides and bound to MHC 3) Bind the outer surface of Class II proteins and Vb region of many TCRs 4) A superantigen can activate 2 – 20% of all CD4+ T cells 5) Leads to massive cytokine production -> systemic toxicity 6) Examples: Staphylococcal enterotoxins (food poisoning), S.aureus toxic shock syndrome toxin-1 (TSST-1) Bacterial Superantigens TSS Summary 1. The immune system employs a multifaceted approach to recognise and combat bacterial pathogens. 2. Bacterial superantigens are toxins produced by certain bacteria that can activate a large proportion of T cells in a non-specific manner by binding simultaneously to the T cell receptor (TCR) and major histocompatibility complex (MHC) class II molecules. 3. This massive T cell activation results in the release of pro- inflammatory cytokines, leading to systemic immune dysregulation and potentially severe conditions such as toxic shock syndrome.