2 - Immunophysiology Flashcards
- Organs of the immune system
-Primary (central) •Thymus •Bursa (B-equivalents): Embryonic liver, Bone marrow -Secondary(peripheral) •Lymph nodes •Spleen •MALT: Mucosa Associated LymphTissue •GALT: Gut Associated LymphTissue
- Natural immunity
-Non-specific, less effective, immediately acting response
•Main molecular components:
Complement factors and their receptors, Heat shock proteins, Fc receptors, Inflammatory cytokines, histamine,
•Main cellular components: Macrophages, Natural killer cells, Granulocytes, Dendritic cells
•Functional characteristics:
-None antigen specific
-No immunological memory
-Rapid reactivity
-Linear amplification of the reaction
•Humoral factors: Complement system, Lysosin, C-reactive protein, Interferon
- Natural immunity; The complement system
-A part of the immune system that enhances (complements) the ability of Abs and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen’s plasma membrane
-Activated in 3 ways:
1.Classic adaptive pathway: known Ag-Ab complex
2.Natural hereditary -
alternative pathway: unknown Ag appears
3.MBL: mannose binding lectin: binds oligosaccharides of certain virus/bacteria
-Functions:
1. Intrinsic ability to LYSE bacterial membrane.
2. Initiates CHEMOTAXIS, Complement-factors attract phagocytes to site of reaction
3. Stimulate OPSONIZATION, facilitating bacterial phagocytosis (resulting in Inflammation)
- Adaptive immune response
- Antigen specific - activated by antigens.
- Immunological memory - requires prod. of specific antibodies or immune cells.
- Cellular/humoral.
- Activated after a longer period (days/weeks)
- Very effective, specific response
- Exponential amplification of reaction
- Cells: lymphocytes (T, B), APC (DC, DGC)
- Humoral factors: Antibodies (IgM, -G, -A, -E, -D), MHC, T- and B- cell receptors, lymphatic cytokines
- Adaptive immune response: structure of the antigens
-A substance, which is recognized by T cell and/or B cell receptors, and it is able to induce active immune response or tolerance according to the host MHC haplotype
Classification
-Antigenicity:
*Auto-antigens (self-matter), allo-antigens (matter of the same species), or xeno-antigens (matter of another species), depending on their origin
*Determined by the epitop:
Binding force:
1.Affinity (one epitop)
2.Avidity (more than one epitop)
Specificity: the Ab is specialized to bind one well defined chemical structure.
-Immunogenicity: the Ag can react with the Ab produced against it.
*Determined by the whole molecule:
-Grade of foreigness: Autoantigen, Alloantigen, Xenoantigen
-Molecular weight
•Under 4000 – weak
•Over 100 000 - strong
-Complexity of the chemical structure: immunogenicity increases with the complexity
- Adaptive immune response: structure of the immunoglobulins
- Large glycoproteins secreted by plasma cells and function as Ab in the immune response by binding with specific Ag.
- Production:
- Synthesized by plasma cells
- During humoral immune response a selected Ag specifically activates B-cells, which will produce Igs.
- Structure of antibodies:
- FAB (fragment antigen binding)
- FC (fraction crystallisable): responsible for the biological effect
- Variable region: two hypervariable Ag binding sites. Each of these pairs binds one Ags.
- Joint region (hinge): Makes the molecule more flexible while binding the Ag. Disulfide bond.
- Two H-chains (heavy chains) and two L-chains (light chains): two different types; lambda and kappa.
- Amino acids in the variable (V) domain.
- Constant (C) chains have constant amino acid components.
- Humoral immunity
-Antibody-dependent specific immune defense (B-cell defense)
•Igs are synt. only by B-lym
•During the humoral immune response a selected Ag specifically activates the B-cells, that will produce Igs
•B-lym both recognize Ag and produce Ab in the different phases of their maturation.
•B-lym with cell surface Igs are also called “recognizing cells” as they specifically bind to a given Ag
•Ag binding triggers cell differentiation which leads to transformation of B-lym into plasma cells secreting Ab
-Ag-binding receptors located in the cell membrane of B-lym are Ab-molecules. A given Ag-binding receptor can only react with one particular Ag epitope.
-When an Ag enters the body it is immediately recognized by B-lym containing the proper Ag-binding receptor. The activated lym within this clone then begin to divide rapidly. The daughter cells differentiate into plasma cells or memory cell.
- B-lymphocytes: differentiation
- Plasma cells:
- Contain more cytoplasm and are larger than B-cells
- Produce and secrete Ab identical to the receptors on B-cells that recognized and bound the Ag epitope.
- Die after a few days of intensive Ab production, since Ab are proteins
- Most of the cells are differentiated into plasma cells - Memory cells:
- Do not participate in the immediate attack on the Ag, but continue to live for months and years after the Ag has been eliminated, ready for stimulation if the Ag is encountered again
- For further activation to occur in the form of clonal expansion and substantial Ab synthesis, the B-cell In most cases needs the assistance of a T-cell
- Humoral immunity - types of response
- Primary response: On first exposure to Ag, several days elapse before formation of Ab begins. The Ab formation is then moderate
- The delay is mainly due to the time required for the lymphocyte of the correct clone to come in contact with the antigen. The lymphocyte of this clone must also undergo a proliferation phase before a substantial antibody production can begin. - Secondary response: When a previous encountered Ag reenters the body, the Ab formation changes character, resulting in the secondary response.
- Numerous memory cells will then be present as a result of the previous attack.
- The memory cells and their progeny produce a large amount of Ab
- The attack on the Ag will therefore be quicker, more potent and longer lasting
- B-lymphocytes - maturation
- Antigen-independent phase:
- pre-B-lym mature and become virgin-B-lym
- On the surface of each virgin-B-lym there will be an IgG-like molecule appearing against a certain Ag - Antigen-dependent phase: begins when the cell get into blood ciculation
- If there is an APC presented Ag, which the virgin B-Ly has an Ig structure, then it binds the Ag and gets activated
- Activation may be Th-independent or Th-dependent.
- Cell signals expressed during binding activate B-lym
- Activated B-lym can settle in B-dependent zones of the secondary lymphatic organs, where it goes through blastic transformation
- The one activated cell starts to reproduce very intensively and a clone of the original cell carrying the original Ig structure appears.
- Some cells transform into memory cells, but most of them as plasma cells, where they produce free Ig.
- T lymphocytes
- Produced and matured in thymus, but it is possible for maturation to take place elsewhere.
- Dark nucleus.
- Separated into Tc-cells, Th-cells and Treg-cells.
- Tc-cells: acting in cellular immunity by killing virus and bacteria infected cells.
- Th-cells: helps stimulate activation of Tc-cells and the B-lym needed for immune response. Cause selective death among Th-cells
- Treg-cells: helps regulate activation of Tc-cells and B-lym needed for immune response. Removing of these cells will result in an autoimmune reaction that makes the immune system attack the organisms own cells.
- T lymphocytes - development
- Antigen independent phase: prepare for when pre-T-lym mature and become “virgin T-lym”. On the surface of virgin T-lym, there will be an Ig-like molecule appearing against a certain possible Ag structure. As this cell (Ti, initiator cell), gets into the circulation, the second phase begins.
- Antigen dependant phase – If the Ti-cell carries a CD4 cell surface Ag as well as the IgG-like molecule, it can recognise an Ag on the surface of an APC that has MHC-II also -> Primary stimulation. On the surface of some Ti-cells, there is a CD8 Ag appearing, that can recognise Ag that are expressed beside MHC-I and immediately kill the cells carrying them.
- T lymphocytes - maturation
In thymus:
- Origin: Bone marrow & liver
- Maturation: Thymus
1) TCR – T-cell receptors appear.
2) Immature T-lym surface receptors can bind most MHC structures and Ag.
3) Positive selection: T-lym that can bind self-MHC molecules will survive, the rest will die.
4) Negative selection: T-lym that can bind self matters expressed together with self-MHC molecules will be killed or inactivated
- MHC structure of cells
-Major histocompatibility complex: a set of cell surface proteins essential for the acquired immune system to recognize foreign molecules
-The natural ability to distinguish self from non-self.
-Function: “identity card” of cells
-MHC-I: Composed of extracellular component encoded by an MHC-gene, plus some transmembrane and intracellular components.
•Different Ag of MHC-I group are recognized by cytotoxic T-lym, if the cell binds some non-self Ag beside MHC-I too.
-MHC-II: Composed of cell surface Ag similar to Igs. Found on APC.
•APC send parts of the non-self Ag together with the MHC-II structure onto the cell surface. The signal to the helper T-cell is the presence of MHC-II structure together with the non-self Ag.
MHC-III
•Cell surface signals encoded by the MHC gene group.
•Do not play a role in the immune response directly.
