Tcells/MHC 2 Flashcards
What are Acute-phase proteins (function/importance)
Normal serum constituents that increase (or decrease) rapidly by at least 25% due to infection, injury or trauma in tissue (nonspecific indicators of inflammation)
• Mainly produced by hepatocytes (liver parenchymal cells) within 12 to 24 hours • May bind the microbe and promote adherence, first step of phagocytosis
• Produced in response to an increase in the intercellular signaling polypeptides called cytokines
CRP function and importance
A serum protein that attaches to foreign substance; neutralizes surface charge thus making it easier for cells to approach one another (opsonin)
• Promotes phagocytosis by binding to specific receptors found on monocytes, macrophages and neutrophils
• Primitive, non-specific form of an antibody molecule
• As the levels rise and decline so rapidly, CRP is the most widely used indicator of acute inflammation
• Increases within 4 to 6 hours following infection or trauma
• Non-invasive to follow the course of malignancy and organ transplants
What is an antigen
Any substance that can be specifically bound by an antibody or T cell receptor
Types of antigen by receptor
Ags bound by TcR : peptides
Ags bound by Antibody/Ig/BcR : sugars, phospholipids, nucleic acids, proteins
What is immunogen
Molecules that stimulate immune
response -> important when we pick an Ag for a vaccine
Characteristics of immunogen
- Foreigness
- Size
- Chemical composition
- Processability
- Presentability
How immunogen characteristics influence the immune response
- Foreigness - less similar to body -> better response
- Size - bigger -> more potent ig
- Chemical composition - Proteins more ig than carbohydrates, pure nucleis acids and lipids need carrier molecule to be immunogenic
- Processability - must be degraded to be complexed
- Presentability - must be seen by MHC and bound for response
Factors that influence immune response (other than immunogens)
Individual factors - Age (middle age best), overall health, and
genetic capacity
Dose of immunogen - If tiny amount, poor response; too large may see failure of a response (due to high-dose “tolerance” or specific unresponsiveness)
Route of entry - oral, SQ,IM,IV, resp, genitourinary
Genetic predisposition - MHC, T-,B-cells development
What is an Epitope
The portion of an immunogen that is recognized by the immune system
How epitopes interact with T cells and B cells
- T cells only recognize an epitope (linear) as part of a complex formed by the MHC proteins; immunogen must be degraded by the antigen-presenting cell (APC)
- B cell can recognize both linear and discontinuous/conformational epitopes
What are Haptens
- Small substance (antigen) that by itself does not initiate an immune response (not an immunogen); can be immunogenic by conjugation to a suitable carrier
- Once antibody production is initiated; can bind to antibody
Hapten interaction with Natural complexes vs Laboratory
- Poison Ivy
- Drug reactions : Ex. Penicillin reacts chemically with proteins in the body to form a hapten-carrier complex = can lead to anaphylaxis in hypersensitive individuals
Adjuvant function
- Substance administered with the immunogen to increase the immune response
- Acts by inducing a local response, attracts a large number of immune system cells to site
Adjuvant influence on immune system
- Increases the size of the immunogen (multi-molecular aggregates)
- Prolongs the existence of the immunogen (traps antigen at injection site)
- Increases recruitment and activation of antigen-presenting cells (targets PRR on phagocyte -> release cytokines)
3 types of antigens
Autoantigens, Alloantigens, Heteroantigens
Autoantigens and immune response
belong to host; do not elicit an immune response under normal circumstances
• Autoimmune disease
Alloantigens and immune response
From other members of the host’s species; elicit an immune response
• Tissue transplants; blood transfusions
Heteroantigens and immune response
From other species (animals, plants or microbes); elicit an immune response
How MHC varies by species/function
Different names by species; Human Leukocyte Antigen (HLA)
Same function - Genetic region in humans (and other mammals) responsible for presenting antigen lymphocytes (essential to “turn on” T cells)
MHC expression
Expressed in Antigen-Presenting Cells (APCs: DCs, Macs, activated B cells: MHC II) or all nucleated cells (MHC I)
MHC genomic importance
Most polymorphic genes present in genome
• 4000 different class I alleles and 1300 class II alleles
• MHC genes are co-dominantly expressed (both paternal and maternal genes are expressed at same level)
• Genes are so close together, they travel together during
inheritance (haplotype – consists of genes for A, B, C, DR, DP and DQ)
• One haplotype inherited from each parent
• Individual’s MHC type is almost as unique as a fingerprint
Endogenous pathway and MHC
Synthesized in same cell. Self antigens/intracellular peptides : viral particles, tumors, bacterial antigens
* infected cells displays antigen on its surface with MHC 1 to TcR of CD8 Tc. HLA - A,B,C
MHC - main class; bind peptides within cells (internal orgin/virus/tumor) and transport/present them to the plasma membrane for recognition by CD8 T cells/cytotoxic T cells; Found on all nucleated cells; synthesized in ER
Exogenous pathway and MHC
Antigen into cell via phagocytosis/endocytosis,
binds peptides within cells (extternal source/bacteria) and transport/present them to plasma membrane for CD4 T cells/helper T cells; found on antigen presenting cells; synthesized in ER
MHC to Tc to Pathway to Gene
C1
MHC class 1 / Endogenous / TcR of CD8 Tc / HLA - A,B,C
MHC to Tc to Pathway to Gene
C2
MHC class 2 / Exogenous / TcR of CD4 Th / HLA - D: DP,DQ,DR
MHC Medical significance
Transplant compatibility, Autoimmune disease (Type 1 diabetes, rheumatoid arthritis), Cancer prevention/development
Heteroantigens vs heterophile antibodies
