Immunology Midterm

-The bonds that hold the antigen to the antibody combining site are all non-covalent in nature. These include hydrogen bonds, electrostatic bonds, Van der Waals forces and hydrophobic bonds. Multiple bonding between the antigen and the antibody ensures that the antigen will be bound tightly to the antibody.

-Since antigen-antibody reactions occur via non-covalent bonds, they are by their nature reversible.

-A hapten is a small molecule that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself. (In general, only large molecules, infectious agents, or insoluble foreign matter can elicit an immune response in the body.) Once the body has generated antibodies to a hapten-carrier adduct, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.

·      Molecules that are not Ag specific until they are incorporated into a carrier molecule (protein). Ex) Penicillin

·      Combination of carrier + happen = Ag that can initiate an immune response.

·      A substance that enhances the body's immune response to an antigen.

-In immunology, an adjuvant is a component that potentiates the immune responses to an antigen and/or modulates it towards the desired immune responses.[1] The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid.[2] "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."

In innate immunity:  Natural Killer Cells

Adaptive Immunity:  Cytotoxic T-Cells

·      Effector CD4+ Th-1 & Th-2 cells

·      Effector CD8+ T cytotoxic cells

·      CD4+/Foxp3+ T regulatory cells

·      Mature naïve B cells (primary follicles)

·      Ag-primed activated B cells (germinal centers)

·      IgM Ab-secreting Plasma cells

·      Somatic hypermutation (affinity maturation)

·      Isotype switching

·      All isotypes Abs-secreting Plasma cells

CD4, CD8, alternatively B7 (CDC activated)

·      CD19, CR20 and cd81

The coreceptor complex is composed of CD21, CD19, and Tapa-1(CD81). CD21 binds opsinized antigenic particles, such as bacteria or enveloped viruses, via its affinity for the C3d complement fragment.

-CD19 is primarily responsible for signal transduction.

  -The function of the tetraspan protein Tapa-1 is unknown; but it may be involved in signal transduction leading to homotypic adhesion

·      CD28 receptors and CD40L ligands are expressed on the T cells

·      B7 ligands and CD40 receptors are expressed on DC and B cells

(B7.1 ligand is CD80, and B7.2 is also called CD86)

·      Differences in the heavy chain C regions define five main isotypes

·      IgG (g)

·      IgM (m)

·      IgD (d)

·      IgA (a)

·      IgE (e)

·      The light chains have only two isotypes, or classes: kappa (k) & lambda (l), with no functional differences

the killing of antibody-coated target cells by NK cells having the receptor CD16, which recognizes the Fc region of the bound antibody

-in advanced or secondary response, antibodies take time

Fab- proteolytic fragment of IGG that consists of the light chain and the amino-terminal half of the heavy chain held together by interchain disulfide bond.  Fragment with antigen binding specificity

Fc-fragment of antibody that consists of the carboxyl-terminal halves of the two heavy chains disulfide-bonded to each other by the residual hinge region, produced by proteolytic cleavage of antibody

• primary immune response (first exposure to a pathogen) takes 10-17 days to get going and destroy the pathogen. during this time many B and T cells are generated to engage the pathoge
• secondary immune response(sexond exposure to pathogen) is much faster taking 2-7 days as the memory cells quickly clone more B and T cells to attack the pathogen

MHC I – composed of one membrane bound heavy chain and noncovalently bound B2 microglobulin. Heavy chain with 3 extracllular domains, of which amino-terminal alpha ½ domains resemble each other

MHC II – composed of two membrane-bound chains, an alpha chaind and a beta chain.  These have two extracellular domains each

Alternative- C3Bb, C3bBb, C3B2Bb, C3 and C5 convertase

Lectin- C4b2a classical C3 convertase, c5 convertase           

Classical – c4b2a classical C3 and C5 convertase

-lymphocyte lineage

MHC I – all cells     

MHC II – all antigen presenting cells and thymus

secondary tissues, in activated B cells, first switch occurs born as IGM switched to IGG

IGG, IGM, monomeric IGA – Blood     

Extracellular fluid – IGG

Secretions – dimeric IGA

Connective tissues – IGE

Infant – only IGG crosses placenta

Primary- IGM more than any other

Secondary- IGG more than any other

a molecules ability to induce response or be a strong antigen, ability to provoke immune response

- factors include structure as organic molecule, protein temp/pH no effect on induction

-large group of small proteins involved in guiding white blood cells to sites where functions are needed, central role in inflammatory response

-CCR7: lymphoid tissue, responsible for both B and T cells, not cell specific

1^st:  TCR and MHC class II presenting antigen

2^nd:  CD-28 and B7 of dendritic cell 

MHC/antigen complex on DC + TCR on Tcell and

the second CD80 on DC with CD28 on T-cell

Anergy:  state of nonresponsiveness to an antigen     

Achieved through lack of second signal to enter activated status, peripheral tolerance to self antigens

Cellular: adaptive immune response in which antigen-specific effector T cells dominate, cannot be transferred

Humoral:  immunity mediate by antibodies and can be transferred

Receptor expressed in various lymphoid tissues and activates B and T cells. It has been shown to control the migration of memory T cells home to secondary lympho-organ, such as lymph nodes, as well as stimulate dendritic cell maturation.

Chemokine receptor 7; provides the balance between immunity and tolerance

Plasma cells (B-cell lineage)

There is twice as much CD4 than CD8.

2:1

During the extracellular presence of the viruses, antibodies have a neutralizing effect.  They block viruses from binding to epithelial/host cells.

1. central tolerance: occurs in primary lymphoid organs (thymus & BM), thymic deletion of autoreactive T cells, BM deletion of autoreactive B cells

Complement plays a role in innate immunity by opsonizing bacterial and extracellular viral peptides for phagocytosis and forming pores/lysis of bacterial and virally-infected eukaryotic cells.

B/T cells: The CD40 on B cells interact with the CD40L on Th cells, which results in B cell differentiation into plasma cells (with IL-10) or memory cells (with IL-4).                            B/DC: The CD40 on B cells interact with the CD40 L on dendritic cells and inhibits apoptosis of B cells                                                                                                                                  T/DC: The CD40 L on T cells interacts with the CD40 on DCs that causes T cell proliferation into Th1 and Th2.

Antigen-binding STRENGTH is not affected by temperature and pH, but the RATE of binding is affected.

CD8, TCRs, and inhibitory receptors on self-MIC will interact with NKFR on NK once infected.

Recognition of antigen and processing, affinity maturation  clonal expansion  isotype switching

Primary beginning: innate immunity  Primary advanced: innate immunity and adaptive begins  Secondary responses: combination of both.  Secondary responses are faster due to immunological memory from the adaptive primary response.

Cytotoxic granules are pre-formed.  Natural killer cells do not kill self cells because of the presence of inhibitory receptors (KIRs) on the NK cell and MHC I on the self cell.

It is a protein that regulates the activities of white blood cells(leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self".

b.      Antigen binding to the TCR stimulates the secretion of IL-2, and the expression of IL-2 receptors IL-2R. The IL-2/IL-2R interaction then stimulates the growth, differentiation and survival of antigen-specific CD4+ T cells and CD8+ T cells.  As such, IL-2 is necessary for the development of T cell immunologic memory, which depends upon the expansion of the number and function of antigen-selected T cell clones.

No. This ‘signal 2’ is not required for interaction between effector Tc cells and the target cells. 

a.    Phagocytosis of pathogen

b.    Classical pathway of complement fixation

1.    TCR complex and its 8 chains’ functions

a.      TCRs recognize the peptides of these proteins after being processed and presented by APCs as a complex with MHC molecules

b.      The effector function of the T cells is carried out via Ag-specific direct interactions with other either pathogenic or normal cells, or via effects of the cytokines secreted by the T helper cells.

c.      The TCRs are similar to the BCR, as they:

i.        Have Immunoglobulin protein structure

ii.        Are highly diverse in their Ag-specificity

iii.      Have a unique Ag specificity in each T cell

iv.      Have the variability in the V region is a result of gene rearrangement

d.      However, they are different in that:

i.        no somatic hypermutation, and no isotype switching occur in the T cells after priming with Ag

ii.        TCRs are always cell membrane-bound

iii.      Each chain has a variable (V, binding an Ag) & a constant (C) regions

e.      TCR 8 chain functions

i.         and  chains of TCR- main part; recognition of an AG

ii.        2  chains- signal transduction

iii.      CD3 receptors- transfer newly synthesized TCR to the cell surface

1.       and  chain

2.      2  chains

Not always, because sometimes the body attacks itself (autoimmunity) or overreacts, which could be detrimental.  Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.

b.      Mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts

c.      Leads to tissue destruction, fibrosis, necrosis

d.      Non-immune diseases with etiological origins in inflammatory processes include cancer,atherosclerosis, and ischaemic heart disease