L6: Adaptive immune response: Recognition phase

Question 1

What cell is essential for an immune response?

Answer 1

Antigen presenting cells

Question 2

What are naive T cells?

Answer 2

Cells that have not encountered any antigen

Come out of thymus ready to encounter antigen

Question 3

How are naive T cells activated?

Answer 3

Pathogen (microorganism that can cause disease e.g. bacteria, virus, fungi) engulfed, broken down and presented on APC
APC present it to naive T cell which can then cause an immune response

Question 4

What is the difference between intracellular and extracellular microorganism?

Answer 4

Intracellular–> inside the cells –> virus

Extracellular–> extracellular tissue–> bacteria, fungi and parasites

Question 5

What do antigen presenting cells do?

Answer 5

Sense the pathogen
Capture the pathogen
Process the pathogen–> Degrade bacteria/virus into peptide which it presents on the surface
Present the pathogen–> specific T cell

Question 6

What are the different types of antigen presenting cells? Who do they present to? What is their function?

Answer 6

Dendritic cells –> Naive T cells–> Response against most pathogens
Langerhans cells–> Naive T cells–> Response against most pathogens
Macrophages–> Effector T cells–> Phagocytic activities
B cells–> Effector T cells–> Antibody response (humoral response)

Question 7

What are effector T cells?

Answer 7

T cell–> previously encountered antigen–> effector functions

Question 8

What are the features of antigen presenting cells?

Answer 8

Strategic location

Diversity in pathogen sensors (PRRs)

Diversity in pathogen capture mechanism

Question 9

What are the different strategic locations?

Answer 9

• -> Mucosal membrane–> gut, lung (MALTs mucosal associated lymphoid tissue)
• -> Skin–> Langerhan cells (SALTs)
• -> Blood–> Plasmacytoid cells
• -> Lymph nodes–> follicular dendritic cells
• -> Spleen

Question 10

Why is there diversity in pathogen sensors (PRRs)?

Answer 10

–> Extracellular pathogens
–> Intracellular pathogens
different locations on and within the cells
Best PRR Toll like receptor

Question 11

What are the different pathogen capture mechanisms?

Answer 11

• -> Phagocytosis (whole microbe)- opsonisation followed by phagocytosis
• -> Macropinocytosis (soluble particles) - toxins

Question 12

What are the different PRRs?

Answer 12

Toll Like receptor (TLR) most common PRR
Extracellular –> TLR1, 2, 4, 5, 6,
Intracellular–> TLR3, 7, 8, 9

Question 13

What happens if the TLR becomes overactive?

Answer 13

Sepsis

Question 14

What happens when pathogen breach the innate barrier?

Answer 14

Skin breached
Sensor capture mechanisms–> Macrophages (innate response) OR –> enter blood OR –> Antigen presenting cells
Antigen processing
Expression of microbial antigen on APC–> Travel in blood OR lymphatics to lymphoid tissue
–> spleen, lymph nodes, MALTs
Presentation of microbial antigen to right T cell
Best adaptive immune response
Humoral immunity–> extracellular microbes
Cell mediated immunity –> intracellular microbes

Question 15

What is the protein called that presents the pathogens?

Answer 15

Major Histocompatibility Complex
Encoded by HLA region on haplotype
Haplotype= set of MHC alleles that are inherited together from one parent and present on chromosomes

Question 16

What are the two classes of MHC? Where are they presented?

Answer 16

Class I molecules –> all nucleated cells

Class II molecules –> Antigen presenting cells –> dendritic cells, macrophages, B cells

Question 17

What are the key features of Class I and Class II MHC molecules?

Answer 17

Co-dominant expression–> MCH molecule received from mother and MHC molecule received from father are both expressed on cell–> more you have the better

Polymorphic genes–> different individuals have different ones therefore they respond to different microbes,

Presentation of microbial peptides--> APC of intracellular microbes via MHC class I molecule (A, B snd C)
--> APC of extracellular microbes via MHC class II molecules (DP, DQ, DR)

Question 18

How are intracellular microbes processed?

Answer 18

Endogenous pathway
1. Viral protein present in cystol
2. Marked for destruction by proteasome
3. Proteasome generated viral peptide transported to ER by TAP (transported associated with antigen processing) proteins
4. Formation of viral peptide MHC class I complex if right MHC molecule found –> Presented on cell surface
5. APCs and Non-APCs present peptides from intracellular pathogens to CD8+ T cells
occurs in all cells
Cells also present self pepetide–> T cells only activated if foreign peptide spotted

Question 19

What is the weakness to the endogenous pathway?

Answer 19

• Need to have correct MHC molecule for that peptide from microbe
• Virus may mutate all peptide sufficiently so that no peptide is presented e.g. HIV

Question 20

What do we mean by ‘APCs and Non-APCs present peptides from intracellular pathogens to CD8+ T cells’?

Answer 20

APC cells can migrate to the lymphoid tissue and activate naive CD8+ T cells
Non APC cells such as epithelial cells present it on their cell surface signalling they are infected–> activated CD8+T cells search and kill infected cells

Question 21

How are extracellular microbes processed?

Answer 21

Exogenous pathway

1. Microbes captured by phagocytosis or micropinocytosis
2. Degraded into small peptides in the endosome
3. Peptide rich vesicles fuse with vesicles containing MHC Class II molecules
4. Formation of peptide MHC class II complex if right match
5. Occurs only in APC including dendritic cells, B cells and macrophages
6. APCs present peptides of extracellular pathogens to CD4+ T cells

Question 22

What is the structure of an MHC class I and class II molecule?

Answer 22

MHC Class I–> single transmembrane chain, 3 different subunits α 1, 2, 3, small β chain for stability, peptide molecule between α 1 and 2
MHC Class II–> two transmembrane chains, α 1 and 2, β 1 and 2, peptide molecule between α 1 and β 1

Question 23

Whats is the region where the peptide binds called?

Answer 23

Peptide binding cleft
Variable region with highly polymorphic residues (several different forms)
Accommodate variety of peptides 
MHC Class I present up to 9aa
MHC Class II present up to 30aa

Question 24

What is meant by broad specificity of peptides?

Answer 24

Born with all MHC molecules
Can only bind one polypeptide (at a time?) but different types of polypeptide–> size and sequence must fit
Bind at different angles

Question 25

What are the specific responsive T cells for each of the MHC molecules?

Answer 25

MHC Class I recognised by CD8+ molecules on T cells
MHC Class II recognised by CD4+ molecules on T cells
Narrows down specificity

Question 26

What is the clinical importance of MHC molecules?

Answer 26

• Can deal with variety of organisms–> genetic polymorphism and gene families
• No two individuals have the same MHC molecule–> prevents whole population being wiped out by a single microbe/ epidemic disease
• Different susceptibilities to infections–> strong vs weak immune response against infectious microbes (some people will become more ill with same infection) –> excludes the high risk groups (young, elderly, pregnant and chronic illness)

Question 27

What are people that don’t get affected by HIV viral infection called?

Answer 27

Elite controllers
Long-term nonprogressors (LTNP)
Maintain a CD4+ count >800 without antiviral therapy
-Pt heterozygous for HLA (MHC)–> pt present the protein from the HIV that is essential for the virus replication–> meaning it cannot be mutated by the virus or else it will kill itself
MHC presents it to T cell which kills it so pt positive for virus, remains in cell but load stays low as it cannot replicate

Question 28

What are the clinical problems with MHC molecules?

Answer 28

• Transplant rejection -> Human Leukocyte Antigen (HLA) (specific human version of MHC) mismatch between donor and recipient –> Graft-versus-Host reaction (GVH)
• HLA association with autoimmune disease
• -> Ankylosing Spondylitis
• -> Insulin-Dependent Diabetes Mellitus