Immunology – Immunoglobulin (Ig)

Chapter 1: Immunoglobulin (Ig)

• What are Immunoglobulins? Where are they produced?

– Immunoglobulins are glycoproteins, produced by plasma cells.

• What holds the two heavy and light chains together?

– Disulfide covalent bonds.

• Which of the following regions is the heaviest?

– VH region (variable heavy chain). The VL, CL, and CH regions have only about 110 amino acids, while VH has 330-440 amino acids.

• To which constant region of Ig does the carbohydrate attach?

– CH2 region (mostly).

• Are the hypervariable regions (CDR/HVR) and the complementarity determining regions (determinant) the same? What are they? Is the framework region the same? How many CDR/HVR regions are there in total?

– The hypervariable regions (CDR/HVR) and the complementarity determining regions are the same.

– They are variations on the Ig molecule, specifically where the antibody exhibits its specificity for an antigen.

– The framework region lies between the hypervariable regions.

– There are a total of 3 CDR/HVR regions.

• 1. Fab: Digestion with …. breaks …. forming?

2. Fc: Digestion with …. creates …. called Fc because it can ….

3. F(ab’)2: Treatment with …. cleaves …. into ….. and Fc is further degraded by pepsin

4. What are the differences that create the above components?

– 1. Papain – hinge region before the disulfide H-H bridge – light chain x VH-CH1

– 2. Papain – remaining part containing CH2-CH3 – crystallization

– 3. Pepsin – after the disulfide bridge

– 4. Location of the cut and the chemical used.

• What is the smallest valence of an antibody? What is the largest? What is the significance?

– The smallest valence is 2, the largest is 10.

– The number of valencies determines the number of antigens that can be bound.

– Antibodies can recognize multiple antigens, but only one specific antibody for a specific antigen.

• Fill in the names of the heavy chains in the blanks:

1. IgG – gamma

2. IgM – mu

3. IgA – alpha

4. IgD – delta

5. IgE – epsilon

• Names of the two types of light chains?

– Kappa – Lambda

• Fill in true or false, correct if false :)) : IgG

1. IgG is the most versatile Ig, capable of performing all functions. (True)

2. IgG is the main Ig in serum, accounting for 60%. (False) IgG accounts for 75%

3. IgG is the second most abundant Ig in serum. (False) IgG is the most abundant)

4. It is one of the Ig types that can be transmitted through the placenta. (False) IgG is the only Ig that can be transmitted through the placenta)

• Of the IgG subclasses, which has the most different structure? Which cannot pass through the placental membrane?

– IgG3 has a longer hinge region.

– IgG2 and IgG4 lack Fc regions and cannot pass through the placental membrane.

• True false correct :)) : IgM

1. IgM on B cells and in serum is in monomer form. (False) IgM on B cells is a monomer, in serum it is a pentamer)

2. The theoretical valence is 10. (True)

3. The second Ig produced in the fetus, the first when antigen stimulates. (True)

4. It is a good agglutinin, strongly activates complement. (True)

• Which Ig has the CH4 domain?

– IgM and IgE

• What protein does IgM bind to on the surface of B cells?

– Ig-alpha and Ig-beta

• True false correct : IgA

a. In serum, IgA is a dimer, but in secretions it is a monomer. (False) The opposite is true)

b. Secretory component (T component) is produced in plasma cells attached to A in secretions. (False) Epithelial cells)

c. The T component helps protect and transport IgA through the mucosa. (True)

d. IgA strongly activates complement. (False) It does not activate unless it binds)

• Arrange the prevalence of Igs:

– IgG (No1)

– IgA (No2)

– IgM (No3)

– IgE (Last place)

• True false correct : IgD x IgE

a. IgD exists as a monomer. (True)

b. It is mainly found on the surface of T cells. (False) B cells)

c. IgE binds tightly to basophils and mast cells. (False) Basophils)

d. Plays an important role in allergic diseases. (True)

• Antigen binding receptor on the surface of B cells:

– IgM in monomer form and IgD (with an additional aa sequence at the C-terminus to help bind to the cell membrane, non-covalently linked to Ig alpha and beta)

• Of the following Igs, which activates complement?

– IgM

Chapter 2: Antigen (Antigen)

• Regarding hapten, choose the correct statement:

a. It is a substance that does not have antigenicity, but can react with products of specific immune responses. (False) Hapten has antigenicity)

b. They are small molecules. (True)

c. They cannot elicit an immune response on their own, but when hapten binds to a suitable carrier protein molecule, the immune system can be activated. (True)

d. Hapten is immunogenic. (False) Hapten is not immunogenic)

• True false correct : Antigen

a. Only non-self substances elicit an immune response. (False) Only substances that are “foreign” to the immune system)

b. The larger, more complex, and more difficult to phagocytose, the more immunogenic. (False) The easier to phagocytose)

c. The more soluble, the more immunogenic. (False) The opposite)

d. The more natural, the more immunogenic. (False) The opposite)

• DSSS2 :

a. Most antigens are proteins and are very potent. (True)

b. Polysaccharides are also potent immunogens. (True)

c. Nucleotides are also potent immunogens. (False) Weak)

d. Lipids are usually weak immunogens. (False) None)

e. Usually nucleotides are thymus-independent antigens. (False) Polysaccharides)

• Of the following properties, how many are properties of thymus-independent antigens? Which ones?

a. Polymer structure with repeating antigenic determinants. (True)

b. Strong antigenicity to elicit an immune response. (Not related)

c. Complex structure. (Not related)

d. Usually combined with… (Not related)

e. Resistant to degradation. (True)

f. Long-lasting in the body. (True)

g. Activates B cells at high concentrations. (True)

– There are 4 properties: a, e, f, g.

• Thymus-dependent antigens are usually? Why?

– Proteins.

– Because T cells only recognize antigenic determinants that are protein in nature.

• Carrier?

– Determines the antigenicity of the hapten -> hapten-carrier complex

• DSSS 3 : Superantigen :))

a. Unlike conventional antigens that only activate a small number of T cells, superantigens can activate over 40% of T cells. (False) 25%)

b. Superantigens are usually thymus-independent antigens. (False) Dependent)

c. Superantigens often activate CD4+ T cells to release a lot of cytokines. (True)

d. Superantigens react with T cells because they have specific receptors. (False) Due to their similar structure)

• Factors influencing immunogenicity, choose the correct statement:

A. Subthreshold doses do not elicit optimal immune responses, threshold or supra-threshold doses elicit optimal immune responses. (False) Both supra-threshold and sub-threshold doses do not elicit optimal immune responses)

B. Introducing antigens intravenously is less effective than orally. (False) Intravenous is more effective than oral)

C. Different methods of immunization (injection, oral, spray) do not change the nature of the response. (False) They can change the nature of the response)

D. Adjuvants should be used to enhance the immune response to antigens. (False) Adjuvants are not recommended because they can cause fever and inflammation)

• The following regions have isotypes, EXCEPT:

A. CL

B. CH1

C. CH2

D. CH3

– B. CH1. Isotype of the heavy chain is found on the Fc portion of the constant region, isotype of the light chain is found in the constant region.

• True false correct : isotype – allotype – idiotype

a. Isotype is species-specific, allotype is individual-specific, idiotype is antibody-specific. (True)

b. Isotype is found in the constant region of the Fc of the heavy and light chains. (True)

c. Idiotype, allotype, and isotype are antigenic determinants on antibodies. (True)

d. Idiotype is located in the constant region of the antibody, like the other two. (False) Fab fragment of the hypervariable region)

• True false correct :

a. Fab and F(ab’)2 are the same in terms of structure. (False) F(ab’)2 still has a link, Fab are two fragments)

b. The Ag-Ab reaction is a manifestation of the key-lock mechanism. (True)

c. The bonds holding Ag-Ab together are all covalent bonds in nature. (False) Non-covalent: hydrogen, electrostatic, vdw,… )

d. Avidity is the sum of Affinities. (False) Avidity is more than the sum of affinities due to the influence of both antigen and antibody valencies)

Chapter 3: Specific – Non-specific Immunity

*(Most of it is already in microbiology, so just review it :)))*

• a/ The birth of immunology is marked by L.Pasteur in 1885 when he vaccinated Joseph Meister against rabies.

• b/ Father of natural immunity Probiotic : Elie Metchnikoff

• c/ Lysozyme has an antigen that cuts the glucosamine and muramin bonds in the bacterial membrane

• d/ Cytokine are the inflammatory proteins produced earliest

• e/ The central molecule of complement activation is C3a

– a/ False (Edward Jenner – smallpox in 1798 – pioneered vaccination)

– b/ True (and introduced the phenomenon of phagocytosis)

– c/ True

– d/ False (CRP)

– e/ False (C3b)

• a/ The classical pathway of complement activation requires a specific immune mechanism, while the alternative pathway does not.

• b/ Antibody-dependent cell-mediated cytotoxicity: ADCC

• c/ Central tolerance is the immune system’s ignorance of allergens, gut bacteria, etc…

• d/ The alternative pathway is usually triggered by antigen presentation.

– a/ True

– b/ True

– c/ False (peripheral tolerance)

– d/ False (bacteria and their toxins)

Chapter 4: Complement system

• True false correct :

a. There are 3 pathways of complement activation: the classical pathway, the alternative pathway, and the lectin pathway. (True)

b. The classical pathway is labeled with C and numbers according to the order of the reaction. (False) Order of discovery)

– c. The lectin pathway is named after capital letters, the alternative pathway starts with #%@$ and the rest is similar to the classical pathway. (False) MASPs, the opposite)

– d. Complement system production: all cell types. (False) Liver cells, monocytes)

– e. Activated proteins are split into two unequal fragments, the larger a fragment is attached and the smaller b fragment is free. (False) Reverse the order of a,b)

• Of the following organs/systems, which produces complement?

a. Liver

b. Digestive system

c. Urinary

d. All 3 are correct

– D

• Dsss: Classical pathway

a. C1 complex: C1q(C1r,C1s)2 has C1q activated to bind to IgM, IgG2/3/4. (False) IgG1/2/3)

b. C1r activates to cleave C4 into C4a/C4b and C4a cleaves C2 into C2a/b. (False) C1s, C4b)

c. C4b + C2a = C3 convertase. (False) C2b)

• Dsss: MBL – lectin pathway

a. MBL # C1q, MASP1# C1s, MASP2#C1r. (False) MASP reversed)

b. MBL binds to glucose on disease cells. Normal cells: sialic acid. (False) Mannose)

c. MBL binds to the surface, activating MASP1/2 to cleave C4,C2 -> forms C3 convertase as above. (True)

• Dsss: alternative pathway

a. Does not depend on binding to pathogens. (True)

b. C3 -> C3 H2O + FactorB — (catalyzed by factor D )—-> Ba/b. (True)

c. C3 H2O + Bb forms C3 convertase. (True)

• Dsss: Forming C5 convertase x MAC

a. C3 + C3 convertase —> C3a/b. (True)

b. C3b combines with H, CR1 and MCP will be brought to Factor I to create an activated form to create opsonization. (False) Inactive)

c. C3 convertase combines with C3a to amplify the cleavage of C3. (False) C3b)

d. In the classical pathway, C5 convertase is formed from C3b, C4b, 2b, while lectin and alternate are C3b, C3b and Bb. (False) Classical + lectin)

(MAC: membrane attack complex)

• There is a passage in the book that you and your friends don’t know what will happen to C5b if it doesn’t bind to C6 and stabilize within 2′.

– C5b is unstable, but it remains bound to the activated complex for a short time (~ 2 minutes), during which it either binds to the single C6 from the surrounding fluid to form C5b,6 or it decays.

• a. C5b678 complex begins to be able to penetrate the cell membrane.

• b. 7-10 C9 come to combine with the complex and polymerize the C9 molecule.

• c. The pore size is about 70-100 Micromet.

• d. CD59 inhibits the process of C7 binding to the complex.

– a. False (C5b67)

– b. False (10-17)

– c. False (angstrom)

– d. False (inserts into the C9 polymer)

• a. Factor H has an affinity for sialic acid, catalyzing the degradation of C3b by I.

• b. C1 inh: separates C1r/s from C1q.

• c. Complement regulatory proteins have a high affinity for sialic acid.

• d. The primitive complement system only consists of C3,B,D.

– All true:

Chapter 5: MHC – TCR

• What are the products of MHC genes responsible for?

A. Transplantation

B. Controlling the immune response

C. AxB are both correct

D. AxB are both incorrect

– C

• True false correct : MHC class 1

a. T helper binds to MHC class 2, cytotoxic T class 1. (True)

b. MHC class 1 consists of non-coding alpha, coding beta. (False) Alpha codes)

c. The peptide binding region is formed by alpha 1 and alpha 3. (False) Alpha 1 and alpha 2)

d. The region carrying the allotype antigenic determinant is at the end of the peptide groove. (True)

e. The alpha 3 region binds to beta 2, is the constant region of MHC, and is where CD8 binds, consisting of a transmembrane region of 25 aa and a cytoplasmic region of 30 aa. (True)

f. The greatest amino acid diversity is in the wall and bottom of the binding groove (alpha 1 x 2). (True)

• True false correct 2 :

a. Peptide binding region: alpha 1 x beta 1, alpha 2 beta 2 region carries CD4. (False) Alpha 1 x alpha 2)

b. Beta is shorter than alpha, carrying the allotype antigenic determinant. (True)

c. All regions have disulfide bridges except beta 1. (False) There are disulfide bridges)

d. Region of amino acid diversity: beta 1. (True)

• True false correct 3

a. Allen suggested that MHC is codominant, expressed on the cell surface. (True)

b. Cytokines reduce MHC expression levels. (False) The opposite)

c. The maximum number of MHC1 that can be expressed is 8. (False) 6)

d. Intracellular protein fragments bind to MHC class 1 while extracellular fragments bind to MHC class 2. (True)

• True false correct : TCR :))

1. 2 chains: alpha contains constant region, beta contains variable region. (False) Both alpha and beta have both regions)

2. Delta-gamma T cells have both CD4 and CD8. (False) None)

3. TCR diversity is due to V,C (constant) and H (hinge) regions. (False) VDJ)

4. Alpha and beta have a structure similar to immunoglobulin. (True)

• CD3 consists of … gamma chains, one …. chain, 2 …… chains and ……… ……. chains linked from 3 tightly linked genes, while the …. chain is due to a separate gene related to signaling

– CD3 consists of 1 gamma chain, one delta chain, 2 epsilon chains and zeta chain.

– The gamma, epsilon, delta chains are linked from 3 tightly linked genes, while the zeta chain is due to a separate gene related to signaling.

• What is the function of CD3?

– Ensure surface expression of the T cell receptor and transmit activation signals into the T cell.

• True false correct :

a. Costimulatory and accessory molecules support T cell activation along with the peptide-MHC complex. (True)

b. Accessory molecules have diverse and variable structures, while costimulatory molecules are the opposite. (False) Both are less diverse and variable)

c. Cytokines increase the expression levels of costimulatory molecules. (False) Accessory molecules)

d. Important costimulatory molecules are CD29 binding to B7-2 (CD60) or B7-2 (CD80). (False) CD28 – B7-1 (CD80) – CD86)

e. Costimulatory molecules enhance the activation of peptide-MHC and TCR, while accessory molecules enhance the binding ability of the two. (False) Delivering the second signal for T cell activation – increasing the binding ability of T cells and antigen-presenting cells/target cells)

• True false correct : role of MHC in transplantation

a. HLA is human MHC, H-2 antigen is mouse MHC. (True)

b. Xenograft is a graft between two individuals of the same species. (False)

c. Allograft is a graft between two individuals of the same species. (True)

d. Grafting foreign tissue into a host will induce an immune response that will reject the graft. (False) The opposite)

e. Survival time of graft: xeno < allo < iso = auto. (True)

f. Donor with different MHC, second or rejected grafts will be rejected quickly. (False) Same MHC)

g. All transplantation antigens participate in the rejection process. (False) Except class 3)

• MHC class 1 contains mainly genes in 3 regions: …….. ….. chain helps express MHC class 1, ……. forms the antigenic determinant

– MHC class 1 contains mainly genes in 3 regions: A, B, C.

– The beta-2 chain helps express MHC class 1, alpha forms the antigenic determinant.

• MHC class 2 also has 3 regions including:………..

– MHC class 2 also has 3 regions including: DP, DQ, DR.

Chapter 6: Anatomy

• Structure of the immune system

• Dsss :

a. Naive lymphocytes are produced in the bone marrow and mature in the thymus. (False) T matures in the thymus, B in the bone marrow)

b. Peripheral lymphoid organs: lymph nodes, spleen, MALT,… capture antigens and present them to mature T lymphocytes. (True)

c. B lymphocytes in birds mature in the Bursa of Fabricius. (True)

d. Tooth cells express high levels of MHC2 on the cell surface. (True)

• a. To distinguish lymphocytes, monoclonal antibodies against various CDs are used and analyzed by flow cytometry.

• b. Null cell : CD19+, CD3- (NK)

• c. NK are cells that lack CDs to define them as a lymphocyte lineage, but still have immune memory and specificity.

• d. CD3+ can be either T lymphocytes or B lymphocytes.

– a. True

– b. False (CD16,CD56, CD3-)

– c. False (They don’t have these properties at all)

– d. False

• Lymphoid tissue-like structures are located in: mucous membranes, intestines, bronchi? Describe how lymphoid tissue-like structures in the mucosa protect (Transporting cells, activating B lymphocytes, antigen protection?)

– MALT, GALT, BALT

– (M cells carry antigens in to activate B lymphocytes and activated B lymphocytes leave the follicle into the MALT to secrete specific IgA)

• a/ Lymphocytes that encounter specific antigens live longer than normal lymphocytes.

• b/ Factor P is the reason the classical pathway is also called the properdin pathway.

• c/ Factor C3 was formerly called factor A.

• d/ Factor B, in the presence of C3b, acts as an enzyme on factor D to give us the C3bBb complex and the smaller Ba fragment is released.

– a/ True

– b/ False

– c/ True

– d/ False

• Factors involved in the alternative pathway include:

– Factor C3, previously known as factor A, but subsequent structural and functional studies confirmed it to be C3. Thus, C3 is very important because it is the meeting point of the two complement activation pathways.

– Factor B is a β – globulin. Factor B in combination with C3b and the presence of Mg++ ions can partially activate C3. However, this ability increases with factor D to form the complex C3bB into C3bBb.

– Factor D when in the presence of C3b acts as an enzyme on factor B to give us the C3bBb complex and the smaller Ba fragment is released.

– Factor P or properdin does not have the structure of an immunoglobulin. P is absorbed to the complex C3bBb making this complex stable, and people also call the alternative pathway the properdin pathway

• The C3bBb complex?

– The C3bBb complex is an enzyme that acts on C3 as a substrate, so it creates an amplifying loop, also known as a positive feedback loop. In addition, compared to the C3bBb pathway, C3b will be attached to form the C3bBb3b complex, which acts to cleave C5 to form C5b with enzymatic activity, which requires the following steps in the complement reaction chain.

Chapter 7: Cytokine

• a. There are four subpopulations of Th cells: Th0, Th1, Th2 and Th3.

• b. Cytokines secreted by lymphocytes are called lymphokines: IL-1 -> IL6.

• c. If T cells (mainly CD4) are inactivated, lymphokines will be shut down in AIDS.

• d. TCD4 accounts for 1/2 of the total number of T cells.

• e. TCD4 also supports the activation of the other 2 types of T cells.

– a. False (Th17 replaces Th3)

– b. False (Missing: IFN-7, GM-CSF and no IL-1)

– c. True (B lymphocytes do not produce lymphokines)

– d. False (3/4)

– e. True

• a. Cytokines are polysaccharides that regulate immune and inflammatory responses.

• b. They are secreted in large amounts and self-limiting.

• c. The reactions are often multidirectional and overlapping.

• d. Effects are independent of other cytokines.

– Only C :)))

– a. polypeptide

– b. small amount

– c. True

– d. Not independent

• a. External signals can directly regulate the response of cytokines.

• b. Cytokines mainly alter gene expression to create new functions without causing proliferation of target cells.

• c. The two main functions of cytokines are as mediators and regulators of innate/acquired immunity.

• d. Cytokines are specific to each type of immune response.

– a. False (Indirectly through receptor exposure)

– b. False (Can proliferate)

– c. False (Missing: acting as a hematopoietic stimulant)

– d. False (They can have the same effects)

• a. The mononuclear phagocytic system or mononuclear phagocytic system (MPS), also known as the reticuloendothelial system or macrophage system, is the site of production of innate cytokines.

• b. NK cells cannot produce cytokines.

• c. Innate cytokines regulate the population of T lymphocytes and other leukocytes.

• d. Cytokines have the ability to stimulate the production of immature erythrocytes.

• e. Innate cytokines are produced by mononuclear phagocytes, acquired cytokines are produced by lymphocytes.

– a. True

– b. False

– c. False (Innate create early inflammatory responses)

– d. False (Immature leukocytes)

– e. True

• How many types of cytokine receptors are there in total? Classified based on what criteria?

– 5 types, based on the extracellular domain that binds to the cytokine.

• a. Type 1 domain has 2 pairs of …… fixed and near-membrane sequence ……. (X is any amino acid). Accepts cytokines with a structure of …. alpha helix ….

• b. Type 2 differs from type 1 in that it lacks …….

• c. The …… superfamily has …… extracellular domains.

• d. …… receptors carry domains containing many …… molecules, when bound, creating …… or …….. or both.

• e. Snake-shaped receptors have ….. transmembrane, mediating rapid responses of the …… cytokine family.

– a. Cystein – WSXWS – 4 – alpha

– b. WSXWS

– c. Ig

– d. TNF – cystein – apoptosis – gene expression induction

– e. 7 helices – chemokine

• Hematopoietic receptors?

– Type 1

• Of the following cytokine types, which belong to innate immunity?

a. TNF

d. IFN type 1

b. IL-1

e. Interferon gamma

c. IL-2

f. Chemokine

– a, b, d, f

• The following exercises are classic true-false correct exercises

– Try your best :)) gud luck

• TNF:

a. The main mediator of acute inflammation against gram-positive bacteria and severe infections. (False) Gram-negative)

b. The strongest inducer of TNF production is LPS. (True)

c. There are two types of receptors: TNF-RI and TNF-RII. (False) THF-RI)

d. Aggregates neutrophils and monocytes, binds mainly to endothelial cells via ligands. (False) Macrophages and monocytes, selectins are involved in binding)

e. TNF is an endogenous pyrogen, LPS is exogenous. (True)

f. Fever due to TNF and IL-1 is mainly through adrenaline. (False) Prostagladin)

g. It acts on the liver to induce an acute phase inflammatory response. (True)

h. Prolonged TNF production causes depletion of fat and sugar. (False) Fat and muscle)

i. It is a potent anticoagulant. (False) Coagulation causes thrombosis)

j. Septic shock due to bacterial LPS generates a lot of TNF and other cytokines. (True)

• a. The origin of IL2 is similar to TNF.

• b. There are 3 forms of IL1: alpha., beta and gamma. The alpha form is most common in circulation.

• c. The receptor family belongs to the Ig superfamily. Type 1 receptors are mainly on B cells, while type 2 are found on most cells.

• d. The systemic effects of IL-1 are similar to TNF: systemic, mobilize the liver, and cause depletion, except that IL-1 is not involved in apoptosis and septic shock.

• e. Low concentrations of IL1 act as local inflammatory mediators, while high concentrations act as hormones.

• f. Macrophage production of IL-1 is a natural antagonist of IL-1.

– A. False (Also in epithelial/endothelial cells, neutrophils)

– B. False (No gamma, beta is most common)

– C. False (The opposite)

– D, E, F True

• a. Chemokine is a chemotactic cytokine that can guide leukocytes. Chemokine classification is based on the number of arginines at the tail.

• b. The two main families of chemokines are CC and C.

• c. Chemokine receptor family