Who are we defending against in ICU ? • Bacteria • Fungi • Viruses • Parasites • Protozoa • Auto-immunity ? • Malignancy ?
What is the structure of our defence system ? • Innate system ( “old school”Castle with infantry defending ) • - Castle : skin and mucous membrane • -infantry ( phagocytes ) • Adaptive system (“modern “ intelligence gathering , IT and guided missiles and smart bombs)
Where does the enemy attack us ? External epithelia: External surface Wounds & abrasions Insect bites Mucosal surfaces: Airway Gastrointestinal tract Reproductive tract (Fig. 2.2)
MALT ( behind the walls stands a force) • Mucosa associated lymphoid tissue • 80% of all immune cells • 3 functions : • Protect mucous membranes • Prevent uptake of foreign antigens from food • Prevent pathological responses if foreign antigens cross the mucous membrane
If a pathogen breaches the epithelium ?Enemy over the wall • then the innate immune response begins. • The cells of the immune system determine “self” from “non-self” by recognizing molecules on the microbe surface. • Macrophages and dendritic cells are immune cells (phagocytes) that reside within the tissue. Neutrophils are phagocytes that reside in the blood but can extravagate into tissue during inflammation. • There are circulating proteins, called complement, that either kill microbes or mark them for effective phagocytization.
The compliment system Complement is a system of plasma proteins that interacts with pathogens to mark them for destruction. 1. Alternative pathway : pathogen surfaces 2. Mannan binding-lectin pathway : lectin binding to pathogen surfaces 3. Classical pathway : Ag:Ab complexes Functions: phagocytosis inflammation lysis
How do the phagocytes recognise the enemy ? • Through pattern recognition ( genetically programmed ) • PAMPS • Toll like receptors
What do the macrophages do : release IL-1B • • Activates vascular endothelium • Activates lymphocytes • Local tissue destruction • Increases access of effector cells • • Fever, • production of IL-6
Macrophage secret TNF-alpha • • Activates vascular endothelium • Increases vascular permeability • • Increased entry of IgG, complement, and cells to tissues • Increased fluid drainage to lymph nodes • • Fever • Mobilization of metabolites • Shock
Macrophage secret IL-8 • • Lymphocyte activation • Increased antibody production • • Fever • Induces acute-phase protein production
Macrophages secret IL-12 • • Activates NK cells • Induces the differentiation of CD4 T cells into TH1 cells
Acute phase response • Hypothalamusincreased body temperature • Fat, muscleprotein & energy mobilization to allow increased body temperature • decreased viral & bacterial replication & • increased antigen processing & specific immune response
Adaptive immunity ( once bitten twice shy) Antigen specific response to antigen / pathogen Key feature if this system is that subsequent exposure to the initial antigen leads to more rapid and vigorous response ( Immunological memory) T and B lymphocytes drive this response from common stem cell
T and B cell response • T-cell : cellular immunity through differentiation in TH-1 ( cellular )and TH-2 pathways ( humoral) • B-cell clonal response initially producing IgM and then IgG to infections : Memory cells produced that react much faster to future threats from the same pathogen.
Thymus • Positive and negative selection of t-cells • CD-4 , CD-8 and T-killer cells emerge • Thymus continues to work in adult life especially when t-cell pool is damages as in AIDS and cancer chemotherapy
Investigating Immunity • 4 Major components : • Humoral immunity • Cell mediated immunity : lymphocytes • Phagocyts and polymorphnuclear cells • Complement