THE IMMUNE SYSTEM IN HEALTH AND DISEASE

Ainstein Marie Villanueva-Misa, MD, FPCP, DPRA

Introduction to the Immune
System
INNATE IMMUNE SYSTEM
• Ancient defense system that uses germline encoded proteins to
recognize pathogens
• Cells of the innate immune system include the following:
Macrophages
Dendritic cells
NK lymphocytes
• Cells of the innate immune system recognize the PAMPS and use the
PRR molecules facilitate the response

*PAMPS- Pathogen-associated molecular patterns

PRR- Pattern recognition receptors
The Innate
Human innate system
Immune sense “danger signals”

System
Activation/production of the Recognize PAMPs, heat
complement cascade, cytokines shock proteins and
and antimicrobial peptides as fragments of extracellular
effector molecules matrix

Recognition of pathogen molecules by

hematopoietic and nonhematopoietic PRRs recognize PAMPs
cells
PATTERN RECOGNITION
• Major PRR families of proteins include:
Toll-like receptors (TLRs)
C-type lectin receptors (CLRs)
 mannose binding lectin(MBL) (opsonizes bacteria for phagocytosis)
NOD-like receptors(NLRs)
Retinoic acid-inducible gene (RIG-1) like receptors (RLRs)
Toll-like receptors

Proteins in the Toll

Recruitment and
family expressed in
Upon ligation, TLRs activation of
dendritic cells, Killing of bacteria and
activate series of antigen specific T
macrophages and B viral infected cells
intracellular events and B
cells (11 TLRs in
lymphocytes
humans)
NOD-like receptors
Step 1
Step 2
NLRs triggered
Step 3
Formation of large
cytoplasmic Inflammatory
complexes termed caspases and IL-1B
“Inflammasomes” activated in the
presence of
nonbacterial danger
signals and bacterial
PAMPs
ADAPTIVE IMMUNE SYSTEM
• Characterized by antigen specific responses to a foreign antigen or
pathogen
• Key features:
Immunologic priming: initial contact of with antigen
Immunologic memory: subsequent antigen exposure leads to more
rapid and vigorous responses
• Dual limbs of cellular and humoral immunity
• Cellular immunity: T cells -principal effector
• Humoral immunity: B lymphocytes- prinicipal effector
Schematic model
of intercellular
interactions of
adaptive immune
system cells.
KEY POINTS TO REMEMBER
Types of Immune Response
Natural
native
or

Fig. 1 The principal mechanisms of innate and adaptive immunity (Basic Immunology 3rd ed. Abbas)
 INNATE IMMUNITY

Fig. 2The specificity of innate immunity and adaptive immunity. (Basic Immunology 3rd ed. Abbas)
Fig. 2The specificity of innate immunity and adaptive immunity. (Basic Immunology 3rd ed. Abbas)
AUTOIMMUNITY
 Genetic Susceptibility
 Predisposing genes
 Severity modifying genes
 Disease suppressing genes

Female gender Environmental triggers

 Sex hormones  Viruses
 Sex chromosomes  Bacteria
 Drugs
 Chemicals
 Xenobiotics
 Sunlight
Stocastic factors
 diet
 Ig repertoire
 TcR repertoire
Other factors

AUTOIMMUNE DISEASE

Etiology of Autoimmune Diseases

Key Points

 Autoimmunity ranges from physiologic autoreactivity to overt

autoimmune disease, in part reflecting the complexity of the immune
system, the presence of multiple layers of tolerance mechanisms, and
genetic heterogeneity.
Autoimmune diseases can be classified by extent of organ
involvement (organ-specific to systemic), innate immune system
requirements, and effector mechanisms.
Susceptibility to autoimmune diseases is multifactorial involving
genetic, environmental, gender, and other factors, with genetic
predisposition usually playing a central role.
REFERENCES