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
Innate Immune System (click on the title for the full text).
The 2 arms of the immune system: innate immunity and adaptive immunity.
Overview of the innate immune system (a mind map).
Adhesion molecules are on the cell surface and bind to sugar moieties on glycoproteins with mucin.
Overview of adhesion molecules, 3 groups remembered by the mnemonic SIS.
Adhesion molecules, 3 groups - mnemonic SIS: Selectins Integrins Superfamily Ig
Neutrophils (PMN) are the most numerous among peripheral leukocytes (70%) and are the first line of defense against pathogens. PMN circulate in the blood for only 6 hours. PMN migration is regulated via adhesion molecules.
Recruitment of Leukocytes to Sites of Infection SIP of wine:
Penetration of of the basement membrane (BM) by PMN Selectins are first in the chain of events.
They upregulate TNF and IL-1. Integrins cause release of VCAM and VLA.
Adhesion molecules, 3 groups - mnemonic SIS:
Selectins The name selectin comes from the words "selected" and "lectins." Selectins are a type of carbohydrate-recognizing proteins (adhesion molecules).
There are 3 groups of selectins = PEL
E Endothelial cells
Leukocytes Selectin E (endothelial adhesion molecule 1). Image source: Wikipedia. CD62E - E-selectin is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. CD62L - L-selectin is a cell adhesion molecule found on leukocytes. CD62P - P-selectin is a cell adhesion molecule (CAM) found in granules in endothelial cells (cells lining blood vessels) and activated platelets.
CD markers for central vs. effector memory T cells:
Central memory T cells: CD45RA-, CD27+, CCR7+, CD62L+
Effector memory T cells: CD45RA-, CD27-, CCR7-, CD62L-
LAD type 1 is a problem of PMNs binding to integrins (LAF-1). Integration (tight adhesion) is the second phase of the PMN recruitment (see the "SIP" mnemonic above).
LAD type 2 is a problem of PMNs binding to selectins. Selection ("rolling") is the first phase of the PMN recruitment (see the "SIP" mnemonic above).
Integrins In 2014, FDA Approved New Drug for Crohn Disease and UC: vedolizumab (Entyvio), an injectable monoclonal antibody. Vedolizumab, an integrin receptor antagonist http://buff.ly/1lFuRtv LFA (leukocyte function Ag), VLA (very late Ag). For example, LFA 1-3 bind to CD (cluster of differentiation) cell adhesion molecules on the surface of T cells.
Ig Superfamily, cell adhesion molecules (CAM)
VIP: VCAM (vascular cell adhesion molecule)
ICAM (intercellular adhesion molecule)
PECAM (platelet-endothelial cell adhesion molecule) Intercellular adhesion molecule 2 (ICAM 2). Image source: Wikipedia.
The integrin superfamily consists of 30 proteins that promote cell-cell or cell-matrix interactions. The name integrins derives from the idea that they coordinate (i.e., "integrate") signals. All integrins are cell surface proteins composed of 2 polypeptide chains, α and β. Integrins are classified into several subfamilies based on the β chains. The β1-containing integrins are also called VLA molecules. VLA ("very late antigens") received their name because α1β1 and α2β1 were expressed on T cells 2 to 4 weeks after repetitive stimulation in vitro in the early experiments. The β1 integrins are also called CD49a-fCD29. CD49a-f refers to different α chains (α1 to α6). CD29 refers to the common β1 subunit. The β2 integrins are also known as the LFA-1 family or CD11a-cCD18. CD11 refers to different α chains and CD18 to the common β2 subunit. LFA-1 is also called CD11aCD18. Other members of the LFA-1 family include CD11bCD18 (Mac-1 or CR3) and CD11cCD18 (p150,95 or CR4), both of which have the same β subunit as LFA-1.
Chemokines are very small cytokines (proteins secreted by cell), 8-10 kilodaltons in size. Chemokines name is derived from their ability to induce chemotaxis in nearby, i.e. they are chemotactic cytokines. Interleukins are chemokines.
Interleukin-8, a chemokine of the CXC subfamily. Image source: Wikipedia.
More than 50 chemokines interacting with 18 receptors have been described. The position of cysteine residues (C) in the chain subdivides chemokines into 4 structural families.
Interleukins Interleukins mnemonic: Hot T-Bone stEAk
IL-1: fever (Hot) IL-2: stimulates
T cells IL-3: stimulates
Bone marrow IL-4: stimulates
IgE IL-5: stimulates
IgA CD25 is interleukin-2 receptor alpha chain (IL-2Ra).
The IL-2 receptor (IL-2R) was the first interleukin receptor to be described and characterized. Daclizumab (Zenapax) is a humanized monoclonal antibody to the alpha subunit of the IL-2 receptor of T cells (anti-IL2Ra). It is used to prevent rejection in organ transplantation, especially in kidney transplants.
Chemokines Leukocyte adhesion deficiency (LAD) Allergy and Immunology MKSAP, 3rd edition. Chapter 2. Innate immunity. Abbas et al: Cellular & Molecular Immunology, 6th Ed.
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. Daclizumab. Wikipedia, 2009.