Adaptive Immunity Flashcards
How does a naive t cell recognise a pathogen?
Antigens must be presented by Antigen Presenting Cells
What is a naive t cell?
T cell that has not previously encountered the antigen
What do antigen presenting cells do? (4)
1) Sense the pathogen,
2) Capture pathogen (phagocytosis o macropinocytosis)
3) Processing (digestion down to antigen fragments - very small pieces)
4) Presentation of pathogen’s peptides to T cells (using an MHC).
Types of APC (4)
Dendritic
Langerhan (same as dendritic but in the skin, they are called langerhan cells)
Macrophage
B cells
Dendritic cell presenting mechanism:
1) What do they present to?
2) What is the result?
Presents to: Naive T cells
Result: T cells response against most pathogens
Langerhan cell presenting mechanism:
1) What do they present to?
2) What is the result?
Presents to: Naive T cell
Result: T cells response against most pathogens
Macrophage presenting mechanism:
1) What do they present to?
2) What is the result?
Present to: Effector cells (already encountered antigen)
Effect: Phagocytic activities
B cells presenting mechanism
Presents to: Effector T cells
Result: Antibody production (humoral response)
3 Features of APC
Strategically located
Diversity in capture mechanism
Diversity in pathogen sensors (PRRs)
Describe the Strategic location of APC (5)
Mucosal membranes (gut, lung called dendritic cells here) Skin (called langerhan cells here) Blood (called plasmacytoid cells here) Lymph nodes (called follicular dendritic cells here) Spleen (against blood bourne pathogens)
What are the Capture mechanism of APCs?
Phagocytosis (whole microbe invaginated)
Macropinocytosis (invagination of soluble particles)
Describe Pathogen recognition receptor (PRR) diversity in sensing
PRRs sense and looks for PAMPs (Pathogen associated molecular patterns)
These sensors are able to differentiate between extracellular microbes and intracellular microbes
extracellular microbes (bacteria, fungi, protozoa)
Intracellular (viruses)
What PRR senses neisseria meningitidis?
TLR4 (gram negative, extracellular)
(TLR4 is also relevant to sepsis)
Where do the APC travel to once presenting and why?
Migrate via the lymphatics to the lymphoid tissues:
- MALT (mucosal associated lymphoid tissue)
- Lymph nodes
- Spleen
Because all the best effector cells for the adaptive immunity (specifically naive B cells and naive T cells) are here, condensed in a very small environment to maximise interaction.
Adaptive immune response to extracellular microbes (bacteria) (3)
- APC present peptide pathogens using MHC class 2
- Present to Naive CD4+ T cells
- Humoral immunity (antibodies)
Innate immune response extracellular (bacteria)
Complement and Phagocytosis
By macrophages
Describe the innate response intracellular microbes (virus)
- Interferons (INFs) - interfere with virus and prevent it replicating in neighbouring cells
- NK cells - kill infected cells
Describe the Adaptive response intracellular microbes(4)
- APC sense that this is a virus
- They present pathogen peptides to naive CD8+ T cell
- Using MHC class 1
- Cell mediated immunity (cytotoxic t cell response)
- Humoral immunity (antibodies produced)
What molecule helps to present pathogens to APC’s ?
MHC (major histocompatibility complex)
HLA (human leukocyte antigen)
SAME THING (HLA in humans, mammals in general = MHC)
Where are MHC class 1 and 2 expressed?
MHC class 1 - all nucleated cells
MHC class 2 - all antigen presenting cells
(Dendritic both as nucleated and APC)
Key features of MHC
1) Co dominant expression (parental MHC molecules are co expressed in each individal) - 6 of each class
2) Polymorphic genes (different alleles) - different individuals present and respond to different microbes
3) Presentation of microbial peptides:
- Intracellular microbes are always presented via MHC class 1
- Extracellular microbes are always presented via MHC class 2
MHC and which microbes they present
MHC class 1 - presents INTRAcellular
MHC class 2 - presents EXTRAcellular
How are microbes presented using MHC?
- Peptide binding cleft (variable region with highly polymorphic residues)
- Broad specificity (many peptides presented by same MHC molecule )
- Responsive T cells
(MHC class 1 recognised by CD8+ molecules on T cells)
(MHC class 2 molecules on T cells recognised by CD4+ molecules on T cells)
MHC and what T cells recognise
MHC class 1 - recognised by CD8+ molecules on T cells
MHC class 2 - recognised by CD4+ molecules on T cells
Processing extracellular microbes to be presented (5)
Exogenous pathway:
- Microbes captured by phagocytosis or macropinocytosis
- Degradation into small peptides in the endosome
- Peptide-rich vesicles fuse with vesicles containing MHC class II molecules
- Formation of peptide-MHC class II complex if right match
- APCs presents peptides of extracellular pathogens to CD4+ T cells
Processing intracellular microbes
Endogenous pathway:
- Viral protein present in the cytosol
- Marked for destruction by the proteasome
- Proteasome-generated viral peptide transported to ER by TAP proteins
- Formation of viral peptide-MHC class I complex if right match
- APCs and non-APCs present peptides from intracellular pathogens to CD8+ T cells
Clinical importance of MHC molecules
Host can deal with variety of microbes (polymorphism and codominance)
No two individuals have same MHC (not wiped out by single microbe)
Different susceptibilities to infection (strong vs weak immune response)
Clinical conditions with MHC
Rejection of organ transplant (HLA molecules mismatch)
Autoimmune disease
Class 1 MHC HLA equivalent
HLA A,B,C
Class 2 MHC HLA equivalent
HLA DP,DQ,DR
Haplotype
Set of MHC alleles that are inherited together from one parent
