Module 1 Flashcards
(35 cards)
Common myeloid precursor become what? (innate)
Granulocyte macrophage progenitor
- neutrophil, eosinophil, and basophil
- Macrophage and dendritic cell precursor -> monocyte to macrophage + dendritic cell
Common lymphoid precursor become what? (adaptive)
B cell -> plasma cell
T cell -> effector T cell
Second line of defense innate immune system components?
a) immediate - circulating proteins and phagocytosis by resident immune cells
b) induced - innate cell recruitment and effector activities
What are inteferons?
Group of induced proteins that defend against viral infection (specific)
What are NK cells?
Lymphocyte-like cells (non-specific) that lyse/destroy virus-infected cells + cancer cells
Complement system components?
- Circulate in an inactive form
- Opsonization: to promote phagocytosis
- lysis of pathogens
- chemotaxis + inflammation
- cell activation
Pathways of complement system?
Each pathway of induction converges at CLEAVAGE of C3.
1. Alternative pathway - recognition of pathogen surface + environment created for activation
2. Lectin pathway - mannose-binding lectin binds to pathogen surface
3. Classical pathway - CRP binds to specific antigen on pathogen surface. Bind to phosphocholine
CRP importance?
Key acute-phase protein, short pentraxin binds to phosphocholine on microbial cells + damaged host cells. Once bound, CRP activates classical complement pathway
What are pentraxins?
- opsonising agents
- multimeric/cyclic shapes
- short pentraxins -> SAP (serum-amyloid P component) + CRP (C-reactive protein
What are antimicrobial peptides?
They are defensins.
- Amphithatic: creates pores in membranes promote lysis of pathogen
- Target bacteria, fungi + enveloped viruses
- Reduced levels in bowel disorder (IBD)
- Neutralise bacterial toxins
What happens in acute-phase response?
Bacteria induce macrophages to produce IL-6 (cytokine) acts on hepatocytes (found in liver) to induce synthesis of acute phase proteins -> CRP and mannose-binding lectin
Group of effector cells?
Resident macrophages
Mast cells (eg., sneezy)
Monocytes
What are the macrophages doing?
Often first immune cell to encounter a pathogen during infection
Activated macrophages recruit monocytes to site which differentiate into macrophages
4 type of macrophages and their roles
- Alveolar macrophage: in the lung alveoli. Phagocytose small particles, dead cells, or bacteria. Control of immunity to respiratory pathogens
- Kupffer cells: in the liver. Hepatic tissue remodelling and immune response
- Microglia: in the CNS. Elimination of dead or old neurons and control of immunity in the brain
- Splenic macrophages: in the spleen marginal zone. Elimination of old or dysfunctional RBC’s.
What are TLR’s?
Activate immune responses by triggering intracellular signaling pathways that lead to the production of cytokines, interferons, and inflammatory mediators.
2 subsets of TLR’s
Subset 1: Found on plasma membrane. Recognise lipids, carbohydrates and proteins (TLR4).
Subset 2: Located inside the cell and on membranes of endosomes. Recognise pathogen nucleic acids and differentiate from human nucleic acid (TLR 3, 7, 8 and 9).
TLR polymorphisms and disease?
Many are cancers, TLR is too active. Influence macrophage activation and thus septic shock. Activated macrophages produce high levels of the inflammatory cytokine - TNFa.
What are the main cytokines and their roles?
IL-1B & TNFa: induce blood vessels to become more permeable, enabling effector cells and fluid-containing soluble effector cells to enter infected tissue.
Il-6: induces fat and metabolize, makes heat and raise temperature in affected tissue.
CLCX8: Recruits neutrophils for the blood and guides them to the infected tissue
IL-12: recruits and activates NK-cells that in turn secrete cytokines that strengthen the macrophages response to infection
What are neutrophils?
- First type of immune cell to form major response ~1hr
- Can respond inside and outside of body
- Abundant
They reside in bone marrow, upon immune response they are elicited by cytokines, CLCX8, which move out of bone marrow
What role does selectin-mediated adhesion play in neutrophil recruitment?
Selectins sit on endothelial walls and bind with neutrophils. Selectin-mediated adhesion allows neutrophils to tether and roll along the blood vessel walls, slowing them down in response to inflammation.
Steps of pathogen killing by neutrophils
- Bacterium phagocytosed by neutrophil
- Phagosome fuses with azurophilic granules and specific granules
- pH of phagosome rises, antimicrobial response is activated and bacterium is killed
- pH of phagosome decreases, fusion now with lysosomes allows acid hydrolases to degrade the bacterium fully
- Neutrophil dies by apoptosis and phagocytosed by a macrophage
How are neutrophils and macrophages classified in the immune system?
Neutrophils and macrophages are classified as phagocytes and belong to the innate immune system. Originating from the myeloid lineage. They are involved in engulfing and destroying pathogens. Neutrophils are granulocytes, while macrophages are agranulocytes.
How do reactive oxygen species (ROS) contribute to bacterial killing in phagocytes?
Superoxide (NADPH oxidase) start destroying all molecules in that bacteria - DNA, lipids, & proteins. Hydrogen peroxide (superoxide dismutase) is a potent oxygen radical contributes to killing that bacterium. Catalase will the take all of the nasty hydrogen peroxide and inactivate it.
What is NETosis, and how does it help the immune system?
NETosis is a form of programmed neutrophil death where Neutrophil Extracellular Traps (NETs)—web-like structures made of DNA, histones, and antimicrobial proteins—are released. These NETs trap and kill bacteria, fungi, and viruses, preventing their spread.
