Adaptive Immunity Flashcards
What are some examples of antigen presenting cells?
Macrophages, B cells, dendritic cells, Langerhans’ cells
What are some features of antigen presenting cells?
Strategically located (SALT, GALT, NALT, BALT, lymph nodes, spleen etc)
Pathogen capture (phagocytosis, macropinocytosis)
Diverse pathogen sensors (PRRS)
What are pathogen regonition receptors?
They are proteins expressed by cells of the innate immune system to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with cell components that are released during cell damage or death.
Where are dendritic cells located?
Lymph nodes, mucous membranes, blood
What do dendritic cells present to?
Naive T cells
Where are Langerhans’ cells located?
Skin
What do Langerhans’ cells present to?
Naive T cells
Where are B cells located?
Lymphoid tissues
What do macrophages present to?
Effector T cells
What do B cells present to?
Both naive and effector T cells
What does MHC stand for?
Major Histocompatibility Complex
What are PAMPs?
Pathogen-associated molecular patterns are molecules associated with groups of pathogens, that are recognized by cells of the innate immune system
Where are class I molecules found?
On all nucleated cells
What is the function of class I molecules?
To display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein.
Where are class II molecules found?
On dendritic cells, macrophages, B cells
What are the HLAs corresponding to class I molecules?
HLA-A, B, C
What are the HLAs corresponding to class II molecules?
HLA-DR, DQ, DP
Give a difference between class I and II molecules
The antigens presented by class II peptides are derived from extracellular proteins (not cytosolic as in MHC class I)
What are some key features of MHC class I and II molecules
1) Co-dominant expression (greater number of different MHC molecules)
2) Polymorphic genes (presentation of different antigens/microbes)
3) Class I - present peptides from intracellular microbes
Class II - present peptides from extracellular microbes
On which chromosome are the genes for MHC molecules coded?
6 (short arm)
What is the peptide binding cleft?
Variable region with highly polymorphic residues
Between which chains are the peptides presented in MHC class I molecules?
Between alpha 1 and 2
What is the difference in the sizes of peptides that MHC class I and II can present?
Class I - between 9-10 amino acids
Class II - between 13-20 amino acids
Where are the peptides presented in MHC class II molecules?
Between alpha 1 and beta 1
True or False:
An MHC molecule can only present one type of peptide
False
Many peptides can be presented by the same MHC molecule
What does MHC class I activate?
CD8+ T cells
What does MHC class II activate?
CD4+ T cells
True or False:
The viral proteins on the airway epithelial cells are presented by MHC molecules called HLA-DP, HLA-DQ, HLA-DR
False
These are class II molecules
Should be presented by class I - HLA-A, HLA-B, HLA-C
True or False:
All peptides from the same microbe are presented by different MHC molecules
True
Are both self and non-self peptides presented?
Yes
What are long-tern nonprogressors?
Long-term nonprogressors (LTNPs), sometimes also called “elite controllers”, are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load.
What can determine whether a HIV-infected individual is a slow progressor or rapid progressor?
Slow progressors [HLA-B27, HLA-B51, HLA-B57]
MHC molecules able to present key peptides for the survival of the virus (unmutated) so effective T cell response
Rapid progressors [HLA-B35]
MHC molecules present mutated peptides (less crucial peptides for the virus) - poor recognition by T cells, poor T cell response
What are some clinical problems associated with MHC molecules?
Organ transplant rejection, Graft-Versus-Host reaction, association with autoimmune disease
What is the association between HLA molecules and autoimmune disease?
Ankylosing spondylitis -> HLA-B27 in 90% of patients
Insulin dependent diabetes mellitus -> HLADQ2 in 50-75% of patients
Summarise how extracellular microbes are processed and presented
Sensed by APC via the exogenous pathway (inside vesicles)
Presented by MHC class II
Activates CD4+ T cells
Activates humoral response (antibodies, complement)
Summarise how intracellular microbes are processed and presented
Sensed by APC via the exogenous AND endogenous pathway (in cytoplasmic compartment)
Presented by MHC class II and MHC class I (cross presentation)
Activates CD8+ and CD4+ T cells (need CD4+ to become cytotoxic T cell)
Cell-mediated response and cytotoxic T cells activated
Why is cross presentation required?
Need to activate CD4+ as well as CD8+ in order to get cytotoxic T cells (need the T helper cells too)
Where do T cells mature?
Thymus
What is the antigen receptor on the T cell called?
T cell receptor (TCR)
How is TCR diversity generated?
Gene rearrangement
Which kind of T cells are CD4+?
Helper
Which kind of T cells are CD8+?
Cytotoxic
What cytokines are produced by TH1 cells?
TNFalpha, IFNgamma
What cytokines are produced by TH2 cells?
IL-4, IL-5, IL-10
What cytokines are produced by TH17 cells?
IL-17
What cytokines are produced by Treg cells?
IL-10, IL-35, TGFb
How many signals do T cells require to become fully activated?
2 (costimulation)
What are the signals required to fully activate a T cell?
A first signal, which is antigen-specific, is provided through the TCR which interacts with peptide-MHC molecules on the membrane of APCs. A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of APC and the T cell.
What is an example of a costimulatory molecule?
CD28
Which T helper cells are activated in response to extracellular microbes?
TH2, TH17
Which T helper cells are activated in response to intracellular microbes?
TH1
What is the action of TH1?
Activate CD8+ cytotoxic T cells
Produce IFNg which activates B cells (IgG) and macrophages
How do cytotoxic T cells kill cells?
Perforin makes holes in cell membrane
Granzyme enters through holes and initiates apoptotic processs
What is the main antibody that regulates allergies?
IgE
What is the first antibody to appear in response to initial exposure to an antigen?
IgM
Which pathway of the complement system does IgG activate?
Classical
Describe the ratio of IgM to IgG upon first encounter of an antigen
High ratio
What is the main antibody produced upon second encounter of an antigen?
IgG
What is isotype switching?
Biological mechanism that changes a B cell’s production of immunoglobulin (antibodies) from one type to another, such as from the isotype IgM to the isotype IgG
What are the immune functions of IgG?
Enhanced phagocytosis, complement activation, neonatal immunity, toxin/virus neutralisation
What is the main antibody found in breast milk?
IgA
What is the function of IgA?
Mucosal immunity
What are the functions of IgE?
Immunity against helminths
Mast cell degranulation (allergies)
What is the function of IgM?
Complement activation
In a case of chicken pox, which MHC molecules are expressing the viral peptides? Which cells?
MHC class I - all infected cells including APC
In a case of chicken pox, which factors from the adaptive immunity will be used against the virus?
Antibodies, TH1, Cytotoxic T lymphocytes (NK cells used in innate immunity)
How could you tell whether someone has had chickenpox before?
Blood test to look for VZV IgG (+/ IgM)
