Immunology Exam 2 (Complement, Ags/Abs, Cytokines, MHC) Flashcards
Five major classes of antibodies in order of abundance
IgG, IgA, IgM, IgD, IgE
What is the key element of the humoral immune response?
Antibodies
Isotypes
Unique amino acid sequence common to all antibodies of a given class, identical in all individuals of a species and differ between species (IgG is an isotype)
Allotypes
Minor variations of amino acid sequences that are present in some individuals of the same species, but not all
(Such as IgG1, IgA2)
Idiotypes
Variations in variable regions that give individual antibody molecules specificity (Binds to the antigen, different)
Where do antibodies appear on serum electrophoresis?
Gamma band at pH 8.6
What are antibodies held together by?
Noncovalent forces and disulfide interchain bridges
Basic structure of an antibody
2 heavy chains
2 light chains
Fab region at the Y
Fc region at straight part of Y
Purpose of the Fc region
Has no antigen-binding ability
Can bind complement and important for opsonization
White cells that have Fc regions would be which cells?
Neutrophils and monocytes (opsonization –> phagocytosis)
Where are light chains located on an antibody?
Outside portions of the “Y” structure
Purpose of the Fab region
Binds antigens (2 binding sites per Fab region)
Which part of an antibody is obtained by papain digestion?
2 Fab fragments and one Fc fragment, horizontal cut
Which part of an antibody is obtained by pepsin digestion?
F(ab’)2, vertical cut, Fc portion in nonfunctional pieces
What are Bence Jones Proteins?
Light chains, kappa and lambda
Can be secreted by malignant plasma cells and associated with multiple myeloma
What disease states are associated with Bence Jones Proteins?
Multiple myeloma
Heat shock (goes back to normal)
What is unique to each class and gives each immunoglobulin type its name?
Heavy chains
What heavy chain is on an IgG?
gamma chain
What heavy chain is on IgA?
alpha chain
What heavy chain is on IgD?
Delta chain
What heavy chain is on IgE?
Epsilon chain
What heavy chain is on IgM?
Mu chain
What is the hinge region?
The segment of heavy chain located between CH1 and CH2 regions - disulfide bonds
What has a high content of proline, allowing flexibility, and hydrophobic residues?
Hinge region
What allows two antigen-binding sites to operate independently and assists initiation of complement cascade?
Hinge region
What has the longest half life of any Ig?
IgG, 23 days
What IgG molecules are best at activating complement?
IgG3 is the best, then IgG1
Most predominant allotype of IgG
IgG1
Why is IgG3 the best at activating complement?
Super long hinge region
What IgG allotypes are poor mediators of complement activation and why?
IgG2 and IgG4 ; they have shorter hinge segments
Major functions of IgG
Provide immunity for newborn (can cross placenta)
Activates complement
Opsonization
Neutralizing toxins and viruses
Agglutination/Precipitation rxn
T/F: All allotypes of IgG can cross the placenta.
True
T/F: IgG is better at agglutination reactions than at precipitation reactions.
False. IgG is better at precipitation reactions
What is the half life of IgM?
6 days
Where is IgM found as a monomer? Where is IgM found as a pentamer?
Monomer: on surface of B cells
Pentamer: secretions
Which Ig molecule is known as the macroglobulin?
IgM
How many binding sites does IgM have?
5
Which antibody has a high valency, high affinity, low avidity?
IgM
T/F: IgM has memory cells
False
Functions of IgM
Complement fixation
Agglutination
Neutralization
Primary Response Antibody
Opsonization
What is known as the primary response antibody?
IgM
Where is IgA1 found?
Blood
Where is IgA2 found?
Mucosal surfaces
Secretory IgA functions
- Patrols mucosal surfaces and acts as a first line of defence
- Passively transfers immunity to newborn during breastfeeding
- Indirectly activate complement
What cells possess specific receptors for serum and secretory IgA?
Neutrophils, monocytes, and macrophages
What Ig is on the surface of B cells only?
IgD
What Ig attaches to basophils and eosinophils and tissue mast cells?
IgE
What Ig has to do with allergic reactions?
IgE
Somatic hypermutation
Genetic mutations during the course of the immune response that result in stronger binding of antigen (affinity maturation)
Factors influencing the immune response
- Age
- Health
- Route of inoculation
- Dose
- Genetic capacity
Immunogen
A substance capable of stimulating an adaptive immune response
Antigen
A substance specifically recognized by the immune system and is the target of the immune response
Not all ________ are ________, but all ________ are _________.
not all antigens are immunogens, but all immunogens are antigens
_____ are the most effective immunogens, follow by _____.
proteins, polysaccharides
Haptens
substances that are non-immunogenic by themselves
Adjuvants
Enhances immune response, accelerates/increases duration of immunity
Heterophile antigens
Exist in unrelated plants or animals but are identical to or closely related in structure so that antibody to one antigen will cross react with the other
MHC Class I loci
Loci A, B, and C
MHC Class II loci
DP, DR, DQ
MHC Class III loci
Codes for C4A, C4B, C2, and B complement proteins
MHC class I: endogenous or exogenous
Endogenous (viruses + cancer)
MHC class II: endogenous or exogenous
exogenous (bacteria, fungus, + parasites)
MHC Classes I and II are involved in _____________; they influence the antigens to which ________ respond.
Antigen recognition; T cells
Class III is composed of secreted proteins that have an immune function, but they are:
not expressed on cell surfaces
Where are genes coding for MHC molecules found
p arm of chromosome 6
What is the order of the classical pathway?
C1qrs –> C4b2a –> C4b2a3b –> C5b –> C5b6789
What is the order of the lectin pathway?
MBL/MASP –> C4b2a –> C4b2a3b –> C5b –> C5b6789
What is the order of the alternative pathway?
C3 cleaved into C3b + B by water –> Factor D cleaves B to make C3bBbP –> C3bBbP3b –> C5b –> C5b6789
What is the C3 and C5 convertase for the classical pathway?
C3: C4b2a
C5: C4b2a3b
What is the C3 and C5 convertase for the lectin pathway?
C3: C4b2a
C5: C4b2a3b
What is the C3 and C5 convertase for the alternative pathway?
C3: C3bBbP
C5: C3bBbP3b
What are the down regulators of the classical pathway?
C1-INH
Factor I
C4BP
S protein
What are the down regulators of the classical pathway?
C1-INH
Factor I
C4BP
S protein
What are the down regulators for the alternative pathway?
Factor H
S protein
2 IgG can activate complement. What distance must they both be from eachother in order to achieve this goal?
20-40 nm
Which pathway is used for direct bacterial activation?
Lectin
Which pathway includes Factor B, D, and P, and acts as an amplification loop, but can also act independently?
Alternative
What complement deficiencies are associated with Lupus and recurrent infections?
C1 (q, r, or s)
C2
C4
What complement deficiency is associated with Glomerulonephritis?
C3
What complement deficiency is associated with Neisseria infections?
C5-C8
What complement deficiency is associated with PNH?
DAF/MIRL
What is the CH50 test?
Shows which dilution causes lysis of 50% of cells
C5 monoclonal antibody
Eculizumab
What is the end product of all of the complement pathways?
Lysis of invading cell via MAC
What are the four functions of complement?
Opsonization
Increase vascular permeability
Recruit monocytes and neutrophils to area needed
Trigger secretion of immunoregulatory molecules to amplify immune response
All complement factors are synthesized in the liver, EXCEPT? Where are they synthesized?
Factor D –> adipose tissue
C1 components –> intestinal epithelial cells
What can initiate the classical pathway?
IgM/IgG bound to antigen
CRP bound to ligand
Viruses/mycoplasma/GNR/protozoa directly bound
When C4/C2/C3 is cleaved, where does the other half go that is not involved in the convertases??
Pro-inflammation recruitment
A ___________ of an MHC molecule is inherited from each parent.
HAPLOTYPE
Class I MHC molecules are expressed on which cells?
All nucleated cells
MHC Class I has highest expression on which cells?
Lymphocytes and myeloid cells
Structure of MHC Class I
3 alpha subunits, 1 beta-2 microglobulin subunit
Antigen Presenting Cells (examples)
B lymphs
Monocytes
Macrophages
Dendritic cells
Thymic epithelium
Structure of MHC Class II
2 alpha and 2 beta subunits
What T cell recognizes MHC Class I
CD8+ (Cytotoxic) to target viruses/cancer
What T cell recognizes MHC Class II
CD4+ (T helper) to target bact/fung/parasites
Which T helper class provides support in B cell differentiation?
Th2
Class II MHC molecules are expressed on which cells?
APCs
Which HLA allele is associated with Ankylosing spondylitis?
B27(+++)
Which HLA allele is associated with Rheumatoid arthritis?
DR4(+)
Which HLA allele is associated with type 2 diabetes?
DQ8(++), DQ2
Which HLA allele is associated with celiac disease?
DQ2(+++), DQ8
What specific stimuli are cytokines induced in response to?
Flagellin, bacterial lipopolysaccharides, other bacterial products, and ligation of cell-adhesion molecules
Pleiotropy
One cytokine has many different actions
Redundancy
Different cytokines have the same effects
Synergy
Some cytokines enhance the effects of eachother
Antagonism
Cytokines counteract eachother
Which cytokines are associated with pro-inflammation?
IL-1, IL-6, TNF-alpha
Which cytokines “wind down” the immune system?
IL1-RA, TGF-beta,
Which cytokines are made by Th1?
IL-2 and IFN-gamma
Which cytokines are made by Th2?
IL-4 and IL-10
Which cytokines are made by monocytes/macrophage?
IL-1, IL1RA, TNF-alpha, IFN-a, IFN-b
Which cytokines are made by lymphocytes?
IL-7, IL-6
Which cytokines drive hematopoiesis?
EPO
What is a “cytokine storm”?
Massive overproduction and dysregulation of cytokines, can lead to hypotension/fever/edema/organ failure/death.
Roles of cytokines
- Induce inflammation
- Recruit effector cells (neut, monos)
- Produce systemic effects (fever, incr APRs, hematopoiesis)
Roles of cytokines
- Induce inflammation
- Recruit effector cells (neut, monos)
- Produce systemic effects (fever, incr APRs, hematopoiesis)IL
IL1RA
Anti-inflammatory effect
Chemokines
Enhance motility and promote migration of many types of WBCs toward the source of the chemokine (chemotaxis)
TGF-B
Induces antiproliferative activity in many cell types, helps down regulate the inflammatory response when no longer needed
Th1 helps active ________. Th2 helps activate ________.
CD8+ cells
B cells
What cytokine is associated with eosinophils and basophils?
Eosinophils: IL-5
Basophils: IL-3