Adaptive Immunity Flashcards
What are the key players in adaptive immunity?
T cells
Antigen presenting cells (dendritic cells) - These allow T cells to be affective against microbe as they capture, process and present the microbes in a way that leads to T cell activation.
What are the two differen types of mcriobes and two different responses?
Intracellular microbes = Innate. (Naive T lymphocyte interacts with antigen presenting cell.)
Extracellularly microbes = Adaptive response.
What are the features of antigen presenting cells?
- Strategic location (B and T cell interaction)
- Skin (SALT)
- Mucous membranes (GALT, NALT, BALT, GUALT)
- Lymphoid organs (Lymph nodes, spleen)
- Blood circulation (Plasmacytoid and myeloid DCs)
- Pathogen capture
- Phagocytosis (whole microbe)
- Macropinocytosis (soluble particles)
- Diversity in pathogen sensors (PRRs)
- Extracellular pathogens (bacteria)
- Intracellular pathogens (viruses)
What is the spleen?
A major organ that will fight any blood borne pathogen.
So, patients with no spleen are highly susceptible to bacteria in the blood.
What are the different types of antigen-presenting cells?
Dendritic cells - Lymph nodes, mucous membranes and blood. They present to Naive T cells.
Langerhans’ cells - Skin. They present to Naive T Cells.
Macrophages - Various tissues. They present to effector T cells.
B cells (BCR) - lymphoid tissue. They present to effector and naive T cells.
Extracellular microbes?
Activate humoral immunity. -Antibodies, complement and phagocytosis. (MHC II)
Intracellular microbes?
Cell-dependant immunity. - Cytotoxic T lymphocytes, antibodies and macrophages. Need to kill the virally infected cells (Cytotoxic T cells). (MHC I)
What are the two classes of MHC molecules?
Class I - found on all cells. Called HLA-A, HLA-B, HLA-C
Class II molecules are only expressed on antigen presenting cells (dendritic cells, macrophages and B cells) called HLA-DR, HLA-DQ, HLA-DP
What are the key features of MHC class I / II molecules?
More diverse = more effective as active against more pathogens.
Co-dominant expression - Both parental genes are expressed. This increases the number of different MHC molecules.
Polymorphic genes - Different alleles among individuals - This increases the presentation of different antigens / microbes
What are the main functions of MHC Class I / Class II?
MHC Class I = presents peptides from intracellular microbes
MHC Class II presents peptides from extracellular microbes.
What are the strctures of MHC class I / II molecules?
Peptide binding cleft - Variable region with highly polymorphic residues.
Broad specificity - Many peptides presented by the same MHC molecules.
Responsive T cells - MHC class I recognised by CD8+ T cells. MHC class II recognises by CD4+ T cells.
Antigen processing pathways
Both self and non-self peptides are presented.
All peptides from the same microbe are presented by different MHC molecules.
Susceptibility to Infection depends on the types of MHC molecules.
Endogenous pathway = Antigen peptides are loaded onto MHC I in RER after delivery via TAP (a transporter associated with antigen processing). They then present these exogenously synthesied antigens to CD8+ cytotoxic T cells.
Exogenous pathway = Antigen is loaded follwing the release if invarient chain in an acidified endosome. They then present these exogenously synthesied antigens to CD4+ helper T cells via MHC class II.
What happens in rapid HIV progressions?
HLA-B35. Homozygote in HLA-I allelels.
MHC molecules present mutated peptides (less critical peptides for the virus)
Poor recognition by T cells. Poor T cell responses.
What happens in slow HIV response?
Slow progressors = HLA-B27, HLA-B51, HLA-B57
MHC molecules present key peptides for the survival of the virus (unumtated)
Effective T cell response.
How do different MHC molecules correlate to attractiveness?
If MHC molecules are less similar then you are more attracted to a person as children will be healthier.
What clinical problems are associated with MHC molecules?
Major cause of organ transplant rejection
- HLA molecules mismatch between donor and recipient (Allograft)
- Graft vs Host reaction (GVH)
HLA association and autoimmune disease.
- Ankylosing spondylitis - HLA-B27 > 90% of patients.
- Insulin dependant Diabetes Mellitus - HLADQ2 - >50-75% of patients
T cell subtypes?
CD4+ = T helper
CD8+ = Cytotoxic T cells.
How are extracellular microbes processed and presented?
Extracellular microbes (bacteria, parasites, worms and fungi) activate the exogenous pathway.
This causes CD4+ T cells (Helper T cells) to bind to MHC class II.
This causes humoral immunity to occur. (antibodies are produced and the compliment cascade is activated.
How are intracellular microbes processed and presented?
Intracellular microbies (Viruses, Bacteria and Protozoa) enter the cell and activate endogenous and exogenous pathways.
This means CD4+ T cells bind to MHC class II AND CD8+ T cells bind to MHC class I.
This leads to cell dependant immunity (Antibody -B cells, Complement cascade and macrophages) and cytotoxic T cells.
If don’t have CD4+ then CD8+ is useless.
What are co-stimulatory proteins?
These are proteins that require two signals to become fully active.
A first signal, which is antigen-specific, is provided through the T cell receptor (TCR) which interacts with peptide-MHC molecules on the membrane of antigen presenting cells (APC).
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.
The naive TCR could then become TH1 (Intracellular microbes) or TH2 (extracellular microbes).
How do T cells respond to intracellular microbes?
How do T cell respond to extracellular microbes?
What are the functions of IgG?
- fc-dependant phagocytosis
- Complement activation
- Neonatal immunty
- Toxin / virus neutralisation
What are the functions of IgA?
Mucosal Immunty
What are the functions of IgE?
Immunty against helminths
Mast cell degranulation (allergies)
What are the functions of IgM?
Compliment activation
