T Cell Development (Cell-Mediated Immunity) (Lecture 4)

Question 1

UNDERSTAND MICHAEL’S DESCRIPTION OF THE MOUSE EXPERIMENTS

Skin Graft Rejection
- An example of cellular immunity that is mediated by ____ cells.
- Exhibits all of the properties of acquired immune responses:
• ____
• ____
• ____
• ____ Towards Self

• Results from recognition of ____ proteins on the grafted tissue by recipient’s T cells.

Answer 1

T
inducibility
specificity
memory
non-reactivity

non-self major histocompatibility complex

Question 2

Major Histocompatibility Complex Proteins

1. There are 2 classes of MHC proteins: class I and class II molecules.
2. Molecules of both classes are ____ glycoproteins composed of 2 ____ associated polypeptide chains.
3. The 3-dimensional structures of both class I and II molecules exhibit a ____ that acts as a peptide-binding site.

encoded by series of genes that are inherited like a ____

Answer 2

heterodimeric
noncovalently
groove

single gene

Question 3

Major Histocompatibility Complex Proteins

Class I molecule composed of:
Large ____ chain and a ____ (Alpha is much ____)
• Alpha chain has a ____ and ____ domain
• Peptide-binding cleft entirely formed by the ____ chain

Class II molecules composed of:
Has a ____ chain and an ____ chain (about ____ in size to each other)
• ____ protein chains have transmembrane and cytoplasmic domains
• Peptide-binding cleft formed by the interactions of the amino terminal ends of the
____ and ____ proteins

Must understand these structural differences
• Most important aspect for functioning of immune system is the ____

Answer 3

alpha
B2-microglobulin
larger
cytoplasmic
transmembrane
alpha

alpha
beta
equal
both
alpha
beta

peptide-binding cleft

Question 4

Differential Distribution of MHC Molecules

MHC class I molecules are expressed on the surfaces of all ____ cells while class II molecules are expressed by a limited number of cell types including ____ cells, macrophages, ____ cells and activated T cells.

every nucleated cell > expresses ____ molecules on cell surfaces (only ones that don’t qualify are ____)

the cells that express class II are very limited in number (macros, dendritics, b cells and activated T cells)

Answer 4

nucleated
B
dendritic

class I
RBC

Question 5

Genes Of The Major Histocompatibility Complex

1. In humans, the MHC genes are referred to as ____ genes. The HLA complex is located on chromosome ____.

alpha chains of class I molecules and alpha and beta chains of class II are encoded in HLA (do not memorize the map)

genes broken into class I, class II (alpha and beta), and class III (____ functions outside of histocompatability antigens)

bc genes are so closely with one another, inherited with the characteristics of a ____

Answer 5

human lymphocyte antigen
6

diverse

single gene

Question 6

Genes Of The Major Histocompatibility Complex

2. Human MHC genes are highly ____.

Class I genes - A, B, C, D, E, F, G
• Some genes have very few ____ (F has 2 alleles)
• Others have many alleles (____ has 699 alleles)

Class II - ____ isn’t as significant
• But some genes come in large # of alleles, others have less

So likelihood of sharing each and every one of these genes and the proteins expressed on cell
surfaces is very ____!

Answer 6

polymorphic

alleles
B

polymorphism
minimal

Question 7

Genes Of The Major Histocompatibility Complex

3. MHC alleles are ____ expressed.

We receive ____ MHC alleles from each of our parents
• Potentially that no kids have same alleles and none match the parents
◦ Very unlikely to have exact matches within a family
‣ Except ____ twins - genetically identical within genes for MHC
◦ Need ____ MHC for transplants

Again shows very low chance of any of us matching for transplant
MHC has functional capabilities beyond transplants - we must understand MHC to understand
how the body recognizes antigens

Transplantation biology (skipping ahead - may be a tangent)
____ - take piece of own tissue and transplant to somewhere else in your body
____ - grafting tissue from different person
◦ ____ - antigens from different person
◦ Different from conventional foreign antigens - what our body was meant to fight
____ - grafting tissue from different species

Answer 7

codominantly

different
identical
same

autograft
allograft
alloantigen
xenograft

Question 8

CD Molecules

KNOW THIS TABLE

Molecules already mentioned:
• CD19 and CD21 found on surface of ____
• CD16 Fc gamma receptor for IgG that’s found on surface of ____
• For T cells:
◦ ____ found on surfaces of all T cells
◦ ____ and ____ are differentially expressed

Answer 8

B lymphocytes
NK cells
CD3
CD4 
CD8

Question 9

T Cell Differentiation

Brief description of T cell differentiation
• Cells derived from ____ find their way up into the ____. In the thymus they interact
with a number of ____ cell types within the thymus
–◦ Thymic epithelial cells as well as dendritic cells
–◦ These interactions between the T cell precursors and the other cell types in the thymus
initiate the ____ of the genes that encode T cell antigen receptors. Also induce
these cells to express the (above mentioned) CD molecules (____, ____, & ____)

Answer 9

bone marrow
thymus
stromal

rearrangement
CD3
CD4
CD8

Question 10

T Cell Differentiation

in humans, two types of T cells, based upon the type of antigen receptor they express

one group of T cells express the ____ form; the other expresses the ____ form of the antigen receptor

everything we are going to talk about relates to the alpha beta T cells

what molecule is found on all T cells, it is ____, it is called a pan T cell marker***

alpha beta cells are ‘____; express both CD3 and CD8

Double positive cells will start interacting with thymus epithelial cells as well as dendritic
cells, which will drive a number of events
◦ Any T cell that randomly acquires specificity for a self-antigen is induced to undergo
____
‣ Don’t want auto-reactive T cells getting out into peripheral circulation - will be
destructive if ever activated ‣ About ____ of the T cells you produce - are induced to undergo apoptosis b/c they
have a high affinity receptor against a self-antigen
◦ Also, based upon reactions on the double positive cells with other cells within thymus -
they will be induced to stop expressing either ____ or ____
‣ Results in 2 populations of cells - both expressing the alpha-beta form of the T cell
antigen receptor in conjunction with CD3
• One group will only express ____
• The other will only express ____
‣ These cells that leave thymus and enter peripheral circulation - (hypothetically) will
only react against ____ antigens
• But it’s well established that all of us have ____ cells circulating in our
bloodstream. –> So not all auto-reactive cells undergo apoptosis

Answer 10

alpha beta
gamma delta

CD3

double-positive

apoptosis
95%

CD4
CD8
CD4
CD8

foreign

auto-reactive

Question 11

T Cell Differentiation

CD8 molecule on surface > ____ cells

CD4 on surface > ____ cells; with potential to differentiate into TH1, TH2, Tfh, Treg, TH17; what is important in differentiating is the ____ that are present when stimulated by ____ (do not need to know the different cytokines)

the TH subsets differ by the type of ____ they secrete

Answer 11

cytotoxic/killer T

helper T
cytokines
antigen

cytokine