2 - Cells, organs and microenvironments of the immune system Flashcards
Myeloid cells
basophils (and progenitor Eosinophil (and progenitor) Granulocyte-monocyte profenitor -> Neutrophil, monocyte ->macrophage and DC Mast cell Platelets (from megakaryocyte) Erythrocyte (from erythroid progenitor)
Lymphoid cells
DC
TH and TC (from T cell progenitor) [in thymus]
B cell (from B cell progenitor)
Innate lymphoid cell (ILC)
the process by which all red and white blood cells are developed
hematopoesis
HSC
hematopoietic stem cell
Granulocytes
neutrophils, eosinophils, basophils, mast cells
Neutrophils
differentiation in bone marrow, released into blood and circulate for 7-10 h, then migrate into tissues. Life span only a few days.
Developement can be incresed in response to inflammatory molecules. this is called leukocytosis (used as indication of infection)
Swarm site of infection in large numbers in response to inflammatory molecules (among the first on the scene). Defeat cells by phagocytosis, secreting antimicrobial molecules.
Eosinophils
important in coordinating defence against multicellular parasitic organism, including worms. They cluster around invading worms, damage their membranes by releasing the contents of their eosinophilic granules. Motile cells, migrate from blood to tissues. most abundant in small intestine. Contributers to asthma and allergy symptoms. secrete cytokines that may regylate B and T lymphocytes
basophils
nonphagocytic
relatively rare in circulation
potent responders, play a role against parasites
upon binding to circulating Ab/Ag complexes, they release the contents of their granules, including histamine (increase blood vessel permeability and smooth muscle activity). Basophils also secrete cytokines that can recruit other immune cells.
mast cells
combating parasites (worms) + allergy
released from bone marrow into blood as undifferentiated cells. Mature after leaving blood into a variety of tissues; skin, connective tissues of various organs, mucosal epithelial tissue of respiratory/genitourinare/digestive tracts.
MHC class I
all cells have these molecules, and can present Ag on them.
MCH class II
only pAPC have them, Th cells can only rec Ag on them
APC 3 major activities
1) secrete proteins that attract and activate other immune cells
2) internalize pathogens via phagocytosis, digest pathogenic proteins into peptides, and then present these peptide antigens on their membrane surfaces via MCH II
3) upregulate costimulatory molecules required for optimal activation of Th cells
dendritic cells
displaying and presenting Ag to naïve T lymphocytes
can “capture” Ag in 3 ways: phagocytosis, internalize it by reveptor-mediated endocytosis, or imbibe it by pinocytosis
After Ag contact, they mature from a conformation specialized for Ag capture into one for Ag presentation. They lose phagocytosis ability and large-scale pinocytosis, and improve their ability to present Ag and ezpress costimulatory molecules essential for activation of naïve T lymphs. After maturation, they enter blood/lymphatic circulation and migrate to lymphoid organs.
NB! FDC (follicular DCs) are not APC!! they regulate the activation of B cells.
monocytes
regulate inflammatory responses at sites of tissue damage and infection.inflammatory monocytes enter tissues quickly in response to infection.
Patrolling monocytes crawl slowly along blood vessels, monitoring their repair. Also provide a reservoir for tissue-resident monocytes in the absence of infection, and may quell rather than initiate immune responses
macrophages
monocytes that migrate ito tissues in response to infection differentiate into macrophages. Undergo a number of key changes when stimulated by tissue damage or pathogens and have a dual role in immune response:
1) contribute directly to the clearance of pathogens from a tissue
2) act as APC for T lymphocytes
Ab/Ag complexes can bind to macrophages - this increases phagocytosis rate by 4000
erythroids
red blood cells. No nucleus. high concentrations of hemoglobin. deliver oxygen. If damaged, release signals that induce innate immune activiry.
Megakaryocytes
Large myeloid cells that reside in bone marrow and give rise to thousands of platelets, very small cells/-fragments that circulate in the blood and can form blood clots (prevent blood loss and provide a barrier for pathogens if they take place at epithelial barriers. No nuclei.
CD
cluster differentiation (CD) nomebclature. Surface proteins expressed by cells of the IS (and other cells)
effector cells
carry out specific functions to combat pathogens
memory cells
persist in the host, leads to rapid and efficient response upon reencounter with same Ag
B cells
maturation in bone marrow.
distinguished from other cell types bc they express B cell receptors (BCR), a membrane bound immunoglobulin (ANTIBODY) molecule that binds to antigen. Each B cell expresses a surface antibody with unique specificity, and expresses only one type of Ab.
B cells improve their ability to bind Ag through SOMATIC HYPERMUTATION and can generate Ab of several different functional classes through a process known as CLASS SWITCHING (chap 11)
Activated B cells are the only non-,myeloid cells that can act as pAPCs. They internalize Ag very efficiently, and then process and present Ag on their surface. Activated B cells also express costimulatory molecules required for activation of T cells. By presenting Ag directly to T cells, B cells also recieve T cell hepl, in the form of cytokines that induce their differentiation into Ab-producing cells (plasma cells) and memory cells.
Ultimately, activated B cells differentiate into effector cells known as plasma cells. They lose expression of surface immunoglobulin/Ab and become highly specialized for secretion of Ab. Plasma cells do not divide and can either travel to bone marrow and live for years, or sie within 1-2 weeks.
T cells
mature in thymus. also have unique Ab-binding receptors calles T cell receptors (TCR). B cells can recognize soluble pathogens, TCRs cannot, they only rec processed pieces of Ag expressed via MCH complexes.
T cells divided into two major cell types; T helper cells and T cytotoxic cells, distinguished by precence of CD4 or CD8 membrane glycoproteins on their cell membranes. If CD4; T helper cell, recognize MCH class II If CD8; cytotoxic T cell, recognize MCH class I.
Naåive CD8+ cells browse the surfaces of APC with their TCRs. if they bind to an MCH, hey become activated, proliferate and differentiate into a typoe of effector cell called cytotoxic T lymphocyte (CTL), which has vital function in monitoring cells and eliminating cels that display non-self-Ag on MHCI, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft. Need help from CD4+ T clls to differentiate optimally.
Naïve CD4+ T cells also browse the surfaces of APCs with their TCRs, and become activated the same way. They proliferate and differentiate into one of a variety of effector T cell subsets. Th1 and Th17 regulate our response to intracellular pathogens, Th2 and Tfh (follicular halper) regulate our response to extracellular pathogens (bacteria or worms). Each CD4+ Th cell subtype produces a different set of cytokines that enable or help the activation of B cells, Tc cells, macrophages, and various others.
Which helper subtype dominates the response depends on the type of pathogen.
Treg (regulatory T cell) is a CD4+ T cell which can inhibit immune responses. arise during maturation in thymus from cells that bind self proteins with high affinity (autoreactive cells). They can also be induced at the site of an immune response in an antigen-dependent manner (iTreg). Treg are identified by the prescence of CD4 and CD25 on the surface, as well as by the internal transcription factor FoxP3. Treg quell autoreactive responses and play a role in limiting normal T cell responses to pathogens
NKT cells
shares features with both innate and adaptive immune cells
Have T cell receptors, some express CD4, but are not diverse. recognize specific lipids and glycolipids (as opposed to protein peptides) presented by a molecule related to MCH called CD1.
Also have receptors associated with innate immune cells, such as NK cells. activated NKT cells release cytotoxic granules that kill target cells, but also large quiantities of cytokines that can either enhance or suppress the immune response.
Innate lymphoid cells (ILCs)
dont express Ag-specific receptors.
three classes (IILC1, ILC2, ILC3), distinguished by which cytokines they secrete. Many provide a first line of defence against pathogens in the skin and at mucosal tissues.
NK cells (cytotoxic natural killer cells) are often classified as ILC1, and identified by expression of NK1.1 surface protein.
efficient killer cells. 2 strategies for finding abnormal cells:
1) attack cells that lack MCH class I (MCH class I can be downregulated in virus-infected cells or tumor cells). If NK meets MCH class I, they are inhibited from killing.
2) NK cells express receptors (Fc receptors, FcRs) for some Ab. By linking to Ab, NK cells can arm themselves with Ab specific for pathogenic proteins, particularly viral proteins present on the surface if infected cells. When these Ab make contact with cells, NK have contact with cells, and it releases granules and indices cell deatch (ADCC, antibody-dependent cell cytotoxicity)
