WBCs

Question 1

forms of immunity

Answer 1

• Specific vs non-specific immunity (Specific immunity is against a specific antibody – i.e. flu shot (specific for a certain strain), Non-specific immunity is all the other stuff we do to protect ourself (bacteria on our skin, acid base on our skin, inflammatory process that happens when we are invaded, macrophage activity that gobbles stuff up, promiscuous phagocytes))
• The airport model
• Myelocytic vs lymphocytic/monocytic lineages (By definition, you lymphocytes from lymphocytic lineage, etc.)
• Final pathway OFTEN not always phagocytosis (Sometimes the end result is dilution, or sequestering the pathogen, etc.)

Question 2

lineage

Answer 2

• Monocyte lineage gives us most of the white cells (Granulocytes (neut, bas, eos), megakaryocytes, platelets, RBCs)
• Lymphoid lineage just gives lymphocytes – lymphocytes and monocytes look clear

Question 3

WBC counts

Answer 3

• Three factors are clinically important: Leukocyte number – doesn’t tell you what kinds of white cells, Differential counts (by percentage) – this one tells you what kind of WBCs (If you don’t get absolute counts, it can get tricky), Morphology – don’t usually get unless you ask for microscopic analysis
• Blood count used after complete H&P to confirm or eliminate a potential dx, as a guide to therapy or index of prognosis

Question 4

formation of WBC

Answer 4

• Granulocytes and monocytes formed in marrow only
• Majority of lymphocytes formed and matured in lymphoid tissues – reflected in the separate lineage
• Significant storage in marrow and lymphoid organs

Question 5

Life span of WBC

Answer 5

• WBC: RBC = 1:1000
• 4-8 hr in blood – and then enter peripheral tissues and move around in amoeboid movements (Most enter tissue, “surveillance”)
• Monocytes 10-20 hr in blood then months in tissues as macrophages
• Lymphocytes cycle back and forth – spend time in tissues outside of blood and then go into blood and back again throughout their life span

Question 6

neutrophil/polymorph/PMN

Answer 6

• Lobulated nucleus – many different lobes of the nucleus but SINGLE NUCLEUS!
• The granules in these cells don’t have any particular affinity for basic or acidic dyes, they are NEUTRAL, hence neutrophils

Question 7

neutrophils (and macrophages)

Answer 7

• Enter tissues by diapedesis – sequential extrusion through endothelium (Diapedesis – binding and attaching to endothelial layer and then squishing themselves through the blood vessel and out into the tissue)
• Chemotaxis: movement of a cell up a chemical gradient toward its source (Moves up the chemical gradient of the molecule toward its source)
• Molecules involved = “chemokines”, “lymphokines”, “cytokines”, …
• Many are interleukin family – cause WBCs to leave the blood stream

Question 8

phagocytosis

Answer 8

• Selective process (Smooth surfaces, Protein coats, Complement)
• Destruction of target inside by lysosomal enzymes/molecules SOMETIMES – USUALLY, not always (Sometimes the immune cell simply sequesters the target)

Question 9

monocyte - macrophage

Answer 9

• The cytoplasm is generally very clear – it is an agranular leukocyte
• Big cells!
• Tend to be characterized by presence of kidney bean shaped nucleus
• Reticuloendothelial lineage – another term for myelocytic lineage that gives us RBCs and most WBCs
• Histiocytes – in skin (this is what monocytes are referred to in skin)
• Lymphoid organs – sit on tissue scaffolding and surveys the blood for foreign objects or pathogens
• Immune surveillance – we see them in alveoli of the lungs, in the skin, and on other surfaces (They will spend hours in the blood stream but then peripheral tissues for months at a time)
• 400:1 tissue:blood
• 100 day lifespan – not a lot different than RBCs in that regard

Question 10

inflammation

Answer 10

• “the morbid process designated by the term inflammation, being one to which every organ and probably every tissue of the body is liable, and comprehending as it does in its progress and consequences by far the greater number of the ills to which flesh is heir, possesses a deeper interest for the physician or surgeon than any other material subject which could be named”
• Non-specific process – happens in response to a lot of different stimuli
• Dilution important – divide and conquer – fluid dilutes offending or invading organisms
• Also provides phagocytic cells (WBCs) – gobble up the pathogens or molecules that have invaded
• Finally, allows encapsulation (“walling off”) by presence of clotting agents

Question 11

characteristics

Answer 11

• Vasodilation
• Increased permeability of capillaries
• Clotting factors
• Chemokine release draws GM cells
• Tissue cells swell, some lyse
• Immediate response release of histamines and heparin (usually)
• Acute stages alkaline, late acidic, Monocyte resist low pH better

Question 12

cardinal signs

Answer 12

• Calor – heat
• Dolor – pain
• Rubor – redness
• Tumor – swelling
• “fifth sign” - loss of function

Question 13

rolling and extravasation

Answer 13

• Detailed drawing of diapedesis
• White cell is activated, puts receptors on surface
• Rolls along wall of blood vessel – squeezes through cells of blood vessel and follows the chemokines toward the source
• Extravasation = diapadesis

Question 14

Eosinophil

Answer 14

• The granules within the leukocyte soak up the eosin dye and makes it look red and granular
• Eosin is acidic in nature

Question 15

eosinophilia

Answer 15

• 300-400x more in bone than blood
• Attracted to tissue with histamine release
• Neutralize histamine (anti-inflammatory effect) – act as a natural antihistamine
• Common in tissues high in mast cells – the mast cells contain the histamine and heparin that are released to activate the eosinophils
• Systemic gluccocorticoids (stress) cause eosinopenia (These are the cells that take a big hit when you use exogenous steroids)

Question 16

clinical syndromes

Answer 16

• Leukopenia: Reduced production, Death often by massive infection, Can be indicator of infection (early or late)
• Leukemia – leukemia in an of itself is not a diagnosis because leuk- = all WBCs: Uncontrolled production of white cells (overgrowth) (Considered a blood cancer because of the unregulated growth), Lymphocytic or myelogenous, Anemia, bleeding, infection (still), high metabolism (Infection because the white cells being produced in excess are not normal! They are not fully functional), Radiation exposure is thought to be a cause of leukemia

Question 17

bands

Answer 17

• White cell does not yet have a lobulated nucleus that is called a “band” or “band cell”: Thought to be immature neutrophils
• Released into the blood stream slowly under normal conditions, but if we have an infection, we elevate the bands (aka left shift)

Question 18

lymphocytes

Answer 18

• Usually, the cytoplasm is clear or agranular

- Lymphocytes: nucleus is a very large proportion of the cytoplasm

Question 19

immunity

Answer 19

• Specific vs. non-specific (Specific = directing immune function toward specific targets -> usually need to be exposed to that target = ACQUIRED, Non-specific = we were born with it = INNATE)
• Innate vs. acquired

Question 20

acquired immunity

Answer 20

• Specific to targets
• Requires exposure
• Basic mechanism through the production of binding proteins
• Self vs. “not self” (Need to be able to recognize markers that we make vs the potential pathogens that we are exposed to)

Question 21

two forms of immunity

Answer 21

• Humoral (think “B cells”)
• Cell-mediated (think “T cells”)
• Similarities (Activation after exposure, Both responsive to “antigens”, Both based on lymphocytic derivatives)

Question 22

lymphocyte lineage

Answer 22

• Basis of acquired immunity – everything else (neutrophils, monocytes, etc.) are more about the nonspecific (innate) immunity
• Contained within lymphoid structures, greatest volume in nodes and spleen
• Distributed to guard entry portals (around mouth, nose, eyes, neck, groin, etc.
• Two general forms produced

Question 23

Ts and Bs

Answer 23

-“T” matured in Thymus – T Cell U (Thymus is retrosternal and tends to atrophy and go away with age)
-“B” in “Bursa of Fabricius” or Bone
o Pre-processing refers to initial development of cells producing millions or unique binding proteins (antibodies) (Through genetic events (crossing over) and production of proteins themselves)
-Both undergo negative selection for “self-reactivity” (Anything that is shown to react to self is eliminated and killed by apoptosis before it gets out into the blood stream/periphery)

Question 24

T cells

Answer 24

• Lever in the system
• Undergo second layer of “positive selection” for MHC recognition (Its not enough to bind to potential target, they have to also be able to bind to MHC)
• MHC used as control mechanism – controls against overactive immune system

Question 25

antigen binding proteins

Answer 25

- Basically all antibodies - Constant portion and variable portion (Constant is the stem and variable is the arms, Variable portion is the region of the Ab that gives it its specific binding characteristics) - Variety results from realignment of gene segments - Cells activated by binding antigen – induces “clonal expansion”

Question 26

activation

Answer 26

- Macrophages and others (not neutrophils) present antigens to T (or B) cells - Presence of MHC necessary – necessary with the antigen in order to fully activate the immune cell - Cytokines enhance effect (IL-1) - B cells convert to lymphoblasts then plasmablasts before plasma cells mature - Cells in dormant state provide memory

Question 27

antibodies

Answer 27

- Gamma globulins - Large molecules - Light and heavy chains - IgG, IgM, IgE, IgA, IgD (The major classes are the first four, IgM are spiked first, IgG are longer term memory antibodies, Allergic response = IgE (eosinophils go up), IgA = class of antibodies present in secretions (respiratory tract, nasal sinuses, breast milk))

Question 28

basophil

Answer 28

-Granular leukocyte -> granules stain dark blue

Question 29

direct actions

Answer 29

- Agglutination - Precipitation - Neutralization – if we’re talking about an endotoxin, an antibody can neutralize its activity - Lysis (rare)

Question 30

activation of complement

Answer 30

- Complement = protein cascade - 11 proteins in classic pathway – binding of an antigen on the surface of a lymphocyte will uncover a site that activates compliment - Antigen binding uncovers activation site - Numerous products (intermediates) enhance immunity

Question 31

effects of complement

Answer 31

- C3b – opsonization - C5b, 6 & 7 in complex – lysis - C5a – neutrophil chemotaxsis - C3a, 4a, 5a basophil and Mast cell activation - Agglutination - Disruption of viral coats - Inflammation

Question 32

Helper T cells

Answer 32

- (CD4 +) - Most numerous - Regulate all immune function (Th1 effects (IL 2), Th2 effects (IL4 and 5), Costimulation with B7:CD28 binding)

Question 33

Cytotoxic T cells

Answer 33

- (killer; CD8+) - Target cells without MHC - Use binding surface proteins and secretion of perforins – poke holes in the target and cause it to lyse

Question 34

tolerance

Answer 34

- How it happens - Release of self antibodies - Rheumatic fever – antibodies made to react to one thing will cross react and react to self - MG – autoantibody destruction of acetylcholine receptors - SLE - Hashimoto’s Thyroiditis – thyroid binding protein is released into the blood stream and the body doesn’t recognize it and mounts an immune response

Question 35

immunization

Answer 35

- Jenner – exposure to one organism can protect us from other organisms (Milkmaids that were exposed to cowpox were protected from smallpox outbreaks) - Principal - Variation

Question 36

allergy

Answer 36

- Delayed reaction hypersensitivity - Example of poison ivy toxin - Atopic people, indicators - Secretion of inflammatory mediators - Anaphylaxis - Spiking of eosinophils on a CBC

Question 37

allergen load

Answer 37

- Allergies are a cumulative process where the cumulative impact of the allergies we are exposed to determine getting to threshold and having symptoms - You can elevate the threshold with medications like steroids, immune modulators, antihistamines, etc