Immune Response

Question 1

What is an Adaptive Immune response?

Answer 1

Specific and can produce immunological memory.

• Innate immune may be faster but can not change on re-exposure to infectious agent ( complement, phagocytosis, natural killer cells )

Question 2

What two phases usually occur during an immune response?

Answer 2

Antigen recognition involving clonal selection and clonal expansion

Antigen eradication in the effector phase the immune response in coordinated

Question 3

How do different bacterial niches cause differing responses?

Answer 3

EXTRACELLULAR: pathogen multiplies outside of cells and dies if moved into a phagocytes – e.g. staphylococcus, streptococcus, Candida, microbiota, worms

• Are accessible to antibodies and complement

INTRACELLULAR vacuolar: pathogen replicates inside cells – e.g. salmonella, chlamydia, legionella, Coxiella, plasmodium, helminths

§ Not accessible to antibodies and complement so immune cells need to recognise and tackle infected host cell to get to pathogen

SURFACE ADHERENT: enteropathogenic + enterohaemorrhagic E. Coli

INTRACELLULAR CYTOSOLIC: viruses, listeria, burkholderia, mycobacterium

Question 4

Which cellular components are use in innate immunity? (4)

Answer 4

Neutrophils
Macrophages
Dendritic cells
Natural Killer cells

Question 5

Which cellular components are used in adaptive immunity? (5)

Answer 5

Cytotoxic T cell
T helper cells
T regulatory
B lymphocytes
Plasma cells

Question 6

What structure(s) is the Innate system specific for?

How many molecules can be recognised?

Answer 6

Pathogen associated molecular patterns

PAMPs

1000 molecular patterns

e.g. Toll receptors on microbes identical

Question 7

What structure(s) is the Adaptive system specific for?

How many molecules can be recognised?

Answer 7

Antigens

under 10^7

Question 8

What allows the adaptive immune system to have a greater diversity of receptors compared to innate?

Answer 8

Innate receptors are encoded in germline ( <100 )

Adaptive receptors are encoded by somatic recombination of gene segments ( Ig and TCR with millions of variation )

Question 9

How does the innate and adaptive immune system communicate?

Answer 9

Soluble messengers e.g. interleukins and interferons

Question 10

How are phagocyte responses pathogen specific?

Answer 10

Specificity starts w/pathogen-specific responses made by macrophages – leads to activation of those phagocytes turning on specific gene expression programmes + inducing secretion of various interleukins and soluble mediators

Question 11

Which genes are utilised in phagocyte responses?

Answer 11

Antimicrobial genes
Metabolic genes
Immunomodulatory genes

Question 12

What is it about bacterial that triggers phagocytosis?

Answer 12

Alive bacteria phagocytosed released mRNA

Question 13

How do interferons promote antiviral defence?

Answer 13

Release of interferons promotes antiviral defence

Interferons are special cytokines with direct antiviral activities

Antiviral genes include: NucleasesInhibitors of virus entry & exit
Inhibitors of viral uncoating and replication
Inhibitors of protein translation

Question 14

How do phagocytosed microbes be killed - involves macrophages?

Answer 14

Macrophages are tissue resident or circulatory (from bone-marrow)

• Macrophage “activation” = expression of many new genes
• Induced by microbes & cytokines

Question 15

What is enhanced when macrophages are activated? 5

Answer 15

phagocytosis and migration

cytokine/chemokine production

expression of cell surface molecules

antimicrobial activity

antigen presentation and T cell activation

Question 16

What immunomodulatory roles do interferons play?

Answer 16

Enhanced T cell responses

anti Inflammatory

tissue repair

Question 17

How are virus infected cells killed?

Answer 17

CTLs
NKs

They kill infected cells by directly contacting them ( contact-dependent )

• contact independent cell death would be for intracellular bacterial pathogens

Question 18

What are the 4 examples of soluable effector mechanisms ( Humoral )

Answer 18

Complement bacterial destruction

Lectin binding to neutralise cell

Iron chelation to stop replication

Antibiotic like peptides

Question 19

What are are some examples of cellular effector mechanisms?

Answer 19

Reactive Oxygen and Nitrogen radicals

Acidification and digestion within phagosomes.

• Microbes are killed by: phagocyte oxidase, Nitric oxide, phagocytosis
• Inflammatory enhancement by : Cytokines activated by humoral immunity.
• Understand connection between Humoral affects linked to cellular affects

Question 20

Which Interferons promote antiviral responses?

Answer 20

Type I and II

Question 21

Which Interferon promotes antibacterial immunity?

Answer 21

Type II

Question 22

How do activated macrophages and DCs present antigens to T cells?

Answer 22

MHC-1

MHC 2

Question 23

How the APCs activate T cell replication?

Answer 23

Cytokines produced for example IL-12 from APCs trigger T cells

• APCs are macrophages and DCs

Question 24

How can activated macrophages and DCs lead to activated phagocytes?

Answer 24

T cells activated produce cytokines to activate the phagocytes.

e.g. IFN-gamma enhances macrophage expression of more genes and can increase APC presentation

Question 25

How do T cells help B cells produce antibodies?

Answer 25

T cells interact with APCs and become activated themselves by recognising the foreign peptides Then Help B cell to become activated by putting peptide on BCR B cell produce antibody against antigen present on BCR

Question 26

Which T cells work against viruses and bacteria respectively?

Answer 26

Th1 Cell = CD4 T cell Cytotoxic T cell = CD8 T cell

Question 27

How can T cells work independently of MHCs?

Answer 27

Innate lymphoid cells = Gammadelta T cells

Question 28

Effector T cell : Th1 ``` Cytokine? Target cell? Immune effect? What pathogen? Role in disease? ```

Answer 28

Cytokine = IFN- Gamma Target cell = Macrophages Immune effect = Macrophage activation What pathogen = Intracellular pathogens Role in disease = Autoimmunity. chronic inflammation if uncontrolled

Question 29

Effector T Cell : Th2 ``` Cytokine? Target cell? Immune effect? What pathogen? Role in disease? ```

Answer 29

Cytokines = IL-4 , IL-5, IL-13 Target cell = Eosinophil Immune effect = Eosinophil activation What pathogen = Helminths Role in disease = Allergy

Question 30

Effector T Cel : Th17 ``` Cytokine? Target cell? Immune effect? What pathogen? Role in disease? ```

Answer 30

Cytokine = IL-17, IL-22 Target cell = Neutrophils Immune effect = Neutrophil recruitment and activation What pathogen = Extracellular bacterial and fungi Role in disease = Autoimmune inflammation

Question 31

What drives the change from naive to activated immunity?

Answer 31

Gene expression changes through cytokine combinations. Differentiation of precursor cells into specific cells e.g. T cells to Th1 Th2 Th17 etc

Question 32

In the first 12 hours after infection, what occurs?

Answer 32

``` Innate immunity: Phagocytes Mast cells Epithelial barrier DCs NKs ILCs Complement ```

Question 33

What occurs in the days following infection?

Answer 33

Adaptive immunity: B lymphocytes recognise antigen --> proliferate --> differentiate into plasma or memory T Lymphocytes recognise antigen --> Proliferate --> differentiate into Memory or effector

Question 34

What is the impact of age on the immune response?

Answer 34

As age increases: Naive T cells in blood decreases Memory T cells in blood increase Thymic output decreases