Tew's Lectures
Terms
-
Describe important characteristics of Natural Killer Cells
-
- Kill a variety of targets including tumor cells, virus infected cells, bacteria, and fungi
- Two difference approaches to killing
- Perforin
- FasL-Fas system
- Produce IFN-g which activates macrop
- What are the differences between the Innate Immune System and the Adaptive Immune System
-
The innate immune system responds rapidly to invaders, it's recognition mechanism is invariant with a limited number of specificities and its response is constant.
The adaptive immune system's response can take days or weeks, but its recogni -
What are the three major members of the innate immune system?
-
- The Complement System
- Phagocytic Cells
- Natural Killer Cells
-
Name the two major functions of the Complement system?
-
- Destruction of invaders
- Signaling of immune cells
- Describe the general pathway involved in activation of the Complement System.
- The convertase C3 will be generated and converted to its active C3b form through proteolysis. C3b is required to activation C5, which in turn recruits C6-C9 to form a membrane attack complex; which can punch a whole in a cell membrane res
-
What are the three activation pathways for the Complement System?
-
- The Classical Pathway (activated by antibody/antigen interaction)
- The Lectin Pathway (mannose binding protein binds to pathogen surface)
- The Alternative Pathway
-
Define: Lectin
-
Lectins are a class of proteins that bind to sugas and induce agglutination.
-
Name the two major types of Phagocytic Cells
-
- Macrophages
- Neutrophils
- Describe the important characteristics of Neutrophils
-
- Short lived cells
-Unlike macrophages cannot present antigens
-Receptors that bind bacteria stimulate phagocytosis
-70% of White Blood Cells are neutrophils
- Describe the important characteristics of Macrophage
-
-Long lived cells
-Capable of presenting antigens to T-Cells
-The first cells to attack microbial invaders
-Activated by IFN-g
-Secrete a variety of cytokines
- What distinguishes different antibody isotypes from each other?
-
The different heavy chains which determine an antibodies isotype.
- What is unique about the heavy chains of IgM and IgA?
- They have tail pieces which allows IgM to form Pentamers and IgA to form dimers.
-
Ig Domains are formed by what?
- Beta-sheets
-
Define: Wu-Kabat Plot
- A quantitative measure for the variability of aligned sequence data. Allows identification of constant and variable gene sequences
-
Different parts of an Ig protein can be distinguished following enzymatic digestion. What are they?
-
Fab (the upper V) these fragments bind to antigens
Fc (the bottom stem)
-
What two major forms can Immunoglobulin molecules occur in?
-
Membrane forms are found on the surface of B cells
Secreted forms are found in plasma, interstitial fluid of tissues, etc.
-
Which Immunoglobulins can activate the Complement System?
What complement activation pathway is this?
-
- IgM Pentamers
- IgG
This is the classical activation pathway. Duh. -
Describe the process of Opsonization
- Macrophages have Fc-gamma-R receptors for the Fc portion of IgG. IgG's Fab portion can bind and coat an invader, and the Fc portion of IgG will inter
-
Describe the process of Immediate Hypersensitivity
- IgE binds to antigens or allergens; and then binds to the Fc-epsilon-R receptor on Mast Cells causing them to release their basophil granules filled with histamin
-
Describe the process of Antibody Dependent Cell Mediated Cytotoxicity
- IgG mediates ADCC by binding to antigens on the surface of target cells. Monocytes, neutrophils, and NK cells all have Fc receptors that IgG can interact with to activate the effector cell to lyse the target cell.
-
Describe the process of Mucosal Immunity
- IgM and to a lesser extent IgA are able to gain access to mucosal secretions by binding to poly Ig receptor on the epithelial surface that binds only to multimeric Ig isotypes. The multimers are pulled th
- How is immunoglobulin diversity achieve?
- Immunoglobulin genes are rearranged in the B cells. Diversity comes from the existence of multiple variable segment genes, different combinations of gene segments and different combinations of Heavy and Light chains.
- What gene segments are Heavy Chains and Light Chains comprised of, respectively.
-
Heavy Genes: Variable + Diversity + Joining
Light Chains: Variable + Diversity (Kappa or Lambda)
-
What is the 12-23 Rule?
- Between Variable, Diversity, and Joinin, gene segments are highly conserved sequences that seperate these genes by either 12 or 23 bps. A variable gene won't join to another variable gene because they are both preceded by 23 bp spaces. To join one seg
- What enzymes are necessary for immunoglobulin gene segments to join?
- The RAG1 and RAG2 exonuclease ligases
-
What are the two stages B-cell development and wheredo they occur?
-
- Antigen independent development: occurs in the bone marrow
- Antigen dependent development occurs in the lymphoid tissue
- Describe the order Immunoglobulin gene rearrangement takes place in
-
First D-J arrangement occurs and then V to D-J rearrangement takes place. Once a viable Heavy chain protein is produce, heavy rearrangement stops. As a result only 1 heavy chain allele is es expressed on any B-cell. The heavy chain protein is
-
Describe the major characteristics of MHC I proteins
-
There are three classes of MHC I proteins (HLA-A, B, & C)
Everybody expresses 6 proteins (3 from each parent)
MHC I proteins are polymorphic so there are many different forms of each with unique aa sequences.
All MHC I proteins ha
-
Describe the process of Antigen presentation by MHC Class I proteins
- Proteaseomes cut damaged proteins into peptides, some of which are picked up by the TAP1 and TAP2 transporters that carry the peptides into the endoplasmic reticulum where they get chosen to be put MHC I groove. Once an M
-
Name the 3 professional antigen presenting cells
-
- Macrophages
- Dendritic Cells
- Activated B Cells
- Describe the important characteristics of MHC Class II proteins
-
Humans have three polymorphic molecules: HLA-DP, -DQ, and -DR.
MHC Class II expression is only found on professional antigen presenting cells
All MHC II proteins have same 3D structure
Binds to CD4
- Describe MHC Class II Antigen Presentation
-
Exogenous proteins are consumed as a phagosome and attached to the MHC-II protein and dsiplayed on the cell surface
When APC's are activated they express the co-stimulatory B7 protein. T-cells need to see both peptide/M
-
What are three major differences between MHC I and MHC II proteins?
-
MHC-I and MHC-II acquire peptides at different sites and from different sources.
MHC-I is expressed by virtually every cell whereas MHC-II is only expressed by professional antigen presenting cells
MHC-I binds to CD8; MHC-II binds to CD4&nb
- Describe important characteristics of the T-Cell Receptors
-
The T-Cell receptor is usually a alpha-beta heterodimer.
Alpha and beta chains have variable and constant regions
TCR variable regions are assembled from multiple segments
- What is responsible for signal transduction on the surface of T-Cells?
-
The CD3 complex
- Name two important ways that B-Cell Receptors differ from T-Cell receptors
-
Each TRC chain has only a single C-region, whereas the BCR's have multiple C-regions
BCR's recognize intact antigens, while TCR's recognize process antigens presented in the MHC of other cells
-
Describe the proces of T-Cell Activation
- Following recognition of MHC bound antigen, a naive T-Cell will begin to release IL-2. T-Cell's contain IL-2 receptors so they are able to recognize their own signal, this causes the T-Cell to proliferate in the activ
-
Describe the important characteristics of the T-Cell subset TH1 cells
-
Produce cytokines that make it ideal for defense against viral or bacterial attak.
Produces IFNg which activates macrophages
-
Describe the important characteristics of the T-Cell subset TH2 cells
- The cytokines produced by TH2 cells are more inluential on the adaptive immune response and is better at helping B-cells.