I hate immunology

Explain how the CTL and NK cell are complementary, include timing, and targets, and the benefit to the host to have both cell types

CTL and NK cells are complementary:NK cell responds 12-24 hours after viral infection and slows viral progression while adaptive immune response develops/CTLs respond 5-10 days, target and kill viral infected cells and induce antibody production. Staggered timing and overlapping functions of CTLs and NK cells create a more efficient immune response to viral infection. Virus is contained and eliminated and memory is generated.

Describe how dendritic cells and follicular dendritic cells are different, i.e. origin, antigen presentation, locations

Dendritic cells originate from a bone marrow precursor and present process antigen on MHC II to naïve T cells in the lymph nodes Follicular dendritic cells originate from stromal cells. They trap and present intact antigen to B cells. They are found in lymphoid follicles.

List the three professional antigen presenting cells and give brief explanation of how/when they present antigen

Dendritic cells: presents antigen via MHC II to naïve T cells in lymphoid tissue Macrophages: presents antigen to memory T cells via MHC II B cells: presents antigen to memory T cells via MHC II

Compare and contrast the various killing mechanisms used by the immune system

Fas/FasL and TNF receptor/TNF binding both induce apoptosis via the extrinsic pathway. Perforin and granzymepathway induces apoptosis, but does so intrinsically.

Define titration and explain how a titer is determined.

For titration you should dilute the serum out as a series of two fold dilutions-Titer -the highest dilution of the serum that gives a reaction in an immunological test -The titer reported is the last dilution positive for the specific antibody or antigen you are looking for.

Explain the difference between immature and mature dendritic cells

Immature dendritic cells: antigen uptake and processing. Expresses low surface MHC II but has high levels of intracellular MHC II and expresses high numbers of Fc receptors (binds antibody opsonized antigen). Low production of costimulatory molecules and cytokines. Mature dendritic cells: antigen processing and presentation. Expresses high surface MHC II but low numbers of Fc receptors. High production of costimulatory molecules and cytokines.

IL1

Inflammtory cytokine released by dendritc cell and is one of the cytokines that triggers B-cells to clonally expland to sectete IGM IN A PRIMARY PARASITE RESPONSE

Compare Type 1 interferons timing and function to a primary adaptive immune response to a virus

Interferon 1 is measurable within 12-24 hours of infection and functions to make cells resistant to viruses and enhance the killing mechanisms of innate immune cells and adaptive immune cells. Interferon 1 with NK cells slows viral progression until the adaptive immune system can undergo clonal expansion and identify virally infected cells.Primary adaptive immune response takes 5-10 days after infection to become measurable. Functions to recognize and kill virally infected cells. Antibodies important particularly if virus has an extracellular phase.

List two parts of the innate immune response and two parts of the adaptive immune response important for protection against viruses.

Interferons (innate)NK cells (innate) CTLs (adaptive)Antibody (adaptive)

Describe how an NK cell recognizes a cell to kill and describe the killing mechanisms of the NK cell

NK cell recognizes target cells by binding MICA (MICA is expressed by some cells under conditions of stress), not being able to bind to MHCI on a cell (normal cells express MHCI, abnormal cell does not), or binding to Fc of antibodies bound to target cell (antibody dependent cell mediated cytotoxicity).NK cells kill via the Fas/FasLpathway or can induce apoptosis by ADCC.

IL13, IL4

Released from TH2, when combined stimulate memory cell to class switch to IgE!!

Explain what a Langerhans cell is, including where it is found

Specialized immature dendritic cell found in the skin.Uptakes antigen in the skin and migrates to regional lymph nodes where they mature and present antigen to T cells.

IL2

Stimulates LYMPHOCYTE MITOSIS IN TH1, TH2, AND IN B CELLS

IL12

Stimulates secretion of IFNγ Induces TH1 differentiation

CD4 TH17 secretes cytokine IL17 that stimulate

stimulate production of chemokines for neutrophils to get to the site of infection.

CD4 T reg secrete

suppressive cytokines or suppress T cell responses by cell-cell contact

Agglutination

The clumping of particulate antigens by antibody(when excess antigens present). The antigen is a cell/particulate

Compare and contrast Type 1 interferons (alpha and beta) and Type 2 interferon (gamma).

Type 1 interferons (alpha and beta) -Produced by virally infected cells-Part of the innate immune response-Makes cells resistant to viral infection and enhances killing mechanisms of immune cells type 2 -Produced by NK cells and TH1 cells (part of both adaptive and innate immunity) and has antiviral actions-Activates macrophages, neutrophils, and NK cells-Promotes more TH1 development and inhibits TH2-Promotes B cell switching to C' (complement) fixing

Explain how an immune response to one type of pathogen can inhibit the response to another type of pathogen and give some clinically important examples where this may play a role.

You can only make a really good TH1 response or one really good TH2 response at a time, not simultaneously. o These responses occur in the LN, cytokines secreted into LN effect neighboring cells. Ex: Interferon gamma from a TH1 response inhibits TH2's Ex: IL10 from TH2 response inhibits a TH1 response - So if an animal has parasites and the TH2 response is activated, when you vaccinate it, this will inhibit the vaccine from inducing a TH1 response. o If you give a vaccine to a puppy/kitten that has worms the vaccine won't be as effective. - If strong viral infection, TH1 will inhibit TH2 response. This is why when people with allergies (a TH2 response) get sick they will have less allergies for a little while.

Precipitation

forms when soluble antigen and soluble antibody bind together at optimal proportions

IL4

induces differentiation into th2 cells; promotes growth of b cells; enhances class switching to igE and igG

CD4 TH2 secrete cytokines (IL4,5,10,13)

which cause production of IgE to fight parasites and cause allergies

List the different types of lymphocytes and how they recognize antigen

- B cells recognize intact, unprocessed molecules (3D structure is important) - γδ T cells recognize intact unprocessed cell surface antigens. o Secrete cytokines or are cytotoxic for cells with abnormal surface antigens or stress markers - ALL T CELLS (1,2,17 and regulatory) recognize exogenous peptides that are presented on MHC II - CD4 TH1 recognize exogenous peptides that are presented on MHC II - CD8 cytotoxic cells (CTL) recognize endogenous peptides processed and presented on MHC I o Kills cells synthesizing foreign protein - NK cells- not antigen specific-

List major cytokines important in B and T cell growth and differentiation

- IL2- lymphocyte proliferation - IL4, when from antigen presenting cell, influences TH0 to become TH2 - IL12 from antigen presenting cell, causes TH0 to become TH1 - IL13- b cells to differentiate to IgE secreting B cells - Interferon gamma- differentiation of B cells to IgG secretion.

List major cytokines that influence B cell isotype switching

- IL4,13- influence to get IgE - Interferon gamma- IgG - TGF beta (made by supressory cells)- to make IgA

Describe how T cell help is provided to B cells when B cells are responding to a polysaccharide antigen (like a bacterial capsule) which T cells cannot recognize.

- Remember that B cells (along with dendritic cells and macrophages) are antigen presenting cells - If it is a polysaccharide capsule, T cells can't see it. To induce antibody to the capsule of the bacteria you can bind a protein to the polysaccharide to get T cell help where the B cell attaches the polysaccharide. - When the B cell receptor binds the polysaccharide it will endocytose this via exogenous pathway and to MHC II. Then you have TH cell that recognizes this and activates TH cell cytokines and a good antibody response

List the major signals required to get activation of a T helper cell.

- T helper cell must receive three signals (if it is naïve) to be activated- - You need the TCR (to bind the MHC II and peptide, the CD4 to bind constant region of MHC II, then CD3 sends signal to nucleus. That is all one signal.) - You need costimulatory molecules to bind to the ligand on the antigen presenting cell o Costimulatory molecules allow adhesion between antigen presenting cell and T cell and gives information to the T cell about the antigen. - Cytokines in the environment (from the antigen presenting cell) to bind TCR - If there is only a signal from the TCR - no activation - anergic (paralyzed, cannot respond) - If there is only a signal from the costimulatory molecules (no TCR) - no effect

List the major cytokines that inhibit T cell responses

- TGF beta is an important immunosuppressive cytokine that inhibits proliferation and other effector functions - IL10 inhibits TH1 - Interferon gamma inhibits TH2

Explain what determines the subtype of TH cell that predominates in a response.

- This depends on what the antigen is, what cytokines are secreted by antigen presenters and where in the body the antigen is.

Explain what a γδ T cell is and its role in the immune response

- γδ T cells recognize intact unprocessed cell surface molecules without usually recognizing MHC. They also recognize stress proteins on cell surfaces o Secrete cytokines or are cytotoxic for cells with abnormal surface antigens or stress markers

Review role of IL1 in immune response, e.g. when is it secreted, what cells secrete it, and some of its effects

-IL 1 is secreted by sentinel cells (macrophages, mast cells, dendritic cells) in response to PAMPs and DAMPS-IL 1 acts on the hypothalamus to induce fever, anorexia, lethargy-IL 1 promotes inflammation and enhances collagen synthesis, fibroblast activity, and chondrocyte activity

List a few important properties of a vaccine that would stimulate CTLs

-Would have to induce cell to present antigen on MHC I (endogenous pathway).Modified live will be endogenous pathway for MHC I pathway for CTL's and also some exogenous pathway to activate T helper cells.-Induce cell to produce IFN 1 (increases MHC I expression and CTLs killing of cells).

Explain what the precipitate is in a precipitation assay and what the equivalence zone means. Describe why there is no precipitate when there is antibody excess or antigen excess

-Zone of equivalence-when there is crosslinking of antigen and antibody to cause it to fall out of solution (precipitate). What was once soluble now precipitates out and becomes visible. -If excess antibody or excess antigens not specific to that antibody-no cross links therefore there is no precipitation.

List three mechanisms that CTLs use to kill target cells. For each, include the molecules and functions involved -for binding and killing

1.perforin and granzyme pathway: perforin inserts into the target cell membrane creating a pore through which granzyme enters the cell and induces apoptosis via intrinsic pathway.2. Fas/Fasligand binding: All cells express Fas molecules on their membranes and activated CTLs have Fasligand (FasL). Binding results in triggering of extrinsic apoptosis pathway. 3. TNF receptor/TNF: CTLs secrete TNF which binds to target cells and induces the extrinsic apoptotic pathway.

Explain the mechanism of action of Type 1 interferons, where they come from, and explain their role in immunity

nterferon 1 binds to receptors on nucleated cells adjacent to the cell that produced the interferon 1. Binding of interferon 1 induces cells to:Interferon 1 is produced by virally infected cells and makes other cells resistant to viral infection. It is part of the innate immune system.-increase expression of MHC I (makes cell more susceptible to CTLs)-to produce enzymes that degrade viral RNA, inhibit synthesis of viral proteins, and inhibit viral assembly-activates NK cells-upregulates IL12 receptors to enhance TH1 response-upregulate dendritic and macrophage co-stimulatory molecules (enhance antigen presentation)-induce chemokine recruitment of lymphocytes

TH1 cytokines

o IL2- induces lymphocyte mitosis o Interferon gamma- activates macrophages, NK, CTL's Inhibits TH2's o TNF acts on epithelium to upregulate adhesion molecules and activates neutrophils and macrophages

TH2 cytokines

o IL4,13- isotype switching to IgE o IL5 acts on bone marrow to make more eosinophils o IL10 is anti-inflammatory and inhibits TH1

CD4 TH1 secrete cytokines (IL2, TNF, interferon gamma) which activate

phagocytes, NK, CTL's to fight pathogens and influence B cells to make IgG

List the basic principles antigen/antibody binding used in immunodiagnostics.

Antigen antibody reactions go to equilibrium-Antigen or antibody can be bound to a solid surface, e.g. plastic, beads, etcand not negatively affect their ability to bind to antibody or antigen-Labeled antigen or antibody will competeequally with unlabeled antigen or antibody

Describe, in general terms, how apoptosis is induced and what happens in a cell that is induced to undergo apoptosis.

Apoptosis is induced by either extrinsic pathway (Fas/FasLbinding or TNF receptor/TNF v ia CTLs and NK cells) or the intrinsic pathway (granzymesfrom CTLs or NK cells, t cell recognition of antigen in absence of costimulation, DNA damage, noxious stimuli, etc). When a cell has been stimulated to undergo apoptosis:-Capsasesare activ ated-Capsasesinitiate protein cleav age to breakdown the cytoskeleton-Capsasesactiv ate endonucleases to fragment DNA and clump chromatin-Apoptotic bodies form and are phagocytosed and digested by phagocytic cells

Explain the differences between apoptosis and necrosis

Apoptosis occurs without the presence of inflammation, and is characterized by organized apoptotic bodies (no membrane degradation or release of cytoplasmic contents). It is a quiet cell death contained to a small local area.Necrosis is characterized by the presence of inflammation, membrane degradation, and release of cytoplasmic contents. It is a violent cell death occurring in a large area.