Immunology II

Question 1

Primary Lymphoid Organs

Answer 1

Bone marrow- where B cells develop

Thymus (bilobed)- where T cells develop:
Progenitor cells from the bone marrow migrate to the thymus where the cortex contains immature thymocytes, which mature and migrate to the medulla
In the medulla they learn to discriminate between self and non-self during fetal development and short time after birth, then leave the medulla and enter the peripheral blood circulation where they are tranported to the secondary lymphoid organs
Reaches its maximum size and activity at birth
Atrophies with age –almost disappears at puberty

DiGeorge syndrome:
Congenital absence of thymus results in an immediate and drastic reduction in T cells that produces a potentially lethal wasting disease

Question 2

Secondary Lymphoid Organs

Answer 2

The secondary lymphoid organs have two major functions:

1. Trap and concentrating foreign substances
2. Main sites of production of Abs and T cells

The major secondary lymphoid organs include:
Spleen- responsive to blood-borne antigens
Lymph nodes- protect the body from antigens that enter from the skin & internal surfaces via the lymphatic system

Mucosa-associated lymphoid tissue (MALT):
Scattered along mucosal linings
Protect against Ags entering the body directly through mucosal surfaces

Question 3

Spleen: Anatomy

Answer 3

White pulp: has many WBCs and this includes T and B cells, and when the B cells mature they leave and go to the red pulp and are associated with RBCs and other cells
The spleen is important for phagocytosis facilitated by Ab and other opsonization methods, therefore you find phagocytosis of encapsulated cells is important to happen in the spleen because without the spleen it is difficult for phagocytes to capture these encapsulated cells
People without spleen, frequent infections with encapsulated bacteria

Question 4

Lymph Nodes

Answer 4

Lymph nodes are clustered in strategic points in the body: neck, axillae, groin, mediastinum, abdominal cavity
Filter Ags from interstitial tissue fluid and lymph during its passage from the periphery to the thoracic duct

Two types:
Somatic nodes: Lymph nodes that protect the skin
Visceral nodes: Deep lymph nodes protecting the respiratory, digestive, and genitourinary tracts

Question 5

MALT

Answer 5

More than 50% is lymphoid tissue
Mucosa-associated lymphoid tissue is composed of
GALT- line the intestinal tract (Gut)
BALT line the respiratory tract (Bronchus)
Genitourinary tract lining lymphoid tissue

Secretory IgA (sIgA) 
Major effector mechanism; only Ab that can be secreted out of the body/tissue
Secreted directly onto the mucosal epithelial surfaces

Question 6

Examples of MALT

Answer 6

Peyer patches that line the small intestine and mainly secrete IgA; always the cells that makes IgA regardless is the B cell
Appendix
Tonsils

M cells that are associated with the intestine and the purpose of their existence is the increase the surface area that is exposed to the nutrients within the intestines; they have microfolds on only one side of the intestine to increase the absorption of the nutrients
Absorb, transport, process, present antigens to subepithelial lymphocytes

Question 7

Polyclonal Ab

Answer 7

Polyclonal Abs are a heterogeneous mix of Abs that recognize multiple epitopes but Ab specificity against the same Ag (many Ab, one Ag); recognizes many epitopes on only one type of antigen
Produced by variety of Ab-producing cells
They are many clones of cells
Polyclonal Abs recognize & react against different epitopes on the Ag
Avidity- sum of the affinities to the different epitopes or the sum of the members of the polyclonal group
Isolate them by growing them in a mouse

Question 8

Monoclonal Ab

Answer 8

Monoclonal Abs are produced by a single clone of cells (only one B cell)
Resultant Abs are identical in all aspects with the same affinity and same binding specificity
Recognize the same epitope
They are produced in hybridoma between activated B cells and malignant plasma cells (fusion) so lengthen the live of the B cells and give the myeloma cells Ab producing abilities

Question 9

IgG

Answer 9

Antigen binding sites in the variable region
Constant part of light chain doesn’t really have a function associated with it, but the heavy chain part is the Fc fragment where we treat the molecule with papain that is an enzyme that can break the proteins on the certain site and get two identical fragments of Fab, which maintains the function of the Ab because they contain the Ag binding site needed to bind Ag
The Fc fragment (H/heavy chain) crystallizes in the cold and can bind to Fc receptors on other cells and so if you have a complete Ab by binding to the antigen specifically, then the Ab can bind to the cell (phagocyte, macrophage, NK, etc) and this will bring the antigen closer to the cell so it can be phagocytosed and then destroyed
Heavy Chain Designation: gamma
Subclasses: 4
Biologic Activity: opsonin, fixes complement, crosses placenta

Question 10

IgM

Answer 10

IgM heavy chain has an extra domain compared with IgG
J chain- small cysteine-rich protein that initiates cross linking of C3 and C4 of 5 IgM monomers producing the pentameric form of IgM found in circulation

Cysteine rich regions to form disulfide bridges to combine the chains together and bind the whole complex together
When the B cells mature, they produce IgM first; if the B cells matures further in a process called Class Switching, it changes to other Ig’s; the change must keep the specificity the same or it doesn’t serve the purpose; the variable part does not change and the constant region will change
Heavy Chain Designation: mu
Subclasses: 1
Biologic Activity: fixes complement, agglutination, antigen receptor, indicative of acute infections

Question 11

IgA

Answer 11

IgA2: secretory IgA is dimeric and held together by J chain and secretory component
IgA1: serum IgA is monomeric
Heavy chain has three constant regions
Only Ig that is secreted outside of the body/tissue to fight infections in the mucosa in the body; eye (conjunctivitis), intestine, respiratory system
Heavy Chain Designation: alpha
Subclasses: 2
Biologic Activity: secretory Ab and agglutination

Question 12

IgE

Answer 12

IgE is similar to IgG
Has 4 constant region domains on the H-chain like IgM
Allergy
Defense against parsitic infestation
Heavy Chain Designation: epsilon
Subclasses: 1
Biologic Activity: anti-parasitic and allergy Ab

Question 13

IgD

Answer 13

Similar to IgG in structure, but NEVER secreted
Functions as a receptor on the B cell always
Variable parts have specificity and bind certain antigens; determines which Ig that is released from the B cell
Part of the receptor/signaling complex of B cells
Heavy Chain Designation: delta
Subclasses: 2
Biologic Activity: antigen receptor

Question 14

Primary Ag-Ab Reaction

Answer 14

The first interaction between Ag & Ab
Key-lock principle like enzymes, but doesn’t need an enzyme
Ag-Ab interaction is precise = specific
Characteristics of Ag-Ab reaction:
i. Rapid, in seconds
ii. Independent of electrolytes, salt, buffer
iii. Not visible

Question 15

Chemical Interactions for Ab-Ag Reactions

Answer 15

Four noncovalent interactions hold antigenic determinants w/in Ab-binding site:

1. Coulombic (electrostatic, ionic) interactions
2. Van der Waals forces- weak attractive force between atoms or nonpolar molecules caused by a temporary change in dipole moment arising from a brief shift of orbital electrons to one side of one atom or molecule, creating a similar shift in adjacent atoms or molecules
3. Hydrogen bonds
4. Hydrophobic interactions

Question 16

Affinity and Avidity

Answer 16

Affinity is the strength of Ag-Ab bonds between a single epitope and an individual Ab’s binding site
Avidity: The binding strength between a multivalent Ab (polyclonal Ab) and a multivalent Ag

K = [Ag..Ab]/[Ag][Ab] = Ab affinity/association constant
K = Associated complex/dissociated Ag & Ab
Dissociation constant: 1/K, meaning that you put the [Ag] [Ab]/ [Ag….Ab]; the smaller the amount of D, the higher the affinity; reverse of other equation
The higher K, the higher the association between Ab-Ag

Question 17

Secondary Ag-Ab Reaction/Response

Answer 17

Secondary Ag-Ab reaction: the conversion of the invisible primary reactions macroscopically visible ones as in the case of precipitation and agglutination

Secondary response: the immune response which follows a second encounter with a particular Ag

Question 18

Lattice Formation

Answer 18

Occurs when Ag-Ab complexes aggregate in form of precipitation in liquid medium - or -
Agglutination, including particulate components, other than Ag and Ab, such as cells

A regular arrangement of units into an array such that a plane passing through two units of a particular type or in a particular interrelationship will pass through an indefinite number of such units; e.g., the atom arrangement in a crystal.
Reference to a complex between several Ab and Ag at the same time instead of one Ab to one Ag

Question 19

Cytotoxic T cells

Answer 19

Cytotoxic T cells kill infected cells to prevent pathogen production
Cytotoxic T cell receptors detect viral protein fragments on the surface of infected cell
Large numbers of virus specific cytotoxic T cells are produced
EBV infection in B cells cause Tc cells to make up the vast majority of WBCs

Question 20

Resting vs. Active B cells

Answer 20

No Gall bodies
No LGL morphology
Monoribosomes scattered in the cytoplasm
Activated B cells have rough ER whereas inactive ribosomes aren’t attached to the ER

Question 21

T cell Independent Defense Mechanisms

Answer 21

Phagocytosis

Chemotaxis

Question 22

Complement Cascade: Classical Pathway

Answer 22

Classical: requires IgG in a complex with Ag, or IgM; these are the activators; this pathway is associated with acquired or adaptive immunity
Activated after the Alternative pathway via Antigen-IgG (1-3) complex, pentameric IgM
Non-Activators: IgG4, IgA, IgE because they lack C1q receptors and cannot bind C1q
C3b is produced and that point on is the same for both pathways and goes on until it produces the membrane attack complex and destroys the cell

Question 23

Complement Cascade: Alternative Pathway

Answer 23

Alternative: does not require Ab to be activated

activated by components of the infectious agents like cell wall of bacteria, yeast, fungi, LPS, aggregated IgA, cobra venom; NO need for Ab-Ag complex or IgM for activation

This pathway is the first pathway to be activated because only the presence of the bacterium itself is sufficient enough to activate it, whereas the classical needs Ab in order to be activated

C3b is produced and that point on is the same for both pathways and goes on until it produces the membrane attack complex and destroys the cell

Question 24

Complement

Answer 24

Non-immunoglobulin serum proteins
Involved in:
i. Control of inflammation
ii. Stimulation of phagocytosis
iii. Activation of cell lysis
Cascade of different proteins that act upon each other as enzymes, and this system is designed to cause lysis of certain cells like bacteria, or own body cells sometimes as well
Defense: opsonization and stimulation of phagocytosis and inflammation process

Question 25

Opsonization

Answer 25

Preparation for eating/ phagocytosis facilitating process Opsonins are deposited on the Ag Examples: IgG and complement Bacteria can be labeled with IgG or complement fragments C3b or intermediate C3b or C4b can bind to the bacterium and bind to CR receptor so the bacteria is captured and swallowed by the phagocyte

Question 26

Complement Cascade: After Pathways Fuse

Answer 26

We must know that the component C3b is necessary for activation and comes from C3; C3b by itself is always present in the serum at low concentrations (alternative pathway) C3b can bind foreign substance like LPS, and this complex of LPS-C3b can bind to the factor B, which is present in the serum and then we have a complex that is called C3bB (factor B is second B); factor B acts as enzyme which causes separation of b and B so end product: c3bBb (C3 convertase enzyme) to split C3bB to get more C3b C3b has an anaphylactic role and vital to many cells End product is C3 convertase that produces C3b which binds to the same convertase to become C5 convertase (C3bBb3b) Only part of the C3b makes C5 convertase and the rest of the C3b is destroyed by the factors I and H, why? If we have a lot of C3b in the system and serves no function to make C5 convertase, then the C3b has to go somewhere; it is an opsonin and bind any cell in the body and tag them for phagocytosis and cause a lot of damage, so need to get rid of it Start with small amount of C3b in serum and need to generate more to make it more sufficient aka amplification

Question 27

Sites of Complement Synthesis

Answer 27

As opposed to Ig Abs which are synthesized in B (plasma) cells only, complement proteins are synthesized in hepatocytes, macrophages (various tissues), epithelial cells (GI tract), and monocytes in blood

Question 28

Functions Complement

Answer 28

Direct killing of bacteria & virus-infected cells by lysis mediated by MAC, which inserts itself in the membrane of the target to make holes to cause lysis of the cell Indirect killing by opsonization followed by phagocytosis & intracellular killing Immunization does NOT increase complement concentration in the serum part of the innate immune system

Question 29

Steps to Activate the Classical Pathway

Answer 29

Step 1: Activation of C1- C1q + C1r +C1s (C1r & C1s are proteases, activate C4 & C2) Step 2: Activation of C4- C4a +C4b; C4a is soluble and leaves, while C4b is stable Step 3: Activation of C2- C2a + C2b; C2b is the soluble part that leaves, while C2a is stable Step 4: Formation of C3 convertase- C4b2a Step 5: Activation of C3- C3a + C3b Activation of C5- C5a + C5b by C5 convertases: The classical C4b2a3b or the alternative C3bBb3b Classical and Alternative the same: C5b + C6 + C7  C5b67 .. + C8 C5b678 Adding 6 molecules of C9 to C5b678= MAC C5b678(9)6 making holes in the membrane and the cell lyses

Question 30

Split Products of the Complement Cascade with Activity

Answer 30

C4b and C3b = opsonins C3a and C5a = anaplylatoxins (mast cell degranulation) C5a = chemotaxis which attracts neutrophils

Question 31

Role of C3 in Bacterial Clearance and Killing

Answer 31

C3 bound to bacteria as C3b or iC3b binds to CR1 on erythrocytes, which transport bacteria through circulation C3 acts as focus for the deposition of lytic MAC on bacterial cell membrane It ligates complement receptor on phagocytes Complement, in turn, activates the phagocyte leading to bacterial phagocytosis, respiratory burst generation, and bacterial killing

Question 32

Lectin Pathway

Answer 32

Third pathway similar to the classic pathway, but without the need for Ab Activator: Mannose-binding lectin (MBL), a plasma protein Mannose-binding lectin binds to terminal mannose (sugar) on the surface glycoprotein of microbes This lectin activates the classical pathway proteins Protease function [similar to C1r &s] associated with MBL activates C4 and C2 and splits them into a and b to make C4b2a convertase Difference between LP and CP: 1. LP activation does not require antibodies  2. LP activation is part of the innate immune system

Question 33

3 Functions of Complement in Host Defense

Answer 33

1. Opsonization: C3b binds to microbes and so enables the phagocytes to grab the microbe, via their C3b receptor, and phagocytose it 2. Chemotactic activity of C5a: this complement fragment attracts neutrophils and monocytes to the site of infection and C5a promotes inflammation at the site of complement activation 3. Formation of membrane attack complex(MAC) where MAC forms a pore (hole)in the membrane of the microbe leading to the loss of cellular contents, lysis of the microbe and death of the microbe

Question 34

Complement Protein Deficiencies

Answer 34

1. Alternative pathway defects: easier to get H. influenza type B, which causes meningitis 2. Defects of Factor D and properdin via increase: increase Neisseria infections because blocking complement pathway because unable to make C3b 3. C5 deficiency: less severe consequences, but increases susceptibility to N. gonorrhoeae and meningitidis

Question 35

Complement Disease and Pathogenesis

Answer 35

Complement may cause disease pathogenesis by: 1. Systemic production of anaphylaxis such as after Gram-negative sepsis 2. Insertion of MAC into host cell membrane leading to cellular activation and stimulation of membrane arachidonic acid metabolism 3. Fixation of C3b to immune complexes located in tissues causing recruitment and activation of tissue and circulating WBCs

Question 36

Heritable Angioedema or Angioneurotic Edema (HAE)

Answer 36

C1-inhibitor deficiency causing constant activation and proliferation of the classical pathway of the complement system Autosomal dominant trait inheritance Edema in various organs & tissues Especially bad: Edema of intestine and throat causing suffocation Treatment: epinephrine for emergency

Question 37

Acquired Angioedema

Answer 37

Caused by autoantibody to C1 inhibitor and monoclonal B-cell proliferation The ultimate result of both HAE & AAE is absence of C1 inhibitor leaves C1 uninhibited causing continued activation of C4, continuous activation of complement

Question 38

Antigenicity & Immunogenicity

Answer 38

Antigenicity: the ability to bind an Ab or an activated T cell; every immunogen is an antigen, BUT not every antigen is an immunogen; eliciting the BINDING Immunogenicity: ability to elicit immune response, and only proteins can induce cellular immunity Humoral immunity can be induced by proteins, lipopolysaccharides, nucleic acids, and other substances eliciting the IMMUNE RESPONSE

Question 39

Features of an Immunogen

Answer 39

High molecular weight Chemical complexity Solubility or biodegradability Foreignness or nonself

Question 40

Landsteiner Conclusions

Answer 40

Abs react most strongly with homologous Ag Cross-reactions are related to chemical structure of Ags: i. Nature of chemical groups of haptens ii. Position of substitutions iii. Size of substituted groups iv. Charge v. Stereoisomerism Two antigens from two different species that are related (one from E. coli and one from Salmonella); can be different but partly the same; if the Ab is raised against the protein X of E. coli, and tested with protein S from Salmonella, you will find that the same Ab will bind both Ag = cross reaction (multiple antigens with one Ab)

Question 41

Antigenic Determinants (Epitopes)

Answer 41

Ag has 2 functional regions: hapten and carrier Epitopes: immunologically active portions of Ag and recognized by B cells and T cells Antigenic determinants- fingerprint of macromolecules Size of epitope is determined by the size of the Ab’s Ag-binding site Size of recognizable epitope by an Ab:6 sugar residues or 15-20 amino acids Epitopes are antigenic determinants, but sometimes the hapten is used as a reference to an antigenic determinant Usually epitopes are original parts of the molecule, where the hapten is just added and not original; other than that they are similar in function; once the Ab is made, the hapten can bind, but cannot elicit Ab production; needs to be bound to a carrier to make a larger produce and become immunogenic

Question 42

Haptens

Answer 42

usually small molecules, not immunogenic by themselves Always antigenic with a specific Ab Immunogenic when combined with a carrier molecule (large) Simple hapten: only 1 antigenic determinant Complex hapten: > 2 antigenic determinants

Question 43

Antigenic Determinants

Answer 43

``` Small Must be accessible Charge & polarity Conformation dependent antigens when immunogenic produce Ab ```

Question 44

Monoclonal Ab Production

Answer 44

Lymph node cells may be used for cell suspension in addition to spleen cells We need to inject an Ag into an animal like a mouse and after 3-4 weeks we harvest the cells that are producing Ab, and take them from spleen and suspend them in solution that contains HAT (mix of hypoxanthine + Aminopterin (toxic to make cells so all cells will die except B cells that produce Ab) + Thymidine) All B cells/myeloma cells unfused will be killed by HAT because HAT sensitve Myeloma cells give B cells a longer life, and B cells will let myeloma cells will be able to produce Ab All fused cells ONLY make it to culture; only survivors; hybridoma will be further developed and grow; pure clone of hybridoma cell (B cell s+ myeloma), and check for production of Ab (monoclonal) and used for different medical uses like treatment of breast cancer Result: Clone derived from a single progenitor with 2 characteristics: immortal and monoclonal Ab producer

Question 45

B cells

Answer 45

B cells are specialized white blood cells produced in the bone marrow Each B cell contains multiple copies of one kind of Ab as a surface receptor for Ag The entire population of B cells has the ability to specifically bind to millions of different Ags Clonal selection: Ab on the surface of a B cell binds Ag B cell will be stimulated Undergoes proliferation and differentiation

Question 46

Clonal Selection

Answer 46

Cells make same Ab that differentiate into memory cells and plasma cells Plasma cells- first effector cells that secrete large amounts of the Ag-specific Ab Memory cells- insure more rapid response to pathogen in the future T helper cells are required Ab forms complexes with free pathogens and their toxic products Immunocomplexes are inactivate pathogens that eliminate dangers from extracellular fluids by stimulating innate system mechanisms (phagocytes & complement)

Question 47

Ab Immunoglobulin

Answer 47

Y shaped molecule Two identical light chains (LC) of amino acids Two identical heavy chains (HC) of amino acids LC and HC have: 1. N-terminal Variable regions (110-130 amino acids) function as Ag binding site 2. C-terminal constant region (Fc region) Constant region (Fc) of HC responsible for effector function of Ab because capable of binding to the Fc receptors

Question 48

Ab: Heavy vs. Light Chains

Answer 48

Light chains: lambda & kappa (Ab must have either two lambda or two kappa, not one of each) Five classes of heavy chain: IgM, IgG, IgA, IgD, IgE The five classes are determined by the CONSTANT REGIONS OF THE HEAVY CHAINS; LC has nothing to do with this Classes differ: Where located in the body How do they participate in Ag removal

Question 49

Ab Diversity

Answer 49

Billions of different Abs in terms of Ag specificity Limited number of genes How? somatic rearranging DNA segments during B cell development before exposure to Ag Mutations increase Ab gene variation Stem cell turns into a B cell: causing random combination of DNA segments for both HC (VDJ) and LC (VJ) Each B cell gets functional genes encoding one light and one heavy chain making an Ab as a membrane-bound receptor Combination of DNA segments in the Ab determine its specificity resulting in millions of diverse Abs capable of reacting with any antigenic chemical structure in nature

Question 50

Recombination & Ab Variations

Answer 50

We have variable, diversity, and joining= all part of the chains Lambda and H are making the Ab or kappa and H are making the Ab Only changing one component, it gives us a new Ab If we take a kappa and change one of the 45 it will give a new Ab Altogether it can produce over 15 million gene sequences/ Ab types Increased into billions of possible combinations by: imprecise recombination & mutation

Question 51

Ab Class Switching

Answer 51

``` Emerging B cells have IgM molecules only Ag binding causes class switching in plasma cells Class switching= DNA rearrangement changing the heavy chain constant gene in memory cells Loss of coding regions of the constant part of the heavy chain leads to production of IgG, IgA, and IgE With an immunogen that is not a protein, there is NO CLASS SWITCHING; immunogen has to be a protein to have class switching ```

Question 52

Inbred Mice

Answer 52

Produced by sequential, repeated brother-sister matings As many as 20 generations Inbreeding eventually causes homozygous strain All chromosomes have identical sets except the sex chromosomes

Question 53

Congenic Mice

Answer 53

Inbred line of mice with heterozygosity at only one locus without effecting any other loci Identical to other inbred strains except for a single substitution at one histocompatibility locus of a foreign allele Introduction of foreign allele is accomplished by backcrossing an F1 to a parent strain, selecting at each generation for heterozygosity at a specified locus Minimum of 20 backcrosses Follow by intercrosses

Question 54

Transplant Terminology: Autograft, Isograft, Allograft, and Xenograft

Answer 54

Autograft: graft within same individual; tissue autologous; genetics is totally identical Isograft: graft between genetically identical individuals like identical twins, inbred mice; tissue autologous; genetic identity syngeneic or isogeneic Synonyms: isogeneic, isogenic, isologous, isoplastic, syngenic Allograft: graft between genetically different individuals, but same species; tissue homologous; genetic ID allogeneic Xenograft: graft between individuals of different species; tissue heterologous; genetic ID xenogeneic; can transfer viral diseases

Question 55

Alloantigen/ Isoantigen & Alloantiserum

Answer 55

Alloantigen/ Isoantigen: antigen immunogenic in an individual of the same species because transfer from one person to another it will be attacked and rejected; antigen existing in alternative (allelic) forms Induce immune response upon transfer to individuals lacking it ex. blood group antigens Alloantiserum: antiserum derived from immunized individual; immunization was with antigens from another individual of same species

Question 56

Superantigen

Answer 56

Molecules that engage all T-cell receptors: Containing a specific Vb region regardless of other components of the receptor; TCR specificity does not matter and MHC peptide does not matter T cell has a receptor and the APC has an MHC molecule (I or II) and there is a peptide that will be bound and recognized by the T cell receptor; usually the T cell won’t interact with a APC cell that doesn’t carry this peptide (normal situation due to specificity) Superantigens bind to T cell receptor and the MHC of the other cell and connect them and activate the T cell without the presence of the specific antigen and can cause problem such as autoimmune reactions

Question 57

Role of MHC: General

Answer 57

Ag processing precedes presentation by APC 1. Uptake of Ag by macrophage or other phagocyte 2. Fragmentation of the protein Ag into small peptides Ag is presented to lymphocytes in recognizable form MHC II presents Ag to CD4+ helper T cells MHC I presents Ag to CD8+ cytotoxic T cells APCs are usually macrophages, but any nucleated cell may serve as an APC

Question 58

MHC I Structure

Answer 58

``` Composed of two peptide chains (one is large and one smaller); alpha is first chain composed of several domains, which are alpha1,2,3; 4th domain in membrane (hydrophobic facing the lipids in the membrane to be stable there) so called hydrophobic domain; 5th domain is a tail of the molecule in the cytoplasm, which is hydrophilic= total of 5 domains Also beta2microglobin (B2m) Class I and II in same locus, but B2m is from different chromosome and not covalently attached to anything, kept in place via H bonds and hydrophobic bonds Groove between alpha 1 and and 2 = peptide binding site ```

Question 59

Regions of HLA that Encode MHC I and II

Answer 59

Coding Regions: HLA-A, HLA-B and HLA-C code for MHC-I HLA-D [DP, DO, DN, DQ & DR] code for MHC-II Class II is in D region; Class I is in the A, B, and C regions Class III- only contains genes that are not directly associated with MHC, such as components of complement or other organs

Question 60

MHC II Structure

Answer 60

``` It is made up of 2 polypeptide chains: α-chain: Larger, 33K and β-chain 25K chain. Both are composed of 4 domains and members of Ig superfamily Alpha and beta are composed of 4 domains each; Alpha1, 2 with hydrophobic and cytoplasmic domain; same with beta Open groove/binding site between alpha1 and beta1 (class I is alpha1 and 2) ```

Question 61

Ag-MHC II Complex

Answer 61

``` Function of the MHC II: T helper cell is the T cell because it has CD4 and is interacting with the B cell MHC II is carrying a peptide (antigen), and the peptide is recognized by the T cell receptor with its two chains, but that is not sufficient for the interaction - CD4 must bind to the MHC II and recognize/fits MHC II These components (CD4 and receptor) are necessary for recognition and interaction between the APC and T cell Sometimes this is not sufficient- other molecules that make it more productive in activating ```

Question 62

Functions of MHC I

Answer 62

Transplantation Ags- control of graft rejection (MHC II not really involved because only in a few cells) Serologically detected membrane Ags- stimulation of Ab production Cell-mediated immunity with cytotoxic T cells Especially important about MHC I molecules: Found on surface of all nucleated cells Present protein Ag to CD8+ T cells (cytotoxic Tc) Required for recognition of Ags originating in cells (intracellular) Codominantly expressed on nucleated cells of the body- alleles of both chromosomes, inherited from both parents are expressed Acts as receptor for protein Ag fragments Highly polymorphic

Question 63

Functions of MHC II

Answer 63

T- and B-cell reactions, immune response, tumor virus susceptibility, generation of peptides from cytosolic proteins Mixed leukocyte reaction/ GvH- to test compatibility between individuals preventing graft vs. host during transplants because it contains immunologically active cells Peptide transport: TAP-1 & TAP-2: transporters associated with Ag processing MHC II is in all reactions with T helper cells/CD4 TH1 is important in activating the cytotoxic T cells & TH2 that will be all CD4 and will help the B cell activate Ab APCs that present MHC II to T helper cells that have CD4: macrophage, dendritic cell, B cells, Langerhans cell (skin), endothelial cells

Question 64

MHC III

Answer 64

Serum protein molecules with complement components and cytokines like tumor necrosis factors (TNF) a & b Have enzymes such as cytochrome P450 Important: 3 complement molecules included: C2, C4A, C4B TNF-a TNF-b

Question 65

T cell Positive and Negative Selection in the Thymus

Answer 65

Thymic selection is a labyrinthine process of acquiring MHC-restriction, which is not preprogrammed into T cells, but acquired by contact with humoral factors and physical interaction of TCR-expressing cells with MHC molecule-expressing cells during T-cell development in the thymus During positive selection amplification for T cells with alphabeta-TCR that recognize foreign peptides only if presented by self-MHC molecules= survive During negative selection elimination for T cells that have high-affinity TCRs reactive to self-MHC molecules and associated self-peptides= killed ``` Mature T cells are self-MHC restricted and self-tolerant because only thymocytes whose TCRs bind foreign peptides and self-class I or II MHC molecules are left after thymic selection Cells that do not undergo apoptosis are allowed to grow and released into the circulation MHC restricted: do not react without certain MHC MHC II restricted = CD4 for example ```