Introduction and Innate
Immunity
Dr Yusra Shafquat
MBBS, FCPS (Microbiology), CHPE
Strategy
• Overview to immune system
• All about Innate immunity
• All about adaptive immunity
Overview
• Immune system: A complex network of cells, tissues, organs,
and the substances they make that helps the body fight
infections and other diseases.
• The immune system includes white blood cells and organs and
tissues of the lymph system, such as the thymus, spleen, tonsils,
lymph nodes, lymph vessels, and bone marrow
• Function: prevent or limit infections, fungi, and parasites, such as
protozoa and worms
• Two arms:
• 1. Innate 1. Cell mediated
• 2. Adaptive (Acquired) 2. Humoral
Innate immunity
• Resistance that exists prior to exposure to the microbe
(antigen)
• Nonspecific
• Preformed- acts within minutes
• Has no memory so does not improve on exposure
• Includes host defenses such as:
Barriers to infectious agents (e.g., skin and mucous membranes)
Certain cells (e.g., natural killer cells)
Certain proteins (e.g., the complement cascade and interferons)
• Involves processes such as phagocytosis and inflammation
Important components of innate immunity
Important components of innate immunity
Innate immunity as role model for our
immune system
• Performs two functions:
1. Kills microbes
2. Activate adaptive immune response
As not everyone is a role model for
others, not every component of
innate immunity activates adaptive
arm- some only kill microbes
• Components of the innate arm have receptors called
pattern-recognition receptors that recognize a molecular
pattern called a pathogen-associated molecular pattern
(PAMP) that is present on the surface of many microbes
• Surface of cells-
• Toll-like receptors
• mannan-binding lectin receptors
• Cytoplasm of cells-
• NOD receptors
• RIG-I helicase receptors
Pattern recognition receptors
Toll-like receptors (TLR).
• Family of 10 receptors
• Found mainly on the surface of three types of cells:
• Macrophages,
• Dendritic cells
• Mast cells
• TLRs recognize various microbial components and then
activate transcription factors that enhance the
synthesis of several proinflammatory cytokines
• This initiates an immune response appropriate to defend against
that type of microbe.
•LPS combines with LPS-binding protein
•Transfers LPS to a receptor on the surface of macrophages called CD14
•LPS stimulates a pattern-recognition receptor called Toll-like receptor 4 (TLR4)
•production of cytokines, such as IL-1, IL-6,IL-8, and tumor necrosis factor (TNF )
•Induces the costimulator protein, B7, which is required to activate helper T cells and to
produce antibodies
Mannan-binding lectin (MBL)
• Binds to the mannan on the surface of the
some bacteria and yeasts, which then activates complement
• Also enhances phagocytosis (acts as an opsonin) via receptors
to which it binds on the surface of phagocytes, such as
macrophages
NOD receptors
• Part of the
peptidoglycan (cell
wall) of bacteria is
recognized
• These receptors are
located within the
cytoplasm of human
cells (e.g.,macrophages,
dendritic cells, and
epithelial cells)
• Innate response to
intracellular bacteria
such as Listeria
RIG-I helicase receptors
• Recognize the nucleic acids of viruses in the cytoplasm of
infected cells
Proinflammatory cytokines
• The liver synthesizes these proteins in response to certain cytokines,
namely, IL-1, IL-6, and TNF, produced by the macrophage after exposure
to microorganism
• Enhance inflammation
Anti-inflammatory cytokines
• Such as IL-10 and transforming growth factor-β (TGF-β)
• Restore homeostasis after the inflammatory response is no longer needed
Defensins
• Highly positively charged (i.e., cationic)
peptides that create pores in the
membranes of bacteria and thereby kill
them
• α-defensins:
– Neutrophils and Paneth cells in the
intestinal crypts
– Antiviral activity
• β-defensins: Respiratory tract
Interferons
• Alpha and beta interferons
• Antiviral proteins synthesized early in infection within virus-infected cells
• They exit that cell, bind to the surface of an adjacent cell, and induce an
anti-viral state in that adjacent cell
• The anti-viral state is mediated by a ribonuclease and a protein kinase
that, acting together, inhibit viral protein synthesis
• Gamma interferon
• Important mediator of inflammation but has only modest antiviral activity.
• It acts primarily to enhance killing by macrophages and other phagocytes,
and to increase the synthesis of class 1 and class 2 MHC protein
Adaptive immunity
• Highly specific protection
• Takes several days for this arm to become fully functional
• Has memory
• Improves after exposure
• Remarkable diversity and specificity
• The two components of the adaptive arm are:
– Cell-mediated immunity
– Antibody-mediated (humoral) immunity
Immune system at a glance
Active Immunity Passive Immunity
• Resistance induced after • Resistance based on
contact antibodies preformed in
another host
• Long term • Short life span
• Slow onset • Prompt availability
• Mediators: Antibodies and T- • Mediators: Antibodies only
cells • Transferred:
• In response to: • Mother to baby
• Clinical/subclinical infection • Passive immunization
• Immunization
