Nur Atik
Department of Biomedical Scinces
Faculty of Medicine
Universitas Padjadjaran
Innate immunity
– Cellular mechanisms
– Humoral mechanisms
- phylogenetically older
- physical barrier
Functions of epithelia in innate immunty
- physical barrier
- chemical barrier
(production of antimicrobial peptides)
Functions of epithelia in innate immunty
- physical barrier
- chemical barrier
(production of antimicrobial peptides)
- intraepithelial lymphocytes
1. Entry of pathogen
Role of phagocytes in
innate immunity
1. Entry of pathogen
2. Recognition of pathogen
(macrophages and dendritic cells)
- molecular patterns and receptors
Molecular patterns
Common structures for certain groups/classes of pathogens
- essential for their life, replication and/or infectivity
- not present on human cells
Lipoproteins
Flagellin
Examples:
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen (macrophages)
- reactive oxygen species (ROS), nitric oxide (NO)
and lysosomal enzymes
Phagocytosis and
killing of
microbes
Pathogen recognition
Phagocytosis and
killing of
microbes
Zipping of membrane
around microbe
Phagocytosis and
killing of
microbes
Ingestion of microbe
Phagocytosis and
killing of
microbes
Fusion of phagosome
with lysosome
Phagocytosis and
killing of
microbes
Phagocyte activation
Phagocytosis and
killing of
microbes
Killing of
microbe
http://highered.mcgraw-
hill.com/sites/0072556781/student_view0/chapt
er31/animation_quiz_3.html
Role of phagocytes in
innate immunity
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Induction of inflammation (macrophages)
- production of pro-inflammatory cytokines
(TNF, IL-1, chemokines...)
Inflammation induction
Proinflammatory cytokines
TNF ― Tumor Necrosis Factor
IL-1 ― Interleukin-1
Chemokines ― Chemotactic cytokines
Role of phagocytes in
innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site
- adhesive molecules (selectins and integrins)
and chemokines
Leukocytes arrive at the site of infection (extravasation)
http://www.youtube.com/watch?v=WEGGMaRX8f0
http://www.youtube.com/watch?NR=1&v=DMvixApKzKs
Various adhesive
Selectins Integrins molecules
Weak binding
In some inflammatory diseases therapy is directed against
and rolling Activation and
proinflammatory cytokines or adhesive molecules
firm binding Transmigration
(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)
Endothelium
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site
6. Pathogen elimination and/or adaptive immunity activation
7. Tissue repair and remodeling (macrophages)
- enzymes and cytokines (growth factors,
metaloproteinases...)
Role of NK cells in innate immunity
NK – Natural killer
Activation of
macrophages (by IFN-γ)
NK cell killer function
NK cell is inhibited
NO KILLING
NK cell killer function
Depends on balanse of signals by activating and
inhibitory receptors
NK cell is activated
KILLING
NK cell killer function
Depends on balanse of signals by activating and
inhibitory receptors
perforin
NK cell
granzymes
Infected or
tumor cell
apoptosis
FasL Fas
Humoral mechanism of innate immunity
- complement proteins
- cytokines
Inflammation induction
(TNF, IL-1, chemokines...)
Cytokines in innate immunity
• Lymphatic vessels
– Carry lymph to body tissues
• Lymph formed as result of body’s circulatory
system
– Lymph travels through vessels to lymph
nodes
• Material such as protein is removed
– Fluid portion empties back into blood stream
Antigen Presentation
Initial immune response to any
Ag requires the Ag be
recognized by a T cell.
This is best exemplified by AIDS
w/loss of CD4+ T cells.
Two categories of Ags are
processed and presented to T
Dendritic cell
cells by different mechanisms:
B cell
Exogenous Ags
Endogenous Ags
Questions?