Fundamentals of Immunology for Blood Bankers Flashcards
What is the immune system (IS)?
A controlled system of biological components (cells, tissues etc.) that work together to defend the body from invasion/infection.
What is immunity?
A specific response by the immune system to a previosly encountered pathogen via antigen-antibody complexes.
What are Cytokines?
- soluble protein and peptide molecules are powerful mediators of the immune system.
- comminucated between cells through plasma
How do Cytokines work? (3)
- bind to receptors on cells, # of receptors increase as cell is stimulated
- receptor and cytokine internalized, causes taret cell to differentiate
- cells respond to cytokines and react with chemoattraction, antiviral, antiproliferation, and immunomodulation
Name two cytokines?
- Lymphokines - produced by lymphocytes
- Monokines - produced by monocytes and macrophages.
What are Chemokines? (3)
- A type of cytokine
- A signalling protein produced that attracts leukocytes to the site of infection/inflammation. So immune cells can target and destroy invading bodies like microbes
- Form a concentration gradient; cells attracted to gradient and move toward higher concentration.
Compare natural immunity and adaptive (acquired) immunity?
See Pictures
What are the main components of Cellular and Humoral Immunity?
See picture
Humoral - Fluid Component: Complement (missing from table)
What are the Physical and Biochemical Barriers in natural immunity?
Acquired immunity: the antibody that the antigen is made against can be referred to as?
Antithetical Antigen
Antigen-antibody complexes are known to be _____ _______ _____ which do not allow the recognition of near misses.
Three dimensional interactions
What cells are responsible for humoral immunity?
B-cells
When b-cells are activated and start procuding antibodies, they are called?
Plasma cells
What do B cells do when they re-encounter a specific antigen?
What do they do when they encounter and unknown matching antigen?
- Multiple (clone itself)
- Internalizes antigen fragments, combines it with and presents it on its surface using its MHC II molecules.
Represent 60-80% of circulating lymphocytes and are the primary cells in cell mediated immunity.
T cells
What do T Helper (CD4) cells do? (4)
- Activate and direct the actions of other immune cells:
- Secrete cytokines that activate macrophages
- Activate B cells which make antibodies
- Recognise antigen with help of MCH II molecules
What do Cytotoxic T-Cells (CD8) do?
- Attack and lyse infected / damaged / dysfuctional cells
What do regulatory supressor T -cells do?
- Regulate the immune response
- inhibit activities of B and T cells to prevent immune system going out of control.
What are Natural Killer (NK) cells? (3)
- Granular lymphocytes that lyse virally infected cells, malignant cells and antibody-antigen complexs without needing stimulation.
- NK Cells act on cells missing self (MHC I)
- MHC I inhbits NK cells
What is the purpose of neutrophils?
- Phagocytosis
- Use granules in cytoplasm to break down ingested material and kill microrganisms
Where do basophils accumulate and what do they do?
What Ig are they activated by?
- Inflammatory sites
- release histamines
- IgE
What funstions do Eosinophils perform? (2)
- Kill invading microorganisms, incl. some parasites
- control allergic reactions by secreting histaminase, enzyme that breaks down histamine. Stops allregic reaction gettingout of control
Where are monocytes found?
- In the blood, when they enter tissues they become tissue macrophages
What are the two functions moncytes / macrophages perform?
- engulf and ingest antigents via phagocytosis
- Are Antigen Presenting Cells (APCs) that process and present antigens to lymphocytes during the immune repsponse.
What do APCs do?
- Display parts of ingested antigens bound to Major Histocompatibility Complex molecules (MHC) on their surfaces.
- certain T cells recognise this antigen-MHC complex and become active
What steps are involved in antigen presentation by APCs?
- antigen ingested and broken down
- vesicle w/ MHC molecules merges w/ vesicle w antigen bits, form antigen-MHC complex.
- Antigen-MHC complexes expoerted to surface
- CD4 / CD8 cells activated based on type of antigen-MHC complex exposed. MHC molecules help T cells recognise foreign antigens.
What part of the genome encodes MHC?
Human Leukocyte Antigen or Major Histocompatibility Factors
What is critical to MHC?
immune recognition and regulation of antigen presentation in cell-to-cell interations, transplantation, paternity testing, and specific HLA patterns.
Correlates with sucesptibiilty to certain diseases
What the classes of MHC molecules and their roles?
-
Class I -
- on all nucleated cells except trophoblasts (egg) and sperm, key in role in CD8 function.
-
Class II
- presemt on antigen presenting molecules like B-lymphocytes, activated T-cells, and dendritic cells.
What are the 5 classes of Igs?
- IgG
- IgM
- IgA
- IgE
- IgD
What is the function of IgG? (5)
- Can cross placenta - immunity to neonates
- neutralize toxins, fight infections
- Produced in response to antigens in transfusions / pregnancy
- Most involed in immune repose to antigens
- 80% of Igs are IgG
What is the function of IgM? (8)
- Antigenic receptor site on immature B-lymphocytes
- 10 bingding sites
- Neutralizes toxins
- Most effective antibody for agglutintion
- Activates complement w/ 5c region
- Largest, first and main antibody in primary immune response.
- 6% of Igs
What is the function of IgA? (4)
- Protect from bacteria and viruses
- Can cause anaphylactic transfusion reactions
- Secretory antibody
- 13% Igs
What is the function of IgE? (5)
- Moderates release of histamines and heparin from basophils and mast cells.
- Attaches to surface of basophils and triggers immune response
- responsible for immediate hypersensitivity/allergic reactions/parasite infections
- receptors blocked by antihistamines
- <1% Igs
What is the function of IgD?
- Dont really know
- may act as receptors for antigens when found on the surface of b-lymphocytes
What are antigens?
- Any substance capable of interacting with an antibody
- can cause an immune response
- contain antigenic determinants called epitopes.
What us an epitope?
The specific part of the antigen that is recognised by the immune system and part that binds w/ the antibody, b-cell or t-cell
Describe primary antibody structure?
- Y shape formed by:
- 2 large chains (inside)
- 2 light chains (outside arms)
- Bound by covalent bonds and disulfide bridges
What enzymes cleave antibodies into 3 fragments?
What are the 3 fragments antibodies can be cleaved into?
Where are the above sites located on the Y shape and what do they bind?
- Papain
- Pepsin
- 2 antigen binding fragments (FAB - Fragment Antigen Binding sites)
- 1 Crystalizable site (Fc - Fragment Crystalizable)
- FAB - top of antibody ( consists of heavy and light chain) - binds antigens
- Fc - bottom (heavy chains only), binds receptors on specific immune system cells
What is the variable domian of an antibody?
- Upper part of the FAB sites
- this area binds to s specific antigen
- 1 variable region at the top of each light and heavy chain.
What is the Constant domain and its role?
- This is the bottom of the Y on an antibody consisiting of both heavy chains.
- Activates complement cascade
What is the Hinge region?
- Center portion of the antibody
- lets antibody be flexible
- area where antibody can be broken apart by chemical treatment
What does the primary response depend on?
characteristics of the antigen and individual
IgM antibidy response proceeds in four phases after antigen challenge. What are the 4 phases?
- Lag - no antibody detectable
- Log - antibody titre increases logarthmically
- Plateau - antibody titre stabilizes
- Decline - antibody is catabolized
When does the secondary (amnestatic) response occur?
After repeated exposure to the same foreign substance.
- Stimulates proliferation of clonces of memory cells followed by corresponding antibody production.
How is the secondary response different from the primary response phases? (5)
- Shorter lag phase
- longer plateau
- more gradual decline
- IgG is main antibody
- Antibody levels are higher - 10X or greater
What is antibody affinity?
strength of attraction of antibody FAB site and expitope/determinant site on an antigen
What is antibody avidity?
The functional combining strength of antibody with its corresponding antigen.
strength of bonding is increased with multivalent antigen combined with more than one antibody combining activities.
To dissociate complex, all Ag-Ab bonds must be broken simultaneously
What are monoclonal antiodies?
Purified antibodies from a single cell.
- Very pure and very specific for a particular antigen
How were monoclonal antobodies produced?
- Fusing lymphocyes to produce a specific cell line that was immortal and produced specific antibodies. (Kohler, Mildstein, and Jerne 1975)
- Hybridoma (cell hybrid) (developed from myleoma (tumor) plasma cells)
- hybrid cells secrete antibodies characteristic of parent cell
- MAbs (monoclonal antibodies)
What is the greatest impact of MAbs in the analysis of cell membrane antigens in clinical applications? (5)
- Typing Tissue and Blood
- ID infectious agents
- ID tumor antigens and autoantibodies
- ID and quantifify hormones
- delivering immunotherapy
What is complement?
A complex group of > 20 circulating and cell membrane protiens, protienases, and other enzymes.
The larger fragment is designated “b” and the smaller fragments as “a” EXCEPT for C2 which is the other way around.
Most of the proteins are normally inactive, but in response to the recognition of molecular components of microorganisms they become sequentially activated in an enzyme cascade – the activation of one protein enzymatically cleaves and activates the next protein in the cascade. Complement can be activated via three different pathways