Immunity to Infections

 Prof M.I.N. Matee

 Department of Microbiology and Immunology,
 School of Medicine
 MUCHS
The enemies are different…..

BACTERIA -
Clostridium difficile FUNGUS -
(causes antibiotic- Epidermophyton
associated floccosum
colitis & diarrhea) (causes athlete’s foot)

VIRUS- Polio

PARASITE -
Tapeworm
The big picture…Integration of innate and adaptive immunity
Process of Phagocytosis
 contains
hydrolytic
enzymes

reactive oxygen intermediates

Pathogens damage tissue in a variety of ways

(e.g., LPS)
Endotoxin (low dose) causes
macrophages to make TNF.
TNF causes protective
inflammation and Il-6. Il-6
induces protective acute phase
proteins
Endotoxin (high dose) can cause
macrophages to make too much
TNF and cause septic shock and
death
Fig. 2.37
 Pathogens influence cytokines that affect TH0
differentiation into TH1 or TH2

NK1.1 T cell is a T cell sub-

set which expresses a surface
molecule usually associated
with NK cells and do not
express normal TCR
NK cell repertoire
 Mucosal Immunity
(tonsils, adenoids, Peyer’s A somewhat compartmentalize immune
patches, appendix, system that is separate from the systemic
mesenteric lymph nodes) immune system

mucus no mucus here mucus

Transcytosis of antigens
Lymphocyte activation in lymph nodes
Polymeric IgA is the main adaptive immunity that
is present in the gut
Consequences of Antibody Binding
 Relationship Between Cell-Mediated and
Humoral Immunity
2. Antibody Dependent Cell Mediated Cytotoxicity
 Target cell is covered with antibodies, leaving Fc
portion sticking outwards.
 Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targeted
cells.
 Target organism is lysed by substances secreted by
attacking cells.
 Used to destroy large organisms that cannot be
phagocytosed.
Destruction of Large Parasites by ADCC
Overview of the Immune Response
Macrophage Cytokines
pro-inflammatory
a. IL-1 - endogenous pyrogen (fever), activate endothelium,
stimulate IL-6
b. IL-6 - stimulate acute phase response from liver (CRP, MBP,
etc. to opsonize microbes)
d. IL-8 - chemokine to recruit PMNs
e. IL-12 - potentiate IFN-( production by NK cells with help of
TNF-α
 Interferons

 IFN-α - from virus-infected leukocyte; IFN-β - from virus-

infected fibroblast, inhibit viral replication, increase MHC
class I (Ag-presentation), activate NK cells

 IFN-γ produced by NK cells in lymphoid tissues and γδ-T

cells at epithelial tissues; NK cells stimulated by IL-12 and
TNF-α; γδ -T cells by heat shock proteins, etc. IFN-γ
stimulates macrophages to kill intracellular pathogens
Macrophage - NK Cell Cooperation

IL-12 IL-12
IL-12

IFN-γ
IFN- γ IFN- γ NK Cell

Bacteria inside
macrophage

Activated
macrophage kills
intracellular
bacteria
 Classical and Alternative Complement Pathways
Cause Inflammation, Opsonization, and Cytolysis
 VImmunity to Viruses
Natural Immunity

Virus infection directly induce the production of IFN, which inhibit

viral replication and the expression of MHC molecules

NK cells lyse virally infected cells. IFN enhance the activity of

NK.
TThus NK is the primary natural immune response to viral infection.
Acquired Immunity

Ab are important during early viral infection.

Ab prevents entry to the host cells and
opsonize viral particle for phagocytosis.

CTL is important for established infection.

Both CD4 and CD8 CTLs participate.

 IImmunity to Extracellular Bacteria

Live in tissue space and induce inflammation and tissue

destruction

Release toxins:
Endotoxin: bacteria cell wall components
Exotoxin: secreted by bacteria.
Immunity to extracellular bacteria is aimed to eliminate the
bacteria and neutralizing toxins.
Natural Immunity to extracellular
bacteria

Phagocytes
Complement via the alternative pathway: C3b
opsonize bacteria, C9 lyse bacteria and other
by-products promote inflammation.

Toxins could lead to the production of cytokines.

Uncontrolled cytokine production could result in septic
shock. Example: LPS activate macrophages to
produce TNF
 Adaptive Immunity
to extracellular bacteria
Humoral immunity is the principal protective
mechanism
IgG opsonize bacteria by binding to FcR on phagocytes.
IgG and IgM neutralizing bacteria and prevent binding to cells
Activate the complement system. C3b promotes phocytosis
activity.
CD4 T cells help antibody production and produce cytokines to
help phagocytosis.
 IImmunity to Intracellular Bacteria

Natural Immunity

Can survive with in phagocytes due to the ability to interfere with

lysosome movement.
Natural immunity are quite ineffective.
Difficult to eradicate and could cause chronic infections
NK cells are the main force against intracellular infection.
Acquired Immunity to intracellular
bacteria
Mainly CMI.
Type I CD4 cells activated by released antigens
will produce IFNgamma which activate macrophages (RO) to
effectively kill.
CD4 cells also help CD8 cells to kill.

Activated macrophages during DTH cause tissue injury.

 Chronic antigen stimulation leading to granulomas, the
histological hallmark. Granulomas limit spread but also
cause tissue function impairment.
 PImmunity to parasites
Natural Immunity
Not effective
Whenever enter tissue or blood, parasite could
survive and replicate.
Complements are ineffective.
Acquired Immunity to parasites

 Diverse response to various parasites

 IgE and eosonophil are important for helminth
infections.
 Driven by IL-4 and IL5.
 Eosinophil granules are toxic to helminthes.
 Granuloma formation to contain parasites
and eggs.
 ADCC

Effectors:
Innate immunity

Ab:
Adaptive immunity
Destruction of Large Parasites by ADCC