ACAAI board review: cells in immune system

is a highly expressed receptor on monocytes and macrophages, which binds lipopolysaccharide and activates an immune response. It is a component of Toll-like receptor 4 (TLR4).

CD14

Unlike mast cells, basophils do not produce (or produce very little) ___

tryptase, chymase, carboxypeptidase, heparin, PGD2, and LTB4.

Mnemonic P selectins

"P" selectin: think "P"reformed (actually named after platelets)

Thrombotic thrombocytopenic purpura (TTP) (due to antibodies to )

ADAMTS13

mediated by caspase 8.

Active/Extrinsic Pathway. Both pathways converge on caspase 3.

yields membrane versus secretory Ig.

Alternative splicing

What surface markers on the high endothelial venules and naive T cells are responsible for homing to the lymph nodes?

CCL19 and CCL21 by the high endothelial venule, and CCR7 on the naive T cell

What is contained in eosinophil primary granules?

Charcot-Leyden crystals

Primary granules are enlarged in ___, but secondary granules are absent in ___. The exact mediators in each are less important.

Chediak- Higashi syndrome specific granule deficiency

produces different immunoglobulin isotypes. IgD is the only Ig without a switch region; so, class switching will never apply to it.

Differential splicing

Central memory T cells vs Effector memory T cells

Expression of a molecule called Notch commits T cells to develop.

Mnemonic mast cells

For MCT, think Tissue. For MCTC, think Connective Tissue.

Idiopathic thrombocytopenic purpura (ITP) (due to antibodies to platelet's )

GP2b3a

What integrin ligands are found on the surface of activated endothelium?

ICAM-1, ICAM-2, VCAM-1

Which cytokines induce development of Th17 cells?

IL-6, TGFβ, IL-1, IL-21, and IL-23

Neutrophils are attracted to tissue by ___

IL-8 (CXCL8) and LTB4.

In which platelet disorder are platelets abnormally large? Hint: Antibodies to platelet's GP2b3a are also seen.

ITP

Mast cells can also be activated by:

IgG via FcRI; bacterial antigens via TLR 2/6 or 4; C3a or C5a (anaphylatoxins)(MCTC only); cytokines; neuropeptides; physical stimuli (e.g., heat, pressure); substance P; and drugs [radiocontrast media; opioids (MCTC only); muscle relaxants].

Which chemokines produced by keratinocytes are responsible for homing T cells to the skin? What are the corresponding receptors on the T cells?

Keratinocytes produce CCL17 (TARC) and CCL22 (MDC). Skin- homing T cells express cutaneous lymphocyte antigen (CLA) and CCR4 and CCR10.

Which selectin is not found on endothelium?

L-selectin (this is found on leukocytes. E-selectin and P-selectin are found on endothelium)

epithelial cells

Layers of keratinized epithelial cells make up the skin epidermis and contain an extensively cross-linked protein called transglutaminase. Defined by the expression of certain adhesion molecules called e-cadherins. Attached to adjacent epithelial cells by tight junctions, intermediate junctions, and desmosomes (which contain e-cadherins). Attached to extracellular matrix via hemidesmosomes (which use integrins for adhesion instead of cadherins). Contain filament-associated proteins, which bind keratin fibers called filaggrins.

Can be activated by signals, such as IFN and LPS (which binds CD14).

Macrophages

Secrete cytokines, such as TNFα, IL-12, IL-18, IL-1, IL-6 (CXCL-8).

Macrophages

___ can be used to detect the recent presence of eosinophils in tissue, even when eosinophils cannot be seen on biopsy.

Major basic protein

mature in the tissue (unlike basophils and eosinophils).

Mast cells

Highly express CD14 and CD16 after further maturation.

Monocytes

Suppression of eosinophil levels occurs by:

Most bacterial/viral infections (note the exceptions listed earlier, such as HIV). Fever Steroids

Mnemonic. Causes for eosinophilia:

NAACP Neoplasm Atopy Addison's disease Collagen vascular disease Parasites

Migrate into tissues via IL-8 (CXCL-8), IFN, f-met-leu-phe (fMLP), MIP-1, LTB4, and C5a as well as interactions between Sialyl-Lewis X, E-/P- selectins, and LFA-1/ICAM-1.

Neutrophils

Expression of a molecule called ___ commits T cells to develop.

Notch

Heparin-induced thrombocytopenia (due to antibodies to )

PF4

mediated by caspase 9

Passive/Intrinsic Pathway. Both pathways converge on caspase 3.

Which subset of dendritic cells produces type I IFN during viral infections?

Plasmacytoid dendritic cells

At which stage does signaling through the pre-B-cell receptor occur?

Pre B cell

eosinophils granules contents

Primary granules contain Charcot-Leyden crystals Specific/secondary granules contain preformed mediators that include major basic protein, eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin, which are all toxic to surrounding tissue and are released during cytolysis.

Mast cell mediators

Release preformed mediators (<15 minutes) (e.g., histamine, tryptase, chymase, TNF, and heparin). Produce and release lipid-derived mediators (~10-30 minutes) after activation via the arachidonic acid pathway; responsible for late allergic reactions (e.g., PGD2, LTC4, LTB4, PAF). Produce and release cytokines and chemokines (hours to days) after activation (eg, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, GM-CSF, TNFα, MCP-1, MIP- 1α, and RANTES [CCL-5]).

Which mast cell mediator is both preformed and produced in the late phase?

TNF

Where does negative selection occur for T cells?

The medulla, which is also where the AIRE protein functions

HLH is often a fatal consequence of Epstein-Barr virus (EBV) infection in boys with

X- linked lymphoproliferative (XLP) syndrome, which is due to mutations in the SH2D1A gene (encodes SAP protein).

Mutations in Fas(CD95) are the most common defect seen in

autoimmune lymphoproliferative syndrome (ALPS), which results in defective lymphocyte apoptosis.

Migrate to tissue in response to RANTES (CCL-5) and eotaxin

eosinophils

This potentially life-threatening syndrome is characterized by high fever, hepatosplenomegaly, high ferritin and triglyceride levels, and low fibrinogen and circulating NK levels. Hemophagocytosis can often be seen on bone marrow biopsy. The diagnosis is made when five of the eight following criteria are met: fever, splenomegaly, cytopenia involving two or more cell lines, hypertriglyceridemia or hypofibrinogenemia, hemophagocytosis, hepatitis, low or absent NK cell activity, ferritin level >500 μg/L, and soluble CD25 (sIL-2 receptor) >2400 U/mL.

hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome, when secondary to chronic rheumatoid disease.

Uncontrolled activation of macrophages with a marked increase in circulating cytokines is called

hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome, when secondary to chronic rheumatoid disease.

__ is known to cleave CD23 increasing the production of allergen-specific IgE.

the allergen responsible in dust mite allergy (Der-p-1)