COD Immunology Flashcards
What are the 4 main immunological strategies to defend the body?
ANATOMICAL BARRIER - skin and mucosal lining
CHEMICAL BARRIER - anti-bacterial peptides, lysozymes
STRATEGIC OUT POSTS - mucosal associated lymphoid tissue (MALTs)
SENTINELS/ GUARDS - epithelial cells, macrophages, dendritic cells
Which immune system is the 1st line of defense and which is the 2nd line of defense?
Innate immune system
Adaptive immune system
Innate or adaptive immune system?
Humoral components
Cell-mediated components
Adaptive
Innate or adaptive immune system?
Anatomical barriers
Humoral components
Cell-mediated components
Innate
How are lymph nodes useful in immunology?
Checkpoints for meeting pathogens
Meeting point for innate immune cells and adaptive immune cells
What is Haematopoiesis?
Refers to the commitment and differentiation processes that lead to the formation of all blood cells from haematopoietic stem cells. In adults, haematopoiesis occurs mainly in the bone marrow (medullary)
What are some Haematopoietic growth factors?
Act on pluripotent stem cells = Stem cell factor (SCF)
Act on early multipotential cell = IL-3, IL-4
Act on committed progenitor cells = G-CSF, M-CSF
What are some humoral components?
FLUIDS PLASMA INTERSTITIAL FLUID LYMPH SECRETIONS
Name some defensive chemicals, peptides and enzymes
Microbicidal and microbiostatic chemicals: Digestive tract: stomach acid, digestive enzymes, bile salts
Antibacterial enzymes that attack bacterial cell walls
Tears, saliva, Paneth cells: lysozyme and secretory
Antimicrobial Peptides (AMP) Secreted by epithelial cells into mucosal fluids Secreted by phagocytes into tissues
Describe Defensins
Disrupt cell membranes of bacteria and fungi and viral membrane envelopes within minutes
Insertion of the hydrophobic region into the membrane bilayer, which forms a pore
α-defensins: neutrophils and Paneth cells
β-defensins: epithelial cells and keratinocytes
Describe Cathelicidins
Cathelicidins are host defense peptides with antimicrobial and immunomodulatory functions
Constitutively expression: neutrophils, macrophages induced expression:
keratinocytes, lung and intestinal epithelia
Active cathelicidins in neutrophils can remain in phagosome or released by exocytosis
Cationic amphipathic peptide that disrupts membranes and is toxic to a wide range of microorganisms
Complement fragments C3a and C5a act on endothelial receptors to produce Local inflammatory responses. Describe these responses
Increase vascular permeability
Increase fluid to the tissue
Adhesion molecules on vascular endothelial cells
Activate mast cells - release inflammatory molecules
Terminal complement proteins polymerase to form pores (MAC) in the membranes of pathogens. Give some examples of terminal complement proteins
C5b, C6-9
Describe MAC
Membrane attack complex
Forms a pore in the lipid bilayer membrane
Destroys membrane integrity
Destroys the proton gradient across the pathogen’s cell membrane
MAC has a hydrophobic external face & a hydrophilic internal channel
What is opsonisation?
The coating of the surface of a pathogen by antibody and/or complement proteins to aid in the process of phagocytosis and destruction of the pathogen
What is complement-related phagocytosis?
Specific recognition of bound complement components by complement receptors (CRs)
CRs bind pathogens opsonised with complement components
C3b is the major opsonising complement component
Requires C5a binding
Describe a macrophage
Myeloid lineage
Monocytes recruited from the blood to the tissue become macrophages.
Tissue macrophage arise from progenitor cells during embryonic development- self renew in situ
Major phagocyte population in normal healthy tissues
Repeated rounds of phagocytosis
Describe a dendritic cell
Myeloid or lymphoid lineage linage
Arise from bone marrow progenitors
Antigen-presenting cells
Phagocytosis
Process antigen material and present it on the cell surface to the T cells of the immune system.
They act as messengers between the innate and the adaptive immune systems.
Front line defence not primary role
Humoral and cell-mediated innate immune system recognises pathogens via WHAT and damage via WHAT?
PAMPs
DAMPs
Describe PAMPs
PATHOGEN ASSOCIATED MOLECULAR PATTERNS pathogen surfaces small molecular sequences consistently found on pathogens that are recognized by Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) bacterial lipopolysaccharides (LPSs) bacterial membranes endotoxins bacterial flagellin viral nucleic acid variants
Describe DAMPs
DAMAGE ASSOCIATED MOLECULAR PATTERNS
cell and tissue injury
released from damaged or dying cells due to trauma or an infection due to a pathogen
What are PRRs?
PATTERN RECOGNITION RECEPTORS
recognise PAMPs and DAMPs
HUMORAL – Complement proteins (free receptors) recognise PAMPs and DAMPs
CELLS – Innate immune system cells recognise PAMPs and DAMPs via cell surface and cytoplasmic receptors eg membrane bound phagocytic receptors
What are phagocytic receptors?
Receptors induce phagocytosis on binding to pathogen
C-type lectin-like family receptors
carbohydrate recognition – on surface of fungi, bacteria, viruses
– Dectin-1
Scavenger receptors
anionic polymer recognition on pathogen surface and acetylated low-density lipoproteins
– SR-A I, MARCO
Complement receptors
bind to complement proteins on opsonised pathogen. Type of integrin.
– CR3
Membrane bound signalling receptors are also an example of a PRR. One example is Toll-like receptor TLR. Describe TLR.
TOLL-LIKE RECEPTORS
Receptors induce cytokine expression on binding to pathogen
10 TLR genes in humans
Each TLR recognises a distinct set of PAMPs/MAMPs
Expressed by many types of cells including, macrophages
Located on cell-surface and intracellularly
TLRs are single-pass transmembrane proteins with an extracellular leucine-rich repeat region
Ligand binding causes dimerisation and conformational changes
Describe inflammation
Response to damage (injury or burn) and infection.
Injuries and burn mean pathogens can pass first line of defence (skin) easily.
Symptoms: acute* Redness Heat Swelling Pain Loss of function
What causes redness and heat in inflammation?
Vasodilation
What can cause swelling and pain in inflammation?
Plasma leakage
Loss of function can be as a result of swelling
Describe a neutrophil
myeloid lineage- mature state in blood
polymorphonuclear (PMN) leukocyte
major circulating WBC/ leukocyte (50-70%)
first cells to be recruited to site of infection –not found in healthy tissue
Infection = bone marrow increases production of myeloid cells
significantly increases number of circulating neutrophils (leucocytosis)
packed with granules containing defensins and cathelicidins (granulocyte)
major phagocytic cell after macrophages
die after one round of phagocytosis
Also kill pathogens: degranulation
NETosis (NET- neutrophil extracellular traps)
Describe a monocyte
myeloid lineage- monocyte in blood
mononuclear leukocyte
Two types - classical (90%) freely circulate, recruited to infection
macrophage patrolling- roll along endothelial surface looking for injury.
Classical monocytes - second type of leukocyte recruited to the site of infection
Migrate into tissue and differentiate into an activated monocyte/ macrophage in tissue- response to inflammatory cytokines
Repeated rounds of phagocytosis
Describe mast cells
myeloid lineage
precursor mast cell in blood
mast cells mature in tissue
Found in skin, connective tissue, mucosal epithelial tissue, respiratory and digestive tract
contains many granules rich in histamine and heparin
regulate vasodilation, vascular homeostasis, innate and adaptive immune responses, angiogenesis
Describe natural killer cells
lymphoid lineage- lymphocyte –innate immune system
Patrol tissues looking for infected cells, malignant cells, stressed cells
Pre-programmed to kill on contact- immediately with correct stimulus
Forms synapse between NK membrane and target cell
Kill target cells by releasing perforin. Polymerisation creates pores in target cell
NK cell releases granzyme- activate the apoptotic pathway of target cell
Decision to kill based on balance of signals from target cell NK receptors
Activating- target cell surface ligands which indicate infection/ malignancy/ stress
Inhibiting- KIR (killer cell Ig like receptors) – bind MHC I
Describe MHC molecules
Promiscuous- bind and present millions of types of peptides (very broad specificity)
Polygenic- multiple MHC molecules encoded by different genes
Polymorphic- high sequence variability between individuals
Peptides stabilise MHC molecules
MHC class I present self antigens and intracellular pathogen peptides- processed via the proteasome and ER. MHC II present extracellular pathogen antigens- processed via phagolysosomes
