Adaptive immunity Exam 2 Flashcards
Type 1 Helper T cells (Th1)
Recognize antigen and make a lymphokine that attracts thousands of macrophages, to area of antigen recognition.
This intense inflammation can wipe out a serious infection, or a transplanted kidney.
Th17 Helper T cells (Th17)
Similar to Th1 in that their main role is to cause focused inflammation, although they are more powerful than Th1.
Have been implicated in many serious forms of autoimmunity.
Type 2 Helper T cells (Th2)
Stimulate macrophages to become alternatively activated, able to function in walling-off pathogens and promoting healing.
Process usually takes place after the pathogen-killing Th1 response.
Very important for parasite immunity.
Follicular Helper T cells (Tfh
Stimulated by antigen and migrate from T cell areas of lymph nodes into the B cell follicles, where they help B cells get activated and make the IgM, IgG, IgE, and IgA anitbody subclasses.
Regulatory T cells (Treg)
Make cytokines that suppress the activation and function of Th1, Th17, and Th2 cells, so they keep the immune response in check.
Cytotoxic T cells (CTL)
Destroy any body cell they identify as bearing a foreign or abnormal antigen on its surface.
CD4
Marker on all helper T cells’ surfaces which increases their affinity for antigen, helps get them activated.
CD8
Marker on all cytotoxic T cells.
General activators of T cells
IL-2 and IL-15
Cytokines that drive T helper cells to Th1 subtype
IL-12 and IFN-gamma
Cytokines that drive T helper cells to Th2 subtype
IL-4
Cytokine that downregulates Th1
IL-10
Cytokine that downregulated Th1 and Th2
TGF-Beta
FAS
Protein on a target cell that T cells bind and induce caspase activation and apoptosis
Toxic agents that can kill affected cells
TNF, Perforin, and Granzymes
T cell lymphocyte markers
TCR antigen receptor (alpha-beta or gamma-delta), CD3, CD4, CD8, and CD23
B cell lymphocyte markers
Immunoglobulin antigen receptor, CD1, CD19, CD20, CD23, CD40, CD79a, CD79b
IgG
Most abundant anitbody in the blood
Two adjacent IgG molecules, binding an antigen such as a bacterium, cooperate to activate complement.
Very effective at toxin neutralization. Decent bacterial lysis and antiviral activity.
Some lyse the bacterium. Others diffuse away and attract phagocytic cells, primarily PMNs.
Only class of antibodies that cross placenta.
By far the highest serum concentration and longest half life.
IgM
A large polymeric immunoglobulin. Better at activating complement than IgG.
Is first type to appear in the blood after exposure to a new antigen. Replaced by IgG in a week or two.
Very good complement fixation and bacterial lysis. Some antiviral acitivity
Pentamer
Largest Ig.
IgD
The main form of anitbody inserted into B cell membranes as their antigen receptor which seems to be its only biological role.
IgA
The most important class of antibody in the secretions like saliva, tears, gu and gi fluids, and milk.
Associated w/ another chain called secretory component which it acquires from epithelial cells during the process of being secreted. This makes IgA resistant to digestive enzymes.
Important role in first line of defense against microorganisms trying to gain entry to body through mucous membranes.
Very strong antiviral activity and toxin neutralization.
High amounts in colostrum and breast milk that protects vs. respiratory and GI infx.
Dimer (1-3 monomers)
IgE
Designed to attach to mast cells in tissues. When IgE encounters antigen it will cause the mast cell to make prostaglandins, leukotrienes, and cytokines. Also stimulates granule release which contains inflammation mediators like histamine.
These produce the symptoms of allergy, but the real role of IgE is to fight off parasites.
Normally present in very low serum concentrations.
H Chain types
Gamma, alpha, mu, epsilon, delta
IgG, IgA, IgM, IgE, and IgD respectively
L chain types
Kappa or lambda.
Each cell has option for both, but uses only one.
Not switched when antibodies switch cell types (i.e. IgM to IgA)
Hypervariable regions
aka complementary-determining regions (CDR).
3 areas of v domain that contain the bulk of the antibody’s variability. These comprise the actual antigen-binding site.
Valence
The number of antigenic determinants (epitopes) an antibody molecule can theoretically bind.
IgG = 2, IgA = 4, IgM = 10 etc.
Isotypes
On the basis of slight differences in the amino acid sequences of their H chain C regions the 5 main classes are divided into subclasses:
IgG1, IgG2, IgG3, IgG4 IgA1, IgA2 IgM1, IgM2 IgD IgEd
Allotypes
Minor allelic differences in the sequence of immunoglobulins between individuals, just as blood types or eye color differ.
Determined in mendelian fashion.
Occasionally an immunodeficient patients getting immunoglobulin treatments will make antibodies to someone else’s allotype.
Idiotype
Each antibody has its unique combining region made up of CDR amino acids of its L and H chains
Antibodies can rarely be made to these sequences these are known as anti-idiotype.
In other words, an idiotype is an antibody’s unique combining site considered as an antigen.
Allotypic exclusion
Only one H chain (maternal or paternal) and one L chain (kappa or lambda, either maternal or paternal) are synthesized in any one B cell. All other genes are silenced.
Each person can make two allotypes, but each B cell only makes one.
Recombination
Changing the relative positions of two pieces of DNA.
Cell will choose one of its Vs, one D, and one J to make the VH domain gene.
First it brings one random D segment close to one J; the DNA is cut and the ends joined. It then repeats for V. The entire region from the assembled VDJ unit through the end of delta (IgD) constant region that is transcribed into RNA.
These primary RNA transcripts are alternatively processed using different poly-a sites and splicing to make VDJ-u and eventually VDJ-u and VDJ-delta messages.
Similar in light chain only there is V and J segments, no D and only one C domain gene.
This is done by RAG recombinases RAG-1 and RAG-2
Somatic variation
The production of the V-D and D-J joints are sloppy. Exonucleases chew away a few nucleotides after DNA is cut before D-J or V to D are joined.
Then the cell adds a few nucleotieds with an enzyme called terminal deoxynucleotidyl transferase (tdt) which works at random.
Adds a great deal of variability
Two out of three times the N region, being a random length, will create a frame-shift mutation that is a nonsense mutation that will terminate transcription.
Receptor editing
When a rearrangement is detected as faulty the RAG genes can try again. This is sometimes successful.
Somatic hypermutation
The VDJ unit is hypermutable; each time a b cell divides after antigenic stimulation.
There is a good chance that one of the daughters will make a slightly different anitbody.
Selection is for the best fitting antibody which results in a gradual increase in anitbody-antigen affinity.
This is known as affinity maturation.
Activation-Induced Cytidine Deaminase (AID) converts random cytosines in CDR region to uracil. This newly made U:G mismatch gets excised and repaired w/ error prone DNA pols.
Class switching
A single mature B cell starts making both IgM and IgD which can later switch to IgG, IgE, or IgA. In all cases, the L chain and the VH domain stays the same but the C region of the H chain changes.
B Cell pro-proliferative cytokines
IL-2, IL-4, IL-5
Cytokines that induce class switch to IgE
IL-4 and IL-5
Cytokines that blocks class switch to IgE induced by IL-4
IFN-gamma
Cytokine that induces class switch to IgG2a
IFN-gamma
Cytokines that induces class switch to IgG1
IL-4
Cytokine cause differentiation
IL-2, IL-4, IL-5, IFN-gamma, and TGF-Beta
Important complement factors for clearance of immune complexes and apoptotic cells
C1, C2, C3, C4
Complement factor important for opsoninizaiton
C3b
Complement factor important for amplifying adaptive immunity
C3b
Complement factor important for inflammation and T cell regulation
C3a and C5a
Complement factor important for lysis
C5b, C6, C7, C8, C9
C4b/C2a
C3 convertase in classical pathway
C4b/C2a/C3b
C5 convertase in classical pathway.
Bigger complement proteins that act as enzymes
C 4b, 2a, 3b, and 5b
Smaller complement proteins that float off and recruit
C 4a, 2b, 3a, 5a
Covalently binding tag complement proteins
C4b and C3b. Good if on bacteria and bad if on us.
Classical pathway
C1q C1r C1s c4 and c2
Mannose binding pathway
MBL, MASP-1, MASP-2
Alternative pathway
Factor B, Factor D, and properdin
Common to all pathways
C3
Terminal lytic pathway
C5, C6, C7, C8, C9
C3bBb
C3 convertase in alternative pathyway
C3bBbC3b
C5 convertase in alternative pathway
Properdin
Acts to stabilize the alternative pathway C3 convertase (C3bBb)
