Lecture 2

Question 1

What is a leukocyte?

Answer 1

Nucleated cells of the blood; white blood cells. When you centrifuge anticoagulated blood, they sediment on top of the packed red cells, forming the “buffy coat.”

Question 2

Mononuclear cells

Answer 2

Leukocytes whose nucleus has a smooth outline; monocytes (immature, becoming mature macrophages in the tissues/phagocytes/can present to t-cells), and lymphocytes (large nucleus inside/T-Cell/B-cell). In tissues it’s sometimes hard to tell the difference between macrophages and lymphocytes, hence the blanket term “mononuclear.”

Question 3

Polymorphonuclear cells

Answer 3

Cells whose nucleus is lobulated, also called granulocytes because they have (usually) rather prominent cytoplasmic granules. They are:

Eosinophils; Basophils (closely related to tissue mast cells); and Neutrophils.

Question 4

Plasma cell

Answer 4

a B-cell that is activated and spits out an antibody

Question 5

Granuloctyes

Answer 5

Also called polymorphonuclear cells; have cytoplasmic granules

Question 6

Monocyte

Answer 6

mononuclear;
phagocytic cell
can also present to T-cells (so that would be part of specific)
-can become macrophages

Question 7

Lymphocyte

Answer 7

Mononuclear; large nucleus; -T-cell and -B-cell

Question 8

neutrophil

Answer 8

polymorphonuclear; first responders/puss

Question 9

Eesonophils

Answer 9

polymorphonuclear; look like “sunglasses”; parasites, allergy, asthma

Question 10

Basophils

Answer 10

polymorphonuclear; two nuclei and granules (that are full of histamine)

Question 11

Mast cells

Answer 11

Like a basophil (granules with histamine); however basophils are in blood and mast cells are in tissue

Question 12

serum

Answer 12

plasma without fibrinogens

Question 13

main central lymph organs

Answer 13

Central organs are ones in which lymphocytes develop: the bone marrow and the thymus. (In mammalian embryos, bone marrow function is first found in the yolk sac and then in the liver.)

Question 14

Peripheral lymph organs

Answer 14

In the peripheral organs, mature cells are organized to trap and respond to foreign invaders:

these organs include lymph nodes, spleen, Peyer’s patches and mesenteric lymph nodes of the gut, tonsils and adenoids. MALT/GALT

At any moment many lymphocytes are found in the blood and lymph, too, but most are in the peripheral lymphoid organs.

Question 15

Antigen

Answer 15

a substance which can be recognized by the immune system.
An antigen frequently is also an immunogen, which is an antigen in a form which can give rise to an immune response, that is, which can immunize.
An antigen can also be a toleragen (no immune response)

Question 16

epitope

Answer 16

The part of the antigen that we see and can ID as foreign (a good antigen an antigen repeated over and over). Can also be called an antigenic determinant

Question 17

How to antigens activate lymphocytes?

Answer 17

immediate: neutrophils, monocytes–> macrophages and phagocotize; maybe we stop here or keep going…

if we keep going, dendritic cells (the bridge between);
the DC presents antigen: DC excretes cytokines (activate other parts of the immune system)
then goes to lymph node and present antigen to B and T cells

Question 18

Define toleragen

Answer 18

tolerogen is antigen delivered in a form, or by a route, which does not give rise to an immune response, and which furthermore prevents an immune response to subsequently administered immunogen which has the same antigenic determinants—to be discussed later.

Question 19

Describe the pattern of lymphocyte recirculation

Answer 19

a lymphocyte in the blood encounters the cells lining certain postcapillary venules in the peripheral lymphoid tissues, especially lymph nodes.
These endothelial cells are unusual⎯not flat as is the usual case, but high and cuboidal.

Recirculating lymphocytes may bind to and pass between the endothelial cells into the lymph node, where they may stay, or move eventually into the lymph which drains from that lymph node to the next in the chain. Lymph works its way into the largest lymph channels such as the thoracic duct near the heart; from there it is emptied into the venous blood and the circulatory loop can start over again.

Thus there are two lymphocyte circulations, blood and lymphatic, in which lymphocytes cross from blood to lymph at the nodes, and from lymph back to blood at the heart.

Question 20

What are the specialized features of lymph node blood vessel endothelium that permit recirculation.

Answer 20

Unusual endothelial cells in post-capillary venules in the peripheral lymphoid tissues (e.g. lymph nodes); they are not flat—the lymphocytes can bind to them and pass in between them into the lymph node—eventually if it goes into the lymph it will be dumped into the venous blood.

Question 21

Discuss lymphocyte activation by antigen with respect to: receptor binding, proliferation, differentiation.
(RECEPTOR BINDING)

Answer 21

Each lymphocyte has receptors for antigen; (thousands on each cell); all are identical so that each cell has just a single specificity, different from nearly all the others.

T cell receptors are composed of alpha and beta chains;

B cell receptors are samples of the antibodies that the cell will eventually secrete.

The part of an antigen that fits into the receptor is the antigenic determinant or epitope. To activate the T or B cell several conditions must be met: the fit between receptor and the antigen it sees must be good (specific) enough, several nearby receptors must be simultaneously bound by antigen, and other cell surface molecules must be involved too (accessory interactions or costimulation).

Question 22

Discuss lymphocyte activation by antigen with respect to: receptor binding, proliferation, differentiation.
(PROLIFERATION)

Answer 22

Once the cell is correctly activated it begins to proliferate. Lymphocytes can divide as fast as every 6 hours, so in just a few days you have thousands of cells specific for the antigen that got the process started.

Question 23

Discuss lymphocyte activation by antigen with respect to: receptor binding, proliferation, differentiation.
(DIFFERENTIATION)

Answer 23

These cells also differentiate: into effectors that do the job (B cell blasts and plasma cells that release antibodies into the blood; helper T cells that pour out cytokines; killer T cells that induce their targets to die) and into memory cells that recirculate efficiently and are very easily triggered by another exposure to antigen.

Question 24

Humoral (antibody) vs. cell mediated immunity
Lymphocytes involved:
nature of the molecules they release:
types of inflammatory cells they preferentially involve:

Answer 24

Lymphocytes involved:
cell-mediated involves T-cells; can’t transfer person to person (they see antigen on antigen presenting cell) and can kill
humoral involves B-cells; plasma cells, secrete antibodies
nature of the molecules they release:
types of inflammatory cells they preferentially involve:

Question 25

H-chain vs. L chain

Answer 25

H chain is a heavy chain on an antibody (5 types total–gamma, alpha, mu, epsilon and delta); there are two of them(MW about 5000); L chain is light chain and also two of them (MW 2500) (lambda and kappa and each antibody only has one of these)

Question 26

Hinge region

Answer 26

Where the arms attach to body (where light chains attach to heavy chains); it is technically in the heavy chain

Question 27

Fab, F(ab2), Fc

Answer 27

After Porter broke up an antibody, it broke up into 2 fragments
Fab: 2 identical pieces; they came from the S-S bonds between the H-chains (univalent–binds only 1 antigen)
F(ab2): If you leave the 2 Fabs still joined; divalent

Fc region–backside of antibody (when they bind to the antigen, the Fc region “sticks up”); macrophages and complement have Fc receptors

Question 28

Complementarity-determining regions (CDR)/hypervariable regions

Answer 28

A heavy chain and light chain come together to form a CDR; the CDR binds to the epitope on the antigen; so a CDR is where the antigen (the light and heavy chains) binds to the epitope; remember, amino acid sequence variability is not uniform along V-domain–most of the variability in 3 aries called “Hypervariable” or CDR regions. Remember, the AAs in this region COMPRISE THE ACTUAL ANTIBODY BINDING SITE>

Question 29

Variable (V) vs. Constant (C) domains

Answer 29

There are variable and constant regions on light and heavy chains; light chains have one variable domain (VL) and one constant domain (CL); heavy chains have one variable domain (VH) and 3-4 constant domains (CH1, CH2, CH3 and (CH4)). There is homology between the domains such suggests there was once an ancestral gene for one domain.

Question 30

The 5 antibody classes and their characteristic heavy chains

Answer 30

The major variable are the heavy chains in antibody classes
Each class has different function but same CDR
1) IgD: Y—> stays on the B-cell as a B-cell receptor so don’t really isolate from bloodstream; 2 light and 2 gamma chains (2 light and 2 delta)
2) IgG: composed of 2 heavy chains and 2 light chains; most prevalent antibody in blood; co
3) IgM: One of first antibodies made by the B-cell a bunch of “y”s stuck together that look like a snow flake—can combine 10 antigens; it is decovalent; “J chain”; (10 light, 10 mu, and 1 J chain)
4) IgA: secreted in our mouth; IgA deficiency can cause oral problems; 2 antibodies stuck together with J chain, 4 binding sites; has special protection; when IgA secreted into saliva, it has a special secratory component which protects it from degradation; most prevalent in secretion and thus, the most prevalent in the BODY (4 light, 4 alpha, 1 J and 1 S.C. chain)
5) IgE: Y; 2 binding sites; low amount in blood unless you have allergies or parasites (2 light and 2 epsilon)

Question 31

Antibody concentration in serum

Answer 31

GAMBDE:
G: 1000, A: 200: M: 100 D: 5 E: 0.2

Question 32

Describe the structure of antibody combining sites

Answer 32

binds to the antigen, made up of V domains of both the H and L chain (VH and VL)

Question 33

subclass

Answer 33

Class–based on slight differences in AA sequences in H chain C regions; so IG1, IG2, IG3, IG4; IgA1; IgA2; IgM1, IgM2 (others only have one)
so 10 cubclasses/isotypes

Question 34

allotype

Answer 34

Minor allelic differences in immunoglobulins for different people–some allotropes could be better than others

Question 35

idiotypes

Answer 35

Each antibody has its unique combining regions with a sequence of CDR A.A.s of its L and H chains; so an idiotype is an antibody’s unique combindined site (and is considered an antigen)?