Immune Response To Infection Flashcards by Sumaiya Butt

What are the 4 different pathogen niches during infection?

Extracellular e.g. Staphylococcus, Streptococcus, Candida, microbiota, worms
Surface adherent e.g. enteropathogenic & enterohaemorrhagic E. coli
Intracellular vacuolar (that occupy specialised compartment in host cell e.g. modified lysosome or ER) e.g. Salmonella, Chlamydia, Legionella, Coxiella, Plasmodium
Intracellular cytosolic e.g. viruses, Listeria, Bukholderia, Mycobacterium

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How does an immune response to an infection start

Tissue damage (e.g. injury or by toxins produced by infectious agent)
Molecular detection of microbes- wrong thing in wrong place at wrong time
Then, intercellular communication happens e.g. interleukins
This leads to priming of the adaptive immune response

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How does an immune response to infection end

Clearing infection
Stopping inflammatory cytokine production- more production of these can lead to tissue damage
Repairing tissue damage
Remembering the infection- immune memory

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What are the 3 broad differences between innate and adaptive immunity?

Innate:

Fast acting

First line of defence

Germline encoded receptors

Adaptive:

Slower but long lasting

Variable receptors that mature over time

Also innate provides physical barriers whereas adaptive doesn’t.

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Physical barriers provided by innate immunity

Skin,mucous,epithelial cells

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Is complement part of innate or adaptive

Both

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What are the key cellular components of innate immunity?

Neutrophils, macrophages, dendritic cells and natural killer (NK) cells

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What are the key cellular components of adaptive immunity?

Cytotoxic T-cells, T helper cells, T regulatory cells, B lymphocytes and plasma cells

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What is the difference in specificity between innate and adaptive?

Innate is less specific than adaptive as innate detects broad classes of pathogens via PAMPs (e.g. cell membrane components such as peptidoglycan) whereas adaptive can detect structural detail of antigens and may even recognise non-microbial antigens

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Why is there greater diversity in adaptive immune receptors in comparison to innate immune receptors

Adaptive immune receptors are encoded by genes produced by somatic recombination hence they produce TCRs and Ig’s that have millions of different variations

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List the general sequence of molecular and cellular events of an immune response?

Microbial molecules detected

Naïve host-cells are changed - gene expression leads to their activation

Production of antimicrobial molecules which send communication signals to alert neighbouring cells

Leads to the production of activated and specialised host cells

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First responders to site of injury

Neutrophils are short lived~6 hours
Followed by monocytes that differentiate to become macrophages
Uncontrolled activity can lead to granulomas,excessive inflammation and tissue damage

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How do phagocytes and other immune cells identify the class of pathogen?

Bacteria- typically cell wall components like LPS in E. coli

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How does live vs dead bacteria elicit different immune responses?

- Live E. coli elicits immune response-
  - inflammatory cytokines produced (e.g. IL-1beta that’s responsible for fever)
  - antimicrobial genes (that are directly toxic to bacteria)
  - metabolic genes (that help macrophage cope with these high, demanding jobs)
  - immunomodulatory genes (so that adaptive immune system appropriately primed)
- Dead E. coli results in no immune response- macrophage tries to resolve inflammation rather than causing more

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Cell surface molecules unique to fungi

Beta glucans

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What type of immune response do fungi produce

Different kind of proinflammatory cytokines
Antimicrobial genes
Metabolic genes
Immunomodulatory genes

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What type of immune response do viruses produce?

Interferon production that interfere with viral replication
Proinflammatory cytokines
Antiviral genes
## Immunomodulatory genes

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What do activated macrophages display

Phagocytosis and migration

Cytokine/chemokine production

Expression of cell surface molecules

Antimicrobial activity

Antigen presentation and T cell activation

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What are interferons

Are special cytokines
Have direct antiviral activities
Detects viruses and gram negative intracellular bacteria

3 types of interferons

Type I-IFN alpha/beta
Promotes antiviral response
Every primary infected cell can produce type I IFN

TypeII-IFN gamma
Only produced by lymphocytes
Promotes antibacterial immunity

Type III-lambda
Only produced at epithelial surfaces
Promote antiviral responses

What are the immunomodulatory roles of IFNs?

Enhanced T-cell responses
Anti-inflammatory actions
Tissue repair

How are virus infected cells killed

Cytotoxic T lymphocytes or natural killer cells

2 anti microbial enzymes that are produced by a cytokine binding to a cytokine receptor

Phagocyte oxidase which produces reactive oxygen species

Inducibke nitric oxide synthase produces nitric oxide

What are the soluble effector mechanisms of innate immunity?

Complement mediated bacterial destruction
Lectin-binding to neutralise cell attachment or entry
Iron chelation (siderophores) to prevent replication
Antibiotic-like peptides

What are the cellular effector mechanisms of innate immunity?

- **Reactive oxygen** and nitrogen radicals made by **phagocyte oxidase and iNOS** respectively- these genes never present in naive cells- only expressed when pathogen encountered - **Acidification** and digestion within **phagosomes** -

How are T cells activated

Activated macrophages and DCs present antigens in combination with MHC I and MHC II Cytokines produced by apc produce suitable millieu for T cell activation eg IL12 promotes T cell replication T cells provide cytokines that activate phagocytes eg IFN gamma upregulates MHC II expression for antigen presentation

How are dendritic cells better able to respond to viral infections than macrophages?

Produce type I IFN

How do T cells help B cells produce antibodies?

- APCs become activated by infection and cytokines and present antigen to T cell which becomes activated to Th cell - Th cell helps activate the B cell with the correct BCR which produces antibodies against original antigen

What are the 2 main T cell types?

- Th1 cell (CD4 T cell) produced during bacterial infections that produce IFN-gamma and other cytokines that promote inflammation, phagocytosis and killing of microbes - Tc cell (CD8 T cell) produced during viral infections and will directly kill virus infected cells leading to apoptosis of the host cell, removing viral replicating niches

What are some T cell functions

- Phagocyte activation- T cell derived cytokines activate phagocytes which leads to enhanced killing of pathogens and more inflammation - Direct killing of infected cells- removal of replicative niches - B cell activation- antibody production and affinity maturation - Innate lymphoid cells (aka gamma delta T cells)- reside in mucosal surfaces and are a type of early responders to infection (act independently to MHC)

Impact of age

Immune response gets weaker due to reduced thymic output

What kind of genetic dysfunction leads to chronic granulomatous disease?

Loss of reactive oxygen soecies

What genetic dysfunction leads to chediak higashi syndrome

Compromised lysosomes

What genetic dysfunction is in immunosuppresion

Depletion/impairment of lymphocytes

What kind of genetic dysfunction is present in HIV

Reduced CD4 T helper cells

genetic dysfunction in the genes controlling what leads Severe Combined Immunodeficiency (SCID)?

Reduction of T and B cells

What genetic disfunction leads to X-linked aggamaglobulinaemia?

Decreased **serum** IgG of all types -

To which pathogens are Th17 made?

Fungi Extracellular bacteria

To which pathogens are Th1 made

Bacteria Protozoa

To which pathogens are Th2 made

Helminths Allergens Venom

Intracellular pathogens

Macrophages are activated causing release of interferon gamma which causes T cells to differentiate into Th1 Excessive can cause autoimmunity and chronic inflammation

Helminths

Causes mast cells and eosinophils to be activated which causes lease of IL-4,IL-5, IL-13. This causes T cells to differentiate into Th2 Excessive can cause allergy

Extracellular bacteria and fungi

Causes neutrophil activation which causes release of IL-17 and IL-22. This causes T cells to differentiate into Th17

PAMPs vs DAMPs

PAMPs are released by pathogens and are conserved structures eg bacteira have lps,fungi have beta glucan cell walls,viruses have surface glycoprotein DAMPs are released by distressed or dying tissues recognized by ato released from dead cells,alarmins and some cytokines

Apoptosis vs pyroptosis

Caspase 8,9,3,6,7 Caspase 1,4,5 for pyroptosis

Phagocyte and T cell response

Intracellular pathogens cause macrophages to be activated causing release of IFN-gamma. Thus causes T cells to differentiate into Th1 cells. If left for too long it can cause autoimmune disease and chronic inflammation Helminths activate eosinophils causing release of IL-4,5,13 which causes T cells to differentiate into Th2 cells. If left for too long ca cause allergy Extracellular bacteria and fungi activate neutrophils to release IL-17,22 which activates Th17. If left for too long it causes autoimmunity and inflammation