Lect 1 and book notes Flashcards
1
Q
What is an immunogen?
A
A substance that induces an immune response
2
Q
What is an antigen?
A
A substance that reacts specifically with the immune system – can be from external or internal source and can be protein, polysaccharides, lipids, organic and inorganic molecules or nucleoproteins
3
Q
What is immunogenicity?
A
The capacity of a substance to react with and activate the immune system
4
Q
What is the criteria for immunogenicity?
A
Foreign, molecular size, chemical complexity (increased with larger size and more complexity)
5
Q
What are immunodominant epitopes?
A
Epitopes that induce an antibody response in the majority of individuals of a population
6
Q
What is another name for epitope?
A
Antigenic determinant
7
Q
How big are epitopes?
A
Usually 5-7 AA for proteins, or 5-7 monosaccharides or polysaccharides
8
Q
What are haptens?
A
Small, chemically defined molecules that are not immunogenic but can react with antibody of appropriate specificity - univalent
9
Q
What is an example of an antigen that is not an immunogen?
A
Haptens
10
Q
What is univalent?
A
A molecule that only has a single epitope
11
Q
What do haptens need to act as a complete epitope?
A
Must be coupled to a protein carrier
12
Q
What is a conformational determinant?
A
Epitope is based on overall structure of a substance such as being globular or helical
13
Q
What is a sequential determinant?
A
When a specific sequence of AA or monosaccharides defines the epitope – which may be terminal or internal but usually in the hydrophilic region
14
Q
Where are sequential determinants usually found?
A
Hydrophilic regions of molecules
15
Q
What can destroy confirmational determinants but uncover some sequential determinants?
A
Denaturation
16
Q
What is cross-reactivity?
A
When an antibody made against one antigen or hapten can react with another – usually less strongly
17
Q
What is affinity?
A
A measure of the strength of the interaction between a single antigen epitope and a single antigen binding site of an antibody
18
Q
What is the antigen binding site of an antibody called?
A
Fab
19
Q
What is avidity?
A
The strength of the interaction of antigen molecules with multiple eptiopes with antibodies
20
Q
What are the parameters that avidity is dependent on?
A
The affinity of the antibody for the epitope, the valence of both the antibody and antigen, and structural arrangement of the parts of interaction
21
Q
What is an immune complex?
A
Antigen-antibody complexes
22
Q
What does the formation of an immune complex depend on?
A
Nature of the antigen and ratio of the antigen and antibody concentrations
23
Q
What forms agglutination and what forms precipitation?
A
Agglutination - when antibody interacts with particulate antigens (ex - intact cells)
Precipitation - when antibody binds to soluble antigens
24
Q
What are the three zones of precipitation?
A
Antibody excess, equivalence, and antigen excess
25
What is antibody excess?
When the concentration of antibody is in excess relative to the concentration of antigen
26
What is antigen excess?
When the concentration of antigen is in excess relative to that of the antibody -- crosslinking of two antigens to one antibody
27
What can form at equivalence?
When antigen and antibody concentrations are equivalent - antibodies can bind bivaletly to form insoluble lattice with mutivalent antigens
28
How can antibodies lead to tissue damage?
If antigen exposure persists - like in autoimmune disease- the formation of immune complexes overwhelms the pagocytic cells causing tissue damage
29
What are antibodies or immunoglobulins?
Special proteins that recognize and bind foreign substances on invaders known as antigens
30
What types of cells produce antibodies?
B cells which differentiate into plasma cells
31
What are the relative sizes of the light and heavy chains of antibodies?
Light = 25 kD, and heavy = 50-65 kD
32
Which portion of the antibody is the antigen binding site?
The N-terminal region or variable region
33
What are domains?
Compact globular regions with 100-110 AAs formed by intra-chain disulfide bonds -- light chain has 2 domains and heavy chain has 4 or 5
34
What is the hinge region of an antibody?
Protease-sensitive region that is flexible and is between the first and second constant regions of the heavy chain
35
What enzyme acts in the hinge region and what does it do?
Papain -- cleaves antibody to give 2 Fab and 1 Fc gragments and Pepsin -- then degrades Fc fragment
36
Which portion of the antibody is responsible for antigen binding and which is responsible for biological activity?
Antigen binding -- Fab
| Biological activity -- Fc
37
What are the classes of light chains? How do they differ?
Kappa and lambda and differ by residues found in constant region
38
What are the classes of heavy chains? How do they differ?
Gamma, mu, alpha, delta, epsilon which differ structurally and therefor biologically in activity
39
Which isotypes of antibody has the highest proportion in human serum and what are its subclasses? What is its structure?
IgG -- IgG1, IgG2, IgG3, IgG4 -- 2 gamma heavy chains and either 2 lambda or 2 kappa light chains with 3 constant region domains in its heavy chains
40
Which antibody isotype has the longest half life by far?
IgG has 23 days compared to 2-6
41
What is the structure of IgM?
2 mu heavy chains and 2 lambda or kappa light chains -- makes up 10% serum, heavy chain has 4 constant regions -- has pentameric form
42
What is the structure of IgA?
2 alpha heavy chains and 2 lambda or kappa light chains -- 15-20% in circulation and exists as monomer or dimer with subclasses IgA1 and IgA2 -- also found in mucous secretions
43
Which isotypes are found at the lowest proportions?
IgD and IgE
44
What are hypervariable regions of an antibody?
Regions within the variable domain that show the greatest difference between Ig of the same class or subclass -- 3-4 in heavy chain and 3 in light chain
45
What are framework regions of an antibody?
Relatively constant portions of the variable region and are involved in proper orientation of the binding site
46
What is the complementarity-determining region?
Same as the hypervariable region because the antigenic determinant and antigen-binding site of antibody must complement each other and bind by noncovalent interactions
47
Which immune cells are most responsible for keeping viruses in check?
NK cells that release granules that lyse the cell including viruses and tumors
48
Which immune cell is the key player of the immune system working to control virus, bacteria and parasites?
Lymphocytes -- which can differentiate to form plasma cells which do the same thing
49
Which immune cells are most responsible for keeping bacteria at bay?
Neutrophils - also monocytes that are the precursors for macrophages but these are suicidal in nature
50
Which kind of immune cells are most responsible for keeping parasites at bay?
Eosinophils, Basophils and mast cells
51
Which immune cell is the gate keeper that activates the initiation of an immune response?
DCs
52
What are some characteristics of innate immunity?
Born with, active upon first exposure to a pathogen, similar degree of responses to subsequent exposures, response occurs quickly
53
What are the primary barriers to infectious agents?
Physical barriers like the epithelium -- mechanical like flow of fluid, mucus, saliva, tears, sloughing off skin -- chemical like proteases for acidity in GI tract, lysozyme in nasal secretion and tears to break down cell walls to lyse bacteria and defensins to poke holes in bacterial membranes -- microbiological like normal flora of the various organs
54
What is the process of inflammation?
Surface wound allows introduction of bacteria before clot can form -- immune system recognizes bacteria which sends out cytokines to recruit other immune cells from bloodstream -- macrophages open up blood vessels to allow cells through to tissue to kill bacteria -- RBCs are able to come through to cause redness in infected area
55
How do macrophages kill bacteria?
Engulf bacteria by phagocytosis -- lysosome fuses with phagosome to form phagolysosome that breaks down bact.
56
What are PAMPs?
Pathogen-associated molecular patterns -- how our cells allow us to distinguish from self -- LPS, peptidoglycan cell wall, teichoic acid, double membrane
57
What recognizes PAMPs?
Pathogen recognition receptors on cells of immune system (PRRs)
58
What is involved in phagocytosis of bacteria?
Specific receptors on macrophages critical for recognition of bacteria by PAMPs
59
What kind of receptors on macrophages are most important for signaling and what does their signaling lead to?
TLRs -- transcription of genes that encode for cytokines that recruit other kinds of immune system cells
60
Where were TLRs initially discovered?
Drosophila - in embryo development and later found to be key in ability to respond to fungi
61
How many TLRs have been discovered now and what is their structure?
11 found -- structure is a single polypeptide chain that functions as a dimer
62
What is the cellular locations of TLRs?
On plasma membrane of immune cells to recognize extracellular pathogens (2,1,6,4,5) and on endosomes to recognize intracellular pathogens (3,7,8,9) -- each one recognizes specific PAMPs
63
What is the general signaling pathway of TLRs?
PRRs on TLRs recognize PAMPs on pathogen like LPS, binding leads to intracellular signaling cascade which leads to production of cytokines -- cytokines react with receptors on other immune cells to lead to signaling within immune cell
64
How does JAK/STAT work with cytokines?
Cytokines bind to JAK and bridge together allowing for authophosophylation -- leads to recruitment of STATS which also leads to phosphorylation and the new dimer can interact with promoter site to induce transcription and lead to response
65
What are cytokines?
Proteins produced by different cell types that mediate immune responses -- interact with specific receptors on specific cell -- they are the prinicipal mediators of communication in immune response
66
What do the cytokines IL-1B and TNF-a do?
Induce blood vessels to become more permeable to allow effector cells and molecules to enter infected tissue
67
What does the cytokine IL-6 do?
Induces fat and muscle cells to metabolize to make heat and raise the temperature in the infected issue
68
What does the chemokine CXCL8 do?
Recruits neutrophils from the blood and guides them to the infected tissue
69
What does the cytokine IL-12 do?
Recruits and activates NIK cells that in turn secrete cytokines to strengthen macrophage response to infection
70
What are the cytokines and chemokines associated with inflammation?
TNFa, IL-1B, IL-6, CXCL8, IL-12
71
What is autocrine, paracrine and endocrine and examples?
Autocrine - cytokine binds to cytokine receptors on same cell (ex. IL-2 on T cells to activate)
Paracrine - how cells talk to eachother - cell produces cytokine to induce change in nearby cells such as INF-y between T-cells and macrophages - can give mutual activation
Endocrine - cytokines produced during an immune response which makes its way into the circulatory system where it's carried towards distant target organs (fever or IL-6 inducing liver to synthesize acute-phase proteins to lead to phagocyte enhancement and complement activation)
72
What do neutrophils do and how?
Get rid of bacteria by engulfing them and destroying with lytic granules
73
Where are neutrophils stored and how do they get into infection site?
Stored in bone marrow -- attracted to chemokines during immune response -- bind weakly through selectins -- but anchor to ICAMs with LFA-1 (leukocyte functional antigen) where they are able to get inside blood vessel
74
Is the process of chemokine binding energy dependent on independent?
Dependent relies on GTP for signaling
75
What facilitates humoral immunity of the adaptive immune response?
B cells respond to presence of microbes and generate plasma cells to secrete antibodies that bind microbe and block infection
76
What facilitates cell-mediated immunity of the adaptive immune response?
Phagocytosed microbes in macrophages get bound by helper T cells to activated macrophages to kill phagocytosed microbes, and intracellular microbes replicating within infected cell get bound by cytotoxic T cells to kill infected cell
77
What is clonal selection-expansion?
Each lymphocyte has a very specific cell surface receptor and can interact with specific pathogens that signal to only those clones to differentiate into effector cells and expand
78
What are the four functional units of the adaptive immune response?
Recognition - amplification/differentiation - effector mechanism by which foreign substances are eliminated and regulation/control
79
What are the 3 components of blood and how do they relate to immune responses?
Plasma at the top is responsible for humoral immune response, white blood cells and plateletes in the middle are important for cell-mediated response by T-cells, and RBCs sit at the bottom
80
What are the antigenic receptors?
Immunoglobulins for B-cells and T-cell receptors or TCRs
81
How do B cells differentiate into plasma cells and why?
B cells bind to antigen of bacteria and wait to become activated by helper T cell through cytokines -- activation signals to differentiation of plasma cells and memory cells and plasma cells are able to release antibodies to bind bacteria and recruit macrophages to engulf
82
Where in lymph nodes do B and T cells reside?
Lymph node is compartmentalized, B cells aggregate in germinal centers where they can differentiate and T-cells have their own area
83
What are the T-helper subsets?
TH1 - help enhance phagocytes
TH2 - help with parasites
TFH (folicular) - make antibodies more effective and generate memory B cells
84
Which subset of T-helper subsets get to enter germinal center?
TFH to help make memory cells during differentiation - other subsets remain inside T cell area
85
What do dendritic cells do?
Pick up pathogen and break down into components in inflammed site and transfers to lymphoid tissue where antigen naive cells of adaptive immune response reside, DC uses scaffolding molecule (major histocompatability complex MHC) to present antigen to T cells and activate them to respond to infection site -- they are transient
