Lecture 5

Lecture 5

1. Injury to Host

   • Exotoxins
     • Secretion of Electrolytes
       • Important in pathogens causing diarrhoea e.g. Vibrio cholerae.
     • Necrosis
       • Death of host cells e.g. leukocidin produced by S. aureus.
     • Apoptosis (programmed cell death)
       • Triggered by Shiga toxins produced by some Escherichia coli strains.
     • Nerve Synapse Inhibition
       • Inhibition of release of compounds which transmit signals across nerve synapses e.g. Clostridium species causing tetanus and botulism.
     • Superantigens
       • Trigger cytokine release e.g. toxic shock syndrome toxin produced by S. aureus.
   • Endotoxins
     • Lipopolysaccharide in cell wall of most Gram negative bacteria causes an inflammatory cascade.
   • Other Cell Wall Fragments
     • Lipotechoic acid occurring in Gram positive bacteria causes an inflammatory cascade.
   • Hydrolytic Enzymes
     • Enable bacteria to spread through tissues e.g hyaluronidase and proteases produced by S. aureus.
   • Inhibition of Secretory Products
     • Inhibition of stomach acid secretion e.g. Helicobacter pylori. Inhibition and degradation of digestive enzymes e.g. Giardia lambda (protozoan).
   • Invasion and Intracellular Multiplication
     • Viruses. Some parasites e.g. malaria parasite and bacteria e.g. Salmonella, Mycobacterium tuberculosis. Damage/lysis of host cells occurs.
   • Induction of Autoantibodies
     • Microbial antigens similar to host antigens evoke an autoantibody response e.g. rheumatic fever caused by S. pyogenes
   • Mutation
     • Some viruses carry oncogenes e.g. HTLV-1
   • Obstructution
     • Occurs particularly with parasites which form large masses e.g. hydatid cysts of the parasite Echinococcus.
   • Host Response to MOs
     • Non-Specific Response (Inflammation) and Specific Immune Responses (antigen-specific)

2. Inflammation

   • Location of Inflammation
     • Suppuration: Solid tissue (e.g. kidney, brain, liver, skin). Pyogenic (pus-forming) organism.
     • Abscess: Localised fibroblast boundary. Necrotic, pus-filled centre
     • Ulcer: Epithelial surfaces.
     • Cellulitis: Spreading through connective tissue planes.
   • Effects of Inflammation
     • Pyrexia (fever): Mediated by inflammatory mediators such as cytokine called IL-1 released by monocytes from the bone marrow.
     • Leukocytosis: Increased production and release of neutrophils and monocytes from the bone marrow.
     • Acute Phase Proteins: Increased liver protein production involved in limiting tissue damage and resolving infection and inflammation (e.g. fibrinogen and complement proteins.
     • Endocrine Changes: Increased production of glucocorticoid steroid hormones as a response to stress. Other endocrine organs may also be affected when physiological stress is severe or sustained.
   • Basic response of the body to tissue injury.
     • Cause of tissue injury may be ischaemic, physical, chemical, infectious or immunological
   • Non-specific response to MOs
   • Characteristics
     • Redness
     • Heat
     • Pain
     • Swelling
     • Loss of Function
   • Suffix is usually -itis
   • Alterations of Blood Flow
     • The initial response to tissue injury involves the release of mediators both from activated cells and plasma.
     • Vascular changes occur with increased blood flow, increased vessel permeability and abnormal movement of fluid and plasma proteins into extravascular sites.
       • Increased blood flow to the injured area is called hyperaemia and causes redness and heat.
       • Also, an increase in the net pressure in the capillaries and post capillary venules resulting in an outflow of fluid.
     • Migration and activation of leukocytes follows in response to attractant substances.

3. Lymphatic System

   • Lymphoid Organs
     • Primary
       • Where lymphocytes are made
       • Thymus (T cells)
       • Bone Marrow (B cells)
     • Secondary
       • Where mature lymphocytes formed in the primary organs migrate to.
       • They filter foreign matter out of the body fluids and they are places where immune response to foreign antigens usually occurs.
       • Spleen
       • Lymph Nodes
       • Peyer's Patch
       • Tonsils
       • Adenoids
       • Skin
       • In order for specific immune responses to be generated against MOs, material (antigens) from the organisms must get to secondary lymphoid organs.
     • Organs all connected together and to the rest of the body's tissues by blood vessels and lymphatic vessels through which fluids and cells are constantly flowing.
     • Most lymphocytes reside in lymphoid organs but both T and B cells are able to circulate throughout the body through blood and lymph.
     • About 10% of total lymphocyte repertoire is circulating at any time.
   • Function of the lymphatic system is to provide the transport network for antigens to be carried to the secondary lymphoid organs.
   • Takes fluid from the tissues and return it to the bloodstream.

4. Antigenic Material Transport

   • The response of the immune system to a foreign substance depends of the nature of the substance and the route of entry.
   • For example, a bacterial infection in a local site of inflammation under the skin.
   • Specialised antigen presenting cells (the ones under the skin are called langerhans cells) take material from the MOs at the site of infection and transport it through the lymphatic system to the nearest second lymphoid organ.
   • Lymphocytes in that secondary lymphoid organ then recognise and respond to the antigenic material.