Exam 1 Flashcards
What is immunology?
branch of biomedical science concerned with the response of the organism to antigenic challenge, recognition of self from non-self, and physical and chemical aspects of immune phenomenon
Define antigen
substance that is recognized by the immune system as foreign and stimulates an adaptive immune response
How can antigen recognize foreign particles?
- immunoglobins (antibodies)
- T cell receptors
- Innate immunity receptors
What are on the surface of bacteria that the immune system can recognize?
- capsule
- LPS
- toxins (and other extracell. proteins)
- flagellum
What part of the virus can the immune system recognize?
- capsid proteins on virus
- viral proteins on surface of cell
If tumor cells generate from our own cells, how does the immune system recognize it?
- a mutant protein
- cancer cells may express fetal proteins which are recognized as foreign
- overexpression of a specific protein
What are the components of innate immunity?
- cellular
- humoral or molecular
- physical barriers
What are the cellular components of innate immunity?
- phagocytes
- natural killer [NK] cells
What are the humoral or molecular components of innate immunity?
- natural/maternal antibodies
- cytokines
- complement
- toll-like receptors
What are the physical barrieres of innate immunity?
- skin
- mucosal surfaces
What are the components of adaptive immunity?
- cellular
- humoral and molecular
What are the cellular components of adaptive immunity?
- antigen presenting cells (APC)
- T cells
- B cells
What are the humoral or molecular components adaptive immunity?
- specific antibodies
- cytokines
Define cytokine
signaling molecules that allow cells to talk to each other
Immunity vs. Susceptibility
- Immunity: exposed to it before and develop immune response
- Susceptible: never been exposed to it
Define tolerance
the immune system’s ability to recognize a foreign substance that’s not a threat; ex. food
alloimmunity
a foreign substance from the same species; ex. tissue from another human
Define biologics
drugs derived from a living source
What are the different types of biologics?
- Active immunizing agents
- Passive immunizing agents
- Diagnostic biologics
- Blood and blood derivatives
- Allergenic extracts
- Biological response modifiers
- Misc. biologics
- Cellular therapy
What are unique products of biologics?
- Natural products
- Relatively crude
- Active constituents are macromolecules
- Standardize by bioassay
- Immunogenic
- Special hazards
What does “relatively crude” mean?
complex mixtures of whole organisms, tissues, or cells
What does it mean to be standardized by bioassay?
units are units by activity; usually unique to the individual drug
With respect to biologics, what does it mean to be immunogenic?
contains complete immunogens that may induce an immune response in the patient
What are examples of nonspecific host defenses?
- physical barrier
- chemical (pH)
- cellular (phagocytes)
- microbiome
What are the types of specific immunity?
- Acquired (adaptive)
- Innate (inborn)
Besides the components, what is a characteristic of innate immunity?
recognizes pathogen associates molecular patterns
How does bacteria damage the body to create an inflammatory response?
- exotoxin release
- endotoxin release
- direct cytopathic effect
Define defensins
antimicrobial peptides that penetrate & disrupt microbial membranes; synthesized by a number of cell types; found in a lot of different tissues; some are induced and some are produced by the body all the time
How does phagocytes signal macrophage activation?
they have specific cell-surface proteins that detect microbial products which signals the activation
How does complement proteins trigger phagocytosis?
some complement proteins can directly act with bacterial structures; complement fragment binds to bacteria and this complex binds to receptor on effector cell which triggers phagocytosis of the complex
Where is TLR3 located and what does it recognize?
- located in endosome
- recognizes viral RNA
What are the three major characteristics of acquired immunity?
- specificity
- ability to discriminate between self and non-self
- memory
What are characteristics of acquired immunity?
genetically determined; delayed 7-10days onset; memory; produce multiple antibodies that fight against virus
What are the ways in which inflammation can be classified?
time course or appearance
Describe innate immunity and inflammation at site of infection
bacteria enters host -> neutrophil engulfs bacteria in an attempt to destroy it -> neutrophil release cytokines -> cytokines cause tight junctions of epithelial cells to loosen up and allow fluid to come into the area -> complement proteins and phagocytes can enter the site and join in the fight -> coagulation to seal off wound -> fibroblasts start to repair
What is the importance of arachidonic acid in inflammation?
they are the site of attack for COX1 and COX2 inhibitors which relieves swelling
afferent phase vs efferent phase
- Afferent: information gathering stage; stimulation of a specific response to an antigen
- Efferent: production of effector cells, antibodies, and molecules that follow the antigenic stimulation
What kind of effect can the efferent phase have on inflammation?
- initiate inflammation (via immune complexes)
- augment inflammation (via opsonization)
- amplify inflammation (via complement fixation)
What are the majority of granulocytes?
leukocytes ~ 75%
What are the types of leukocytes?
- Neutrophils (PMN): 40-75%
- Eosinophils: 1-6%
- Basophils: 0.2-1%
- Monocytes: 2-10%
- Lymphocytes: 20-50%
What are neutrophils?
life time is 8-12 hours but can live up to 5 days in the bone marrow reserve pool; this pool can be stimulated to be released to fight infection;
What is neutropenia and what does it result in?
- quantitative deficiency of neutrophils
- serious condition rendering a patient susceptible to bacterial infection
What are eosinophils?
important in the immunity against parasites; uses IgE
What are basophils?
good against parasites as well (eosinophils are the other ones)
How are mast cells different from basophils?
mast cells strongly bind to IgE
What are monocytes?
released from bone marrow; has a half life of 8 hours; they find a tissue for residence then differentiate into macrophages; can live in tissue for a long time (years); important in late phase of inflammation
What are dendritic cells?
a type of monocyte; activate T cells; most potent APC known
What are the types of T-lymphocytes?
- Regulatory T cells
- Effector T cells
- Cytotoxic and Delayed Hypersensitivity Cell (CD8+)
- can also produce memory cells
What are the types of regulatory T cells?
- Helper cells (CD4)
- Sueppressor cells
What does effector T cells do?
they can attack and infected cell and kill them; can also attack tumor cells
What are the types of B-lymphocytes?
- Memory B cells
- Plasma cells
- can produce antibodies
What are plasma cells?
antibody synthesizing and secreting cells; derived from B cells
What are the types of lymphocytes?
- T-lymphocyte
- B-lymphocyte
- Natural killer cells
What are the function NK cells?
they can recognize virally infected cells; they are cytotoxic for some target cells without having to have prior exposure
What is the importance of CD numbers?
they identify specific cell-surface proteins (or carbohydrates) that are associated with particular cell populations or functions
Where is the location for the source of cells?
bone marrow
What are the primary lymphoid tissues?
- bone marrow and thymus
- sites of lymphocyte development
What are the secondary lymphoid tissues?
- generally the sites of the immune response (where T and B cells are stimulated)
- nodes/nodules, spleen, liver, MALT, BALT, GALT
Describe the immune response in the lymph node.
molecules enter via the afferent lymphatic vessel; stimulation of lymphoid follicle (mostly B cells) -> germinal center; stimulation of T cell area; exit efferent lymphatic vessel
What is lymphocyte traffic?
1-2% of lymphocytes are in transit at any give moment and will migrate towards a lymph node if needed and takes up residence there
Order of operation starting from stimulation of T cell
- Stimulation of T cell
- Produce T helper cell
- Interacts with B cells
- Production of antibodies
What can effector-antigen interactions lead to?
- Precipitation
- Agglutination
- Complement fixation
- Neutralization (e.g., toxin, virus)
- Cytotoxicity
What are the different classes of immunoglobins and what are they derived from?
- also called gamma globulins
- IgA, IgD, IgE, IgG, IgM
- derived only from B cells
What are characteristics of immunoglobulins?
have antibodies which bind specifically to the antigen that stimulated their formation
What is another name for antigen binding site?
- CDR
- part of the antibody that actually interacts with the antigen at the chemical level
What is a hybridoma?
a fusion of B cell with myeloma to ensure that B cells that produce useful antibodies do not die off because their normal life expectancy is weeks-months
Differentiate between the different types of monoclonal antibodies
- Animal: whole antibody produced from animal
- Chimeric: genetically engineered antibody; human antibody but animal CDR
- Humanized: genetically engineered antibody; human antibody but specific parts of CDR preserved
- Human: whole antibody produced from human
What happens in the primary antigen-antibody reaction?
Basic combination of an antigen with a specific antibody (binding via the antigen binding site)
What happens in the secondary antigen-antibody reaction?
combinations to produce a
precipitate or agglutination
Define affinity
the strength of the reaction between a single antigenic determinant and the single combining site on the antibody
Define avidity
easure of the overall strength of binding of an antigen
What are the three major ways in which the complement system acts?
- Causes lysis of cells, bacteria, and enveloped viruses
- Mediate opsonization
- Generates peptide fragments that regulate features of the inflammatory and immune responses
What is opsonization?
preparing a target antigen that will be better eaten by a phagocyte; can be done with antibodies or complement proteins
What is the key protein for each complement pathways?
Complement protein C3
What are characteristics in the alternate pathway with respect to complement activation?
- this is the first pathway to activate
- is antibody-INdependent
- triggered directly by microenvironment of microbial surface
- direct binding and activation of protein 3 on pathogen surface
- when gets to C8, it recruits multiple copies of C9 which forms a pore and what’s in the cell comes out and cell dies
What are characteristics in the mannose pathway with respect to complement activation?
- this is the second pathway to activate
- binds to mannose residues (bacteria uses mannose on their surfaces)
- activated C3B on bacterial surface
How is IL-6 produced?
- interleukin-6
- bacterial infections induce macrophages to
produce cytokine IL-6
What does IL-6 do?
stimulates liver to produce acute phase proteins which are:
- C-reactive protein
- fibrinogen
- mannose-binding lectin
What are characteristics in the classical pathway with respect to complement activation?
- initiated by one IgM molecule OR two or more IgG molecules bound side by side to a cell or virus surface OR C-reactive protein
- causes binding and activation of protein C1
Describe the lag phase (latent period).
3-14 day period where cells proliferate and differentiate before antibodies appear in serum
Describe the exponential phase.
4-10 day period when the rate of antibody synthesis exceeds the rate of catabolism.
Define the steady state phase.
when the rate of antibody biosynthesis and catabolism are approximately equal
Define the declining phase.
when body is no longer exposed to threat or when it’s been significantly long since you’ve had your vaccine, antibodies in serum begin to decline
Duration of immunity depends on two factors. What are they?
- amount of antibody formed
- efficacy of antibody
What are the difference between the phases between primary and secondary response to immunogenic stimulation?
Secondary response is:
- Lag phase is much shorter
- Exponential phase is steeper
- Steady state phase is higher and shorter
- Declining phase lasts longer and is slower
What is antibody interference?
When you give second exposure/booster shot too soon after primary exposure and it clears out the antibodies produced during the primary exposure
What are the fates of the T helper cell?
- cytotoxic T cell
- memory T cell
- B cell
Define immunogen
A substance capable of inducing an immune response in a susceptible animal and reacting with the products of that response.
Define epitope
part of an immunogenic molecule that determines specificity and binds with an antibody or gives rise to the MHCbinding peptide the is recognized by the T-cell receptor
Define antigen
a substance that can react with immune effectors
Define haptens
- small molecules that are not capable by themselves of inducing an immune response but may do so when covalently bound to a suitable carrier
- once you generate the immune response, you no longer need the carrier
What are the common functional groups in covalent bonding with respect to hapten + carrier?
- COOH
- NH2
- SH
What is valency?
having several binding sites on a molecule
What are some examples of immunodominance?
- Terminal epitopes are usually immunodominant in linear proteins.
- Conformation is usually immunodominant over primary amino acid sequence in globular proteins
- Primary structure is usually immunodominant in less structured linear proteins.
- Hydrophilicity is often an immunodominant feature and hydrophilic epitopes are more immunogenic than lipophilic epitopes.
What are characteristics of thymic-independent immunogens?
- only makes IgM
- does not make memory cells
What are the restrictions for T-cell response?
- response only to processed antigen
- MHC-restricted
What are the groups of HLA proteins that are recognized by WHO?
- Class I: HLA-A, HLA-B, HLA-C
- Class II: HLA-DR, HLA-DQ, HLA-DP
Note some differences between Class I and Class II HLA proteins.
- Class I: made up of one subunit, present antigen directly to CD8 T cells
- Class II: made up of two subunits, present antigen directly to CD4 T cells
There are some accessory HLA proteins. What are they?
- Class I: HLA-E, HLA-G (found on surface of cells and form ligands for NK cells), HLA-F (intracellular, recycling)
- Class II: HLA-DM, HLA-DO (regulate peptide loading on DR, DP, DQ)
Define haplotype
alleles on chromosome that are closely linked together and tend to be inherited together
What are the main antigens involved in allograft rejection?
HLA-A, HLA-B, HLA-C
Where are class II proteins expressed?
on APC
What are the different types of APC?
- macrophages
- B cells
- dendritic cells
What is MHC restriction?
you need both the correct antigen and receptor to initiate a response
