Med Micro 4.1 - 2nd Line (blood) Flashcards
What makes up second line of defense?
cells, anti microbial chemicals and processes (mostly in blood): phagocytosis, complement, interferon, inflammation, fever. No physical barriers except blood clotting. Most components are not just sitting there but are recruited.
What is the second line for?
When pathogens penetrate skin or mucous membranes (some things like defensins are present on the mucous membranes already). It is non-specific, but lots of communication
Major goals of second line
Containment (as limited as possible), and signal adaptive immunity (induces the 3rd line)
Plasma
Water with electrolytes, gases, nutrients, protein (clotting factors, complement proteins, ABs)
Serum
Name for plasma when coagulation proteins removed
Functions of innate immune system (6)
- Physical and chemical barrier 2. Recruiting immune cells to sites of infections (cytokines) 3. Activate complement cascade to identify bacteria, lyse cells and attract and promote phagocytosis (opsonize bac) 4. Identify and remove of foreigners by WBC 5. Activate inflammation and fever 6. Activate adaptive immune system with antigens etc.
Functions of innate immune system Acronym
BRCA WI: Barrier, Recruit, Complement, Activate Adaptive, WBC, Inflammation
How do we sequester iron? How do bacteria circumvent this?
We have lactoferrin (in tears, mucous). They have siderophores (membrane-bound or secreted) and hemolysin. Siderophores still from hemoglobin with high binding affinity. Lactoferrin binds even tighter. Competition.
Nutrient immunity
a term to describe how we generally sequester nutrients so they are not available
Platelets: Origin and function
from megakaryocytes. Clotting, secrete TGFß and FGF
Leukocytes
aka WBC. 2 types: granulocytes (secrete toxins in granules, and phagocytosis) and agranulocytes (B cell, secrete AB
3 types of granulocytes
Basophils (heparin and histamine, bind IgE ABs, in allergies); eosinophils ; neutrophils
Macrophages
Some fixed (specific names, like dendritic cell), some mobile and phagocytose throughout body. Release cytokines to attract neutrophils and signals for tissue repair
Neutrophils
lactoferrin, defensins, other chems; Phagocytize pathogens, Capable of diapedesis
Eosinophils
cationic proteins, reactive O2 species; Phagocytize pathogens, Capable of diapedesis
Diaspedesis
can squeeze out of blood vessels to enter an area. (in veins, not out of arteries). Bind to sites on vessels before squeezing out
2 types of agranulocytes
Lymphocytes and monocytes
Lymphocytes
most involved in specific immunity (T and B cells)
Monocytes
leave the blood and mature into macrophages (dendritic cells, etc). Phagocytosis
Mononuclear phagocyte system
All macrophages, plus monocytes attached to endothelial cells, constitute the mononuclear phagocytic system
Lab analysis of leukocytes
Increase can signal signs of disease. eosinophils: allergies or worms; neutrophils and lymphocytes: bacterial disease; lymphocytes: virus
Nonspecific chemical defense
Lactoferrin (direct and not), lysozyme (direct), complement (direct and not), interferon (indirect), PRRs (indirect), transferrin (indirect), defensins (direct)
Direct and indirect chemical defense
Direct is killing directly; indirect is enhancing killing by others
Categories of indirect chemical defenses
Opsonizing, nutrient immunity, PRR stimulates complement, inflammation (chemokines)
Inflammation
Important of containment, brings in phagocytes etc. Nonspecific, increases defensins
Purpose of Fever
Goal is to inhibit growth
Problem with chronic inflammation
(cancer), Leaky blood vessels, collateral damage from granules
Make a diagram and label all important steps in the phagocytosis and destruction of a bacterial cell by a langerhans cell
Picture
Steps in phagocytosis
- Chemotaxis (chemicals from bacteria or other phagocytes) 2. Adherence (opsonizing and binding). 3. Ingestion. 4. Digestion (phagolysosome) 5. Elimination (may include antigen presentation of epitope)
Pattern recognition receptors (2 types)
Secreted molecules in blood and lymph: opsonize, trigger complement; surface receptors on phagocytic cells that bind for engulfment; TLR and cell surface receptors: bind pathogen, lead to release of cytokines and defensins; NOD: intracellular, same as TLR
Similarity and difference b/w secreted PRR and AB?
Similar: both opsonize, trigger complement; difference: ABs can bind toxins, ABs very specific
Mast cells
increase leakiness of blood vessels, easier for neutrophils to enter.
Fixed macrophages examples
Dendritic cells, Kuppfer cells (liver), microglia (CNS)
3 cell types that kill extracellularly
Eosinophil, natural killer cells, neutrophils. Secrete granules. Non-phagocytic
Killing by eosinophils
Attach to helminths, secrete toxins (cationic proteins) that weaken or kill worm.
Killing by natural killer lymphocytes
secrete perforin (makes pore) and granzyme (stimulates apoptosis) onto surface of virally infected cells and tumors; differentiate from normal cells (have similar antigens). Not restricted, kills anything different.
Killing by neutrophils
Produce H2O2, NaClO, nitric oxide (inflammation); extracellular fibers called NETs that bind and kill bacteria. Platelet TLR4 activate NETs
NETs
Neutrophil extracellular traps - form of suicide where nuclear and cytoplasmic components mix and then get released, trap gram + and - bac along with antimicrobials, get phagocytosed
Killing by cytotoxic T cells
Similar to NK cells, perforin and granzyme. Difference is they are MHC-restricted: only attack cells with the MHC with the right epitope.
Is humoral immunity MHC-restricted?
Level of MHC-restriction initially (T cell-dependant humoral immune response is MHC-restricted), then Antibodies produced which are not MHC-restricted
Systemic infection
In the blood. Serious because it’s not localized. aka Sepsis
Transferrin
Like lactoferrin, binds Iron tightly
