3 - Immune Physiology Flashcards
What are the six types of leukocytes?
- Neutrophils (62%)
- Eosinophils
- Basophils
- Monocytes
- Lymphocytes (30%)
- Plasma Cells
Which leukocytes are granulocytes?
neutrophils
eosinophils
basophils
In progenitor cells, what are the two main lineages of WBCs?
myelocytic and lymphocytic
The myelocytic lineage begins with _____
The lymphocytic lineage begins with ______
Myeloblasts
Lymphoblasts
Which white blood cells are formed in the marrow?
Granulocytes and monocytes
Which leukocytes are not formed in bone marrow?
Lymphocytes and plasma cells
What happens to granulocytes and monocytes once they leave the bone marrow?
Circulate for a few hours, then move into tissues
when monocytes move into tissues they swell into tissue macrophages
How do WBCs enter tissue spaces?
How do they travel through tissue spaces?
Diapedesis
Amoeboid movement
What is chemotaxis?
The migration of a cell toward or away from a chemical gradient
When a tissue becomes inflamed, a dozen different products are formed that attract neutrophils and macrophages
What is a chemotactic substance?
A chemical beacon
In this case, something that attracts WBCs
Why is it noteworthy that chemotaxis is effective up to 100micrometers away?
Because most tissues are only 50 micrometers away from a capillary
makes it very easy for tissues to recruit macrophages etc from the capillaries into the inflamed area
The major function of neutrophils and macrophages is:
phagocytosis
How do antibodies and phagocytes cooperate to kill certain cells?
the immune system develops antibodies
those antibodies adhere to the infectious agent’s membrane, making it especially susceptible to phagocytosis
The process in which a pathogen is selected for phagocytosis and then destroyed is called:
opsonization
Describe a neutrophil’s phagocytic process
Neutrophil attaches itself to the particle
projects pseudopodia in all direction around the particle
pseudopodia meet up on the other side of the particle and fuse, creating a closed chamber
chamber invaginates and forms a phagocytic vesicle
Phagosome joins up with a lysosome and eats the particle
debris expelled via exocytosis
Macrophages are the end stage product of ______
monocytes that enter the tissues
Which is a more effective phagocyte: neutrophils or macrophages?
Macrophages! Can eat up to 100 bacteria, vs neutrophils’ 3-20
They can eat much larger particles, like RBCs and whole parasites
Macrophages survive much longer than neutrophils
What’s the difference between the reticuloendothelial system and the monocyte-macrophage system?
Same thing
In the lungs, macrophages phagocytize particles that become entrapped in the alveoli. What do they do with the digestive products?
Dump them into the lymphatic system
How are debris and old RBCs filtered in the spleen?
arterial blood to the spleen squeezes through trabeculae in the red pulp lined with macrophages
They phagocytize debris and old cells, then return the blood via splenic veins
What are the five basic characteristics of inflammation?
- vasodilation
- vascular permeability
- clotting of the interstitial fluid d/t large amounts of fibrinogen and proteins leaking from the capillaries
- migration of granulocytes and monocytes to the tissue
- swelling of the tissue cells
Why is it significant that the interstitial space and lymphatics are filled with fibrinogen clots during inflammation?
This is the walling off effect
prevents bacteria or toxin from spreading
Explain why staphylococcus is more likely than streptococcus to be isolated to a specific tissue, even though staph is much more destructive
staph releases extremely lethal cellular toxins that spark an inflammatory walling off that outpaces the ability of staph to multiply and spread
strep produces fewer toxins, and is able to reproduce and spread before inflammation walls it off
When a pathogen enters a tissue, what is the first line of defense?
What is the second?
The tissue macrophages
Neutrophil invasion
How do tissue signal for neutrophils to come to their aid?
- increased expression of adhesion molecules on the capillary endothelium literally sticks to circulating neutrophils and moves them into the tissue
- endothelial cell junctions loosen to allow diapedesis/extravasation
- chemotaxis
How is neutrophilia in response to a pathogen achieved?
Inflammatory mediators travel to the bone marrow, acting on stored neutrophils and mobilizing them into the circulation
When a pathogen enters a tissue, what is the third line of defense?
Monocytes
Enter from the blood to the infected tissue and swell into macrophages
This is a much slower response than that of neutrophils, but is much more effective and long lasting
When a pathogen enters a tissue, what is the fourth line of defense?
The production of more granulocytes and monocytes by the bone marrow
Takes 3-4 days
What is pus?
necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid
How do eosinophils compare to neutrophils?
They are very weak phagocytes but are not significant in protection against the usual types of infection
Eosinophils react to two types of inflammation/disease:
- Parasites!
- Allergic reactions
What is the most likely reason eosinophils are involved in allergic reactions?
Basophils and mast cells are the primary participants in reactions, and both of them release eosinophil chemotactic factor
What is the role of eosinophils in allergic reactions?
They help “buffer” some of the substances released by mast cells and basophils, controlling the amount of inflammatory mediators released
Why are eosinophils well designed for parasitic attack?
their granules release hydrolytic, highly reactive oxygen species, and a highly larvicidal polypeptide called major basic protein
Name two common parasitic infections that cause eosinophilia
schistosomiasis
trichinosis
Both mast cells and basophils liberate ____ into the blood
heparin
histamine
bradykinin
serotonin
Why are mast cells and basophils so heavily involved in allergic reactions?
because IgE has a special propensity for mast cells and basophils
There are two general kinds of leukemia:
lymphocytic and myelogenous
In myelogenous leukemia, the acuity of cancer is dependent on:
the level of differentiation in the abnormal WBCs
The less differentiation, the worse the acuity
Why does leukemia cause bleeding, low platelets, and anemia?
displacement of normal bone marrow and lymphoid cells with nonfunctional leukemic cells
What is humoral immunity?
B cell Immunity
the body develops circulating immunoglobulins, produced by B Cells
What is cell-mediated immunity?
T cell immunity
formation of large numbers of activated T lymphocytes, specifically crafted in lymph nodes to destroy a foreign agent
Both cell mediated and humoral immunity are initiated by ______
presentation of antigens
What is antigen short for?
Antibody Generators
For a substance to be antigenic, it must be capable of _____
generating antibodies
Usually has to be a relatively large molecule
Antigenicity relies on recurring molecular groups called:
epitopes
Why are proteins and large polysaccharides almost always antigenic?
They almost always have epitopes
T- Lymphocytes are responsible for:
forming activated lymphocytes to provide cell-mediated immunity
B-Lymphocytes are responsible for:
forming antibodies that provide humoral immunity
All lymphocytes originate from ______ in the embryo.
Where are T cells differentiated?
Where are B cells differentiated?
multipotent hematopoietic stem cells
The Thymus gland (T is for thymus)
Bone Marrow (B is for bursa, but pretend it’s for bone)
Describe how T-cells are developed in the Thymus?
They divide rapidly and develop diversity against different antigens
What happens to T-cells once they leave the thymus?
They spread out through the blood to various lymph tissues to “stand guard”
Pretty much all large proteins are antigenic, including those native to the body. How do T cells know not to react with self-antigens?
Before T-cells are released, the thymus mixes incoming T-cells with a pool of all the self-antigens. If any of them react, they’re phagocytized and aren’t let out of the thymus
How are B cells different from T cells?
- In T cells the entire cell is reacting. But B cells secrete antibodies that are the actual reactants.
- B lymphocytes are way more diverse
What happens to B lymphocytes after they’re released from the bone marrow?
Also travel to lymph organs to stand guard and await invaders
What happens when a T cell encounters an antigen?
T cell becomes activated and forms more activated T cells
What happens when a B lymphocyte encounters an antigen?
The B lymphocyte enlarges and forms lymphoblasts
these differentiate into plasmablasts
the plasmablasts divide into plasma cells (about 500 plasma cells per plasmablast)
Plasma cells produce gamma globulin antibodies
When activated, B cells produce high numbers of antibodies, and T cells produce high numbers of activated T cells. What are both of these products called?
Clone of lymphocytes
They are each a perfect clone of their progenitor
How is it possible for a single type of stem cell to produce millions of distinct lymphocytes?
Prior to processing, all of the cells produced by hematopoietic stem cells do not have whole genes. They just have hundreds of gene segments
During processing, these segments are mixed in random combinations, forming unique whole genes
When an invader hits lymph tissue, what is the first thing that happens?
A macrophages lining the sinusoids of the lymph tissue eats it, then passes the antigens by cell-to-cell contact directly to the lymphocytes, who get to work developing activated T cell and antibodies
What do macrophages secrete that amps up lymphocyte production?
Interleukin-1
How are T-cells involved in B-cell activation?
Most antigens activate B cells and T cells, but some of the T cells that are then formed are T-helper cells
These secrete lymphokines, which activate B lymphocytes
B lymphocytes are very dependent on T helper cells!
How quickly can a plasma cell produces antibodies?
2000 molecules/second per plasma cell
How are memory cells formed?
When B cells are activated and start transitioning to lymphoblasts, some of those lymphoblasts don’t go on to form plasma cells
Instead, they form new B lymphocytes that are identically sensitive to the same antigen
These are called memory cells. They circulate and increase sensitivity to a particular invader
Why does a second exposure produce a more rapid antibody response?
Memory cells are lying in wait
If plasma cells only stick around for a few days or weeks, How is it possible that a 90-year-old can still be immune to a disease they had as a 4-year-old?
When B cells are activated, they form large numbers of short-lived plasma cells that are highly productive, but they also form long-lived plasma cells
The long-lived plasma cells hang around in lymph tissues and are slow-and-steady responders
All immunoglobulins are composed of:
light polypeptide chains and
heavy polypeptide chains
The number of chains varies, but they always exist in heavy-light pairs
If there are ten heavy, there will be ten light etc.
What is the main function of the complement system?
Enhance the actions of antibodies and phagocytes
How is the classical pathway of the complement system activated?
When an antibody binds with an antigen, a reactive binding site on the constant portion of the antibody becomes uncovered
The uncovered site binds to C1, which sets the rest of the chain into motion
How does the complement system contribute to phagocytosis?
Opsonization:
activated phagocytosis of the bacteria to which the antigen-antibody complexes are attached
How does the complement systems contribute to lysis?
Membrane attack complex:
composed to multiple complement factors bound together
inserts itself into the lipid bilayer, causing osmotic rupture
What are the seven effects of activating the complement cascade?
- Opsonization
- Lysis
- Agglutination
- Virus Neutralization
- Chemotaxis
- Mast cell/basophil activation
- Inflammation
B cells are able to recognize any intact antigen, but T cells respond only to antigens:
that are bound to Major Histocompatibility Complex (HMC) proteins
Where are MHC proteins found?
on the surfaces on antigen-presenting cells
What are the three types of antigen-presenting cells?
Macrophages
B Lymphocytes
Dendritic cells
What are the three groups of T cells?
T-helper Cells
Cytotoxic T Cells
Regulatory (suppressor) T Cells
75% of T cells are _____ cells
T-helper
How do T-helper cells regulate immune function?
Form a series of protein mediators called lymphokines
lymphokines act on other immune cells and the bone marrow cells
Why does HIV cause immunodeficiency?
Destroys T-helper cells, leaving the body almost totally unprotected against infectious disease
What are the (4) major actions of lymphokines?
- Stimulation and growth of cytotoxic T cells and regulatory T cells
- Stimulation of B cell growth and differentiation
- Activation of macrophage system
- Feedback stimulation of T-Helper Cells
Cytotoxic T cells are ______ cells
Killer
What causes the autoimmune destruction that follows rheumatic fever?
the body becomes immunized against tissues in the joints and heart (especially heart valves) after exposure to a specific type of strep toxin that has an epitope very similar to some self-antigens
How can you achieve passive immunity?
Transfusion of antibodies, activated T cells, or both obtained from the blood of someone who’s immune
Lasts 2-3 weeks
Any delayed reaction allergy is caused by:
activated T-cells, NOT antibodies
Poison ivy is the result of:
T cell reaction
What is an allergen?
an antigen that reacts specifically with a specific type of IgE reagin antibody
IgE antibodies have a strong propensity to attach to:
mast cells and basophils
Name four diseases caused by IgE activation
- Anaphylaxis
- Urticaria
- Hay Fever
- Asthma
What causes the circulatory collapse of anaphylaxis?
What causes the respiratory collapse?
Massive vasodilation and increased permeability cause circulatory collapse
Slow-reacting substance causes respiratory collapse
What is slow-reacting substance?
mixtures of leukotrienes released from activated basophils and mast cells
Is inflammation specific or non-specific?
Non-specific
It follows the same course regardless of cause of damage
What are the three pathways of complement activation?
- Classical (activated by antibodies binding to antigens)
- Lectin (activated by mannose-containing bacteria)
- Alternative (activated by gram negative bacterial and fungal cell wall proteins)
All of the complement activation pathways converge at:
C3
What are the three plasma protein systems?
Complement
Clotting
Kinin
What does the kinin system do?
What is its primary product?
augments inflammation
Bradykinin
What does bradykinin do?
- vasodilation
- stimulates nerve endings to cause pain
- causes smooth mm contraction
- increases vascular permeability
- increases leukocyte chemotaxis
What are cytokines?
intercellular-signaling molecules that are secreted, bind to specific cell membrane receptors, and REGULATE innate or adaptive immunity
can be either pro-inflammatory or anti-inflammatory
What are the two major types of cytokines?
Interleukins
Interferons
Interleukins are produced by ______
macrophages and lymphocytes
What are the effects of interleukins?
- Molecular adhesion
- Chemotaxis
- Proliferation/maturation of leukocytes in marrow
- Enhance/Suppress inflammation
- Mediate development of acquired immune response
Which interleukin is pyrogenic?
Interleukin 1
Which substance is probably responsible for fatalities from shock caused by gram-negative bacterial infections?
Tumor Necrosis Factor (TNF) Alpha
Which cytokines primarily protect against viral infections?
Interferons
Prostaglandins are produced from ____ by _____
arachidonic acid
cyclooxygenase
Which COX is associated with inflammation?
COX 2
Generally, activating a platelet does three things:
- relocates plasma membrane phosphatidylserine to cell surface, allowing adhesion
- degranulates to release mediators
- synthesis of thromboxane A2 from prostaglandin H2
The two most important phagocytes are ____ and _____
neutrophils
macrophages
The three primary systemic changes associated with acute inflammation are:
Fever
Leukocytosis
Increased levels of plasma proteins (acute phase reactants)
Only three types of cells are capable of complete mitotic regeneration:
epithelial
hepatic
bone marrow
Why does ongoing bleeding delay healing?
excess blood cells at the site must be cleared
Formation of a clot increases the amount of space that granulation tissues has to cover
Hypovolemia hinders inflammation (less factors circulating)
Adhesions can form in which cavities?
Pleural
Pericardial
Pertioneal
Why do steroids prevent wound healing?
prevent macrophages from migrating to site and releasing collagenase and plasminogen activator
inhibit fibroblast migration into the wound, delaying epithelialization
What the difference between a hypertrophic scar and a keloid?
A hypertrophic scar stays within the original boundaries of the wound
A keloid does not
