6. Adaptive Immune Response Flashcards
When can naive T cells trigger an immune response?
After they have been activated by antigen presenting cells
What does the antigen presenting cell do?
Senses the pathogen
Captures the pathogen
Processes the pathogen (degrading protein from virus/bacteria)
Presents the pathogen
What do dendritic cells and langerhans cells present the pathogen to?
Naive T cells
What are naive T cells?
Tc ell that have not previously encountered the antigen
What do macrophages and B cells present pathogen to?
Effector T cells
What is the function of effector T cells with macrophages?
Phagocytic activities - enhance processes
What are effector T cells?
T cells that have previously encountered the antigen and are capable of performing effector functions during an immune response
What is the function of B cells and effector T cells?
T cells when presented with pathogens from B cells produce a different antibody
It is IgM in host cell, if cell is seeing antigen for second time the IgM changed to IgG by T cells
What are the features of antigen presenting cells?
Strategic location
Diversity in pathogen sensors (PRRs)
Diversity in pathogen capture mechanisms
What are the strategic locations of antigen presenting cells?
Mucosal membranes Skin Blood Lymph nodes Spleen
Describe the diversity in pathogen sensors (PRRs)
Extracellular pathogens (bacteria, fungi, Protozoa) Intracellular pathogens (viruses)
What is the diversity in pathogen capture mechanisms of antigen presenting cells?
Phagocytosis
Macropinocytosis
Which PRRs can sense extracellular pathogens?
TLR1 TLR2 TLR6 TLR4 - important in sepsis TLR5 TLR11
What do TLR1 and TLR2 detect?
Gram positive: staphylocccus aureus, streptococcus pneumoniae
What do TLR4 and TLR5 detect?
Gram negative: neisseria meningitidis, E. coli
What are the PRRs that can sense intracellular pathogens?
TLR3
TLR7
TLR8
TLR9
What can TLR9 detect?
Adenovirus
What can TLR8 detect?
Norovirus
What happens when a pathogen enters the body through a breach of innate barriers?
Macrophage starts engulfing pathogen, pathogen enters blood stream
Antigen presenting cells capture the pathogen
Antigen presenting cells move into the lymphatics to the lymphoid tissues
Moves into mucosal associated lymphoid tissues (MALT), lymph nodes and spleen
Antigen presenting cells present microbial antigen to the right T cell
What type of immunity are extracellular microbes?
Humoral immunity
What type of immunity is intracellular microbes?
Cell mediated immunity
What are pathogens presented by?
Major histocompatibility complex (MHC) molecules
What are the differences in classes of MHC?
MHC class 1 molecules - expressed on all nucleated cells (including macrophages) MHC class 2 molecules - expressed on antigen-presenting cells, dendritic cells, macrophages, B cells
What is a haplotype?
Set of MHC alleles that are inherited together from one parent and present on chromosome
What a the key features of MHC class 1 and class 2 molecules?
Co-dominant expression
Polymorphic genes
Presentation of microbial peptides
How does the presentation of microbial peptides change?
Antigen presenting cells present intracellular microbes via MHC class 1 molecules Antigen presenting cells present extracellular microbes via MHC class 2 molecules
Describe the endogenous processing of intracellular microbes
Viral protein present in cytosol
Marked for destruction by proteasome
Proteasome-generated viral peptide transported ER by TAP proteins
Formation of viral peptide-MHC class 1 complex if right match
APCs and non-APCs present peptides from intracellular pathogens to CD8+ T cells
What is a disadvantage of endogenous pathway processing intracellular microbes?
Have to have correct MHC molecule
What happens after a viral peptide-MHC class 1 complex is made?
Antigen-presenting cell will express viral peptides on MHC class 1 molecules
Activation of naive CD8+ T cells in lymphoid tissues
Search and kill all infected cells by activated CD8+ T cells
Any infected target cell will express viral peptides on MHC class 1 molecules
Describe the exogenous processing of extracellular microbes
Microbes captured by phagocytosis or micropinocytosis
Degradation in small peptides in the endosome
Peptide-rich vesicles fuse with vesicles containing MHC class 2 molecules
Formation of peptide-MHC class 2 complex if right match
O
APCs presents peptides extracellular pathogens to CD4+ T cells
Describe the features of peptide presentation by MHC class 1 and class 2 molecules
Peptide binding cleft - variable region with highly polymorphic residues Broad specificity - many peptides presented by the same MHC molecule Responsive T cells - MHC class 1 recognised by CD8+ molecules on T cells, MHC class 2 recognised by CD4+ molecules on T cells
What is the clinical importance of MHC molecules?
- Host can deal with a variety of microbes
- No 2 individuals have the same set of MHC molecules (not being wiped out by a single microbe)
- Different susceptibilities to infections
- Major causes for organ transplant rejection
- HLA association with autoimmune disease