Innate immune system

Last updated: July 17, 2023

Summarytoggle arrow icon

The innate immune system provides an immediate, nonspecific first line of defense against pathogens. It operates based on inherited cellular receptors that respond to broad pathogen-related patterns and common threat signals. The innate immune system develops in utero and, unlike the adaptive (acquired) immune system, does not require imprinting or adaptation to specific antigens nor does it provide permanent pathogen-specific immunity. For this reason, it is also referred to as “nonspecific immunity.” Response to pathogens is rapid, occurring within minutes to hours of exposure. The innate immune system comprises physical, chemical, and biological barriers (e.g., the skin, gastric acid, commensal organisms) and both cellular (e.g., granulocytes, natural killer cells, mast cells) and humoral (complement system) defense mechanisms.

Overviewtoggle arrow icon


Immune cells

Host barriers to infection

  • Physical barriers (e.g., skin and mucous membranes)
  • Biochemical barriers (e.g., body secretions, exocytosis of cytotoxic molecules and proteins)

Humoral defenses

Innate vs. adaptive immunitytoggle arrow icon

Key features of innate and adaptive immune systems
Innate immune system Adaptive immune system
Key components
  • Germline encoded
  • Does not change over the course of a lifetime
  • Inherited
  • Not inherited
Response time
  • Fast: within minutes to hours
  • Slower (longer lag between antigen exposure and full effect)
  • Nonspecific
  • Highly specific, constant expansion over time
Memory response
  • Absent
Effector proteins

Physical barrierstoggle arrow icon

Biochemical barrierstoggle arrow icon

Cellular mechanismstoggle arrow icon

HLA system

Overview of MHC molecules
MHC class I (MHC I) MHC class II (MHC II)
  • HLA‑A
  • HLA‑B
  • HLA‑C
  • HLA‑DP
  • HLA‑DQ
  • HLA-DR
  • Two polypeptide chains of different length
    • Long-chain contains the alpha domains (α1, α2, α3).
    • Short-chain (β2-microglobulin, B2M) contains the β2 domain.
  • Intracellular pathway: Presentation of intracellular antigens to CD8+ T cells cytotoxic T‑cell reaction → destruction of cells that are infected with intracellular pathogens (endogenous, e.g., viruses) and/or produce atypical proteins (e.g., malignant cells).
Antigen presentation
HLA and disease association

MHC I-associated loci (HLA-A/-B/-C) only have 1 letter after the hyphen, while MHC II-associated loci (HLADR/‑DP/‑DQ) have 2 letters.
HLA A3: Fe3+ is increased in HE3mochromatosis.
HLA B8: If you go fishing for HLA, use MAGgots (Myasthenia gravis, Addison disease, Graves disease) for b8 (bait).
HLA B27: They are Both 27 and a PAIR (Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis).
HLA C: Psoriasis is a Cutaneous Condition.

HLA DQ2/DQ8: I 8 2 (ate too) much gluten at Dairy Queen.
HLA DR2: At DooR 2, they sell multiple good hay products (SLE, Multiple sclerosis, Goodpasture syndrome, hay fever).
HLA DR2/DR3: 2, 3, S-L-E.
HLA DR3/DR4: 3,4sugar no more (DM type 1).
HLA DR4: 4 walls make 1rheum” (room).
HLA DR3/DR5: DR. Hashimoto is odd (odd numbers: 3, 5).

Pattern recognition receptors (PRRs)

Respiratory burst (oxidative burst)

Catalase-positive organisms can degrade H2O2 into H2O and O2 and prevent the formation of hydroxyl-halide radicals.

Immune privilege

Humoral mechanismstoggle arrow icon

The humoral mechanisms of innate immunity are mediated by proteins that are secreted into bodily fluids or the bloodstream. These proteins often initiate immune responses via:

Acute phase proteins

  • Set of biomarkers whose plasma concentration increases (positive markers, e.g., CRP) or decreases (negative markers, e.g., transferrin) in response to an ongoing inflammatory process.
  • See “Acute phase reaction.”

Complement system

Activation pathways

IgG and IgM activate the classic pathway: General Motors (GM) makes classic cars.


C3b binds to bacteria.

C3a, C4a, C5a lead to mast-cell activation and anaphylaxis.

Complement receptors [3][4]

Overview of complement receptors
Receptor Major ligands CD number Cell types Function
Complement receptor type 1 (CR1)
  • C3b
  • C4b
  • CD35
Complement receptor type 2 (CR2)
Complement receptor type 3 (CR3)
  • CD11b/CD18
Complement receptor type 4 (CR4)
  • CD11c/CD18
C3a receptor
C5a receptor
  • CD88

Defects of innate immunitytoggle arrow icon

Overview of innate immune defects [5][6]
Defective element/complement Associated conditions

Increased susceptibility to


  • Recurrent nonsuppurative bacterial infections of skin and mucosa

Referencestoggle arrow icon

  1. Carolina Berger, Suzanne Xuereb, David C. Johnson, Kathe S. Watanabe, Hans-Peter Kiem, Philip D. Greenberg, and Stanley R. Riddell. Expression of Herpes Simplex Virus ICP47 and Human Cytomegalovirus US11 Prevents Recognition of Transgene Products by CD8+ Cytotoxic T Lymphocytes. Journal of Virology. 2000.
  2. Janeway CA, Travers P, Walport M et al.. Immunobiology: The Immune System in Health and Disease. Garland Science ; 2001
  3. Kastin AJ. Handbook of Biologically Active Peptides. Academic Press (Elsevier) ; 2013
  4. Rosenzweig SD, Holland SM. Recent Insights into the Pathobiology of Innate Immune Deficiencies. Curr Allergy Asthma Rep. 2011; 11 (5): p.369-377.doi: 10.1007/s11882-011-0212-9 . | Open in Read by QxMD
  5. Andrews T, Sullivan KE. Infections in Patients with Inherited Defects in Phagocytic Function. Clin Microbiol Rev. 2003; 16 (4): p.597-621.doi: 10.1128/cmr.16.4.597-621.2003 . | Open in Read by QxMD
  6. Valdez JM, Scheinberg P, Young NS, Walsh TJ.. Infections in patients with aplastic anemia.. Seminars in Hematology. 2009.
  7. Lawrence RA, Lawrence RM. Biochemistry of Human Milk. Elsevier ; 2010: p. 98-152
  8. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P . Molecular Biology of the Cell. Garland Science ; 2002
  9. Murphy K, Weaver C. Janeway's Immunobiology. Garland Science ; 2016

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 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer