Download Innate(non-specific)immunity

Innate(non-specific)immunity
Dr
Sahar Saad Zalam
Lecture Objectives
 By the end of this lecture the student will be able to:
1) Define innate immunity
2) Know the importance of the innate immunity
3) Know the different components of the innate
immunity
4) Understand how each one work and communicate
with other components
Innate(non-specific)immunity
 It is the natural inborn barrier against invasion by
microorganisms. It is non-specific, acting against any foreign
invader. It is not acquired through previous exposure to the
infectious agents. It functions through:
I. First line of natural defense: which include:
1. Mechanical ( physical) barriers at the portal of entry.
2. Chemical barriers at the portal of eatery.
3. Normal bacterial flora.
First line of natural defense
1)
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•
•
•
Mechanical barriers at the portal of entry. These include:
The intact skin and mucous membranes .
The hair at the nares, coughing and sneezing help to expel
foreign particales.
Mucous secretions trap many organisms which are pushed
outside the body by the continuous movement of cilia in
the respiratory tract.
The blinking reflex and tears expel forign particles or
bacteria entering the conjunciva.
First line
2) Chemical & biochemical inhibitors and barriers
- Sweet and sebaceous secretion
- Hydrolytic enzymes in saliva
- HCl of the stomach
- Proteolytic enzyme in small intestine
- Lysozyme in tears
- Acidic pH in the adult vagina
First line of natural defense
 3-Normal bacteria flora: Present at the portal of entry
suppress the growth of many pathogenic bacteria and fungi
by competition for essential nutrients or the production of
inhibitory substances as acids or colicins . For example, in the
adult vagina an acidic pH is maintained by normal flora
namely lactobacilli, that interfere with the establishment of
pathogenic organisms. Suppression of normal flora by
antibiotics leads to superinfection with potential pathogens
Second line of natural defense
 If the invading microorganism gets through the first line of
defense and enters the tissue, other non-specific host
defenses operate. These include:
Innate(non-specific)immunity
I.
1.
2.
3.
4.
Second line of natural defense: which include:
Circulating effector proteins.
Cells of innate immunity.
Inflammatory barriers.
Cytokines of innate immunity.
Second line
1- Soluble factors
1- Acute phase protein (Plasma protein, CRP=C reactive protein, Fibrin.)
2- Complement
(proteins in serum, body fluids)
2- Interferons
3- Properdin
(Proteins against viral infections)
(Complement activation)
4- Beta lysine (Antibacterial protein from Platelets)
5- Lactoferrrin,Transferrin (Iron binding protein)
6- Lactoperoxidase
(Saliva & Milk)
7- Lysozyme
(Hydrolyze cell wall)
Complement Activation
Cambridge University Immunology Lectures (www)
Second line of natural defense
 Acute phase proteins: These are substances that increase in
response to inflammation and include; C-reactive
protein(CRP), fibrinogen, serum amyloid A protein,
mannose binding lectins. They are synthesized in the liver in
response to certain cytokines namely IL-1, IL-6 and TNF-α,
these are produced by macrophages when stimulated by microbial
products. For example CRP can bind to microbes resulting in
activation of the complement and deposition of C3b on the surface
of microbes and enhancing phagocytosis. Measuring CRP is a
useful laboratory test to assess activity of inflammatory diseases.
Second line of natural defense
 Interferons (IFNs): These are a family of proteins which are important
in the non-specific defense mechanisms against viral infections. There is
type Ι IFN which consists of IFN-α produced by mononuclear
phagocytes (MQ) and leukocytes and INF-β produced by fibroblasts and
type ΙΙ INF or INF-γ produced by T cells and NK
2) Cells of innate immunity are the phagocytes and natural killer (NK)
cells.
• Natural killer cells (NK): They are a group of nonphagocytic granular
lymphocytes present in small numbers. NK have Fc receptors on their
surface that are capable of binding IgG, which have been shown to
trigger antibody – mediated cytotoxicity. NK are responsible for
recognizing and destroying virally infected cells, bacteria, fungi,
helminths and tumors.
Second line of natural defense
 Phagoctes are body cells specilized for capture,
ingestion, and destruction of invading microorganisms
i.e phagocytosis. There are 2 main types of phagocytic
cells:
1. Polymorphonuclear leucocytes ( especially
neutrophils).
2. Mononuclear phagocytes ( monocytes in the blood and
macrophages in the tissues) .
Second line of natural defense
 The process of phagocytosis includes the following steps:
1.
2.
3.
4.
5.
6.
•
Chemotaxis (delivary) of the phagocytic cells to the site of
infection.
Attachment of the foreign particle to the phagocyte.
Engulfment or ingestion of the foreign particle.
Fusion with a lysosome and formation of the phagolysosome
Intracellular killing and digestion.
Release of the contents and antigen presentation.
All phagocytes contain membrane vesicles filled with
destructive and degradative compounds (Lysosomes) that are
available for the destruction of engulfed microbes.
Second line of natural defense
 How do phagocytes distinguish between self and non-self?
 The phagocytes have many receptors on their surface e.g.
Toll-like receptors, scavenger receptors, Fc receptors and
C3b receptors; these are called pathogen recognition
receptors ( PRR) through which they attach to molecular
structures widely expressed on viruses and bacteria. These
are called pathogen associated molecular patterns (PAMPs).
These may be sugars, proteins, lipids, nucleic acids or a
combination of these molecules.
4) Inflammatory Barriers
* Tissue damage by a wound or by invading pathogen induce
* Inflammatory response:
Tissue damage
Release of chemical mediators from Leukocytes
(Histamine, fibrin, kinins, cytokines)
Invading microbe
Redness of tissue
Tissue temperature
Vasodilatation of capillaries
Capillary permeability
Influx of fluids
Influx of phagocytes
into tissues
Second line of natural defense
Definition of cytokines: they are a large and heterogeneous group of
secreted proteins produced by many different cell types, mediate
and regulate all aspects of innate and adaptive immunity.
5)Cytokines of innate immunity: A)Several pro-inflammatory
cytokines play a key role in inflammation, they are secreted by
monocytes and macrophages(MQ) as IL-1, IL-6, IL-8,
IL-12 ,TNF- α and IFN- γ
B) Interferons (IFNs) : IFN- γ produced by NK cells activates
MQ. IFN- α produced by viral infected cells inhibits viral replication
and prevents spread of infection to uninfected cells