Immunology Flashcards

Question 1

Q

What is the function of IFN-α and IFN-β:

Answer

A

Released by phagocytes in response to TLR-3 binding viral dsRNA

o Protects uninfected cells (inhibits translation of viral mRNA)
o Activates NK cells (kill virus infected cells)
o Increase expression of MHC class I (promote killing by Tc cells)

Question 2

Q

What is the function of IFN-γ:

Answer

A

Produced by TH1 cells
o Activates macrophages and NK cells
o Upregulates MHC class II and class I
o Induces B cells to produce IgG3 (complement)
o Stimulates the Delayed Hypersensitivity Response (and thus takes a role in graft rejection)
o Inhibits formation of TH2 and TH17 cells
- Involved in class switching
- Inhibited by cyclosporine (also inhibits calcneuronin) and tacrolimus
- Produced by NK cells (dr. Kong lecture)

Question 3

Q

What is the function of IL-1?

Answer

A

PROINFLAMMATORY
Released by activated macrophages; released by dendritic cells in response to uptake of infectious agents
o Local: activates endothelium and lymphocytes by increasing expression of LFA-1 integrin so that lymphocytes/WBC can bind to endothelium and migrate into blood vessel
o Systemic: induces fever and stimulates IL-6 production

Question 4

Q

What is the function of IL-2

Answer

A

o Growth factor for T cells (CD4, CD8) and NK cells
o Produced by CD4+ cells (TH1) and SOME CD8+ cells

o Interaction of CD28 (T cells) and B7 (APCs) stimulates T cell and its production of IL2 (by increasing transcription and halflife of IL-2 mRNA)

o Production decreased by interaction of CTLA4 and B7
o Inhibited by cyclosporine (inhibits calcneuronin which then leads to less NFAT transcription factor and thus less IL-2) and tacrolimus

Question 5

Q

What is the function of IL-3?

Answer

A

-Macrophage differentiation in the bone marrow (similar to GM-CSF)

Question 6

Q

What is the function of IL-4?

Answer

A

Parasitic worms and allergens stimulate synthesis of IL-4, promoting formation of TH2 cells
-TH2 cells release IL-4
o Induces B cells to produce IgE and IgG4 (along with IL-13)
o Prevents development of TH1 and TH17 cells
Involved in class switching
IL4 gene cluster possibly involved in genetic component of allergy
Released as a preformed substance from mast cells during type I hypersensitivity
Inhibited by cyclosporine and tacrolimus

Question 7

Q

What is the function of IL-5?

Answer

A

Released by TH2 cells
o Growth factor for eosinophils
Released as a preformed substance by mast cells during type I hypersensitivity

Question 8

Q

What is the function of IL-6?

Answer

A

Released by activated macrophages
o Local: activates lymphocytes and increases Ab production
o Systemic: induces fever; induces liver to produce acute phase proteins (CRP, MBL, SPA, SPB-opsonize bacteria, activate complement)

Question 9

Q

What is the function of IL-7?

Answer

A

Required for development of B cells from stem cells (along with stromal cells)
Required for development of T cells in the thymus (along with contact from dendritic and epithelial cells)

Question 10

Q

What is the function of IL-8

Answer

A

Released by activated macrophages
o Chemokine that attracts PMNs, basophils and T cells
Released as a preformed substance in mast cell granules during Type I hypersensitivity
o Chemokine that attracts PMNs

Question 11

Q

What is the function of IL-10?

Answer

A

Release of IL-10 + TGF-β by Treg cells suppresses the formation of TH1, TH2 and TH17 cells

Question 12

Q

What is the function of IL-12?

Answer

A

Released by activated macrophages; released by dendritic cells in response to uptake of infectious agents
o Activates NK cells (kill virus infected and tumor cells; cells that are deficient in MHC I)
o Induces CD4+ TH0 cells to become TH1 cells

Question 13

Q

What is the function of IL-13?

Answer

A

Released by TH2 cells

o Induces B cells to produce IgE and IgG4 (along with IL-4)

Question 14

Q

What is the function of IL-17 + IL-22?

Answer

A

Released by TH17 cells
o Recruit and activate PMNs
o Induce epithelial cells to produce proinflammatory cytokines (IL1, IL6, TNFα)

Question 15

Q

What is the function of IL-21?

Answer

A

Release of IL-21 + TGF-β by dendritic cells leads to formation of TH17 cells

Question 16

Q

What is the function of TGF-B

Answer

A

Release of IL-21 + TGF-β by dendritic cells leads to formation of TH17 cells
Release of TGF-β alone by dendritic cells leads to formation of Treg cells
Treg cells release TGF-β + IL-10 to suppress the formation of TH1, TH2, and TH17 cells
Activated TH2 cells released TGF-β, IL-4 and IL-10 [discrepancy between Kong and Sundick]
Can be secreted by tumor cells in tumor-induced immunosuppression (suppress T cell function)

Question 17

Q

What cytokines cause upregulation of MHC I? MHC II?

Answer

A

MHC I = IFN A, B, G, TNF-A, TNF-B

MHC I = IFN - G

Question 18

Q

What is the function of TNF -A

Answer

A

PROINFLAMMATORY
Released by activated macrophages; released by dendritic cells in response to uptake of infectious agents
o Local: activates vascular endothelium by inducing adhesion molecules- selectins (E), ICAMs (E), integrins (L); induce permeability (promotes diapedesis)
o Systemic: fever and shock
Produced by NK cells (Kong’s Tumor Immunity lecture)

Question 19

Q

What is the function of TNF-B

Answer

A

Promotes diapedesis of fresh macrophages to site of infection
Released by activated TH1 cells in delayed-type hypersensitivity reaction against tissue grafts (cytotoxic to graft)

Question 20

Q

What is the function of GM-CSF?

Answer

A

Released as a preformed substance by mast cells during type I hypersensitivity
Macrophage differentiation in bone marrow

Question 21

Q

What is the function of 5a?

Answer

A

chemotactic factor for PMNs; vasoactive; activate mast cells

Question 22

Q

What is the function of 3a?

Answer

A

vasoactive; activate mast cells

Question 23

Q

What is the function of C2b?

Answer

A

buildup causes swelling (as seen in C1 inhibitor deficiency- hereditary angioneurotic edema)

Question 24

Q

What is the function of ECF?

Answer

A

eosinophilic chemotactic factor; preformed substance in mast cells

Question 25

Q

What is the function of thromboxane/Prostaglandins?

Answer

A

chemotactic for PMNs and eosinophils

Question 26

Q

What cell markers can be found on the T-cell and what are their functions?

Answer

A

• TCR Complex:
o TCR: heterodimer Ag-specific receptor (first signal necessary to activate T cells)
o CD3: pan T cell marker; signal transduction, transports TCR to cytoplasmic membrane; invariant
o Zeta chains (2): signal transduction; invariant
• CD2: pan T cell marker; lymphocyte adherence and signaling
• Integrins (LFA-1 and VLA-4): adherence to APC and endothelial cell
• CD62L/L-Selectin: homing molecule that binds addressins on the endothelium; facilitates migration of T cell into LN
• ICOS: interacts with ICOSL on B cell; facilitates germinal center formation in LNs and other lymphoid tissue
• CD4: on Th cells; stabilizes binding and involved in signaling
• CD8: on Tc cells; stabilizes binding and involved in signaling
• CD28: binds B7 on APC (required for activation of T cell)
• CTLA4/CD154: upregulated in activated T cells; interaction with B7 on APC shuts down T cell
• Class I MHC: on all nucleated cells
• FasL: on CD8+ T cells; allows for killing of Fas+ cells
• CCL2 (MCP-1): allows for migration of TH1 cells to site of infection

Question 27

Q

What is the function of CD3?

Answer

A

pan T cell marker; signal transduction, transports TCR to cytoplasmic membrane; invariant

Question 28

Q

What are the cell markers found on B-cells? What are each of their functions?

Answer

A

• BCR: Ig + Igα and Igβ (signal transduction molecules associated with the Ig H chain)
• B-Cell Co-Receptor:
- CD21: binds C3dg (cleavage product of C3b) on bacteria to increase Ag signaling 100x; also a receptor for the Epstein Barr Virus
- CD19
- CD81
• CD22: downregulate B cell activity
• CD32: downregulate B cell activity (bind Ag-Ab complexes)
• CD5: on the surface of B-1 cells
• B7: interacts with CD280 (stimulation) or CTLA4 (inhibition) on T cells
• CD40: interacts with CD40L on T cells to allow for Ab class switching
• FcR: receptor for Fc portion of Igs (one for each class); delivers signal to B cell
- MHC molecules

Question 29

Q

Differentiate between MHC Class I and MHC Class II

Answer

A

• Class I MHC: on all nucleated cells

3 loci (A,B,C) encode alpha chain only
Alpha chain combines with invariant beta-2 microglobulin
Alpha3 domain interacts with CD8 on T cells
Alpha1 and 2 domains form CLOSED peptide binding groove (8-9 aa)

•Class II MHC: on APCs

3 loci (DP, DQ, DR) encode both alpha and beta chains
Beta2 domain interacts with CD4 on T cells
Alpha1 and Beta1 domains form OPEN peptide binding groove (12-20 aa)

Question 30

Q

What are the different receptors that can be found on Phagocytes? What does each one bind?

Answer

A

Mannose-Binding Lectin Receptor: binds MBL bound to mannose on bacterial surface (increases binding affinity)
Mannose Receptor: binds mannose on surface of bacteria
Surfactant Protein A and D Receptors: binds SPA/SPD bound to bacteria (increases binding affinity)
Scavenger Receptors: react with lipoproteins
fMet-Leu-Phe (N-formylated peptides) Receptor: receptor for these peptides, which are chemotactic factors for phagocytes
Toll-Like Receptors:

Question 31

Q

What are the different Toll-Like Receptors and their functions? what cells have TLRs?

Answer

A

found on phagocytes;
o TLR-4: binds bacterial LPS and triggers activation of NFkB (genes transcribed to fight bacteria)
o TLR-3: binds viral dsRNA triggering synthesis of IFN alpha and beta
o TLR-5: bacterial flagellin
o TLR-9: unmethylated CpG DNA
o TLR1:TLR2 heterodimer: peptidoglycan and zymosan

Question 32

Q

What marker is found on lymphocytes that is important in immune responses?

Answer

A

Integrins (ie: LFA-1?) : bind ICAMs on endothelium and APC (strong binding)

Question 33

Q

What are some examples of Type I sensitivity reactions?

Answer

A

Systemic anaphylaxis
Allergic rhinitis
Asthma
Food allergies

Question 34

Q

What are some examples of Type II sensitivity reactions?

Answer

A

ABO/Rh incompatability reaction
Myastenia gravis
Grave’s Disease
Penicillin drug allergy (can also be IgE mediated-type I)

Question 35

Q

What are some examples of Type III sensitivity reactions?

Answer

A

Serum sickness
Arthus reaction
SLE
Rhematoid arthritis

Question 36

Q

What are some examples of Type IV sensitivity reactions?

Answer

A

Posion ivy (contact dermatitis)
Tuberculin rejection
Graft rejection
Hashimoto’s Thyroiditis
Multiple Sclerosis
IDDM

Question 37

Q

What are the different types of transplant grafts and what is the donor source for each type?

Answer

A

Allograft: self (from a different part of the body)
Synergic: from a genetically identical twin
Allogenic: w/in the same species, but not genetically identical (ie: any other human but a twin)
Xenogenic: from a different species

Question 38

Q

What are the two types of graft rejection and how are they mediated? What are some key features of tissue rejection?

Answer

A

First Set Rejection: 1st time you see something: 7-10 days post transplant rejection occurs
Second Set Rejection: the second time you are grafted with the same source: 2-3 days layer; much faster “memory” type response

Rejection occurs by: 1. Foreign alloantigen is recognized 2. memory cells (adaptive immunity) generate and remember the alloAg

GRAFT REJECTION CAN BE ADOPTIVELY TRANSFERRED if you transfer the lymphocytes (serum) of the first mouse that rejected the graft into a new mouse that hasn’t been exposed to the graft yet, the second mouse will respond like a second set rejection (fast)

Question 39

Q

What genes are associated with MHC Class I? MHC II?

Answer

A

MHC I: HLA -A, B, C to CD 8+ T cells
MHC II: HLA- DR, DP, DQ to CD4+ Tcells

the genes are codominantly (both mom and dad) expressed; and they are the most polymorphic genes in the human genome
**MHC I peptide is SHORTER than MHC II peptide binding site

Question 40

Q

What is the difference between direct presentation and indirect presentation with respect to transplantation?

Answer

A

Direct Presentation = the donor’s APC presents the UNPROCESSED allogenic MHC to the Host T-Cell (Self MHC recognizes struture of an intact MHC molecule of the graft); involves BOTH CD 8+ and CD4+

Indirect: HOST APC presents a PROCESSED peptide of the allogenic MHC to the host T-cell; (host sees MHC as foreign Ag and handles it like any other foreign Ag–it presents it on the host APC); ONLY INVOLVES CD4+ (presented by MHC II of the host APC)

Question 41

Q

What is needed to activate alloreactive T-Cells?

Answer

A

Presentation of donor MHC as ‘foreign Ag’ (direct/indirect)
Stimulation: APC MHC –> TCR
Costimulation via:
(**APC MOLECULES WRITTEN FIRST):
B7/CD28
CD40/CD40L
LFA-3/CD2
ICAM/LFA-1
Release of cytokines from APC to simulate Tcell: IL-12, IL-18

** If no costimulation occurs then CTLA4 is expressed and induces clonal anergy

Question 42

Q

What is the mixed lymphocyte reaction? What is the purpose of it and how is it performed? How is it different from cell mediated lympholysis (CML) ?

Answer

A

Both: Measure of how compatible two people are for transplant by seeing how reactive their T-Cells are – “In vitro test of T-Cell Regulation of allogenic MHC”

MLR:
Simulators = donor irradiated mononuclear cells (treated with mitomycin C to make the cells mitotically inactive)
Responders = recipient mononuclear cell
Measure: proliferative response of responders
Mix inactive donor cells with blood mononuclear cells of recipient to see if normal T-cell function occurs; if so the recipient views the donor cells as “foreign”, and donor/recipient are of different MHC II Class; donor acts as the Ag and Recipient as the normal functioning immune system;
You add Radioactive Thymidine and see if there is any cell proliferation and DNA Synthesis; If there is this indicates that CD4+ proliferated … MEASURE OF MITOGENESIS (suggest that MHC’s are incompatible)

CML:
Basically the same thing, except you measure cell lysis instead of mitogenesis; a measure of CTL mediated response (and that MHC I are incompatible)

Question 43

Q

What are the three types of allograft rejection mechanisms?

Answer

A

Hyper-acute Rejection
Acute Rejection
Chronic Rejection

Question 44

Q

What are the characteristics of Hyperacute Rejection in solid organ transplants? In bone marrow transplants?

Answer

A

DOESN”T EXIST IN BONE MARROW TRANSPLANTS!
For solid organ transplants: its the fastest mediated response– within minutes/hours

** Due to PRE-EXISTING IgG (due to a history of blood transfusions, transplantations, or multiple pregnancies); activates the complements system, inflammation, thrombosis, and epithelial damage

Question 45

Q

What are the characteristics of Acute Rejection in solid organ transplants? In bone marrow transplants?

Answer

A

Response occurs within a few days
Solid organ: due to CD4+ and CD8+, Ab response; causes parenchymal damage and inflammation (endothelitis)

Bone Marrow: due to Host NK causing lysis of donor stem cells

Question 46

Q

What are the characteristics of Hyperacute Rejection in solid organ transplants? In bone marrow transplants?

Answer

A

Response occurs up to 6 mo (BM) or 1 year (SO) post transplant
Solid Organ: due to CD4+ (TH2), CD8+, MACROPHAGES; causes chronic fibrosis + atherosclerosis and chronic DTH reaction in vessel wall and SMC

Bone Marrow: due to autologous CD4+ and CD8+ lysing donor stem cells

Question 47

Q

What cytokines play a role in graft rejection and how?

Answer

A

IL -2: promote T-cell proliferation and generation of TH1
IFN-G: Increase MHC I and II expression and promote delayed hypersensitive response
TNF B: cytotoxicity to graft
IFN A, B, G, TNF A, B = all upregulate MHC I expression
IFN G also upregulates MHC II

Question 48

Q

What types of organs can be transplanted and what is the relative survival rates?

Answer

A

Kidney > Heart > Pancreas > liver > lung
Skin can also be grafted
Need to be immunosuppressed because a lot of time they aren’t MHC matched

Question 49

Q

What is the most tolerated allograft and why?

Answer

A

Fetus;
Fetal trophoblasts DO NOT express MHC I or MHC II
Only express HLA-G (Class Ib) which is actually used as a ligand for KIR to prevent maternal NK from killing the fetus

Question 50

Q

What are the transcription factors that promote IL-2 transcription?

Answer

A

NF-kB, NFAT, AP-1

Question 51

Q

What are some of the ways that allograft rejection is prevented (and describe the qualities of each method)

Answer

A

MHC allele close matching
ABO Compatibility: to prevent hyper acute rejection in solid tumors and transfusions in BM/PBSC
Calnineurin Inhibitor: causes inhibition of NFAT and thus inhibition of IL-2 transcription so T-Cells aren’t proliferating and inducing an immune response; aka cyclosporine immunosuppressant
IMPDH inhibitor (inosine monophosphate dehydrogenase): inhibits guanosine nucleotide synthesis

Question 52

Q

B cell deficiencies have an increased susceptibility for infections from ___.

Answer

A

bacterial infections with high grade extracellular encapsulated pathogens;
Ex: otitis media, pneumonia

Question 53

Q

T cell deficiencies have an increased susceptibility for infections from ___.

Answer

A

low grade oppotunistic fungus, virus, protozoa; Ex: pneumocystic carni infection

Question 54

Q

B + T cell deficiencies have an increased susceptibility for infections from ___.

Answer

A

virus, fungus, protozoa, braceria

Question 55

Q

Phagocyte deficiencies have an increased susceptibility for infections from ___.

Answer

A

systemic infection of bacteria of LOW VIRULANCE, superficial skin infections, infection w/pyogenic organisms, impaired pus formation and wound healing

Question 56

Q

NK deficiencies have an increased susceptibility for infections from ___.

Answer

A

viral infections; associated with several T-Cell disorders and X-lymphoproliferative diseases

Question 57

Q

Complement activating deficiencies have an increased susceptibility for infections from ___.

Answer

A

pyogenic micro-organisms, bacterial infections, autoimmunity
**difficult to differentiate between B-Cell deficiencies; thus look at B-cells def first (more prevalent) and if not then test for complement component

Question 58

Q

What are the characteristics/cause of DiGeorge (congenital thymic aplasia) syndrome/?

Answer

A

Chromosome 22q11 deletion leads to no thymus formation;
Extreme immuno-suppressed because NO T-CELLS;
Have certain facial characteristics (fish lips, low ears) and heart defects (great vessels) which leads to surgery and thats how they first realize there isnt a thymus; then they do flow cytometry on the cells using ANTI-CD3 ANTIBODY to check for T-Cells (CD3 = pan marker of all T-Cells)

Question 59

Q

What are the characteristics/cause of chronic mucocutaneous candidiasis?

Answer

A

Normal T-Cell function EXCEPT for candida albincans (a fungus) thus frequent infections by it

Question 60

Q

What are the characteristics/cause of X-Linked SCID?

Answer

A

No transcription factor for the Gamma-Chain of IL-2, 4, 7, 9, 15;
NO T -CELLS present which leads to decreased (to no) B-cells functioning

Question 61

Q

What are the characteristics/cause of autosomal SCID?

Answer

A

JAK3 Tyr Kinase mutation results in no activation of Gamma-Chain of IL-2, 4, 7, 9, 15;
Presents just like X-SCID except it isn’t linked to the X-chromo
NO T -CELLS present which leads to decreased (to no) B-cells functioning

Question 62

Q

What are the characteristics/cause of ADA deficiency?

Answer

A

No Adenosine deaminase, resulting in toxic amounts of ATP and dATP in B and T cells so then they can’t form properly.. results in NO B or T cells (aka bubble boy until they get a bone marrow transplant)

Question 63

Q

What are the characteristics/cause of PNP deficiency?

Answer

A

Autosomal recessive; no PNP enzyme so it presents just like ADA deficiency (NO B OR T CELLS)

Question 64

Q

What are the characteristics/cause of Recombinase deficiency?

Answer

A

Mutation in RAG-1 and RAG-2 leads to no gene rearrangement of B or T cells and thus these cells stay in the pre-B/pre-T cell state

Answer 65

A

Problem with MHC due to TAP (transporter protein) gene mutation
Type I: No MHC I– ASYMPTOMATIC; just a decrease in CD8+
Type II: No MHC II: No presentation of Ag to T or B cells so effectively NO B OR T FUNCTIONING

“T + B+”

Answer 66

A

No signal cascade that TCR is bound to a peptide; thus NO CD8+ T-Cell! All CD4+ T-cells in circulation, but they are unresponsive and thus B-Cell functioning is also decreased
NO B OR T CELLS basically;

“T + B+”

Answer 67

A

Neurodisease due to INABILITY TO REPAIR DNA/CHROMOSOMAL BREAKS IN IG CELLS;
Result = decreased functioning in T cells; decreased concentration of IgA, IgE, and some IgG

Answer 68

A

X-linked; 3 hallmark features:
1. Thrombocytopenia
2. eczema
3. recurrent pyogenic bacterial infections
causing otitis media, meningitis, pneumonia, from normally low virulent organisms;

T Cell response = ineffective (signaling pathway screwed up) and decreased IgM

Answer 69

A

due to X-linked BTK Brutun Tyrosine Kinase mutation resulting in so signal that the pre-B cell is mature (and has H chain bound) and so the cell can start making L chain; thus all B-cells are stuck in the pre-B state

realize at 6 mo that baby has no IgG (because at this point it used up all of moms IgG passed down)

Answer 70

A

NOT X LINKED; usually in pre-mature babies until age 2 and then resolves
serum IgM, IgA and B-cells = normal
IgG = lost (and thus T-cell function also decreases)

Answer 71

A

Unknown causes of B-cells not maturing into Ab secreting cells (@ 15-35 y/o)

Answer 72

A

MOST COMMON B-CELL DEFICIENCY!
unknown cause
NO MAJOR Sx; but its important for individuals to know that they have the disease because if they get a blood transfusion they could react with an immune response to the transfused IgA

Answer 73

A

recurrent infection by POLYSACCHARIDE ENCAPSULATED ORGANISMS like pneumococci and the flu

Answer 74

A

NO CD40L (CD154) on T-Cells so there is no isotype switching of B-cells resulting in high IgM but low IgG, IgA, IgE; 
Sx = recurrent resp infection
***Sx present like a B-Cell deficiency (low Igs) but really it caused by a T-Cell deficiency!!

Answer 75

A

due to T-cell failure to regulate B-cell Growth

Result = Bcell lymphoma (usually occurs after EBV-infection) ie: Burkitts lymphoma

Answer 76

A

Normal: ***ALL MEDIATED BY IL-8

E-selectin on epi binds to PMN = weak, slow “roll” down epi cells
ICAM on epi binds to integrin on PMN = strong; PMN stops
diapedesis
Migration to infection
LAD I: mutation for CD 18 INTEGRIN: results in NO ICAM (stopping) bonding and WBC doesn’t adhere or migrate into tissue
LAD II: mutation in SELECTIN on WBC (which thus can’t bind to E-Selectin on epi) so WBC doesn’t slow down or migrate

Answer 77

A

monocytes do not respond to IFN gamma with TNF-Alpha secretion thus increase in myobacterial infection

Answer 78

A

Autosommal recessive;

Microtubiles and lysosomal defect in which they can’t release enzyme and lyse bacteria after phagocytosis

Answer 79

A

= NADPH Oxidase Deficiency
Peroxidase not generated and thus no oxygen free radial to digest catalase + phagocyted bacteria; thus the bacteria just stays inside the phagocyte (alive and able to multiply)

Nitoblue Tetrazolium (NBT) Test: if -  (purple) = can oxidize; thus don't have the disease
if blue = +; cannot oxidize; thus have the disease

Answer 80

A

Early components (C1, C4, C2) = problem with capsulated organelle ingestion
Middle component (C3) = rhuematic disaese (esp SLE)
Late components (C5-C9, MAC) Neisseria infections

Answer 81

A

Lack of C1 esterase inhibitor (C1INH) causing uncontrolled production of vasoactive peptides and local edema

Answer 82

A

Deficiency in Decay Accelerating Factor (DAF) results in increased sensitivity to complement mediated lysis of RBC (occurs at night mainly)

Answer 83

A

TREC assay to see if they have T-Cells (confirm with flow cytometry) and make treatment decision (ie: BM transplant)

Answer 84

A

tumor cells are formed in normal individuals and then destroyed by the normal immune cells; the immune system can recognize and destroy nascent transformed cells

Answer 85

A

Immune system kills and induces changes in the tumor that can result in tumor escape and reoccurance

Answer 86

A

mutation
gene amplification
clonal mutation

Answer 87

A

Because they are:

foreign
Hig molecular weight
Complex chemically
Degradable and so can be presented by MHC

Answer 88

A

We have a repertoire of T-cells with low affinity agains self proteins (due to positive/negative selection) in the thymus; thus expression of altered self proteins by tumors increases the affinity of T-Cells for the tumor Ag

Answer 89

A

Spontaneous Regression (melanoma, lymphoma)
Regression of metastases after removal of 1’ tumor (pulmonary metastases from RCC)
Inflitration of tumor by macrophages/lymphocytes (breast cancer, melanoma)
Lymphocyte proliferation in the draining lymph node
Increased incidence of cancer following immunosuppression, immunodeficiency, aging, etc.

Answer 90

A

A tumor Ag that was present on fetal cells, but disappears with normal adult cells, then reappears (ie: prostate cancer, colo-rectal cancer)

Answer 91

A

Tumor Ag on normal cells, but overexpressed

Answer 92

A

virus that transforms normal cells into cancerous (HPV –> cervical cancer)

Answer 93

A

Substance that activates normal genes into a tumor
lacks cross reactivity in physically or chemically induced tumors
responsible for clonal amplificiation

Answer 94

A

damages/mutates DNA;
Melanoma = metastatic, highly immunogenic, spontaneous rejection
Nonmelanoma = BCC (rarely spreads), Squamous CC(can spread)

Answer 95

A

Free radicals + other oxidants ‘steal’ electrons from DNA leading to cancer;
Anti-oxidants (vit A/C)

Answer 96

A

highly immunogenic because of viral antigen;
DNA viruses = papova (papilloma, Hepatitis, EBV)
RNA viruses: retrovirus (Human T-Lymphotropic disease causes T-Cell leukemia)

Answer 97

A

Act as an antigen
- self Ag gets mutated to act as a foreign Ag
- viral Ag act as molecular mimcry of a self Ag
- can express a ‘hidden’ epitope
Expression of costimulatory molecule in tumors (or cross presentation of tumor Ag by APC —- exogenous Ag causes CD 8+ effector)

Answer 98

A

NK cells: when MHC I is low, they bind and lyse the tumor; secreted TNF Alpha (+ hemorrhage and tumor necrosis)
gamma-delta T cells
NKT Cells
Macrophages/Neutrophils: Ag specific Tcell becomes activated by the tumor Ag, and causes release of cytokinds including IFN gamma to activate macrophages and make them highly toxic; macrophages damage/kill the tumor by releasing lysosomal enzymes and TNF-alpha
* *increased tumor resistance accompanies increased number of activated macrophages

Answer 99

A

Ab-mediated: leads to opsonization and Ab dependent cell-mediated cytotoxicity
B-Cell blocking: Anti-IL2R ab displaces IL-2 at the IL-2 receptor and causes decreased T-Cell production (in T-Cell leukemia)
T-Cells: CD8+ release IFN-Alpha and TNF for virally induced tumors; CD4+ induces/regulates CD8+

Answer 100

A

TGF - B = + tumor growth due to angiogenic and immunosuppressive properties
TNF-A = + inflammation
IFN-G = upregulated MHC I and MHC II on tumors

Answer 101

A

Tumor fails to provide Ag Target (due to no tumor Ag, No MHC I, antigenic masking of tumor, poor Ag processing, OR resistance of tumor to tumoricdal pathway)
Tumor fails to induce effective immune response (No antigenic epitopes, decreased MHC or tumor Ag expression, no costimulatory signal, tumor produces negative response, shedding of tumor Ag, tolerance induction, t-cell signaling defects by tumor )
Host fails to respond

Answer 102

A

= pathologic condition resulting from failure of tolernace mechanism to self antigens (damage of self tissues):

self reactive and foreign reactive cells arise from the SAME POOL of lymphocytes (no specific that is more/less prone to autoimmunity)
autoimmune pathogenesis resembles that of invading pathogen
Both T cells and Ab mediate the response (although some lean more towards one mediator than another)

Answer 103

A

according to their immune mechanism or via target of attack
Organ-specific = targeting Ag expressed within a particular organ; usually Cell mediated immune response
Systemic = pathology not limited to a single organ; generally associated with humoral response

**note some AI diseases can involve both cellular and Ab

Answer 104

A

MHC genes = best indications of genetic contribution/susceptibility for disease

Other non-MHC genes that affect:

genes related to Ag clearance and presentation (ie: AIRE.. expressed in the thymus activated negative selection and deletion of autoreactive cells)
genes associated with cell signaling
genes associated with co-stim molecules (CTLA-4)
genes associated apoptosis (Fas/FasL.. if not expressed, then no apoptosis and then increased AI response)
genes related to Treg development (Foxp3)

Answer 105

A

Geographic: incidence in the northern hemisphere = higher in north than south (*MS if you move from north to south before age 12, then you assume risk of south)
Infection: inflammation and expression of co-stim molecules break tolerance to self-antigens (some viral infections exacerbate/stimulate AI response)
Anatomical injury: release of immune privileged site Ag
Hormonal: incidence of AI is higher in women (perhaps estrogen plays a role?)
Exposure to radiation, drugs, and toxins (sometimes transient sx that go away after drug removed; UV light stimulates SLE flares)

Answer 106

A

General:

Autoantibodies agains Ach Receptor of NMJ blocks the transmission of nerve impulses = sever muscle weakness
Affects at any age, predominantly FEMALES AGE 20s (3:2 F:M) or males age 50s

Genetics:
HLA-DR3

Diagnostic Features:

FATIGUE
abnormal chewing, talking, swallowing, breathing, eye movement (muscle movements that may present)

Pathogenesis:
Auto-Ab agains Ach Receptor, so Ach can’t bind; also can destroy the ACh receptor by complement fixation (formation of immune complex)
PURELY Ab DEPENDENT DISEASE (Auto Ab can transfer the disease)

Treatments:
Acetylcholinesterase inhibitors, immunosuppressants

Animal Model
Animals immunized with ACh receptors purified from torpedo fish or electric eel to generate symptoms

Answer 107

A

General:
-Women 20-40 y/o (10F:1M)

Genetics:

increased risk among family members
HLA-DR2, DR3 associated

Diagnostic Feature:

skin rash (malar)
joint pain
kideny lesions = primary cause of mortality

Pathogenesis:

IgG autoAb agains constituents of cell surfaces, cytoplasm, nucleus (since IgG of high affinity, implies involvement of T Cells);
usually anti-nuclear antibodies (ANA) such as anti-dsDNA that form immune complexes
location of immune complex dictates the location of disease presentation: skin = sensitive to UV light (rash), joints = non erosive arthritis, kidney = glomerularnephritis

Treatment:

Too many Ag so you can’t remove the Ag or target it
Mainly just immunosuppression of B and T cells

Answer 108

A

General:

Thyroid gland produces thryoid hormones thyroglobulin which is the precursor of T3 (triiodthyronine) and T4 (thyroxine) for regulation of cellular metabolism
6F:1M

Genetics:
DR3, DR5

Diagnostic features:
LOW thyroid hormones (T3, T4)
High TSH due to feedback regulation
High anti-thyroglobulin and anti-thyroid peroxidase Ab
Sx = dry skin, brittle hair and nails, weight GAIN, depression, extreme depression

Pathogenesis:
AutoAb to thyroid peroxidase and thyroglobulin cause Ab-mediated destruction of thyroid gland; T-Cells also contribute via + macrophages, CD8 cells destroy follicular cells

Treatments:
Thyroid hormone for life

Answer 109

A

General:
primarily affects North American and European whites
2.5F: 1 M

Genetics:

Familial aggregation
HLA-DR2

Diagnostic features:
Muscle weakness including: paralysis, urinary incontinence, vision functions, difficulties with coordination and balance, problems in speech/swallowing
-can take on a slow progressive course, or a relapse/remission course

Pathogenesis:
Demyelination of the myelin sheath around neurons which forms plaques on MRI (white matter);
Mediated by CD4+ TH1 cells that secrete IFN-G and TH17 that secrete IL-17; oligoclonal IgG is present in CSF but unclear function of B-Cells;
AutoAg = components of the myelin sheath:
Myelin Basic Protein (MBP), Proteolipid Protein (PLP), Myelin Oligodendrocyte glycoprotein (MOG)

Treatments:

INF-B = non-specific anti-inflammatory molecule that inhibits the T-Cells from being activated, so they can’t enter the CNS
Copaxone = resembles MBP and has neuroprotective properties
Tysabri = Anti-integrin monoclonal Ab that prevents Tcell migration to brain and spinal cord

Animal model = Experimental autoimmune encephomyelitis (EAE)

Answer 110

A

General: AI of pancreas
NO GENDER BIAS

Genetics:
HLA-DR3/4 heterzygous

Diagnostic Features:

Hyperglycemia, increased hunger, frequent urination, and excessive thirst;
weight loss, nausea, fatigue

Pathogenesis:
AutoAb against cytoplasmic islet cell Ag generated;
Chronitc inflammatory destruction of the Insulin producing B-cells in the islet of Langerhans causing little/no insulin production
- CD8+ cause B-cell destruction
-Cytokines include: IL-1, IL-6, IFN-A

Treatment
Lifelong insulin (2+ injections a day)

Animal Models
Nonobese diabetic mouse (NOD)

Answer 111

A

General:
Most common rhuematic disease in US
3F:1M

Genetic
HLA-DR1 HLA-DR4

Diagnostic feature
Sx = pain, swelling, and stiffness of joints

Pathogenesis:

Affects primarily peripheral synovial joints
Previous theory: RF = IgM that binds to IgG forming immune complexes that deposit in the joints; but 30% of pt dont have detectable levels of RF
Synovium is densely packed with dendritic cells, macrophages, T/B cells, NK, and plasma cells;
some autoAg stimulates a CD4+ cell which produces IFN-G and IL-17 to induce activation of synovial macrophages and fibroblasts; macrophages secrete IL-1 and TNF-alpha causing tissue damage and destroy the integrity of the catilage
Suspected Ag = type II collage, proteoglycan, heat shock proteins

Treatments

NSAIDs
anti-TNF-A (infliximab)
anti-CD20 (rituximab) on B-cells
nonbiologic and biologic disease modifying antirheumatic drugs
immunosuppressants
corticosteroids

Answer 112

A

Sequestered Ag not exposed to selection during tolerance induction– absence of low concentrations of self Ag escaping negative selection
Pathogens as trigger of autoimmune disease via molecular mimcry, heat shock proteins (homology between some HSP and self proteins is so similar, that immune system thinks self are HSP!)
Superantigen as a polyclonal activator of autoreactive T cells (superAg are unprocessed and stimulate all T-cells that have a certain TCR V-B gene segment; thus some of these T-cells activated could be self-Tcells)

Answer 113

A

Replacement Therapies (ie: insulin for TIDM, thyroid hormone for HT)
Immunosuppressant drugs (corticosteroids, cyclosporine for Tcell signaling/IL-2, NSAIDs, cytokine inhibitors)
Monoclonal Ab to block accessory molecules/signal molecules
Altered Peptide Ligands– to interact with TCR instead of peptide (induces clonal anergy)
Oral tolerance
Bone Marrow/tissue transplant

Answer 114

A

Genetics:
HLA DR3

Diagnostic Feature:
Hyperthyroidism, Goiter

Pathogenesis:
AutoAb to TSH receptor (acts as a TSH agonist without any feedback control)
Thyroid produces thyroid hormones with TSH binds to receptors on epithelial cells;
AutoAb to TSH receptors also induce production of T3 and T4, thus bypassing normal Feedback inhibition mechanisms resulting in excess thyroid homorne

Answer 115

A

State of indifference/non-reactivity towards a substance that would normally be expected to excite an immunological response

Tolerance is immunologically specific
Immature or developing lymphocytes are more susceptible to tolerance induction than are mature or functionally competent cells
Tolerance to foreign antigen is induced even in mature lymphocytes when these cells are exposed to Ag under particular conditions

Answer 116

A

Self Ag
suppresion of Allergic rx
allowing chronic infectin instead of rejection and elimination
preventing attack of fetuses by maternal immune system
* *TOLERANCE INDUCTION THRESHOLD FOR TCELLS IS MUCH MORE STRINGENT FOR T CELLS THAN B CELLS becuase if you block the T cells (more upstream of Bcells) then you don’t need to worry about B cells!)

Answer 117

A

Central: immature cells in primary lymphoid organs; during the development of the immune system AKA negative selection by clonal deletion, clonal anergy, receptor editing, and clonal ignorance

Peripheral: post-thymic and bone marrow; mature cells in secondary lymphoid organs mediated by:

deletion: activation induced cell death, superantigens, due to high concentration of self-Ag
clonal anergy
functional deviation
regulatory/suppressory T cells
FAS/FASL interactions (and immune privelege sites)
oral tolerance

Answer 118

A

Anergy = functional inactivation of lymphocyte resulting in unresponsiveness upon contact with self Ag
-occurs as a central mechanism mainly when a B-cell expressing Ab agains self Ag doesn’t cause appropriate response; B-Cell is arrested in IMMATURE STATE

**usually for B-cells of moderate affinity to self

Answer 119

A

ONLY OCCURS ON B-CELL LIGHT CHAINS!
= ongoing receptor gene rearrangement to alter/edit Ag receptor specificity
-RAG-1 RAG-2 expression leads to rearrangement of the already rearraranged L-chain to be replaced by upstream V and downstream J genes in order to lead to a BCR that has a new specificity (not for self)… continues until a non-self Ab is produced; if non then DELETION

**usually for B-Cells of high affinity to self

Answer 120

A

= autoreactive B and T cells eliminated by APOPTOSIS
-if B/T encounter a self Ag, then extensive cross-linking results and there is delivery of a STRONG signal which induces deletion (if encounter involves just MODERATE cross-linking then ANERGY results)

-occurs in: double negative T-cells, double + T cells with high self affinity (negative selection) to prevent mature autoreactive Tcells from exiting the thymus

Answer 121

A

= expressed by THYMPIC EPITHELIAL and DENDRITIC CELLS;
facilitates the expression of peripheral self Ag on thymic MEDULLARY CELLS in order to assist in NEGATIVE SELECTION of self reactive T cells

** PRevents the escape of thymic deletion (and autoreactive cells from leaving thymus into periphery)

Answer 122

A

= autoreactive lymphocytes (mainly B cells) that have escaped tolerance mechanisms because they have a “weak” affinity for self-Ag or becasue the self Ag is present in such a low concentration, can mature and move out into periphery although they persist in the host in an UNACTIVATED

**usually for B-cells of weak aviditiy

Answer 123

A

= AVIDITY (strength) of BCR/TCR interaction with AutoAg

BCELLS: 
depends on: 
- [autoAg]
- density of surface BCR
- BCR affinity

High avidity = receptor editing (if that fails = deletion)
Moderate = anergy
Low = clonally ignorant

TCELLS:
depends on: affinity for TCR for peptide/MHC, level of TCR on surface, level of MHC molecule expressed

High Avidity for peptide/MHC = Negative selection or Deletion
**anergy and receptor editing not present in Tcells

Answer 124

A

BCells:
Autoreactive T-cells are usually deleted in the thymus and not available in the periphery to provide costimulatory signal (ie: CD40L) needed to activate autoreactive B-Cell, thus the B-Cell becomes anergized; Anergic Bcells cannot compete successfully for entry into B-Cell follicles in the spleen/lymph nodes so they are arrested in development at the T/B border in follicular exclusion and die by apoptosis

TCells:
if MHC/peptide-TCR is not accompanies by B7/CD28 interaction, then IL-2 mRNA is rapidly degraded, and no IL-2 = no TCell proliferation; APC must be activated before they present costimulatory molecules, such that even if a macrophage preset the Ag to the T-Cell its not activated becasue its a self Ag and doesn’t express costim molecules and so T-Cell anergy happens.

Answer 125

A

BOTH ARE ON LYMPHOCYTES;
the interaction of the two induces apoptosis via stimulation of a caspsase (cysteine protease) cascade;
Fas/FasL causes Fas to trimerize and thus stimulate FADD formation which goes on to simulate a caspase cascade that terminates in DNA Fragmentation leading to CELL APOPTOSIS

MUTATED FAS = autoimmune lymphoproliferative syndrome (no apoptosis, therefore tons of lymphocytes)

Answer 126

A

Treg = a CD4+ that downregulates Tcell function

express CD25, the IL-2 receptor (so do ALL T-cells)
express Fox3p = TF for suppressive activity unique to Treg
*Treg requires specific TCR engagenemnt to be activated, but once they are activated, their suppressive activity is Ag NONSPECIFIC– they can suppress autoreactive effector CD4+ CD8+ cells that are specific for an Ag DIFFERENT then the one the Treg recognized
also can suppress B cells, dendritic cells, NK cells, and via TGF-B they inhibit tTH1, TH2, TH17

Two classes:

Natural T-reg: involved in + selection in thymus
- secrete IL 10 (prevents IL-12 secretion) and TGF B
- Express CTLA 4 at high affinity (competes with B7 on APC)
- Express FoxP3 = interferes with AP-1/NFAT thus prevents IL-2
induced Tregs (iTreg)
= arise from naive CD4+ T-cells in the tissues
A). FOXP3 Tregs: induced by TGF-B on CD4+ naive Tcells and secrete TGF B
B). TH3 = NO FOXp3; found in mucosal immune system; produce IL-4, IL-10, TGF-B (which distinguishes them from TH2)
C). TR1: differentiate invitro: produce IL-10 and TGF-B but not IL-4

MECHANISM:
inhibit IL-2 production through IL-10 and TGF-B
Downregulate B7 (CD80/CD86) on APC through CTLA-4

Answer 127

A

= where lymphocytes are generally excluded

in Testes, stromal cells constitutively express FasL which induces apoptosis in any immune cells entering the tissue
In the placenta maternal/fetal tissues are tolerant to eachother due to absence of HLA Ag

Answer 128

A

Normal immune responses involve:

TH1– produce IFN-G (inhibits TH2), and TNF-A
TH2– produce IL-4 (inhibits TH1), IL-5, IL-10, IL-13
TH17

Altered peptide ligands (changes one or two amino acids in the peptide) may switch a TH1 cell to perform TH2 functions

Answer 129

A

= lack of humoral or cellular immune response to ingested food antigens
Low doses induce TH3 suppressor cells
High doses induce Tcell anergy/deletion

Answer 130

A

Naive T-Cells (matuer) migrate to and enter the peripheral lymphoid tissue to encounter their specific antigens; Immature dendritic cells from infection sites pick up pathogen peptides by phagocytosis and migrate to the peripheral lymphoid tissue (lymph node, spleen, MALT) where they present MHC/peptides to naitve T-cells for activation

Answer 131

A

Naive T-Cells circulate between blood and the lymphoid tissues in search of specific antigens necessary for development into effector T-cells;
To enter the lymphoid tissues, naive T-Cells bind to HIGH ENDOTHELIAL VENULES (HEV) through cell-cell mediated interactions by ADHESION moleculess:
-selectins
-integrins
-ICAM (intracellular adhesion molecules)

Answer 132

A

L-Selectin on T-cells bind to Addressins on the vascular or mucosal endothelium = “slow roll” along surface
CCL21 (chemokine) activates LFA-1 (an INTEGRIN ON ALL T-CELLS) as the TCell comes into contact with HEV
LFA-1 (T-cell) binds ICAM-2 and ICAM-1 on endothelial surface = FIRM ADHESION that stops the T-cell so it can enter lymphoid tissue
Transmigration along the endothelial layer into the paracortical areas of the T-Cell Zone

Answer 133

A

Naive TCell migrates into T-Cell zone of peripheral lymphoid tissue, and CCR7 (on its surface) bind to CCL21/CCL19 stromal ligands, which makes the T-Cell stay in this area
Dendritic Cells in the T-Zone produce CCL19/CCL18 and which attracts T-Cells to bind its CCR7 to
Naive T-Cell scans the surface of the dendritic cell for specific peptide/MHC complexes and if they find it then they are trapped in the lymph node.. PRIMING (if not activated, then the Naive T-cell leave node back into circulation)

Answer 134

A

**Only 3 APC present the costimulatory molecule necessary for activation of T-Cell (No co-stim = no infection = no T-cell response)

Dendritic Cell:
Ag = any source
Present to T-Cells located in = all areas of lymphoid organ
**drive INITIAL cloning expansion and differentiation of naive T-cells into effector T-Cells; note: as immature, they are better at phagocytosis than presentation (flips once matured)
Macrophages
Ag = intracellular pathogen
Present to T-Cells already primed as effector CD4 Tcells (CANT PRESENT TO NAIVE T-CELLS!!!!)
BCells
Ag = soluble Ag
Present to T-Cells already primed as effector CD4 Tcells (CANT PRESENT TO NAIVE T-CELLS!!!!)

Answer 135

A

Using complementary receptors
Fc Receptors (Ag/Ab uptake)
C-Type lectins (mannose receptor etc)

Answer 136

A

Receptor Mediated Phagocytosis
Pathogen = extracellular bacteria
MHC pathogen loaded onto = MCH II
Naive T-Cell activated = CD4+
Macropinocytosis
Pathogen = NONSPECIFIC Extracellular Ag/bacteria/virus
MHC pathogen loaded onto = MHC II
Naive T-Cell activated = CD4+
Viral Infection
Pathogen = Virus
MHC pathogen loaded onto = MHC I
Naive T-Cell activated = CD8+
Cross-Presented phagocytic macropinocytosis
Pathogen = Extracellular virus/pathogen
MHC pathogen loaded onto = MHC I
Naive T-Cell activated = CD 8+

**Dendritic cells are able to detect pathogens using TLR signaling receptors

Answer 137

A

TLR signaling facilitates entry of the dendritic cell into the peripheral tissues (LICENSING) by:

TLR picks up pathogen and induces CCR7 and pathogen processesing
CCR7 directs migration into lymphoid tissues and augments co-stim molecules and MHC
Mature dendritic cell in T-CEll zone primes naive T-Cell (program of differentiation = activation of naive T Cells)

Answer 138

A

cause dendritic cell to no longer engulf antigens by phagocytosis or macropinocytosis
have high level of co-stim and adhesion molecules
secrete chemockine CCL 18 to attract naive T-Cells

Answer 139

A

binding of Tcell and APC is initally through LFA-1/ICAM-1 interaction; after TCR binds MHC, there is a conformational changes in LFA-1 that causes it to have an increased affinity for ICAM-1/ICAM-2; this causes a stable association between the Tcell and APC (prolongs cell-cell contact)

Answer 140

A

Activation = Interaction of specific peptideMHC/TCR
Survival = co-stimulatory signal that promotes survival and expansion of the T-Cell
Differentiation = co-stimulatory signal that directs the differentiation of four effector Tcell subsets

** antigen recognition in the absence of co-stim leads to clonal anergy or clonal deletion of peripheral cells

Answer 141

A

Re-enters cell cycle (G1 phase) and divides rapidly
Production of IL-2
* *CD28 signaling activates PI3-kinase which increased the production of AP-1 and NFkB (not NFAT) which prolongs the lifetime of mRNA IL-2 and promotes cell growth and survival

Answer 142

A

TH1 secretes IFN-G = killing of intracellular bacteria inside macrophage
TH2 secretes IL-4, IL-5, IL-13 = promotes eosinophil and mast cells to the site; production of IgE
TH17 secretes IL-17 which acts on fibroblasts and epithelial cells to cause them to secrete chemokines which attract neutrophils towards the infection
THF (follicular) = bind to B-Cells in the follicule and promote class swithcihng, affinity maturation (somatic maturation)
TReg = inhibit immature dendritic cells resulting in inhibition of CD4+ and TCell inactivton

Answer 143

A

Function: control BACTERIAL INTRAVESICULAR infection in MACROPHAGES by stimulating microcidal actiity of macrophage (and its lysosomes) to kill the resident bacterial;

Secrete: IL-2 (promote more T-Cells) and IFN-G (promote macrophage acidic killing)

Induced by: IFN -G (from activated NK of innate system) and IL-12, which go on to stimulate STAT1 transcription factor which induces T-bet Transcription Factors which codes for IL-2 and IFN-G expression; STAT4 also promotes expansion and differentiation of the committed TH1 cells

Answer 144

A

Function: 
Control infections by PARASITES (esp helminths), but promoting responses mediated by EOSINOPHILS, MAST CELLS AND IgE Ab ISOTYPE
**TH2 cytokines are required for class switching to IgE

Secrete: IL-4 and IL-5

Induced by:
IL-4 induces TH2 development from naive CD4 Tcells which activates STAT6 which promotes expression of GATA3 which switches on genes for TH2

Answer 145

A

Function:
Induced early in adpative immune responses agains EXTRACELLULAR BACTERIA AND FUNGI; stimulate neutrophil responses to clear the pathgens

Secrete:
IL-17: acts on local tissue to produce IL-8
IL22: Acts on the gut, skin, and lungs to promote local innate defense to pathogens

Induced by:
IL-6 and TBG-B, which in the abscence of IL-4 and IL-12 induce development of TH17, which produces IL-21 and activates STAT3 to turn on ROR-G-t TF that drives IL-17 expression

Answer 146

A

=Follicular Helper Cells = (unlike Th1/TH2), they provide B-Cell help for production of Ab production

Secrete: cytokines characteristic for either TH1 or TH2

Induced by:
IL-6; also Bcl6 is required for expression of CXCR5 which is produced by stromal cells of C-cell follicle

Answer 147

A

Classified by killing mechanism:

Release of cytotoxic granules upon contact with target cell
- perforin = causes a pore to form in the target cell plasma membrane for granzymes to pass through

-granzymes = trigger apoptosis in the target cells by activating CASPASE 3 (a protease that Cuts after ASPartic acid residues) and a cascade that acivates CAD (caspase-activated deoxyribonuclease) which degrades DNA

granulysin (only in human) = has antimicrobial activities that induce apoptosis at high concentrations
** NOTE: cytotoxic proteins are replenished each time ligation of a TCR occurs so a SINGLE CTL can kill a SERIES of targets

Fas-FasL interaction induced apoptosis
= mainly for regulating lymphocyte numbers (not for killing infected cells); activated lymphocytes have both Fas/FasL and when they bind they induce a trimeric Fas = FADD which activates caspases leading to apoptosis and degradation of DNA

Answer 148

A

Neutralization = binding to pathogen presents the pathogen from entering target cells
Opsonization = promotion of phagocytosis
Activation of of the complement system = promotes opsonization and lysis of pathogen

Answer 149

A

Common allergens:
drugs, venom, peanuts

Route of entry:
IV, food, oral

Response: 
Vascular permeability (leads to rapid decrease in BP), laryngeal edema (leads to constriction), and shock

Answer 150

A

= inflammation of upper resp tract

Common allergens
pollen, dust mite feces

Route of entry = inhalation

Response = nasal edema, sneezing

Answer 151

A

Common allergens = dander, dust mite, pollen
Route of entry = inhalation
Response = bronchial constriction, mucus production

Answer 152

A

common allergen = peanuts, shelfish, eggs
route of entry = oral
response = vomiting, hives, anaphylaxis

Answer 153

A

Sensitization Period = first exposure to the allergen induces B cells to produce IgE;
IgE production requires TH2 cells which produce IL-4, IL-5, IL-13; IgE is short lived in blood, but persists for months bound to mast cells in tissues and basophils in blood via a receptor for the Fc portion of IgE (FcERI)

Answer 154

A

Environment:

early exposure to infectious agents
pollution (diesel exhaust increases IgE 20x)

Genetic:

Chromosome 5: IL-4, IL-13, GM-CSF associated with elevated IgE
some MHC Class II are associated with a SPECIFIC allergen
if both parents have allergy risk for the child increases from 10% to 40-60%

Answer 155

A

DERp1 = enzyme in dust mite feces that breaks down the tight junctions in mucosal epi cells and allows allergens to enter into the tissue more easily

Answer 156

A

IgE (already present on mast cells) is crosslinked by a reexposure to allergen (**ALLERGEN MUST BE AT LEAST BIVALENT*) which causes activation and rapid release of granules
-activated mast cells also secrete more IL-4 and express CD40L so more B-cels will produce IgE

Answer 157

A

= allergic symptoms due to substances produces/released by mast cells
Preformed substances = histamine, heparin, proteolytic enzymes and chemotactic facotrs (IL8 for PMN, Eosinophil chemotactic factor for eosinophils), other cytokines (IL13, 4, 5, GMCSF = attract and activate INFLAMMATORY cells)

Synthesized substances = leukotrienes, thromboxanes, prostaglandins, platelet activating factor

Answer 158

A

(a) binds H1 receptors on smooth muscle (bronchial constriction) and on endothelial cells (vascular permeability); lead to systemic anaphylaxis
(b) binds H2 receptors involved in mucus secretion, vascular permeability, and secretion of stomach acid

Answer 159

A

play major roles in antihistamine release-resistance asthma

(1) leukotrienes: cause prolonged constriction of smooth muscle
(2) thromboxanes, prostaglandins: constrict bronchi, also chemotactic for PMNs and eosinophils
(3) platelet activating factor (PAF): cause release of histamine and thromboxanes

Answer 160

A

Eosinophils and PMNs come to site and prolong symptoms (occurs 7-8 hours after exposure)

(1) eosinophils release: leukotrienes, PAF, toxins for helminths (eosinophilic cationic protein), enzymes and chemotactic factors
(2) PMNs release: leukotrienes, PAF, lysosomal enzymes

Answer 161

A

prevents blood vessel leakage AND relaxes bronchial/tracheal smooth muscle

Answer 162

A

inject patient with small amount of allergen and increase the does weekly for several months

(1) mechanism: elevates IgG antibody which binds allergen and prevents it from reacting with IgE on mast cells; also induces a switch from TH2 to TH1 cells; may induce Treg cells
(2) useful for: allergic rhinitis, bee stings, asthma, and peanut allergies

Answer 163

A

Beta agonists = epinephrine, causes antagonist of histamine, used in anaphylaxis
Xanthine derivatives = aminophylline, causes relaxation of smooth muscle, used in asthma
Mast cell membrane stabilizers = cromolyn sodium, causes prevention of degranulation, used in asthma
Leukotriene modifiers = binds leukotriene receptor or inhibit formation of leukotrienes, used in asthma
Antihistamines = benadryl, Block H1 receptors, used in rhinitis, dermatitis
Corticosteroids = anti-inflammatory, used in asthma, rhinitis

Answer 164

A

(1) patient history
(2) skin tests: small amount of allergen injected; positive reaction is wheal and flare, swelling and redness (occurs in 10-15 minutes)
(3) radioallergosorbent test (RAST): quantitates the amount of serum IgE for a specific allergen

Answer 165

A

protect against parasitic worms

(1) worms stimulate IgE production
(2) mast cells recruit eosinophils that bind IgE and IgG on the worm and release cytotoxins

Answer 166

A

(1) more allergies prevalent in rich versus poor countries
(2) theory: in industrialized countries, improved hygiene exposes children to fewer bacterial and viral infections early in life; this directs maturing immune system away from TH1 type responses leading to unrestrained TH2 responses that allow for an increase in allergy
(3) early exposure to infectious agent in poor countries induces a prolonged TH1 bias to subsequent exposure to foreign substances including potential allergens
(4) this hypothesis was tested by comparing kids in rich countries exposed to many infectious agents (early day care; farm life; many siblings) versus children with fewer exposures (single child, stays at home). the early exposure group had fewer allergues

Answer 167

A

immune reactant = IgG (or IgM)
Antigen = cell or matrix associated antigen

Effector mechanism = 1. activate complement 2. attract FcR+ cells (phagocytes, NK cells) to bind IgG (NOT IgM) = Ab Dependent Ceullular Cytotoxicity (ADCC); these can damage self-cells

Examples: some drug allergies (ie. penicillin-however can also stimulate IgE release), chronic urticaria, ABO or Rh incompatibility

Answer 168

A

Immune reactant = IgG
Antigen = soluble antigen

Effector mechanism: formation of immune complexes that activate complement and attract phagocytes resulting in localized tissue damage

Examples: serum sickness (immune complexes deposit in vascular system), SLE (Ab to DNA)

Answer 169

A

= Delayed Type Hypersenstivity
= MEDIATED BY CYTOKINES AND CHEMOKINES!!
Two major pathways
1. Immune reactant TH1:
antigen: soluble, stimulates TH1 cells to be produced
effector mechanism: TH1 cells secrete 1. Chemokines (recruit macrophages to Ag site) 2. IFN-G (induces vascular adhesion molecule expression, macophages activated, increases release of inflammatory mediators) 3. TNF-A + TNF-B (local tissue destruction, increased expression of adhesion molecules of local blood vessels)
4. IL-3/GM-CSF (stimulate monocte production by bone marrow stem cells)

examples: contact dermatitis, tuberculin reaction

immune reactant CD8+ T cell
antigen: cell associated
effector mechanism: cytotoxicity
examples: contact dermatitis (poison ivy), graft rejection

Basically: Types of Type IV:
1. Delayed-Type Hypersensitivity:
Ag: proteins (insect venom, mycobacterial proteins like tuberculin and lepromin)
Consequence: local skin swelling (erythema, induration, cellular infiltrate, dermatitis)

Contact Hypersensitivity:
Ag: haptens (poison ivy, DNFB), small metal ions (nickel, chromate)
Consequence: local epidermal reaction (erythema, cellular infiltrate, vesicles, intraepidermal abscess)
Gluten-Sensitive Enteropathy (Celiac Disease):
Ag: gliadin
Consequence: villous atrophy in small bowel, malabsorption

**T cell mediated hypersensitivity takes many hours: need to recruit cells to the site

Answer 170

A

o 2 chains (alpha,beta/delta,gamma): bind Ag + self-MHC
o CD3: made of gamma-epsilon and delta-epsilon chains; transduces signals when TCR combines with peptide + MHC; transports TCR to cytoplasmic membrane; invariant
o 2 zeta chains: transduce signals when TCR combines with peptide + MHC; invariant

Answer 171

A

TCR = recognizes only linear peptides
BCR = recognizes proteins that are linear or globular; also recognizes carbohydrates, lipids, and nucleic acids

Answer 172

A

Consist of VJ-C or VDJ-C
o α and γ Loci: VJ-C
o β and δ Loci: VDJ-C
o Note: alpha and delta loci located together

-Genes are rearranged during T cell development, requiring the use of RAG1 and RAG2 enzymes

-Variability again due to:
o Random utilization of 2 chains
o Multiple V, D and J alleles
o Junctional variability

-Allelic exclusion: prevents simultaneous rearrangement of beta and gamma chains, but NOT all alpha; as a result, many T cells express 2 different alpha chains

Answer 173

A

• CD28: a costimulatory molecule that interacts with B7 on B cells (and other APCs); stimulates the T cell and also induces the production of IL-2
• CD152 (CTLA-4): interacts with B7; triggers a negative stimulus to the T cell (turns off T cell)
-Clinical Correlation: recombinant CTLA-4 used in the treatment of rheumatoid arthritis patients

• Adhesion molecules: facilitate adherence to APC and endothelial cell
o CD2
o Integrins (LFA-1 and VLA-4)

Homing Molecules (CD62L or L-selectin): binds addressins on the endothelium
CD40L: binds CD40 on B cells and APCs; activation occurs both ways
CD40L on T cell binding CD40 on B cell stimulates B cell to class switch
CD40 on APCs binding CD40L on T cell stimulates activation of T cell

• ICOS: interacts with ICOS ligand on B cell; facilitates germinal center formation in LNs and other lymphoid tissue

Answer 174

A

Location: skin, lungs and intestines (much lower in number than alpha-beta T cells in the blood)
Structure: gamma and delta chains associated with CD3 and zeta, but no CD4 (some have CD8)
Function: may be important as first line of defense against pathogens; respond to a limited number of proteins (not necessarily to peptide + MHC; phospholipids and heat shock proteins)

Answer 175

A

1) Stem cells from bone marrow travel to thymus (beginning in utero until puberty, when thymus atrophies)
- Clinical Correlation: DiGeorge Syndrome results from lack of a thymus, which prevents T cell development

2) Stem cells proliferate and mature in the thymus due to 2 factors:
1. Physical contact of dendritic and epithelial cells in the cortex
2. Cytokine influence (IL-7)

3) TCR beta, gamma and delta genes rearrange
- Gamma-delta T cells leave the thymus
- Cells with a beta chain express beta attached to an invariant chain (pre-T alpha); this forms the pre-T cell receptor

4) Formation of the pre-T cell receptor (and its appearance at the surface of the cell) prevents beta chain rearrangement, and stimulates rearrangement of the alpha chain gene

5) Rearrangement of the alpha chain stops expression of the delta chain (located on the same chromosome; therefore, beta chain can never bind delta chain)
- Remember: allelic exclusion is not complete for the alpha chain, and therefore, both alpha chains may rearrange (results in 2 cell with 2 different alpha chains and 1 beta chain)

6) CD4 and CD8 markers appear on the surface, forming a double positive cell
7) THYMIC SELECTION

Answer 176

A

•T cells in thymus are selected for based on:

Recognition of their own MHC
Unresponsiveness to self-peptides (in order to prevent autoimmune disease)

Steps:

1) Cells expressing both CD4 and CD8 interact with cortical epithelial cells expressing MHC class I and class II, promoting further maturation of the T cell. Cells with weak or no interaction with self MHC die by apoptosis (positive selection)
2) T cell interacts with dendritic cells at the corticomedullary junction and epithelial cells in the medulla. Both of these cells have MHC class I and II, and some have self-peptide present. If the T cell reacts strongly with self-peptide-MHC, they are killed by apoptosis (negative selection).
3) Finally, CD4+CD8+ double positive cells downregulate one or the other, and become single positive cells (mature T cells). Mature T cells leave the thymus and circulate.

AIRE (Autoimmune Regulator Gene);
- Expressed in the thymus; allows it to express various important self antigens from other organs, facilitating the killing of T cells specific for various “sequestered antigens” (ie. from the pancrease, thyroid etc.)

Answer 177

A

NK Cells: no TCR or CD3; kill virus infected cells and tumors expressing low MHC
NKT Cells: have a TCR with limited variability and an NK marker; regulate other T cells
Treg Cells: subset of CD4+ cells that are CD25+ and Foxp3+ as well; inhibit the immune response

Answer 178

A

Highly motile
Express TLR that can recognize a reagent as ‘infectious’
uptake of injection agents stimulates the production of proinflammatory cytokines IL-1, TNF-A, and IL-12 to produce TH1

Answer 179

A

Peptide/MHC - TCR
MHC II and CD4 = increases the activation 100x
Costimulator pairs: B7/CD28 or CD40/CD40L (which upregulates B7)
Adhesion molecules to increase binding affinity: ICAM-1/LFA-1, LFA-3/CD2

Answer 180

A

Peptide/MHC interacts with TCR to activate CD3 and Zeta chains
Tyrosine kinases are activated = Lck and Fyn, which phosphorylate ITAMS on CD3 and Zeta, respectively
Phosphorylated CD3 and Zeta attach to ZAP-70 and Lck activates ZAP-70
ZAP-70 activates adapter molecules LAT and SLP-76 which go to the membrane
Adapter proteins bind PLC-Gamma which is then phosphorylated by ZAP-70; Adapter proteins also activate MAP Kinases
Activated PLC breaks down PIP2 into DAG and IP3
DAG leads to activation of NFkB transcription factor
IP3 leads to increased Ca2+ which activates calcineurin which activates NFAT
MAP kinases activate Ap-1
NFkB, NFAT, and Ap-1 all activate IL-2 and IL-2alpha Receptor transcription

Answer 181

A

B7-CD28 = costimulation needed for T-Cell activation because it:

increases transcription of IL-2 mRNA
increases half-life of IL-2 mRNA
mobilizes lipid rafts which facilitate kinase pathways

When B7-CTLA4 (which is upregulated on activated T cells and has a higher affinity for B7 than CD28), IL-2 production and cell proliferation is blocked.

Answer 182

A

Down regulation of CD62L (L-selectin) a receptor that facilitated migration INTO the lymph node
Upregulation of integrins/chemokines out of the lymph node

Answer 183

A

Superantigen pinding to specific Vbeta chains of the TCR causing activation of 10% of T0Cells
Plant proteins like ConA (Concanavalan A) and PHA (Phytohemaggluntinin) adhere to TCR and cause mitogenesis
NKT Cells are activated by lipids

Answer 184

A

DO NOT induce class switching or generate memory B Cells;
Poorly immunogenic in young children

but, if polycassharide is conjugated to a protein then TH2 cells will be activated by the protein and provide help to B-Cells that react to the polysaccharide

Answer 185

A

by MHC I, B7-CD28, and IL-12 (thus CD4+)
In abscence of CD4+, via cross priming in which viral derived peptide is presented by MHC class I on dendritic cells (which present B7 for co stim)

Answer 186

A

Thymic Independent antigens (TI) = large polymeric molecules with mulptiple REPEATING antigenic epitopes
EX: LPS and bacterial polysaccharides.
Type I TI antigens (LPS) but NOT Type II TI antigents (polysaccharides) also act as B Cell mitogens

ONLY CAUSE IgM RESPONSE AND NO MEMORY B CELLS

Answer 187

A

Initial step is cross-linking of Ig receptor molecules which sends a signal via IgAlpha and IgBeta which causes activation of Src kinases (LYn, Fyn, Blk)
Src Kinases phosphorylate ITAMs on IgAlpha/beta and this recruits Syk which is activated
Activated Syk recruits and activates adapter proteins which go on to activate signalling pathways similar to T-Cell .. activating NFkB, NFAT, Ap-1 TF, which promotes transcription of Ig genes and cytokine RECEPTOR genes

Answer 188

A

Enhanced:
When complement component C3d is deposited on bacteria, it binds to CD21 on a Bcell and provides a costimulatory signal that augments B-cell activation

Dimininshed:
When CD32 on the Bcell surface binds to Fc region of an Ig, it causes a phosphatase to bind which leads to inhibition of Ig synthesis

Answer 189

A

small, organic molecule that becomes part of an antigenic determinant when coupled to a carrier molecule (ie. small molecule that can only elicit an immune response when attached to a larger carrier)
- Ab interactions with haptens are the most simplistic of interactions

Answer 190

A

number of sites reacting with Ag on an Ab molecule

IgG: 2
IgA: 2 or 4
IgM: 10
IgD: 2

Answer 191

A

Addition of a fixed amount of Ab to various amounts of protein in test tubes; incubate and spin to form precipitate and supernatant
-The relative amounts of precipitate and supernatant can be plotted to form a QP curve
o Weight of protein added on X axis
o Weight of ppt on Y axis
o Ab excess occurs on the left side of the curve (where ppt is increasing as protein is added)
o Ag excess occurs on the right side of the curve (where ppt is decreasing even though protein is being added)
o Equivalence point occurs slightly to the left of center, due to the fact that ppt actually briefly gets heavier as the lattices become stringier past the equivalence point

Answer 192

A

Ag placed in 2 wells (can be the same or different); Ab placed in another opposite those
As Ag and Ab move towards eachother, a ppt line can be visualized representing equivalence zones
The pattern of the equivalence ppt line shows the relatedness or differences in the Ags being tested

3 Basic Precipitin Patterns Exist:
1. Both Ags are the same (Identity): a continuous, smooth ppt line will be present
2, Ags are completely different (Non-Identity): two crossing ppt lines will be present
3. Ags are have similarities but are not the same (Partial Identity): spur in the direction of the deficient Ag (ie. the one missing a piece that would react with Ab)

Example: If Abs Ab1 and Ab2 are present, and Ag1/3 is also present, Ab1 will react with the Ag1 portion, but Ab2 will move past the ppt line to interact with Ag2 from the other Ag well, creating the spur in the direction of Ag1/3.

Answer 193

A

an adaptation of the precipitin reaction in gel
- Method used to quantitate Ags
- A series of known quantities of Ag are placed in wells in the gel, along with the unknown quantity of Ag you wish to determine
- The diameter of the diffusion ring of the known quantities are used to create a standard plot of:
o Log[Ag] vs. Ring Diameter
- The diameter made by the unknown quantity of Ag can then be measured, and plotted on the graph to elicit the [Ag] in that sample

Answer 194

A

• Aggluntination: particulate Ags (RBCs, bacteria)
- Major Blood Groups: ABO system is one of the major histocompability systems in humans
A: polysaccharide backbone- N acetylgalactosamine
• Isoantibodies: anti-B

B: polysaccharide backbone- galactose
• Isoantibodies: anti-A

O: polysaccharide backbone
• Isoantibodies: anti-A and anti-B

AB: polysaccharide backbone- both N-acetylgalactosamine and galactose
• Isoantibodies: none

**Isoantibodies: do not appear until roughly the first year of life (unclear how they develop)

Answer 195

A

Immunize mouse with AgX; produce Anti-AgX Abs
Fuse Anti-AgX cells with immortal mouse myeloma cells
Creates a clone of Abs to AgX

Applications:

Diagnostic: leukocyte identification, HLA antigen detection, typing of leukemias and lymphomas, detection of tumor-related Ags
Therapeutic: antitumortherapy, immunosuppression, fertility control, drug toxicity reversal (ie. digitalis)

Answer 196

A

good for measuring minute quantities of things**

Radioimmunoassay:
- Particularly useful for measuring concentrations of drugs and hormones
o Need Ab to drug/hormone
o Need to couple drug/hormone to a radioisotope
-Read out in a gamma counter
ELISA:
- Enzyme linked immunosorbent assay
- Good for measuring Ab levels to an Ag
- Process:
o Ag binds matrix (ie. plastic)
o Add Ab (Ab1) to Ag; wash
o Add Ab (linked to enzyme) to Ab1 (anti-Ig Ab); wash
o Add substrate that changes color when reacting with enzme
- Read out spectrophotometrically (ELISA plate reader)
- Plotted on a [Ab] vs. Optical Density standard curve (unknown value should fall in linear region)

Answer 197

A

Use: primarily to detect Ags (ie. microbes like chlamydia inclusion bodies in vaginal smears, immune complexes in kidneys)
Basic Process:
o Cells fixed to glass slide (Ag)
1. Direct Test:
• Fluorescent labeled Ab to Ag of interest added to slide; look for interaction
***MEAURES CELLS NOT Ab!! to test if there is protection post vaccination

Indirect Test:
• Unlabelled Ab to Ag of interest added to slide
• Followed by fluorescently labeled anti-Ag Ab to the Ab added 1st; look for interaction
• Much more sensitive
Sandwich Test:
• Example: you want to know if a plasma cell is making Ab to an Ag of interest
-Add Ag of interest to coat the plasma cell
• Add fluorescently labeled Ab to the same Ag; look for interaction

Answer 198

A

Used to analyze and sort cell populations (measures kinds of cells you have in a mixture)
o Example: quantitate lymphocyte subsets (CD4, CD8); sort lymphocyte subpopulations
Have fluorescently labeled Abs to cell markers; cells pass through small tube 1 by 1 and if they have fluorescently labeled Ab attached, that will be detected and they will be sorted accordingly
Uses:
o Leukocyte/tumor cell phenotyping
o DNA analysis (determine aneuploidy)
o Leukocyte cross matching in transplant recipients

Answer 199

A

• Use: measures the presence of Abs to specific microbial Ags (ie. confirmatory test for Abs to HIV)

•Process:
- Disrupt virus particle and subject to electrophoresis
- Transfer blotting to nitrocellulose sheet
- Incubate patients serum (with Abs) with nitrocellulose; wash and add enzyme or radioactive anti-human Ig Ab
o Enzyme linked- add chromogen to visualize; radioactive viewed on X-ray film

Answer 200

A

Apoptosis: occurs when cell responds to cell-bound self Ag
Anergy (Inactivation): occurs when cell responds to soluble self Ag
Receptor Editing (to produce different specificity): also response to soluble self Ag

Answer 201

A

Stem Cell: further development to B cells requires stromal cells and IL-7
Pro-B Cell: D-J rearrangement (H chain); no membrane Ig
Pre-B Cell: V-DJ rearrangement (H chain); μ + surrogate light chain at surface and with Igα and Igβ (signal transduction molecules). BtK signals for light chain rearrnagement
Immature B Cell: V L chain rearrangement (kappa or lambda); IgM expressed on surface, which combined with Igα and Igβ, is called the B CELL RECEPTOR
Mature B Cell: no gene rearrangement; IgM and IgD on surface (due to alternative splicing); can encounter infectious agents and proliferate to clones of cells (plasma or memory)
Memory B Cell: isotype switched to have IgG, IgA or IgE on surface after Ag exposure; long-lived and express IgA, IgG or IgE on their surface, along with adhesion molecule CD44;serves as protection for future infections with the same agent
Plasma Cell: no membrane Ig expression; secretes IgM, IgG, IgA, or IgE (switches from membrane bound form of IgM to secreted form via alternative splicing)

Answer 202

A

• Pre-B Cell Receptor = μ + surrogate light chain + Igα + Igβ

Expression of the Receptor has 4 Effects:

Cell proliferation
Shuts off surrogate light chain production
Starts light chain rearragments
Stops H chain rearrangements

Clinical Correlation: X-Linked Agammaglobulinemia
-Defective BTK enzyme causes B cells to be arrested at the pre-B cell stage of development

Answer 203

A

In germinal centers of LNs, spleen and Peyer’s patches (secondary lymphoid organs)

Cells:
APC usually follicular dendritic cell = exposes BCell to Ag T helper cells = allow for isotype switching and memory cell formation
Plasma cells = go back to bone marrow for proliferate

Answer 204

A

When B cells are activated by Ag and proliferate, the V regions are subject to high mutation rates

Results in some cells producing Ab with higher affinity for Ag, and these cells are positively selected by Ag yielding more cells

This results in the affinity of the Ab increasing with repeated/prolonged exposure to Ag, which is known as affinity maturation

Answer 205

A

T cells have CD40 ligands and release cytokines that augment B cell activation and Ig class switching

Clinical Correlate: in the absence of CD40 ligand, only IgM is found in serum (Hyper IgM Syndrome)

Answer 206

A

Igα and Igβ: part of the B cell receptor for Ag (BCR); associated with the IgH chain
B Cell Co-Receptor (CD21, CD19 and CD81): associated with the BCR

Binding of C3d (a proteolytic cleavage product of C3b, along with C3dg, that remains bound to bacteria after complement activation) to CD21 increases Ag signaling 1000x; results in an enhanced signal through the BCR

CD21 is also a receptor for the Epstein Barr virus

Negative Signals: downregulate B cell activity = CD22 and CD32 (binds Ag-Ab complexes to downregulate B cell activity)

Answer 207

A

MHC Class II: binds peptide and interacts with TCR of CD4+ T cell; allows B cells to act as APCs for T cells
B7: interacts with CD28 and CTLA-4; allows B cells to act as APCs for T cells
CD40: receives signals from CD4+ T cells (CD40 ligand) that allow for Ab class switching

Answer 208

A

Location: subset of B cells found in peritoneal and pleural cavities
Features:
- CD5 on surface
- Produce low affinity IgM in response to pathogens at mucosal surfaces
- Do not require/receive T cell help, therefore generating an early response to pathogens
- V region repertoire for these cells is limited
- Little to no memory developed

Answer 209

A

The MHC is on a single chromosome (6), and therefore you inherit the complex as a single unit called the MHC haplotype
Any of your siblings have a 25% chance of inheriting the same 2 chromosome 6’s, resulting in identical MHC
Note: you would still differ at minor histocompatability loci that are encoded for by other cs

Answer 210

A

Expression: constitutively on all nucleated cells, including APCs

Encoding:
Coded by 3 separate loci (A,B,C), with each locus coding for an α chain only (highly polymorphic)
- Alpha chain combines with a nonpolymorphic/invariant chain, β2-microglobulin
-Each cell will simultaneously express HLA-A, HLA-B and HLA-C

Structure:

Alpha1 and Alpha2 domains interact with peptide (closed binding groove; 8-9 aa)
Alpha3 domain interacts with CD8 (on cytotoxic T cell)

Function: to present foreign peptide antigens to CD8+ T cells (endogenous Ag)

Infectious agent (virus, bacteria, parasite) penetrates the cell in order to replicate
Undergoes protein synthesis, and some protein is degraded by proteosome
Peptides from proteosome transported to ER by TAP-1 and TAP-2 transporters
If peptide has sufficient binding affinity for the MHC molecule (immuodominant epitope), it becomes associated with MHC class I
MHC class I + foreign peptide move to the surface of the infected cell to present to CD8+ T cells

Answer 211

A

Expression: constitutively only on APCs (dendritic cells, macrophages, and B cells) and thymic epithelial cells; can also be induced on fibroblasts and endothelial cells

Encoding:

Coded by 3 separate loci (DP, DQ, DR), with each locus having an A and B gene encoding for an α and β chain, respectively (chains are highly polymorphic)
An APC will simultaneously express HLA-DP, HLA-DQ and HLA-DR; this enhances the likelihood of binding to and presenting foreign peptide to T cells

Structure:

Alpha1 and Beta1 domains interact with peptide (open binding groove; 12-20 aa)
Beta2 domain interacts with CD4 (on helper T cell)

Function: to present foreign peptide antigens to CD4+ T cells (exogenous Ag)

Mechanism

Extracellular Infectious agent is phagocytosed by an APC and enclosed in an intracellular vesicle
Vesicle fuses with an endosome or lysosome, and proteins are digested into peptides
Vesicle of degraded peptides fuses with vesicle containing newly formed MHC class II with CLIP attached
If peptide has sufficient binding affinity for the MHC molecule (immuodominant epitope), it binds MHC class II in exchange for CLIP, a process mediated by HLA-DM

CLIP: MHC class II is assembled in the ER/Golgi with CD74 attached
• CD74 (invariant chain) acts as both a chaperone and an inhibitor of endogenous protein binding
• When the Golgi releases the vesicle with the newly formed MHC, CD74 is degraded down to CLIP, which is eventually replaced with foreign Ag
- MHC class II + foreign peptide move to the surface of the infected cell to present to CD4+ T cells

Answer 212

A

Peptides can bind MHC at the cell surface
APCs can take up exogenous protein and process them both in the class I and class II pathway (will be presented by both); this is called cross-priming
Superantigens: proteins that binds both MHC class II and the germline configuration of the TCR Vβ simultaneously
These areas that it binds on MHC II and the TCR are highly conserved and therefore, they can interact with a large percentage of T cells (up to 10%)
Leads to overactivation of T cells

Answer 213

A

Many self reactive T cells eliminated in thymus

- Self-peptides do not activate T cells in the absence of costimulatory signals

Answer 214

A

Basic Steps:

First rearrangement occurs, bringing D and J together
Second rearrangement occurs, bringing V and DJ together
This fragment is then joined to the C region to form a primary RNA transcript, which is spliced to form the mature mRNA that can be translated to a polypeptide chain

Details:
1. Recombination begins on only one chromosome (maternal or paternal) in an immature B cell (Pro-B cell)
2. A primary RNA transcript is made with constant region μ (IgM) and δ (IgD); only IgM is expressed in the immature B cell
3. mRNA transcript is translated into protein, and this synthesis of IgM heavy chain prevents the rearrangement of the other chromosome (allelic exclusion)
Note: if rearrangements on the first cs are non-productive, the other parental cs will undergo rearrangement

Answer 215

A

Basic Steps:
Only one rearrangement occurs to bring V and J segments together
- This fragment is then joined to the C region to form a primary RNA transcript, which is spliced to form the mature mRNA that can be translated to a polypeptide chain

Details:
• There are 2 light chain loci (one on each cs): κ and λ
• Rearrangement begins once the heavy chain rearrangement has been successful and IgM μ chain is at the cell surface
• Kappa rearranges first, and if successful, prevents lambda from rearranging (allelic exculsion- ensures Ab has one single specificity)
• If the first kappa locus is unsuccessful, the other kappa locus will rearrange, followed by each of the lambda loci if necessary
**Note: kappa:lambda ratio is roughly 2:1 in serum
•Clinical Correlate: B cell tumor may result in all serum Ig being light chain homogenous (that is, all kappa or all lamba)

Answer 216

A

V(DJ) Recombinase: found in all cells
RAG-1 and RAG-2: only in lymphocytes; directs V(DJ) recombinase

Clinical Correlate: defects in RAG-1 or 2 will prevent T and B cell development
-L Gene (Leader Peptide): helps direct protein to secretory pathway (cell surface) and is then cleaved

Answer 217

A

Junctional Diversity: splicing between V, D and J is imprecise leading to changes in amino acid sequence at critical sites for Ab specificity
Insertional Diversity: small numbers of nucleotides can also be added at this site; mediated by terminal deoxynucleotidyltransferase (TdT)
Note: 2/3s of these amino acid changes are out of frame and non-productive, signaling the other chromosome to undergo rearrangement

Occurs before exposure to Ag

Answer 218

A

Occurs when a mature B cell is activated by Ag and produces a clone of cells
Recombined V regions very prone to mutations (especially in hypervariable region)
Mutated B cells with highest affinity are selected by Ag (proliferate)
Result: increased affinity for Ag with each exposure

**Occurs after exposure to Ag

Answer 219

A

Occurs when an immature B cell is expressing an Ab that is reactive to self Ag (autoantibody)
Additional rearrangement of the light chain gene occurs in an attempt to change the specificity of the cell (cannot occur in the heavy chain since D would be totally lost upon rearrangement)

**occurs after exposure to Ag

Answer 220

A

Cells initially only express IgM on the surface
Mature B cells express both IgM and IgD on the surface due to alternative splicing of mRNA
Mature B cells are induced to produce other classes of Ab upon second exposure to Ag and T cells

Activated T cells secrete cytokines that result in further rearrangement of the H chain gene

Constant region for IgM and IgD is spliced out, and VDJ region is put together with the constant region for IgG, IgA or IgE

Result: cell produces Ab with the original specificity, but with a different isotype

**occurs after Ag exposure

Answer 221

A

Nature and physical state of the antigen.
- Degree of foreigness
- Chemical features
- Particulate (usually better Ags) vs. soluble (often leads to tolerance)
- Adjuvants (non-specific potentiators; most are pretty toxic)
Route of Immunization:
- Natural: infection (more potent route of immunization)
- Deliberate: vaccination
Normal vaccination route is through the tissue (epidermal, dermal or subcutaneous), Other routes include via the blood, tonsils and Peyer’s patches
Antigen Dosage: no generalizations (need to work out optimal dosages; dose/response curves)
Lymphocyte Traffic:
- Homing receptors on lymphocytes react with vascular addressins on HEVs for transepithelial passage

Answer 222

A

Sites of Ab Synthesis = Plasma cells in spleen and LNs
Appearance of Ab = Serum
Predominant Ig = IgG
Ig Structure = IgA can be monomer, dimer, or trimer + a J chain

Answer 223

A

Sites of Ab Synthesis = Plasma cells in glandular tissue and lamina propria of mucosal surfaces

Appearance of Ab = Secretions
1. Internal: Aqueous humor, CSF, Synovial fluid, Pleural fluid, Peritoneal fluid
2. External: Saliva, Lacrimal fluid, Nasal fluid, Tracheobronchial fluid, Intestinal fluid, Bile, Cervical fluid
Predominant Ig = IgG (internal secretion) sIgA (external secretion)
Ig Structure = IgA is a dimer with a J chain and a secretory component (sIgA)

***IgM and IgG are the same in both systemic and mucosal immune systems; however, in patients that are IgA deficient, IgM can make it through the epithelial barrier and enter secretions (contains a SC)

Answer 224

A

IgM (19S)
Low affinity Ab
Low Ab titer
Longer lag in response (longer response time)
IgG turns on late

Answer 225

A

IgG (7s)
Higher affinity Ab
Higher Ab titer
Short lag in response (faster response time)
IgM may appear early

Answer 226

A

IgG > IgA, IgM > IgD, IgE

Answer 227

A

Functions as a first line of defense
Produces Abs at sites of microbial replication
GI produces more Ig than spleen, bone marrow, and LNs
IgA accounts for 60% of the total Ig produced (much of it ends up in the feces, however)

When an antigen enters:
- Ag enters the small intestine and is transported to Peyer’s patches across M cells
- Peyers patches are rich in IgA precursor cells, which encounter the Ag
- IgA precursors travel to mesenteric node and then through thoracic duct to enter the blood stream
- From the blood stream, they travel to several destinations, become plasma cells, and produce IgA:
Small intestine (intestinal IgA); most cells end up going back here*
• Note: released from plasma cell as dimer IgA; picks up SC in intestinal wall
Mammillary gland (milk IgA), Salivary gland (salivary IgA), Bronchial tube (bronchial IgA), Urogenital tract (vaginal IgA), Lacrimal gland (tear IgA)

Answer 228

A

Barrier defense
Antigen transport
Intracellular viral neutralization

Answer 229

A

One single mRNA codes for H chains; a separate single mRNA codes for L chains
H and L chains made on separate polyribosomes
H and L chains are translated (including the leader sequence, which is eventually cleaved off) and then the chains associate

Note: there are alternate pathways of association for different Ig classes

Disulfide Bond Formation: intrachain form first, interchain form last
Golgi complex adds carbohydrate to the molecule
Vesicle breaks off of the Golgi complex, travels to the cell membrane where it fuses and is secreted by reverse pinocytosis

Answer 230

A

IgM and IgA: L, H and J chains all produced in the plasma cell
- J Chain = Limiting factor in polymerization , Catalyzes polymerization, which occurs shortly before secretion

sIgA: L, H and J chains produced in plasma cell; SC produced in epithelial cell

Steps for Producing sIgA:
• pIgA released from plasma cell (dimer with J chain)
• Binds poly Ig receptor on epithelial cell (SC component of receptor)
•Taken into the cell, and released to the acinar lumen along with the SC to form sIgA
• Membrane bound portion of poly Ig receptor remains behind

Answer 231

A

Polysaccharides

• Example: glucose/glucouronic acid (strep. pneumonia III)

Answer 232

A

Fetus:

6-7 wks in utero = thymus develops
10-12 weeks: surface Ig; lymphocytes; fetal contribution of IgM into circulation (IgG present, but comes from mother across placenta)

•Human Neonate:
- Limited capacity to mount a B-cell response at birth
-Compensation via Natural Passive Immunity:
Transplacental passage of maternal IgG: systemic protection
- sIgA in mother’s colostrums/milk: provides local protection of infant’s GI tract

Answer 233

A

Active: immunization directly carried out in the host; long-lived
Passive: immune components (Abs or cells) transferred into the host; transient protection
Adoptive: cells transferred into an irradiated host (ie. bone marrow transplants)

Answer 234

A

H Chain = gamma
Subclass = 1-4
L chain = K or Lambda
Size = smallest
Serum conc = highest
Main functions: passes through placenta, fixes the complement system, primary responder in the memory response, longest halflife, Fc portion binds for opsonization (does do bacterial lysis and antiviral, but not as good as IgM and IgA respectively)

Answer 235

A

H chain = mu
Sublass = none
L chain = K or Lambda
Size = largest (900,000 kD); IgM»>sIGA»IgE>IgD>IgA>IgG
Serum conc = middle; IgG>IgA>IgM>IgD>IgE
Key Features: Best at complement fixation (due to size), made in fetus but does not cross the placenta, on all B-cell surfaces (first to respond in primary exposure to Ag, acts as evidence of recent infection) BACTERIAL LYSIS

Answer 236

A

H Chain = alpha
sublass = 1,2
L Chain = K or lambda
Size = monomeric = small, dimeric = middle sizes; IgM»>sIGA»IgE>IgD>IgA>IgG
Serum conc= IgG>IgA>IgM>IgD>IgE
Key Features: best for mucosal responses (secretory form), secreted from mammary gland, ANTIVIRAL
dimeric form is secreted

Answer 237

A

H Chain = epsilon
subclass = none
L Chain = K or Lambda 
Size = IgM>>>sIGA>>IgE>IgD>IgA>IgG
Serum conc = IgG>IgA>IgM>IgD>IgE
Key Features = Mas cell/basophil degranulation (allergic reactions) and parasitic infection; least prevalant in serum

Answer 238

A

H Chain = delta
subclass = none
L Chain = K or Lambda 
Size = IgM>>>sIGA>>IgE>IgD>IgA>IgG
Serum conc = IgG>IgA>IgM>IgD>IgE
Key Features: found on B-cell surface along with IgM; no clear secretory function

Answer 239

A

located between the CH1 and CH2 on heavy chains; provides segmental flexibility (allows molecule to interact with antigens)

Answer 240

A

Fab: 2 per IgG; light chain + ½ heavy chain
Fc: 1 per IgG; 2 x ½ heavy chain
Fv: smallest fragment that retains site for reaction with Ag; 2 per IgG; made up of the variable regions of both light and heavy chains

Answer 241

A

Reduction/Alkylation of Disulfide Bonds:
- Results in separation of the chains from one another
- H chain has reduced (but not completely absent) binding capacity
- L chain has NO binding capacity
- Conclusion: both H and L chain needed for full Ag binding capacity
Papain Fragmentation:
- Results in 2 Fab fragments and 1 Fc fragment
- Monovalent Fab fragments retain full Ag binding capacity
- Fc portion did not bind Ag
Pepsin Fragmentation:
- Results in 1 F(ab’)2 and peptides
- Divalent F(ab’)2 retained full Ag binding capacity
- Fc function totally lost, resulting in:
- Inability to fix complement
- Inability to bind cells with FcR
- Inability to cross placenta (IgG)

Answer 242

A

Plasma cell: produces L, H and J chains (MW 16,000)
Epithelial cell: produces secretory component (MW 70,000)
Secretory Component: protects Abs from degradation

Answer 243

A

•Factors to Consider:

Ag-Ab interactions are noncovalent
Variation in capacity to bind Ag
Number of Ab combining sites
Gross architectural similarities

•Parameters Defining Site:

Unique Amino Acid Sequence Defines Site: encoded by genome
Dimensions of the Site: varies from Ab to Ab, but very small (Angstroms)
Location of the Site: contacts residues within the variable regions of L and H chains (Fv)

Affinity Labeling: made us aware of the presence of hypervariable regions/complimentarity determining regions (CDRs) on both heavy and light chains

Variable Regions:
• Hypervariable regions/CDRs: come together to form the antibody combining site, which binds Ag
• Framework regions

Answer 244

A

Isotypic: heavy chains differ in either class or subclass (ie. IgM vs. IgG; IgG γ1 vs. IgG γ2)
Allotypic: variance among different individuals due to genetically determined amino acid insertions
- Insertions usually in the constant regions of the heavy and light chains
- Human allotype reagents come from patients receiving multiple transfusions
Idiotypic: amino acid inserts in the variable regions of both the light and heavy chains
- Inserts can occur in both the hypervariable/CDR region and the framework residue
- Have a shared antigen binding specificity
- Important for: Immune regulatory network, vaccine development

Answer 245

A

Ag injected into 1 → Ab1 produced; injected into 2 → Ab2 produced; injected into 3 → Ab3 produced
• Ab2: anti-idiotype (reacts with Ab1)
• Ab3: anti-anti-idiotype (reacts with both Ab2 and Ag)
Therefore, the injection of an anti-idiotype results in production of Abs against the Ag in question

Answer 246

A

Barriers: epithelial surfaces, mucosa
Antimicrobial molecules: defensins, acidic pH
Phagocytic cells: macrophages, PMNs
TLRs: recognize pathogens
Inflammatory response
Cytokines/chemokines
NK cells
Complement system

Answer 247

A

Penetration of epithelium (activates innate immunity)
Pathogen recognized by tissue macrophages and that macrophage is activated
Active macrophage produces chemotactic factors to recruit PMNs and cytokines (initiate inflammation)
Macrophage phagocytizes the pathogen and kills it
-Inflammatory process allows cells to arrive from the blood (PMNs, monocytes, leukocytes)
… Monocytes entering tissue become either macrophages or dendritic cells, depending on cytokine environment
Complement and clotting proteins also arrive

Answer 248

A

Tight junctions
Mucus/cilia
Low pH
Enzymes (lysozyme)
Anti-bacterial peptides (defensins)
Normal microbial flora (impede growth of pathogens via competition and production of antimicrobial compounds)

Answer 249

A

Low pH in phagolysosome
Toxic oxygen products and NO
*Chromic Granulomatous Disease: patient unable to make superoxides; susceptible to bacterial and fungal infections
Defensins
Lysozyme (gram positive)
Lactoferrin (binds Fe)

Answer 250

A

Mannose Binding Lectin (MBL) Receptor: MBL binds mannose on bacterial surface; MBL + pathogen then bind MBL receptor on phagocyte; increases binding affinity
Mannose Receptor: binds mannose on surface of pathogen
Surfactant Protein A and D Receptors: SPA and SPD both react with pathogen first and then bind these receptors; increases binding affinity
Scavenger Receptors: react with lipoproteins
fMet-Leu-Phe (N-formylated peptides) Receptor: chemotactic receptor (these peptides attract phagocytes)
Toll-Like Receptors (TLRs): signal inducers; 9-10 in humans; any one phagocyte has all receptors; trigger production of anti-fungal peptides. Some are on the outer cell membraine, others on intracellular endosomes

Answer 251

A

TLR-4: binds bacterial LPS; triggers activation of NFkB; genes encoding proteins involved in defense against bacterial infection activated
TLR-3: binds viral dsRNA; triggers synthesis of IFN α and β, which:
• Protect uninfected cells: inhibit translation of viral mRNA
• Activated NK cells: kill virus infected cells
• Increase expression of MHC class I: promote cytotoxicity of infected cell by T cell

Other Targets: 
• Bacterial flagellin (TLR-5)
• Unmethylated CpG DNA (TLR-9)
• Peptidoglycan (TLR-1:TLR-2)
• Zymosan (TLR-1:TLR-2

Answer 252

A

IL1: proinflammatory
- Local: activates endothelium and lymphocytes
- Systemic: induces fever and stimulates IL6 production
IL6: proinflammatory
- Local: activates lymphocytes, increases Ab production
- Systemic: induces fever, induces liver to produce acute phase proteins
Acute Phase Proteins: produced in the liver in response to infectious agents
➢ C Reactive Protein (CRP)/MBL/SPA/SPB: all bind bacteria and act as an opsonin for phagocytes; also activate complement
➢ CRP is used as an indicator for inflammatory response (also elevated in cardiovascular disease)
TNFα: proinflammatory
- Local: activates vascular endothelium (induces adhesion molecules); induces permeability
Adhesion Molecules on Endothelium:
➢ Selectins: on the endothelium; bind carbohydrates on leukocytes to initiate interaction/slow leukocytes; weak binding which slows leukocytes
➢ICAMs (intracellular adhesion molecules): ligands for integrins on leukocytes
Adhesion Molecules on Leukocytes:
➢ Integrins: bind to ICAMs on endothelium and dendritic cells; strong binding
- Systemic: induces fever and shock
IL8: chemokine that attracts PMNs, basophils and T cells (local effects)
IL12: activates NK; induces CD4+ TH0 cells to become TH1 cells (local effects)
Natural Killer (NK) Cells:
• Lymphoid precursor
• Kill virus infected cells and tumor cells
• Targets cells that are deficient in MHC class I
• Also have inhibitory receptors that recognize MHC class I to protect normal cells

Answer 253

A

Initiated by pathogen induced tissue damage and macrophage activation.
Dilation/increased permeability of capillaries= increased blood flow (swelling, heat, redness).
Expression of adhesion molecules on endothelial cells= leukocytes bind.
Secretion of vasoactive peptides increases vascular permeability.
Clot formation prevents spread of pathogen.

Answer 254

A

= a group of plasma proteins that function in both innate and adaptive immunity; plays a key role in host defense

Deficiencies in complement proteins lead to infection
Elevated activation of complement leads to several disease syndromes

Activated by Ag-Ab complexes (adaptive immunity), microbial products, or acute-phase proteins (innate immunity) (Ie: classical, alternative, lectin pathways)
• Activation results in a cascase effect where in each protein becomes enzymatically active and modifies multiple substrate molecules. C3 plays a major role in all 3 activation pathways.

Functions:

Attracts phagocytes: C5a chemotactic for PMNs
Inflammation: C3a and C5a are vasoactive (smooth muscle contraction, activate mast cells)
Opsonization: macrophages and PMNs have receptors to bind C3b and C4b
Direct killing of pathogens: C5b-C9 disrupt cell membranes of pathogens

Answer 255

A

Activation: Ag-Ab complex (adaptive immunity); IgM or IgG

Steps:

C1q binds the Fc portion of the Ab that is bound to the Ag
C1q undergoes conformational change to bind C1r and C1s (serine proteases); C1qrs complex can cleave both C4 and C2
C4 is cleaved into C4a (soluble) and C4b (remains attached)
C2 is cleaved into C2b (soluble) and C2a (remains attached)
Resultant molecule is C4b2a (C3 convertase) attached to the pathogen
C3 convertase cleaves C3 into C3a (soluble) and C3b (remains attached), forming C4b2a3b (C5 convertase)
C5 convertase cleaves C5 into C5a (soluble) and C5b (remains attached)
C5b initiates assembly of (and helps form) the membrane attack complex
C6-C9 forms a pore in the membrane, lysing the cell

Answer 256

A

Activation: MBL (acute phase protein) binds mannose on the pathogen (innate immunity)

Steps:

MBL binds mannose on the pathogen and is then able to interact with MBL-activated serine protease (MASP), which cleaves C4 and C2
The C4b2a C3 convertase is formed
C3 convertase cleaves C3 into C3a (soluble) and C3b (remains attached), forming C4b2a3b (C5 convertase)
C5 convertase cleaves C5 into C5a (soluble) and C5b (remains attached)
C5b initiates assembly of (and helps form) the membrane attack complex
C6-C9 forms a pore in the membrane, lysing the cell

Answer 257

A

Activation: by microbial products (ie. LPS)

Steps:
1. Spontaneous hydrolysis of C3 to C3a (soluble) and C3b (deposited on surface of pathogen)
2. C3b binds Factor B
3. Factor B is cleaved by Factor D to form Ba (soluble) and C3bBb (C3 convertase)
The rest of the process is the same as above
• C5 convertase will be C3bBb3b

**Properdin (Factor P): binds to produced a stabilized C3 convertase (C3bBb is unstable

Answer 258

A

binds to produced a stabilized C3 convertase (C3bBb is unstable)

Answer 259

A

Regulatory proteins exist in plasma and on host cells
o Prevent accidental activation
o Not present on pathogens
C1 Inhibitor: dissociates C1r and C1s from C1q; prevents excessive activation of C4 and C2
Hereditary Angioneurotic Edema: lack C1 inhibitor; C2b buildup causes swelling
o C1b also acts on bradykinin

4. Other Regulators: 
o	C4b binding protein
o	DAF
o	Factor I
o	Factor H

Answer 260

A

Cell Mediated Reactions: carried out by effector cells
- Tissue rejection
- Delayed hypersensitivity
- Graft vs. host reactions
Humoral Antibody Synthesis: carried out by effector molecules
- Agglutination
- Toxin neutralization
- Immediate hypersensitivity

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Immunology Flashcards

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