Innate Immune System: Brief Review

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

Immune system defends against microbes which can cause infection.

Immune System has 2 arms:

- Innate immune system
- Adaptive immune system

The 2 arms of the immune system: innate immunity and adaptive immunity (click to enlarge the image).

Innate immunity (natural or native immunity)
Initial response
Induces adaptive immunity
Integrates with adaptive immunity

Adaptive immune system
Await days = no immediate response
Accurate = specific

An overview of the immune response. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

Innate immunity

Innate immunity is the first line of defense against infections. Innate immunity is specifically against microbes, while adaptive immunity is against any "foreign" substance (including cancer cells, autoantigens, etc.).

Innate immunity is the oldest mechanism of defense. Adaptive immunity (T and B lymphocytes) appeared in jawed vertebrates (sharks) and is superimposed on innate immunity to improve host defense. In a sense, adaptive immunity is an "add-on" to innate immunity.

Innate immunity augments adaptive immunity.

In the initial stages of an immune response, the innate immune system recognizes the presence of pathogens and provides the first line of defense. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

How does innate immunity augment adaptive immunity?

Through TNF, INF alpha/beta, IL-1.

There are no autoimmune diseases mediated by innate immunity, only mediated by adaptive immunity. In a sense, we sacrifice specificity in recognizing our own body in order to gain diversity.

Innate immunity responds to only around 1,000 PAMPs (patterns), 10(3).
Adaptive immunity responds to more than 3,000,000 antigens, 10(7).

Innate immunity recognizes patterns.
Adaptive immunity recognizes protein antigens.

Patterns recognized by innate immunity are not present on mammalian cells, only on microbial cells.

Innate immune system recognizes only a limited number of microbial products (patterns) - 1,000.

Adaptive immune system is capable of recognizing a much wider array of foreign substances (both microbial and non microbial products) - 3,000,000.

Innate immunity - 3 components:

- epithelial barriers (skin, secretions)
- cells - circulating and tissue cells, for example, phagocytes - PMN, macrophages (antigen-presenting cells, APC). Macrophage means a "large eating cell" in Greek.
- plasma proteins, for example, cytokines

Epithelial barriers

Epithelia produce locally peptides that have antimicrobial properties (similar to antibiotics):

- defensins
- cathelicidins

Cathelicidins are small proteins released by epithelial cells that kill bacteria.

Barrier epithelia and serosal cavities contain intraepithelial lymphocytes which respond to commonly encountered microbes:
- T cells in the epithelium
- B1-B cells in serosa

B1-B cells

Certain groups of T and B lymphocytes have little diversity and recognize PAMPs. They are only around 1,000 PAMPs as opposed to more than 3,000,000 Ag.

The peritoneal cavity contains B lymphocytes (B-1 B cells) whose antigen receptors (immunoglobulin molecules) have limited diversity, just like the antigen receptors of intraepithelial T lymphocytes.

B-1 B cells make IgM specific for polysaccharide and lipid antigens found on bacteria. These antibodies are called natural antibodies (product of B-1 cells) or innate Ab.

Overview of the innate immune system (a mind map).

A macrophage of a mouse stretching its arms to engulf two particles, possibly pathogens. Image source: Wikipedia.

Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. Image source: Wikipedia.

Innate immunity is activated immediately and contains the infection until adaptive immunity "kicks in" and resolves the infection.

Pathogen-associated molecular patterns (PAMPs) and receptors (PRRs) (click to read the details)

Toll-like Receptors (TLRs) (click to read the details)

Cells of Innate Immunity

Neutrophils (click to read the details)

Mononuclear phagocytes (monocytes) (click to read the details)

Recruitment of Leukocytes to Sites of Infection

SIP of wine:
Penetration of BM by PMN

Selectins are first in the chain of events. They upregulate TNF and IL-1.
Integrins cause release of VCAM and VLA.

The increasing numbers in CD description correspond to higher affinity:
CD 16 32 64
affinity ---->

Difference between Affinity and Avidity

Affinity describes the strength of a single bond.

A <--> B

Avidity describes the combined strength of multiple bond interactions.

A <-->
A <--> B
A <-->

In avidity, there is more than one A for each B.

An example of greater avidity is the IgM pentamer. Individually, each bond is easily broken but when many are present at the same time the overall effect results in synergistic, strong binding of antigen to antibody: IgM has low affinity but high avidity because it has 10 weak binding sites as opposed to the 2 strong binding sites of IgG or IgE.

IFN gamma upregulates the "killing" of phagocytosed microbes.

The uptake of bacteria by phagocytes is an active process, which requires the triggering of specific receptors on the phagocyte. Fc receptors, which bind antibody-coated bacteria, are one of the receptors capable of triggering phagocytosis. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

Chronic granulomatous disease (CGD) (click to read the full article)

NK Cells (click to read the details)

Complement System (click to read the details)

Adhesion Molecules and Chemokines (click to read the details)


Allergy and Immunology MKSAP, 3rd edition.
Chapter 2. Innate immunity. Abbas et al: Cellular & Molecular Immunology, 6th Ed.

Related Reading

Medical Immunology Syllabus. Columbia University.
Anaphylaxis Due to Contaminated Heparin Causes Multiple Deaths, Trigger Found. Allergy Notes, 04/2008.
FIT Corner Q & A from 5th edition of Cellular and Molecular Immunology, edited by Abul K. Abbas and Andrew H. Lichtman. ACAAI, 2004.


Macrophage cytokine release. Nucleus Medical Art.
Pathogen Recognition. Nucleus Medical Art.

Published: 12/05/2007
Updated: 09/05/2010

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