Elements of Host Protective Response (Part 2) Flashcards
Phagocytic cells
- Neutrophils
- Monocytes
- Macrophages
Phagocyte types/characteristics
- Myeloid progenitor lineage
- Granulocyte (monocyte CFU)
- Polymorphonuclear leukocytes
- Mononuclear
- Dendritic Cells
Phagocytosis definition
- Process by which certain cells of the innate immune system (neutrophils & macrophages) engulf large particles, such as intact microbe
Process of phagocytosis
- Cell surrounds the particles with extensions of its plasma membrane
- Leads to formation of a intracellular vesicle called a phagosome
Chemotaxis
- Movement of a cell directed by a chemical concentration gradient
- Movement of leukocytes into various tissues directed by gradients of chemokines
Cyotkines
- Secreted proteins that function as mediators of immune and inflammatory reactions
In innate immune responses, cytokines are produced by
- Macrophages
- Natural killer cells
In adaptive immune responses, cytokines are produced by
- Mainly T lymphocytes
Chemokines
- A large family of structurally homologous, low-molecular-weight cytokines
- Stimulate leukocyte movement
- Regulate migration of leukocytes from the blood to tissues
Polymorphonuclear leukocytes (neutrophils) important features
- Short-lived
- Comprise 50% to 70% of circulating WBCs
- Primary phagocytic defense against bacterial infection
- Major component of the inflammatory response
Polymorphonuclear leukocytes (neutrophils) physical characteristics
- 9 to 14 μm in diameter
- Lack mitochondria
- Granulated cytoplasm in which granules stain with both acidic and basic stains
Polymorphonuclear leukocytes (neutrophils) nucleus
- Multilobed nucleus
- “Segmented” at terminal differentiation
Polymorphonuclear leukocytes (neutrophils) response to infection
- Leave the bloodstream
- Concentrate at the site of infection in response to chemotactic factors
- Increase in number in the peripheral blood and include precursor forms
Bone marrow in response to infection
- Production of polymorphonuclear leukocytes (neutrophils) from the bone marrow increases rapidly
Polymorphonuclear leukocyte (neutrophil) production is stimulated by
- Cytokines that are secreted by many cell types in response to infection
- Act on bone marrow stem cells to stimulate proliferation & maturation
Band forms
- Precursors of polymorphonuclear leukocytes (neutrophils)
Left shift with an increase in bands versus segs
- Increase in band forms in blood count of polymorphonuclear leukocytes (rather than differentiated forms)
- Major indicator of infection
Polymorphonuclear leukocytes (neutrophils) ingest
- Microbes in the circulation
- Enter extravascular tissue at sites of infection
Polymorphonuclear leukocytes (neutrophils) ingest bacteria by
- Phagocytosis
- Expose the bacteria to antibacterial substances and enzymes contained in primary (azurophilic) and secondary (specific) granules
Azurophilic granules are enzymes such as
- Myeloperoxidase
- β-glucuronidase
- Elastase
- Cathepsin G
Specific granules (polymorphonuclear leukocytes)
- Lysozyme
- Lactoferrin
Lifespan of polymorphonuclear leukocytes (neutrophils)
- Cells die after a few hours
- Dead neutrophils are the major component of pus
Eosinophils
- Granulocyte of myeloid lineage
- Heavily granulated (11 to 15)
- Phagocytic, motile, and granulated
Eosinophil nucleus
- Bilobed nucleus
- Stains with the acid dye eosin
Eosinophil granules contain
- Acid phosphatase
- Peroxidase
- Eosinophilic basic proteins
Role of eosinophils
- Defense against parasitic infections
- Eosinophilic basic proteins are toxic to many parasites
Features/functions of basophils
- NOT phagocytic
- Release the contents of their granules during allergic responses
- Similar chemical mediators as mast cells
- Contribute to immediate hypersensitivity reactions
Myeloid cells
- Differentiate from myeloid progenitor
- Part of the mononuclear phagocyte system
Mononuclear phagocyte system consists of
- Monocytes in the blood
- Cells derived from monocytes in tissues
Different cytokines or tissue environments promote myeloid stem cells and monocytes to
- Differentiate into the various macrophages and dendritic cells
In the lungs, myeloid stem cells and monocytes differentiate into
- Macrophages
- Alveolar macrophages
In the liver, myeloid stem cells and monocytes differentiate into
- Kupffer cells
In the kidneys, myeloid stem cells and monocytes differentiate into
- Intraglomerular mesangial cells
In connective tissues, myeloid stem cells and monocytes differentiate into
- Histiocytes
In bone and joints, myeloid stem cells and monocytes differentiate into
- Osteoclasts
- Synovial cells
In the brain, myeloid stem cells and monocytes differentiate into
- Microglial cells
Characteristics of monocytes
- 10 to 18 μm in diameter
- Single-lobed, kidney bean-shaped nucleus
- Represent 3% to 8% of peripheral blood leukocytes
- Less abundant than neutrophils
Monocyte functions
- Follow neutrophils as an early cellular component of inflammation
- Ingest microbes in the blood and tissues
- Unlike neutrophils, when entering extravascular tissues they survive for a longer time & further differentiate into macrophages
Characteristics of macrophages
- Long-lived cells that are phagocytic
- Contain lysosomes
- Unlike neutrophils, have mitochondria
Main functions of macrophages
- Phagocytosis
- Antigen presentation to T cells to initiate specific immune responses
- Secretion of cytokines to activate & promote innate immune responses
Macrophages express cell surface receptors for
- Fc portion of immunoglobulin (Ig) G
- C3b product of the complement cascade (CR1, CR3)
Macrophage receptors facilitate
- Phagocytosis of antigen, bacteria, or viruses coated with their respective proteins (IgG, CR1, CR3)
Pattern-recognition receptors of macrophages
- Recognize pathogen-associated molecular patterns
- Activate protective responses
Macrophages expresses the class II MHC antigen
- Allows these cells to present antigen to CD4 helper T cells to expand the immune response
Macrophages secrete
- Interleukin-1
- Interleukin-6
- Tumor necrosis factor
- Interleukin-12, etc.
- Stimulates immune & inflammatory responses (such as that seen in fever)
Macrophages respond to interferon-γ
- T-cell derived cytokine that activates macrophages
Activated macrophages
- Enhanced phagocytic, killing, and antigen-presenting capabilities
Macrophages function as receptors for
- Bacterial components, antibodies, complement
Macrophages promote
- Activation & hagocytosis of antigen
Macrophage receptors promote
- Antigen presentation
- Activation of T-cells
Mononuclear phagocytes arise from
- Precursors in the bone marrow
- Circulating blood stage is the monocyte
- Phagocytic vacuoles and lysosomes
In the tissues, mononuclear phagocytes become
- Macrophages
- May be activated by microbes
- May differentiate into specialized forms that are resident in different tissues
The electron micrograph of a portion of an activated macrophage shows
- Numerous phagocytic vacuoles
- Cytoplasmic organelles
Dendritic cells
- Myeloid and lymphoid origins
- Octopus-like tendrils
- Professional Antigen Presenting Cells (APCs) that can also produce cytokines
- Important bridge between innate and adaptive immunity
Types of dendritic cells and where they are found
- Langerhans cells in the skin
- Dermal interstitial cells
- Splenic marginal dendritic cells
- Dendritic cells in the liver, thymus and germinal centers of the lymph nodes
Plasmacytoid dendritic cells
- Present in blood
- Produce large amounts of interferon alpha & cytokines in response to viral & other infections
Follicular dendritic cells
- Present in lymph nodes & spleen
- Not hematopoietic in origin
- Have tendrils and a “sticky” surface to concentrate & present antigens to B cells
Immature dendritic cells
- Capture and phagocytose antigen efficiently
Main functions of immature dendritic cells
- Release cytokines to activate and steer the subsequent immune response, and then mature into dendritic cells
- Move to lymph node regions rich in T cells to present antigen on class I and class II MHC antigens
Dendritic cells are the only antigen-presenting cell that can
- Initiate an immune response with a naïve T lymphocyte and also determine the type of response
Lymphocytes differentiate from
- Lymphoid progenitor cells
Physical characteristics of lymphocytes
- 6 to 10 μm in diameter
- Smaller than leukocytes
- Large nucleus and smaller, agranular cytoplasm
2 major classes of lymphocytes
- B cells
- T cells
B and T cells are indistinguishable by
- Morphologic features
- Basis of function and surface markers
Natural killer (NK) cells
- Lymphoid cells that are not B or T cells (non-B/non-T cells, or null cells)
- Large, granular lymphocytes (LGLs)
Primary function of B cells
- Make antibodies
General functions of B cells
- Internalize antigen
- Process the antigen
- Present the antigen to T cells to expand the immune response
B cells can be identified by the presence of
- Immunoglobulins
- Class II MHC molecules
- Receptors for the C3b and C3d products of the complement cascade (CR1, CR2) on their cell surfaces
The B-cell name is derived from
- Site of differentiation in birds
- The bursa of Fabricius and the bone marrow of mammals
B-cell differentiation also takes place in fetal
- Liver & spleen
Activated B cells either develop into
M-emory cells (express the CD45RO cell surface marker)
- Circulate until activated by specific antigen, or terminally differentiate into plasma cells
Plasma cells
- Small nuclei
- Large cytoplasm
- Producers of antibody
T cells acquired their name because
- They develop in the thymus
Two major functions of T cells in response to foreign antigen
- Control, suppress (when necessary), and activate immune & inflammatory responses by cell-cell interactions & by releasing cytokines
- Directly kill virally infected cells, foreign cells (tissue grafts), and tumors
T cell content
- Make up 60% to 80% of peripheral blood lymphocytes
T cells were initially distinguished from B cells on the basis of
- Their ability to bind and surround themselves with sheep erythrocytes through the CD2 molecule (forming rosettes)
All T cells express
- Antigen-binding T-cell receptor (TCR) that resembles but differs from antibody
- CD2- and CD3-associated proteins on their cell surface
T cells are divided into 3 major groups on the basis of
- Type of TCR
- Cell surface expression of two proteins (CD4 and CD8)
- Most lymphocytes express the αβ TCR
CD4-expressing T cells are primarily
- Cytokine-producing cells
Functions of CD-4expressing T cells
- Help initiate and mature immune responses
- Activate macrophages to induce delayed-type hypersensitivity responses (DTH)
- A subset of these cells suppress responses
CD4 T cells can be further divided into
- TH0, TH1, TH2, TH17 & Treg subgroups
- According to the spectrum of cytokines they secrete and the type of immune response that they promote
TH1 cells
- Promote local, antibody and cellular inflammatory, and DTH responses
TH2 cells
- Promote antibody production
TH17 cells
- Activate neutrophil responses
Treg cells
- Promote T-cell tolerance
CD8 T cells also release cytokines, but are better known for
- Ability to recognize & kill virally infected cells, foreign tissue transplants (non-self-grafts), and tumor cells as cytotoxic killer T cells
- Also suppress immune responses
T cells also produce memory cells that express
- CD45RO
Terminally differentiated effector CD4 and CD8 T cells express
- Class II MHC antigen
A variable number of T cells express the γδ TCR but do not express
- CD4 or CD8
T cell lymphocytes generally reside in
- Skin & mucosa and are important for innate immunity
NKT cells
- T cells which share characteristics with NK cells
Large, granular lymphocyte NK cells resemble
- CD8 T cells in cytolytic function toward virally infected and tumor cells
- Differ in mechanism for identifying target cells
NK cells also have Fc receptors, which are used in
- Antibody-dependent killing
- Also called antibody-dependent cellular cytotoxicity (ADCC or K) cells
Cytoplasmic granules of T cells contain
- Cytolytic proteins to mediate the killing
Innate immunity
- Mediates the initial protection against infections
- Relies on mechanisms that exist before infection
- Capable of rapid responses to microbes, and react in essentially the same way to repeat infections
Adaptive immunity
- Develops more slowly
- Mediated by lymphocytes and is stimulated by exposure to infectious agents
Neutrophil nickname
- Trash collector and disinfector
- Very effective at phagocytosis and killing bacteria
Dendritic cell nickname
- Billboard display
- Phagocytoses antigen & brings it to the lymph node to display to CD4 & CD8 T cells
Macrophage nickname
- Pac man
- Phagocyte which is activated by interferon-γ & then becomes efficient at killing phagocytized microbes and producing cytokines
Lymph node nickname
- Police department
- Repository for B and T cells
- Evidence of infection is brought by the lymphatics or dendritic cells & other antigen presenting cells to the lymph node to activate the T cells to communicate with other cells through cytokines (like a radio) to be dispatched to take care of the problem
CD4 T cell nickname
- Desk sergeant/dispatch officer
- Presented with the microbial problem by antigen presenting cells, it tells other cells to take care of the problems by producing cytokines
CD8 T cell nickname
- “Cop on the beat”/patrol officer
- Activated in the lymph node & then moves to the periphery to patrol for virus infected or tumor cells
- Then grabs the perpetrator and inactivates it
B cell nickname
- Product design and building company
- Pre-B cells and B cells alter the DNA of their immunoglobulin genes to produce the plans for a specific immunoglobulin
Plasma cell nickname
- Factory
- Immunoglobulin-producing factory with a small office (nucleus) and many assembly lines (ribosomes) for making antibody
Mast cell nickname
- Activatable chemical warfare unit
- Fc receptors for IgE that will trigger the release of histamines and other agents upon binding to an allergen signal
