Lecture 22: Immune Response to Infection

Question 1

Outline the 4 steps of the immune response to infection.

Answer 1

1. Microbial detection (bacteria, viruses, fungi etc.)
2. Innate immune response (epithelia, phagocytes, NK cells etc.)
3. Adaptive immune response (lymphoid tissues, T and B lymphocytes)
4. Memory response (memory T and B cells)

Question 2

What areas of difference are there between innate and adaptive immunity?

Answer 2

• timing of response
• cell types
• receptors and ligands
• cytokines and chemokines
• molecular effector machineries

Question 3

What are some pathogen niches during infection?

Answer 3

• Extracellular (e.g. staphylococcus, streptococcus_
• Intracellular (e.g. Salmonella, Plasmodium)
• Surface adherent (e.g. enteropathogenic E. Coli)
• Intracellular but cytosolic (e.g. viruses, Listeria)

Question 4

What immune cells are first to respond once a pathogen has been detected?

Answer 4

Neutrophils followed by macrophages

Question 5

How long do neutrophils live for in the first response to infection?

Answer 5

Approx. 6 hrs

Question 6

What happens to naïve cells when they interact with microbes?

Answer 6

They become ‘activated’

Question 7

What do phagocytes do?

Answer 7

Control infection and limit/repair tissue damage

Question 8

What can uncontrolled activities of phagocytes lead to?

Answer 8

• granulomas
• excessive inflammation and inappropriate adaptive immunity
• tissue damage

Question 9

What is the general sequence of events of communication within the immune system?

Answer 9

Microbial ligands (detection) –> naïve host-cells (gene-expression changes) –> cytokines and chemokines (signal transduction) –> activated host- cells

Question 10

What are macrophages?

Answer 10

large phagocytic cells that ate tissue resident or circulatory (from bone marrow)

Question 11

What is macrophage activation?

Answer 11

Expression of many new genes induced by microbes and cytokines

Question 12

Activated macrophages display enhanced…?

Answer 12

• phagocytosis and migration
• cytokine/chemokine production
• expression of cell surface molecules
• antimicrobial activity
• antigen presentation and T cell activation

Question 13

What are ‘alternatively’ activated macrophages?

Answer 13

They are anti-inflammatory

Question 14

What are interferons?

Answer 14

Special cytokines that have direct antiviral activities - they promote antiviral defence

Question 15

What can be included in antiviral genes?

Answer 15

• nucleases
• inhibitors of virus entry and exit
• inhibitors of viral uncoating and replication
• inhibitors of protein translation

Question 16

What immunomodulatory roles do interferons have?

Answer 16

• enhanced T cell responses
• anti-inflammatory actions
• tissue repair

Question 17

What 2 types of cell are responsible for directly killing virus-infected cells?

Answer 17

Cytotoxic T lymphocytes (CTLs or CD8+)
Natural Killer (NK) cells

Question 18

What is the purpose of cell death when fighting a viral infection?

Answer 18

Removes viral replicative niches

Question 19

Can host cells infected with intracellular bacterial pathogens also undergo forms of cell death?

Answer 19

Yes

Question 20

What are the humoral/soluble effector mechanisms of immunity?

Answer 20

• complement mediated bacterial destruction
• lectin-binding to neutralise cell attachment or entry
• iron chelation (siderophores) to prevent replication
• antibiotic-like peptides

Question 21

What are the cellular effector mechanisms of immunity?

Answer 21

• reactive oxygen and nitrogen radicals

- acidification and digestion within phagosomes

Question 22

What do activated macrophages and dendritic cells do?

Answer 22

present antigens in combination with MHC-I or MHC-II to T cells

Question 23

Give an example of how cytokines produced by APCs produce a suitable type of environment for T cell activation.

Answer 23

IL-12 (interleukin 12) promotes T cell replication

Question 24

Given an example of how T cells provide cytokines that activate phagocytes.

Answer 24

IFNy (interferon gamma) upregulates MHC-II expression for antigen presentation

Question 25

How do T and B cells interact?

Answer 25

T cells help B cells produce antibodies (become activated) against the antigen they recognised via MHCs

Question 26

How do T and B cells enhance antimicrobial activity?

Answer 26

• phagocyte activation
• direct killing of infected cells
• B cell activation
• Innate lymphoid cells

Question 27

The sequence of the immune response depends on what?

Answer 27

The sequential change from ‘resting/naïve’ to ‘activated’ state - differentiation of ‘precursor’ cells into specific lineages of cells

Question 28

What happens within 0-12 hours after initial infection?

Answer 28

Innate immune response:

• microbe detected
• mast cells, phagocytes, dendritic cells
• complement
• NK cells and ILCs (innate lymphoid cells)

Question 29

What happens within approx. 1-5 days after initial infection?

Answer 29

Adaptive immune response:

• B cells –> plasma cells –> antibodies
• T cells –> effector T cells

Question 30

At what point approximately does the primary antibody response peak?

Answer 30

Approx. 2 weeks

Question 31

What is the impact of age on the immune response?

Answer 31

• no. of naïve T cells decreases
• no. of memory T cells increases
• thymic output decreases

Question 32

Innate and adaptive immune responses are specific to what?

Answer 32

The broad classes of pathogens and their virulence strategies