Immune Sequence and Timing Flashcards
What are the 4 steps of the immune response sequence?
- Microbial detection
- Innate immune response
- Adaptive immune response
- Memory response
Which 4 cell types are involved in the innate immune response?
- Epithelia
- Phagocytes
- NK cells
- Innate lymphoid cells
Which 3 cell types are involved in the adaptive immune response?
- Lymphoid tissue
- T and B lymphocytes
- Cytotoxic T cells (CD8)
Which cell type is involved in the memory response?
Memory T and B cells
How are immune responses triggered? (2)
MAMPS and DAMPS
What are MAMPS?
Microbe Associated Molecular Patterns
What are the 3 types of MAMPS?
- Bacterial
- Viral
- Fungal
What are the 2 bacterial MAMPS?
- LPS - gram-negative only
- Peptidoglycan
What is a MAMP in fungi?
Beta-glucan cell wall
What are the 2 viral MAMPS?
- Surface glycoproteins
- Nucleic acids
What are DAMPS?
Danger Associated Molecular Patterns
What are the 3 DAMPS?
- ATP —> released from dead cells
- Alarmins
- Some cytokines
What are the 3 parts of an innate immune response?
- Physical barriers
- Humoral response
- Cellular response
What are the 2 parts of an adaptive immune response?
- Humoral
- Cellular
What is involved in physical barriers as part of the innate immune response? (3)
- Skin
- Mucous
- Epithelial cells
Which molecules are involved in the innate humoral response? (4)
- Complement proteins
- Lectins
- Pentraxins
- Antimicrobial peptides
Which cells are involved in the innate cellular response? (4)
- Neutrophils
- Macrophages
- DCs
- NK cells
Which molecules are involved in the adaptive humoral response? (2)
- Antibodies
- Complement proteins
Which cells are involved in the adaptive cellular response? (5)
- CTLs
- Th cells
- Treg cells
- B lymphocytes
- Plasma cells
What are the 5 differences between the innate and adaptive immune response?
- Timing
- Cell types
- Receptors and ligands
- Cytokines
- Molecular effector machineries
How is pathogen specificity different in the innate vs adaptive immune response?
Innate:
- Differentiates between type of pathogen
- Uses PAMPS (10^3)
Adaptive:
- Differentiates between specific pathogens
- Uses antibodies (10^15)
How are the receptors different in the innate vs adaptive immune response?
Innate:
- Limited diversity
- Encoded in germline
- <100
Adaptive:
- Greater diversity
- Encoded by genes
- Millions of TCRs and antibodies
How is the distribution of receptors different in the innate vs adaptive immune response?
Innate:
- Non-clonal —> identical on same type of cell
Adaptive:
- Clonal —> lymphocyte receptors all different
What are pathogen niches?
Locations where a pathogen thrives
What are the 4 pathogen niches?
- Extracellular
- Intracellular vacuolar
- Surface adherent
- Intracellular cytosolic
What are 5 examples of extracellular pathogens?
- Staphylococcus
- Streptococcus
- Candida
- Microbiota
- Worms
What are 5 examples of intracellular vacuolar pathogens?
- Salmonella
- Chlamydia
- Legionella
- Coxiella
- Plasmodium
What is an example of a surface adherent pathogen?
E. coli (enteropathogenic and enterohaemorrhagic)
What are 4 examples of intracellular cytosolic pathogens?
- Viruses
- Listeria
- Burkholderia
- Mycobacterium
What are the 2 stimulants of an immune response?
- Tissue damage
- Pathogens
Which cell first responds to an infection and how?
Neutrophils
What issues do uncontrolled phagocytes pose? (3)
- Granulomas in TB
- Excessive inflammation
- Tissue damage —> blocks resolution of inflammation
How do phagocytes respond to bacteria? (3)
- Inflammasome activation
- Inflammatory cytokine release
- Antimicrobial, metabolic and immunomodulatory genes expressed
How do phagocytes respond to fungi? (2)
- Proinflammatory cytokines released
- Antimicrobial, metabolic and immunomodulatory genes expressed
How do phagocytes respond to viruses? (4)
- Proinflammatory cytokines released
- IFN production
- Antiviral and immunomodulatory genes
Which chemicals allow for communication between immune cells?
Cytokines
What are 3 examples of cytokines?
- Chemokines
- Interferons
- Interleukins
What is the sequence of activating host-cells in response to an infection? (4)
- Microbial ligand detection
- Naive host-cells recruited —> gene expression changes
- Cytokines and chemokines released —> send signals
- Host-cells activated
What is macrophage activation?
Expression of new genes induced by microbes and cytokines
What is enhanced in IFNγ-activated macrophages? (5)
- Phagocytosis and migration
- Cytokine production
- Expression of cell surface molecules
- Antimicrobial activity
- Antigen presentation —> T cell activation
What are the 2 routes of macrophage stimulation?
- IFNγ-activated
- Alternatively activated
Which 5 cytokines activate non IFNγ-activated macrophages?
- IL-12
- IL-18
- IL-1β
- TNF
- IL-6
What is IFN?
Interferon
What is the function of IFNs?
Viral immune response via transcription of antimicrobial genes
Which cytokines promote antiviral defense?
IFN
What are the 3 types of IFNs?
- Type I —> IFNα/β
- Type II —> IFNγ
- Type III —> IFNλ
What is the action of type I IFN?
Antiviral
What are the 3 actions of type II IFN?
- Antiviral
- Antibacterial
- Th1 skewing
What are the 2 actions of type III IFN?
- Antiviral
- Mucosal immunity
How do IFNs act against viral particles? (6)
Antiviral gene expression:
1. Nucleases produced
2. Inhibits viral entry/exit
3. Inhibits viral uncoating and replication
4. Inhibitprotein translation
Immunomodulatory:
5. Enhance T-cell response via inc MHC expression
6. Anti-inflammatory
What is pyroptosis?
Programmed cell death associated with inflammation via rupture of the cell membrane
Which 2 cells kill virus-infected cells?
- CTLs
- NK cells
- Contact-dependant killing
How are bacteria-infected cells killed?
Cell-intrinsic death
What is contact-dependant killing of infected cells?
Cell death via direct interaction with immune cells (CTLs and NK cells)
What is cell-intrinsic killing of infected cells?
Cell death via inherent cellular mechanisms
What are the 4 molecules involved in soluble effector mechanisms of an innate immune response?
- Complement —> bacterial destruction
- Lectin —> binds to neutralise pathogen attachment/entry
- Siderophores —> iron chelation prevents replication
- Antibiotic-like peptides
What can complement proteins do during an innate immune response?
Stimulates bacterial destruction
What can lectins do during an innate immune response?
Binds to neutralise pathogen attachment/entry
What can siderophores do during an innate immune response?
Iron chelation —> prevents replication
What can antibiotic-like peptides do during an innate immune response?
Kill bacteria
What are the 2 cellular effector mechanisms of an innate immune response?
- ROS and nitrogen radicals
- Acidification and digestion via phagosomes
Which mechanisms lead to killing of microbes in the innate immune response? (2)
- Soluble effector mechanisms
- Cellular effector mechanisms
Which cells activate T cells in the adaptive immune response? (2)
APCs:
1. Macrophages
2. DC cells
Which chemicals create a suitable environment for T-cell avtivation?
Cytokines produced by APCs
- IL-12 and TNF
How can T cells activate phagocytes?
Cytokines
- IFNγ and IL-17
What are the 2 steps proceeding B cell activation?
- APC activation - by infection and cytokines
- T cell activation - by cognate MHCs and foreign peptide recognition
What are the 2 antibody-mediated immune responses?
- Phagocytosis
- Complement activation
What are the classifications of T cell function?
- Phagocyte activation
- Direct killing of infected cells
- B cell activation
- Innate lymphoid cell action (γδ T cells)
Which cells are activated by Th1 cells and how?
Macrophages
- IFNγ
Which cells are activated by Th2 cells and how?
Eosinophils
- IL-4, 5, 13
Which cells are activated by Th17 cells and how?
Neutrophils
- IL-17,22
Which pathogens do macrophages defend against?
Intracellular pathogens
Which cells activate macrophages and how?
Th1 cells
- IFNγ
Which pathogens do eosinophils defend against?
Helminths
Which pathogens do neutrophils defend against?
Extracellular bacteria and fungi
Which cells activate eosinophils and how?
Th2 cells
- IL-4, 5, 13
Which cells activate neutrophils and how?
Th17 cells
- IL-17, 22
What are the 3 stages of lymphocytes?
- Naive
- Activated
- Memory
What drives cell maturation?
Gene expression (via cytokines)
How long does the innate immune response last?
12 hours
When does the adaptive immune response start?
After around 12 hours
How long does it take for lymphocytes to be activated?
Around 3 days
When do naive, active, plasma and memory B cells act?
- Naive —> 1 day after infection
- Active —> 3 days
- Plasma —> 5 days
- Memory —> secondary infection
Why does age affect immunity?
Thymic involution
What is type 1 immunity?
Immune response to viruses, bacteria, protozoa and fungi
What is type 2 immunity?
Immune response to helminths, allergens, venom
Which cells detect the type of pathogen?
DCs
Which lymphocytes primarily act against viruses?
CTLs
Which lymphocytes primarily act against intracellular bacteria and protozoa?
Th1 cells
Which lymphocytes primarily act against extracellular bacteria and fungi?
Th17 cells
Which lymphocytes primarily act against helminths, allergens and venoms?
Th2 cells
Which interleukins are involved in all pathogen responses? (2)
- IL-6
- IL-1β
What are examples of 10 immune-related diseases?
- Complement dysfunction
- Leukocyte adhesion dysfunction
- Chronic granulomatous disease
- Chediak-Higashi syndrome
- Cytokine dysfunction
- SCID (Severe Combined ImmunoDeficiency)
- X-linked agammaglobulinaemia
- HIV
- Immunosuppression by cancer treatment
- Immunosuppression by graft rejection or chronic disease
How does complement dysfunction arise?
Complement gene mutations
How does leukocyte adhesion arise?
Migration and adhesion gene mutations
How does chronic granulomatous disease arise?
ROS deficiency
How does Chediak-Higashi syndrome arise?
Lysosome dysfunction
What does cytokine dysfunction lead to?
Loss of of immune cell-to-cell communication
How does SCID arise?
Sever T and B deficiency/dysfunction
How does X-linked agammaglobinaemia arise?
IgG deficiency
How does AIDS arise?
Th cell deficiency via HIV
How does irradiation/chemotherapy affect immunity?
Loss of bone-marrow precursors —> lymphocyte deficiency
What do complement protein gene mutations cause?
Complement protein dysfunction
What do migration/adhesion gene mutations cause?
Leukocyte adhesion dysfunction
What do ROS deficiency cause?
Chronic granulomatous disease
What do dysfunctional lysosomes cause?
Chediak-Higashi syndrome
What causes loss of immune cell-to-cell communication?
Cytokine/receptor gene mutations
What does severe T and B cell deficiency cause?
SCID
What does IgG deficiency cause?
X-linked agammaglobulinaemia
What does Th cell deficiency cause?
AIDS
What can cause depletion/impairment of lymphocytes?
- Cancer treatments (irradiation/chemotherapy)
- Graft rejection drugs
- Chronic diseases
How do cancer therapies affect the immune system?
Irradiation/chemotherapy —> lose bone-marrow precursors —> lymphocyte deficiencies
