Lecture 1 review

1. What are the four major types of human pathogens?

2. What are the two arms of immunity? __________ and __________
3. What are the two components of adaptive immunity? _________ and _________
4. What is the concept of herd immunity?
5. Immune cells develop the ability to bind the antigen after the exposure to the antigen. (T or F)
6. The innate immune system uses PRRs to recognize the _________ on the pathogen.
7. PRRs of the innate immune system is __________, whereas the antibodies of the adaptive
immune system is ___________. A) Germline encoded; B) Randomly generated.
8. The specificity of B or T lymphocyte receptors is determined in the lymphocyte after it is
exposed to the antigen. (T or F)
9. Skin is an important organ of the immune system. (T or F)
10.What is the concept of clonal expansion? Why does it take time to develop adaptive immunity
against the pathogen, whereas innate immunity acts immediately after the infection?
Lecture 2 review

1. What are the two primary lymphoid organs?

2. If bone marrows are depleted, can T cells still develop?
3. What are the four types of granulocytes? Which one is most responsible for clearing bacteria?
4. What are the professional antigen-presenting cells?
5. What are three types of lymphocytes? Which belong to the innate and adaptive immune
system, respectively?
6. How does a DC activate a TH cell? Where does it happen?
7. How does a NK cell kill the target cell?
8. How does a TC cell kill the target cell? How does a NK cell kill the target cell?
9. What is the difference between TH1 and TH2 cells?
10.Within the lymph node, where are T cells and B cells located?
11. What is a Germinal center? What cells reside in the Germinal center?
Lecture 3 review

1. How many classes of antibodies are there? How are they different from each other?
2. How many antigen molecules can a IgM pentamer bind?
3. How many polypeptide chains are there in a IgG antibody?
4. How many constant regions are there in a IgG light chain and a IgG heavy chain?
5. Which type of protein secondary structure is an immunoglobulin domains made of?
6. How many subclasses of IgG are there in human?
7. What is an epitope and what is a paratope?
8. What is a Fc fragment and what is a Fab fragment of an antibody?
9. How does B cells switch from making membrane bound antibodies to making secreted
antibodies?
Lecture 4 review

1. What is ITAM? What amino acid residue is important for the function of ITAM?
2. What receptor proteins carry ITAMs for TCR signaling and BCR signaling?
3. What is the first step of the signaling transduction for TCR signaling?
4. What are the kinases that phosphorylate the tyrosine in ITAM in TCR and BCR signaling?
5. What enzyme is recruited to the membrane by phosphorylated tyrosine to break down PIP2?
6. PIP2 is broken down into DAG and IP3, which transduce the signaling from the membrane
into the cells. What is function of IP3? Which transcription factor does IP3 signaling activate?
7. What is the function of DAG? What are the two proteins DAG activates? Which transcription
factors are activated through the DAG signaling?
8. What are the three major signaling pathways activated by the MHC II-antigen::TCR
interaction? What is the function of the coreceptor signaling of the TCR and BCR signaling?
Lecture 5 review

1. What is the difference between cytokines and chemokines?

2. What are the TH1 cytokines and what are the TH2 cytokines?
3. What are the six families of cytokines based on structures?
4. What is the function of IL-1?
5. What is the signaling pathway commonly activated by Class I and Class II cytokines?
6. What is the functional difference between IFN-a and IFN-g?
7. What is the consequence of the binding between FasL (membrane-bound TNF) and Fas?
8. What is the receptor of chemokine like IL-8? What is its function?
Lecture 6 review

1. What are the cells involved in innate immunity and adaptive immunity?
2. Examples of antimicrobial proteins and antimicrobial peptides
3. What are PAMPs? They are recognized by _______ on phagocytic cells. For example,
_____ is on the surface of Gram negative bacteria and is recognized by _____ on the
surface of innate immune cells.
4. What receptor recognizes dsRNA from virus? What receptor recognizes bacteria DNA
that is unmethylated at CpG dinucleotides?
5. Downstream of the TLR signaling, what transcription factors are activated? What is
the consequence of activating those transcription factors?
6. What cellular organelles are important for phagocytosis? Oxidative attacks involve the
generation of _______ and _________.
7. What is the most important type of cells that connects innate and adaptive immunity
and how?
Lecture 7 review

1. What genes in which cells go through somatic recombination in the immune system?
2. What DNA segments encode the variable region of light chain and heavy chain variable
regions, respectively?
3. How much Ab diversity can be generated in the variable region through combining
different segments alone? Why is there much more diversity than that?
4. V, D, and J segments are flanked by Recombination Signal Sequences. What are the two
types of RSSs? How do they recombine?
5. What enzymes mediate the V(D)J recombination?
6. What is P nucleotide addition?
7. Which enzymes adds non-templated random nucleotides during VD and DJ recombination?
8. What is allelic exclusion of antibody gene recombination?
9. What happens to the B cell if both copies of Ab gene failed to generate productively
rearranged locus? What happens to the B cell, if it generates an autoimmune antibody?
Lecture 8 review

1. Where are class I MHC genes expressed and where are class II MHC genes expressed?
2. What are the structural difference between class I and class II MHC molecules?
3. Can a MHC molecule bind to multiple antigenic peptides? In the case of MHC class I,
what have those peptides in common?
4. MHC molecules are highly polymorphic among different individuals and cause immune
rejection during transplantation. Explain why organ donation from children to parents
often cause rejection?
5. What is the self-MHC restriction for T cells?
6. What are the differences in the assembly of class I and class II MHC molecules?
7. What MHC molecule is involved in activating CD4+ TH cells?
8. What MHC molecule is involved in the killing of target cells by CD8+ TC cells?
9. What is cross-presentation?
Lecture 9 review

1. How are humoral immunity and cellular immunity related to innate and adaptive immunity?

2. What are the four major ways of clearing and destroying pathogens by antibodies?

3. After V(D)J recombination, a B cell can only make antibodies with fixed variable regions but can still
switch the heavy chain isotype of the antibodies through “class switch recombination”. Between IgM
and IgG, which one is secreted first during immune response? What are IgM good at? Which one is
better at mediating ADCC?

4. What is the function of IgE antibodies and how? What is IgE receptor? What cells express IgE
receptor?

5. What cells express IgG receptors? List three types of cells.

6. What are the downstream transcription factors of FcR signaling?

7. What signaling motifs do inhibitory FcR (FcgRIIB) have? What is the role of the inhibitory receptor?

8. The nature of the pathogen often regulates B-cell class switching. Extracellular pathogens bias
towards ______, intracellular pathogens bias towards _______, parasites bias towards _______.
Lecture 10 review

1. What are the three types of cytotoxic lymphocytes?

2. What are the signals required for the activation of CTLs (or TC cells)?

3. How does CTLs recognize and kill target cells?

4. How does NK cells recognize and kill target cells?

5. How does NKT cells recognize and kill target cells?

6. What molecular markers can be used to differentiate NKT cells from NK and T cells?

7. What are the cytotoxins released from the granules of CTLs during the killing of target cells?

8. NK cells express express IL-2R and FcgRIII. What are their functions?

9. What are the common targets of Fas-FasL killing and granzyme killing?
Lecture 11 review

1. What are the difference among autograft, isograft, allograft, and xenograft?

2. What types of immune cells are mostly responsible for the specificity and memory of graft
rejection?

3. If the parents are heterozygous in their MHC loci, what is the chance that grafts between
siblings have 100% match?

4. What mediates hyperacute rejection during transplantation?

5. What are the effector mechanisms involved in allograft rejection?

6. What are the ways of immunosuppressive therapy?

7. How can soluble CTLA-4Ig (CTLA-4 fused with an Ig Heavy chain) prevent T cell activation?

8. What is graft-versus-host disease (GVHD)?

Lecture 12 review

1. What is lymphocyte homing? How long does it take for one individual lymphocyte complete a circuit from blood
to tissue and back to blood?

2. How many T cells can be surveyed by a DC in one hour?

3. How do APC and antigens enter the lymph node?

4. What is the process of extravasation? Where do T cells leave the circulation? What are the protein-protein
interaction mediating extravasation?

5. How does T cells find DC in the paracortex (T cell zone)?

6. Can a DC presenting antigens, on average, find the right T cell to activate within 24 hours?

7. How long does it take for a T cell to be activated (time needed for T-APC interaction)?

8. How long does it take for a T cell to be activated? How long does it take for clonal expansion of T cells?

9. How does B cells reach the follicle after extravasation?

10. What is the process of B cell activation? What happens to an antigen-specific B cell after it captures an antigen?
Lecture 13 review

1. What is the difference between monoclonal antibody and polyclonal antibody?

2. What does hemagglutination reaction detect? If the red blood cells fall down to the bottom of the
well, it means some antibodies in the sample bind to the RBCs.

3. What assays can you use to detect the amount of IL-1 in a patient's blood?What is western blot
assay?

4. What is the application of Surface Plasmon Resonance (SPR)?

5. What assays can you use to check whether the breast cancer cells obtained from a patient express
epidermal growth factor receptor 2 (HER2)?

6. How do immunologist use flow cytometry (or FACS) to find out the number of a particular group of
immune cells?

7. How is magnetic cell sorting used to isolate a specific type of immune cells, e.g. NKT?

8. What is adaptive transfer? How can that be used to treat cancer patients?
Lecture 14 review

1. How are monoclonal antibodies generated? What is the principle of HAT medium selection? Why do B-
myeloma hybrid cells survive in the HAT medium?

2. List five ways antibodies are used to detect the expression of a particular protein in a biological samples

3. What is the principle behind hCG detection in the pregnancy test? What are the functions of the reaction
region, test region, and control region?

4. What methods are used for HIV infection diagnosis?

5. Can one antibody bind to different proteins?

6. What are the differences among chimeric mAb (-ximab), humanized mAb (-umab), and human mAb?

7. List a few ways mAbs can be used to treat cancer

8. Rituximab (Rituxan) is a chimeric mAb that binds to CD20. How is it used to treat B cell lymphoma?
Trastuzumab (Herceptin) is an anti-HER2/erbB2 antibody. How doe it inhibit cancer cell growth?

9. How can mAbs be used to treat cancer in general?

Lecture 17 review

1. What are tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs)?

2. How can tumor cells escape immunosurveillance?
3. What is the concept of immunoediting?
4. List a few ways of cancer immunotherapy
5. What is DC reinfusion or DC vaccine?
6. What is the principle behind T cell engineering and CAR-T therapy?
7. What is the mechanism underlying cancer immunotherapy by anti-CTLA-4 and anti-PD1
antibodies?
 Lecture 1 summary

• Type of pathogens
• Adaptive immunity vs innate immunity
• Cellular Immunity vs humoral immunity
• Types of immune cells (see lecture 2 for details)
• Immune molecules that recognize pathogens (germline-encoded vs
randomly generated; see future lectures for details)
• PAMPs and PRRs
• The concept of clonal expansion
• The idea that antigen specificity of immune cells is defined before
encountering pathogens and specific immune cells were just selected for
expansion when particular antigen appears
 Lecture 2 summary
• Leukocyte (white blood cells)
• Granulocyte: neutrophile, eosinophil, basophil (mast cells not in blood)
• Monocyte: differentiate into macrophage and dendritic cell
• Lymphocyte: T, B, and NK
• Professional antigen presenting cells (pAPC): macrophage, dendritic cell, B cell
• Types of T cells
• Th cells (helper T): Th1, Th2, Th17, Treg
• Tc cells (cytotoxic T)
• Markers for T, B, and NK cells
• T: CD3, CD4 for Th, CD8 for Tc
• B: CD19, CD21
• NK: CD56
• Structure of the lymph node
• HEV: high endothelial venule where lymphocyte enters the lymph node
• T cells zone (paracortex); B cell zone (follicle)
• Afferent lymphatics: where antigen and APC enter the lymph node
 Lecture 3 summary
• Heavy chain vs light chain
• Fab, Fc, F(ab’)2
• Antibody classes and heavy chain isotypes
• IgA, IgD, IgE, IgG, IgM
• Subclasses and subisotypes (IgG1, 2, 3, 4)
• Epitope and paratope
• Idiotope and idiotype (anti-antibody antibodies)
• Function of the hinge region
• Glycosylation of the CH domains of the heavy chain
• Membrane-bound versus secreted antibodies
 Lecture 4 summary
• Intercellular signaling (molecular interactions between cells) required to
activate Th / Tc / B cells
• Intracellular signaling (molecular events) required to activate T and B cells
• Main signaling vs co-stimulatory signaling
• TCR / BCR coreceptor vs co-stimulatory receptors
• Tyrosine phosphorylation as the first step to initiate intracellular signaling,
leading to the activation of PLC
• Phospholipids in signaling;
• For main signaling: PIP2 => IP3 and DAG (by PLC) as secondary messenger; IP3
induces Ca2+ influx and activate NFAT; DAG activates Ras/MAPK pathway (leading
to AP-1 activation) and activates PKC / IKK to degrade IkB (leading to NFkB
activation).
• For costimulatory signaling: PIP2 => PIP3 (by PI3K), leading to the activation of
PI3K/Akt for antiapoptotic signaling.
• The lack of costimulatory singaling leads to anergy (unresponsiveness of the T cell),
apoptosis, and immune tolerance.
 Lecture 5 Summary
• Functional classification
• Cytokines that are involved in innate immune response: IL-1 and TNF-alpha
• Cytokines that induce Th1 (IL-12), Th2 (IL-4), Th17 (IL-23), Treg differentiation
• Th cytokines that promote specific immune response (Th1 cytokines: IFN-g;
Th2 cytokines: IL-4, IL-5; Th17 cytokines: IL-17); IL-2 for both Th1 and Th2.
• Antiviral cytokines: IFN-alpha and IFN-beta
• Chemoattractant (chemokines): IL-8
• Structural classification
• IL-1 family: MyD88/IRAK => NFkB and AP-1
• Class I and Class II cytokine families => JAK-STAT pathway
• TNF family => FasL-Fas/FADD/caspase => apoptosis
• IL-17 family => receptor trimer; inflammation and autoimmune
• Chemokines => GPCR => G-protein signaling => Rho => cytoskeletal
rearrangement
 Lecture 6 Summary
• Antimicrobial proteins (lysozymes) and antimicrobial peptides (defensins)
• Opsonin (mannose-binding lectin); opsonization
• Phagocytosis (phagosomes; lysosomes; ROS; RNS)
• PAMPs and PRRs
• TLRs: LPS/TLR4; viral dsRNA/TLR3; viral ssRNA/TLR7 & 8; bacterial DNA/TLR9
• TLR signaling: MyD88/NFkB; MAPK/AP-1; IRF7 and IRF3 => IFN-a and IFN-b
• Antiviral function of IFN-a/b: binding to IFNAR1/2 => JAK-STAT => antiviral proteins
(Protein kinase R; 2’-5’ oligoA synthetase; Mx proteins) => blocking translation, degrading
mRNA, and inhibit viral transcription and assembly
• Positive feedback and negative feedback
• Bridging innate and adaptive immunity by dendritic cells
• Different TLR signaling received by DCs bias the type of cytokines produced and the type
of Th differentiation induced by DCs.
 Lecture 7 summary

• Organization of the genomic loci (germline version) encoding the light (kappa and
lambda) and heavy chains of Ab and TCR. V-J-C<kappa>, V-J-C<lambda>, and V-D-J-
C<m,d,g,e,a> segments.
• Calculation of antibody diversity based on the combination of V,D,J segments
• 23-bp RSS vs 12-bp RSS
• P nucleotide addition (templated DNA addition)
• TdT adds non-templated nucleotides during VD and DJ recombination
• Enzymes involved in recombination (RAG1/2, TdT, etc)
• Allelic exclusion during V(D)J recombination
• Class switch recombination; secreted vs membrane-bound antibodies
• TCR recombination (ab TCR, major; gd TCR, minor)
 Lecture 8 summary

• Structure of MHC class I and class II molecules

• MHC Class I: antigen binding groove formed by a chain; binds short peptides; closed ends; anchor
residues
• MHC Class II: antigen binding groove formed by a and b chain; binds longer peptides; open ends;
internal conserved residues
• MHC molecules as antigens in tissue compatibility during transplantation; co-dominance
• Self-MHC restriction (TCR recognizes self-MHC presenting foreign antigens)
• Antigen presentation
• MHC class I in endogenous pathway (assembly of MHC class I – peptide in ER)
• MHC class II in exogenous pathway (assembly of MHC class II – peptide in endosome)
• Cross-presentation: DC presents to Th and Tc cells through Class II and I MHC, respectively.
• TCR/CD4 :: MHC class II – peptide; TCR/CD8 :: MHC class I - peptide
• CD1 serves as the MHC for lipid antigen; present to TCR; structurally similar to class I but
functionally similar to class II.
 Lecture 9 Summary
• Humoral immunity vs cellular immunity; antigen specific vs nonspecific cellular immunity
• Four functions of antibody in humoral immunity:
• Neutralization
• Opsonization
• Complement fixation (Complement-dependent cytotoxicity or CDC)
• Antibody-dependent cytotoxicity (ADCC)
• Different functions of different classes of antibodies
• IgM: effective in binding and neutralizing antigens and complement fixation; no ADCC
• IgG: neutralization; opsonization; ADCC
• IgA: in secretions and mucosal surface; cannot fix complement; ADCC
• IgE: allergy and asthma; antiparasitic immunity; degranulation of eosinophils and basophils
• Fc receptors
• FceR => degranulation; FcgR / FcaR => opsonization; FcRn => endothelial cells (maintain serum levels)
• FcgR => ADCC; IgA/IgM::Poly IgR => epithelial cells (transcytosis into secretion)
• Inhibitory Fc receptor: FcgRIIB associated with ITIM; ITIM recruits phosphatase instead of kinase
• Isotypes of antibodies produced by plasma cells depend on the timing of the response and
the type of pathogens (extracellular pathogen => IgM; intracellular pathogen => IgG/IgA)
 Lecture 10 summary
• Cytotoxic T cells (Tc cells):
• Recognition: TCR/MHC class I with peptides
• Killing mechanisms: granzyme & perforin; Fas-FasL interaction
• NK cells:
• Recognition: presence of activating receptor (NKG2D; NCR)
• Recognition: Lack of inhibitory receptor (CD94-NKG2A::HLA-E; KIR2DL::HLC-C)
• Killing mechanisms: Fas-FasL interaction; granzyme & perforin; ADCC
• NKT cells:
• Recognition: semi-invariant TCR recognizing CD1d presenting lipids
• Killing mechanisms: Fas-FasL interaction
 Lecture 11 Summary
• Autograft, isograft, allograft, and xenograft
• Both CD4+ and CD8+ T cells are involved in immune rejection & immune memories
• ABO blood-group compatibility and Histocompatibility (MHC); cross-matching assay
• Direct presentation: Recipient TCR recognizes donor MHC presenting donor peptides
• Indirect presentation: Recipient TCR recognizes recipient MHC presenting donor peptides
• Hyperacute rejection: pre-existing anti-ABO blood group or anti-HLA antibodies
• DTH (Delayed-type hypersensitivity): Overreaction of the helper T cells and
overproduction of cytokines damage tissues, cause inflammation, and cell death.
• Immunosuppressive therapy
• General immunosuppressive therapy: total Lymphoid Irradiation; mitotic inhibitors; Rapamycin
• Corticosteroids: inhibiting the expression of cytokines and pro-inflammatory genes
• Specific immunosuppressive therapy:
• Soluble CTLA-4 fused with Ig
• Anti-CD3; anti-CD40L; anti-IL2R;
• JAK3 inhibitors; Calcineurin inhibitors (FK506)
 Lecture 12 Summary
• Lymphocyte recirculation: T cells in blood => extravasation through HEV and enter lymph node (homing) =>
migrate along FRC to search for DC => if found, being activated and proliferate; if not, exit lymph node and
re-enter circulation (once or twice a day; takes 12-24 hours to complete a cycle)
• Time: One DC scan 120,000 T cells a day; one in 105 T cells can recognize MHC + a particular antigen
• Time: T-DC interaction (1-24 h, including transient interaction: 1-3 h, T cell clustering: 3-16 h; T cell
swarming 16-24h); T cell proliferation (>24 h; 5-6 days; doubling time is 8-11 h during clonal expansion)
• FRC (paracortex; DCs and stromal cells; more stable) vs FDC (follicles; mostly DCs; highly dynamics)
• Antigen-relaying mechanism (C3 complement/CR3 on macrophage => FDR through FcR => B cells)
• B cell travelling route:
• B cell in blood => extravasation through HEV and enter lymph node => travel through FRC first and
then FDC into follicle => BCR search for antigens delivered by FDC
• If find antigens, B cells is activated through BCR signalling => B cell relocate from follicle to T-B
boundary (paracortex-follicle boundary) => B cell present antigen through MHC class II to Th cells and
receive CD40L signalling and cytokine from Th cells => B cell is fully activated and move back to the
center of follicle => plasma cells in germinal center
• If not found, B cells exit lymph node and re-enter circulation
• Tri-cell complex (DC – Th – Tc) for Tc activation; understand the molecular interaction among them)
 Lecture 13 Summary
• Rapid antigen test: detect the presence of antigens with two antibodies
• Immunoagglutination: detect the presence of antibodies against specific antigens in serum
• Hemagglutination inhibition reaction: detect the presence of antibodies against HA (hemagglutinin)
• Immunofluorescence: detect the presence and localization of certain antigens/proteins in tissues and cells
• Immunoprecipitation: isolate and enrich specific proteins from cell lysate or solutions
• Radioimmunoassays (RIA): quantify concentration of proteins in solution (e.g., cytokines and hormones)
through competitive antibody binding.
• ELISA (enzyme linked immunosorbent assay): detect antigens or antibodies in microplates.
• Indirect ELISA: measuring antibody concentration
• Sandwich ELISA: measuring antigen concentration
• Western blot: detect proteins in cells and solution by running the protein mix on a gel
• Surface Plasmon Resonance: measure antigen-antibody affinity
• Flow cytometry: quantify the presence of cell surface proteins (membrane proteins)
• Magnetic cell sorting: isolate cells based on the expression of cell surface proteins
• Analysis of apoptosis: Annexin V staining; TUNEL assay; 51Cr Release (CTL and NK killing); caspase
assay
 Lecture 14 summary
• Monoclonal antibodies (same class; same paratope; recognize the same epitope) vs
polyclonal antibodies (a mixture of Ab classes; different paratopes; recognize different
epitopes of the same antigen)
• Hybridoma technology (HAT medium selection mechanism: B cells are mortal and Thymidine
kinase+; myeloma cells cells are immortal but TK-; only fused cells can survival in HAT)
• Application of mAbs for disease diagnosis
• Application of mAbs for therapy (direct effects; targeting effects; conjugation/cross-linking
effects)
• Humanization of mAbs (murine => chimeric => CDR grafted => fully human)
• Use of mAbs in cancer therapy
• Rituximab (anti-CD20 for B-cell lymphoma)
• Trastuzumab (Herceptin): anti-HER2/EGFR; block signaling transduction and inhibit breast cancer growth
 Lecture 17 Summary
• Tumorigenesis: mutations of pro-oncogenes and/or tumor-suppressor genes
• Tumor-specific antigens (TSAs; mutant proteins unique to tumor cells) and tumor-
associated antigens (TAAs; normal proteins highly expressed in tumors).
• Cancer immunoediting both protects against and promotes tumor growth
• Mechanisms for cancer immune escape (reduced MHC; anti-apoptotic signal; poor
costimulatory signaling)
• DC vaccine (tumor antigen/GM-CSF into DC)
• CAR-T therapy (chimeric antigen receptor; extracellular: scFv binding to cancer
membrane proteins; intracellular: CD3 g chain intracellular domain; CD28 intracellular
domain; 4-1BB (CD137) cytoplasmic domain)
• Immune checkpoint therapy (anti-CTLA4; anti-PD1/PD-L1 therapy)
• CTLA-4 (on T cells) :: CD80/86 (on APC)
• PD1 (on T cells) :: PD-L1 (on tumor cells or APC)
• Use monoclonal antibodies to break the above inhibitory interactions
• Innate immunity vs adaptive immunity
• Cells – Molecules; interactions of cells, interaction of molecules, and signaling pathways
• Innate immunity:
• Cells: macrophages, granulocytes (neutrophils, basophils, master cells, and eosinophils), NK cells
• Molecules: PRR recognizing PAMPs (e.g. TLR4 binds to LPS; TLR3, 7, 8, and 9 binds to viral RNA or DNA);
Type I interferons => antiviral activity; NK killing of target cells: inhibitory receptor (e.g. KIRs, CD94-
NKG2A, recognizing MHC class I), activating receptor (e.g. NKG2D, NCRs)
• Signaling pathways: TLR signaling pathways: MyD88 -> NFkB; TRIF -> -> IRF7 and IRF3 -> IFN-a/b
• Processes: phagocytosis (opsonization, endocytosis, oxidative attack); NK killing of target cells
• Adaptive immunity:
• Cells: T cells (CD4+ T cells, CD8+ T cells); B cells; Three professional APCs: (DC, Macrophages, and B cells).
• Molecules: antibodies (structure, VDJ recombination, switch forms, and function); T cell markers
(TCR/CD3, CD4, CD8, CD28, CD40L, etc); B cell markers (BCR, CD79, CD19, CD21, etc); MHC molecules
(class I and class II MHC molecules); cytokines and chemokines (six classes of cytokines)
• Signaling pathways: TCR/BCR signaling: Lck/Lyn -> ITAM -> PLC -> PIP2 breakdown into DAG and IP3 ->
DAG activates Ras/MAPK pathway/AP-1 and IKK and NF-kB pathway, IP3 induces Ca2+ influx and NFAT;
Cytokine signaling pathways: IL1R -> MyD88 -> TAK -> AP-1 and NF-kB; Class I and II cytokine receptors -
> JAK-STAT pathway; FasL/Fas –interaction -> Caspase-8 -> Caspase-3; chemokine receptor GPCR -> G
protein signaling -> Ras, Rho, PLC, and PKC (Rho activation is involved in cell movement).
• Adaptive immunity:
• Process: CD4+ T-cell activation: MHC class II interaction with TCR; where (paracortex) and how
(antigen presentation)? Th1 vs Th2. Th1 cytokine (IL-2, IFN-g) and Th2 cytokines (IL-4 and IL-5).
Costimulatory signaling: CD40L vs CD40 interactions.
• Process: CD8+ T-cell activation: DC cross-presentation; Class I and Class II MHC interaction with
TCRs; costimulatory signaling: CD40L-CD40; CD28-CD80/86
• Process: B cell activation: where and how? Receive antigen, move the B-T boundary, get
activated by Th2 cells; cytokine support; differentiation into plasma cells (germinal center)
• Process: CD8+ T cell killing of target cells: Perforin/Granzyme; FasL/Fas pathway
• Process: antibodies (four functions of antibodies: neutralization, opsonization, CDC, ADCC)
• Application of immunology:
• Transplantation immunology: immune rejection; direct and indirect presentation
• Antibodies: quantitative measurements of hormones (RIA; ELISA; western blot;
immunofluorescence; agglutination assays; flow cytometry assays); pregnancy test; epitopes;
anti-antibody antibodies;
• Generation of monoclonal antibodies (HAT medium selection)
• Cancer immunotherapy: monoclonal antibodies; DC vaccine, adaptive transfer, CAR-T, and anti-
PD1 and anti-CTLA4 treatment