HOST DEFENCE

Who is the Host ?

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)

Major components of the innate system

Where does the enemy attack us ?

External epithelia: External surface

Wounds & abrasions

Insect bites

Mucosal surfaces: Airway

Gastrointestinal tract

Reproductive tract

(Fig. 2.2)

In what compartment of the body is the enemy found ?

The general response to infection

Stages of infection

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

Where does the defence start ?Castle walls

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

Expression of selectins and ICAM

Acute phase response

Acute phase response

Hypothalamus increased body temperature Fat, muscle protein & energy mobilization to allow

increased body temperature decreased viral & bacterial replication & increased antigen processing & specific

immune response

Interferons

NK-Cell

NK recognise virus infected cells

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.

Innate vs Adaptive immunity

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

If we’re so good how does the enemy kill us ?