Cellular and Molecular Tools Needed for Host Defenses Flashcards
Where do immune system cells come from?
All cells of the immune system are descendants of a pluripotent hematopoietic stem cell found in the bone marrow two lineages.
What regulates the repertoire of cells produced during Hematopoiesis?
Growth factors and cytokines
Two important subdivisions of Hematopoiesis are what?
Common Lymphoid Progenitors and Common Myeloid Progenitors.
_______ markers are used to help identify different cell types.
Phenotypic
The pluripotent hematopoietic stem cell expresses _____.
True or false, all descendent express CD45, but not CD34.
Do erythrocytes express CD45?
Pluripotent hematopoietic stem cells express CD34.
True
No
Myeloid cells include what types of cells:
Neutrophils, Eosinophils, Basophils, Monocytes and Dendritic Cells.
_______ transform into macrophage upon entry to tissues. _______ are assume to be populated into tissues by blood borne precursor cells produced in the Bone Marrow.
Monocytes.
Mast cells
Lymphoid cells include what:
B-cells, T-cells, NKT cells and NK cells.
______ are terminally differentiated B-cells.
Plasma cells
B-cells express _______ as the antigen receptor and secrete homologous as antibody. True or false, plasma cells don’t express surface immunoglobulin, but secrete large amounts of antibody.
immunoglobulin as the receptor
immunoglobulins as antibody
True
______ and _____ express T-cell receptors. ____ cells do not express an antigen receptor.
NKT and T cells
NK
Whole blood can be separated into different components based on density. ____ and _____are the most dense and quick sediment during centrifugation. _____ have an intermediate density, while ____ cells are at the top upon centrifugation.
Neutrophils and erythrocytes - most dense
Lymphocytes - intermediate
Plasma
______ release material as they are translated. ______ is immediately transported through golgi and released.
______, on the other hand, collect things and are released from vesicles in triggered fashion. Classic example is mast cells
Lymphocytes. Cytokine.
Leukocytes
Cells derived from hematopoiesis come from what two places?
1) in utero the stem cells originate from fetal liver
2) bone marrow
Myelocytes are derived from where?
Stem cells located in bone marrow
Development occurs in the bone marrow
Lymphocytes fall into two categories and come from what?
Lymphocytes come from stem cells located in bone marrow.
*B cell development occurs in the bone marrow
Life long
*T cell development occurs in the thymus
Newborn through puberty
How do macrophages kill target cells?
DON’T kill bacteria by phagocytosis. Kill by using puncturing target cells and then injecting ROS and digest from there. Dendritic cells do more antigen presentation than macrophages.
The following are types of what cell? Liver Kupffer cell Bone Osteoclast (not immune fnxn) Soft tissue Histiocyte Plaque Foam cell (cholesterol) CNS Microglia Granuloma Multinucleated giant cell
Macrophages
Mast cells: description and location
Large (10-15 um), irregular shaped Large granules (histamine, heparin, TNF alpha) Tissues Skin Lung alveoli GI mucosa Nasal mucosa
Products of mast cells upon injury, antibody or complement:
histimine and leukocytic chemotactic factors
Products of mast cell synthesis:
prostaglandins, thromboxanes & leukotrienes
_____ are FIRST RESPONDERS to sights of inlammation. The are the most common of all _____.
Neutrophils, leukocytes.
True or false, neutrophils have a short half life, are constantly generated and are readily available in circulation for when called upon.
False, while they do have a short half life and are “ready to go”, neutrophils are bound to vessel membranes until called upon.
Cortisol and epinephrine (due to stress) stimulate release of neutrophils in a process called ______. How do these cells kill their targets?
demarginalization. R.O.S. injection/phagotysosis
Neutrophil overview:
50-70% of leukocytes
60% of bone marrow activity, short life at 12 hrs
Fc and Complement Receptors
Phagocytosis
Lytic secretions (Lysozyme, oxidases and defensins)
Bands
Pus
_____ attach to antibody-coated parasites and try to make hostile environment for parasites so they move on.
Eosinophils
Eosinophil overview:
Allergies and helminthic parasites
Large and low abundance
Peroxidase, basic proteins, leukotrienes
Generally in bone marrow and connective tissue
Fc-ε
Phagocytosis
Attaches to target for extracellular degranulation
_____ are now considered regulators of inlammatory process. These cells appear to take resident in lymph nodes where allergens or parasitic infections are. This causes them to release their compounds.
Basophils
Basophil overview:
Smallest (5-7 um) Lowest abundance (>1% of leukocytes) Fc-ε Histamine Short lived (days)
These cells are responsible for killing cells that do not express MHC class I. They do/do not have antigen receptors. Screen cells for what they are hiding.
Natural Killer (NK)
Do NOT have antigen receptors
Work in tandem with T killer(cytotoxic) cells as both induce apoptosis.
Natural Killer (NK) overview:
A part of innate immune response Lymphoid derived No antigen receptor Screen for the absence of MHC class I Induces apoptosis in target cells by releasing lytic granules
_____ are the principal cells responsible for stimulating naïve T cells.
Leukocytes.
Leukocyte overview:
Process Ag for MHC class II display Identifies Non-self using receptors for PAMPs Myeloid derived (mDC) Leukocyte derived (pDC, plasmacytoid) DC, Langerhand’s cell, Histiocyte
Positive selection happens at level of _____cell.
dendritic
Cell found only in the circulation (at all times)
a) Neutrophil b) Macrophage c) Lymphocyte d) Dendritic cell e) Monocyte
Monocyte
Cells communicate through ______. True/false, these cells are readily available. True/false, release of these gives us energy.
Cytokines. False, synthesized on demand. False, release of these makes us feel sick.
Cytokine overview:
Direct cellular differentiation Soluble mediator Synthesized on demand Small glycoprotein Autocrine Paracrine No discrete organ, ubiquitously found Originally coined to emphasis immune function Commonly operate in sequential patterns, cascading
Growth factors and secondary factors associated with Cytokine direction of cellular differentiation:
Growth factors (e.g. GM-CSF, G-CSF) stimulate hematopoietic activity. Secondary factors help to refine the development process (e.g. IL-3, IL4, IL5, IL6).
Active Immunization causes antigen to be expressed by MHC class I MHC class II CD1 Antibody Selectins
MHC Class 1 ...Class II can present live or dead. To give long-lasting robust immune response, live (MHC class 1) is preferred.
Recognition of non-self
Dendritic cell picks up antigen in inflammatory site. Activated by PAMP… presents w/ MHC molecule. T cell recognizes it as non-self. Dendritic cell determines what type of T cell results to perform certain action…gives T its purpose.
Aspects of non-self recognition
Proteins and peptides are scavenged by myeloid dendritic cells
Proteins are processed to small peptides for display to T cells
Antigen display
T cells express surface receptors that weakly recognize peptides
Peptides must be displayed for detection
T cells screen mDCs for Ag
A match results in T cell activation
Antigen presentation:
Peptide fragments (8-15 amino acids) are tethered to a protein platform
Provides access to other cells to sample the displayed peptide
In antigen presentation, which cells express MHC Class II? Is this display self or extracellular proteins?
Dendritic cells, Macrophage and B cells express MHC Class II
Antigen display is of extracellular proteins
Which cells present MHC Class 1? is this display extracellular or self proteins?
All cells (except RBC) express MHC Class I
Antigen display is of self-proteins
T Cell receptor recognizes what in antigen-presenting cell?
Antibody recognizes only surface epitopes.
TCR recognizes peptide displayed by MHC
Epitope could be sequences interior in native protein
Epitope is defined by several (2-4) contacts with amino acids
Antigen Recognition
Immunoglobulin
B cells use cell surface immunoglobulin
T cells use a fragment of the immunoglobulin at the cell surface
How are lymphocytes activated?
Dendritic cells (DC) activate naïve T cells (To) in the lymph node . Depending on the type of PAMP to activate the DC will in turn control how the DC will activate the To. In the lymph node the To will screen MHC class II antigens to find a match. A matched To to the DC is then activated. The To develops into a Th1, Th2 or Th17 cell based on the PAMP.