1. INNATE IMMUNITY/ MUCOSAL IMMUNOLOGY REVIEW
April 23, 2009

2. TWO PHASES OF INNATE IMMUNE RESPONSE
Immediate Response
Induced Response
Cells and proteins involved reside at sites
of pathogen entry
Proteins produced during the immediate response
recruit help. Cells do not reside at the site, but
rather respond to the cry for assitance

3. EPITHELIUM IS AN ACTIVE BARRIER
Figure 8-6

4. Figure 8-9 MICROBES ACTIVATE COMPLEMENT VIA THE ALTERNATIVE PATHWAY
occasionally lyse a pathogen
promotes inflammation
makes the pathogen more appealing to macrophages

5. TISSUE MACROPHAGES RECOGNIZE THE PATHOGEN
Complement Receptors:
CR3 a.k.a. Cd11 and CR4
Pattern Recognition Receptors
LPS, mannose, glycan,
scavenger receptors
recognize bacterial carbs.
TLR (don’t bind pathogen)

6. THE ACTIVATED MACROPHAGE INGESTS PATHOGENS
generates toxic oxygen species..respiratory burst
anti-microbials..eat or destroy pathogens (Immediate Respones)
makes cytokines and chemokines which are responsible
for the induced response

7. THE ROLES OF CYTOKINES AND CHEMOKINES
Local Effects:
Alterations in vascular endothelium:
TNFa, IL-1
Influx of neutrophils and lymphocytes:
IL-8
Activation of Lymphocytes:
IL-1, IL-6 ( antibody secretion),
IL-12 (T cells and NK cells)
Systemic Effects
Fever
IL-1, IL-6, TNFa
Shock
TNFa
Acute Phase Response
IL-6

8. INFLAMMATION RECRUITS CELLS TO THE SITE
Vessel dilation affects blood flow
TNFa/leukotrienes increases expression of adhesion molecules
(selectins)
IL-8 summons neutrophils to site

9. ACTION OF CYTOKINES LEADS TO FEVER
Increased temperature decreases the rate of pathogen replication
At higher temperatures, human cells become resistant to TNFa
Antigen processing and presentation is increased (degradation
of proteins to peptides and association with MHC proteins)

10. Il-6 INDUCES THE ACUTE PHASE RESPONSE
3 PROTEINS
(C-reactive protein, fibrinogen,
Mannose binding protein)
2 EFFECTS
(opsonization and
Complement fixation)

11. THE INNATE IMMUNE RESPONSE TO VIRUSES

12. VIRUS INFECTED CELLS PRODUCE TYPE I INTERFERONS
ds RNA stimulates
IFN production
and produce IFNg
Oligoadenylate synthetase
degrades viral RNA
Activation of
Adaptive Immunity

13. RECOGNITION BY NK CELLS: TO KILL OR NOT KILL
Healthy cells express MHC class I which interacts with an NK cell receptor issuing a “don’t kill” signal that counteracts the “kill signal”
Viruses decrease MHC class I expression so there is no “don’t kill” signal
Viruses stimulate production of type I IFNs which increase MHC class I on
neighboring healthy cells

14. MUCOSAL IMMUNOLOGY

15. THE MUCOSAL IMMUNE SYSTEM
Divided into inductive and effector sites
Inductive sites: lymphocytes are sensitized
to antigen
Effector sites: lymphocytes respond to antigen
GALT IS THE MAJOR INDUCTIVE SITE
PP are major source of IgA secreting cells

16. ANTIGEN ACCESS TO PEYER’S PATCHES
Specialized epithelium: M Cells
Microfolds
Antigen uptake but NOT APC
Target for bacterial cells

17. A COMMON MUCOSAL IMMUNE SYSTEM
Mucosal and systemic immune systems are compartmentalized
Lymphocytes recirculate based on integrin and adhesion
molecule expression
l-selectin: naïve lymphocytes, unrestricted access
Integrin a4b1: systemic and upper respiratory tract
access
Integrin a4b7: gastrointestinal tract access
MAdCAM is expressed on mucosal vasculature and is
the receptor for a4b7

18. MUCOSAL IMMUNE RESPONSES
B cells: hallmark of effective mucosal immunity is a
secretory IgA response
T cells: conventional ab TCR
gd TCR or abTCR/CD8aa
develop locally
direct TH1 responses
interface with innate immune system
ORAL TOLERANCE
Non-living antigens encountered in the gi tract do not
cause local response
Also will not respond to subsequent systemic challenge

19. THE IMUNE SYSTEM Surgeons must be very careful
when they take the knife
For underneath their fine incisions
Stirs the culprit life
Emily Dickinson
THE IMUNE SYSTEM