- Innate immune response
- 1. Phagocytic cell
- 2. Migrates to injures site of inflammation
Usually adaptive immunity
- Precursor of plasma cell
- Lack antigen specificity
- One cell one antibody specificity
- Synthesizes heavy and light chains of immunoglobulins
- Memory cells
- Complement receptors (CD35 and CD21)
- - Produced by thymus
- - Recognize antigen/MHC class II receptors
- - Produces cytokines
- - Stimulates other T cells
- CD8 (T suppressor or T cytotoxic)
- Directs the cell mediated response
- Interacts with MHC class I receptors
Natural Killer Cells
- Originates in bone marrow
- Differentiates T and B Cells
- Enhances cytotoxicity by lysing infected cells
- Responsible for phagocytosis
- Changes to macrophages after migrating into tissue
- Coordinates communication between innate and acquired
- Presents antigen
Integral Proteins in the RBC membrane
Found on membrane surface & possibly throughout membrane.
They are the glycophorin A, B, & C
Peripheral proteins of the RBC membrane
Found in the cytoskeleton just below the lipid bilayer.
Made up mostly of sepctrin, but also includes actin, ankyrin, band 4.2, 4.1, adducin, band 4.9, & tropmyosin to provide RBC support
Effects of ATP loss on RBC
Decreased lattice formation of the spectrin affects surface of membrane.
Calcium also deposits on the membrane affecting the pliability .
Sperocytes, echinocytes, and degmacytes may be seen.
RBC membrane components
- 52% protein
- 40% lipid
- 8% carbs
Describe the chemical composition of the RBC membrane and their functions
The proteins can be found throughout the RBC. Glycophorins A, B, and C are integral proteins. They produce a negative surface charge which keeps the red cells from sticking together. Glycophorin C is a vertical protein which binds with peripheral protein band 4.1. The glycophorins also carry antigens on their surface. Integral protein band 3 (anion exchange protein) is responsible for anion exchange and regulates glycolysis. Band 3 is a binding site to join the lipid bilayer with the cytoskeleton by binding with ankyrin. Band 4.2 is attached to band 3 and ankyrin to stabilizes the binding. Ankyrin is the protein that will also bind to the spectrin. Spectrin is a peripheral protein which forms the membrane skeletal lattice. Spectrin also joins with actin. Band 4.9, along with adducin, tropomodulin, and tropomyosin help to stabilize this interaction along with allowing for a secondary binding site of glycophorin C.
Cytokines are soluble molecules which are responsible for communication between cells by binding to the receptors of other cells. Cytokines decide what type of immune response to elicit, the intensity, and for how long. Each response is different depending on the type situation the patient is experiencing. Cytokines stimulate production of one cell while inhibiting production of another. Cytokines prevent cellular destruction and stimulates cellular division, maturation and their function. There is an autocrine action where the cytokine acts on the cell it produced. Paracrine is another action where the cytokine acts on nearby cells or tissue, then there is the endocrine which is an action on cell far away from the cell that produced it. Some of the cytokines are listed below:
Activates T-helper cells, stimulates the acute phase response, promotes the inflammatory response and increases neutrophils, and fever
Th cells promote T-cell growth, chemotaxis, and macrophage activation
Th cell stimulates activation of B- cell and their differentiation. Also promotes T-cell growth and Tk2 differentiation
Produced by phagocytes, stimulates the acute phase response, increases neutrophils and fever
Produced by multiple cells, increases neutrophils to cite of inflammation and promotes chemotaxis (cell migration)
Produced by Th2 cells, suppresses the Th1 cells, inhibits antigen presentation and cytokine production (IL-1, IL-6, TNFa, and IFN
Kills tumor cells
Promotes tissue repair
IFN α & β
T cells activate the NK cells for phagocytosis
Activation sequence of the classical pathway
The classical pathway is activated by binding antigen to antibody, however, there must be a certain concentration and avidity to work. IgM is large and has multiple binding sites. Theoretically, only one IgM molecule needs to be present. IgG needs at minimum two molecules within close proximity due to the concentration and avidity to bind. When an antibody is present, the antigen binds to the antigen which allows for the C1q[r,s]2 complex (specifically the C1q) to bind to the Fc region. C1r and s then elicit an enzyme which cleaves C2 into C2a and C2b and C4 into C4a and C4b. C4b binds to the antigen as an opsonin where C2a and C4b bind to form C3 convertase which then splits C3 into C3a and C3b. Now C3b joins with C4b2a to form C5 convertase. C5 convertase splits into C5a and C5b. The C5a initiates inflammation and attracts phagocytes. C5b binds to the target cell and binds with C6, C7, C8, and C9. The formation is C5b6789n which forms the membrane attach complex which results in lysis of the cell.
Activation sequence of the alternative pathway
The alternative pathway is similar to the classical pathway. They have the same end result, but are activated differently and some of the proteins are different. The alternative pathway is activated by liposaccharides and polysaccharides. These can be found on the walls of some bacteria, fungal, viruses, tumor cell lines, and some parasites. The activation begins with C3. C3b binds to the surface of the organism. Factor B combines with the C3b to form C3bB. Factor D cleaves factor B into Bb and Ba forming C3bBb. Properdin binds with Bb to form B3bBbP which functions as C3 convertase. C3 is cleaved into C3a and C3b where C3b binds to C3bBb to form C3bBb3b which is also referred to as C5 convertase.
Now both (complement & alternative ) pathways follow the same path with the same proteins. C5a will attract the phagocytes, while C5b binds to the target cell and binds with C6, C7, C8, and C9 to form C5b6789n (MAC) which results in lysis of the cell.