B3.008 T Cell Activation Flashcards
4 main classes of pathogens`
bacteria
viruses
fungi
parasites
primary functions of T lymphocytes
production of cytokines
cytotoxicity
control of other immune cells
primary function of B lymphocytes
production of antibodies by plasma cells
what are 4 components of the acquired immune response, not necessarily exhibited by innate immunity?
specificity - lymphocyte responses are specific for antigens
diversity - immune system is able to produce a number of different responses
memory - lymphocytes respond anamnestically to antigens, memory is long lived
self/non self discrimination
how does a secondary immune response compare to a primary immune response?
secondary response is faster, bigger, and more specific
i.e. double the antibodies generated in half of the time
what is the physical structure of a T cell receptor?
heterodimer usually consisting of an a and b chain
sometimes gamma and delta chain
what is the physical structure of a B cell receptor?
consists of a cluster of molecules involving surface immunoglobulin (IgM or IgD)
coupled with disulfide bonded heterodimers (Ig-a and Ig-b)
where do T cells mature?
thymus
what are the 2 components of a T cell?
TCR (T cell receptor)
CD3 complex of molecules
what are the two major subgroups of T cells?
CD4+ (TH, T helper)
CD8+ (Tc, cytotoxic capabilities)
what are the 4 subtypes of CD4+ T cells
Th1
Th2
Th17
Treg
what is the function of Th1 cells?
cell mediated immunity
produce IFN-gamma and TNF-a (type 4 hypersensitivity)
respond to intracellular pathogens (viruses and some bacteria)
what is the function of Th2 cells?
humoral (blood) immunity
produce IL-4,5,13 (type 1 hypersensitivity)
helminths, allergic reactions, extracellular pathogens
what is the function of Th17 cells?
produce IL-17
acts upon a number of cell types
important in defense against extracellular bacteria and fungi
what is the function of Treg cells?
can suppress/inhibit the effector functions of CD4 and CD8 T cells
make up 5-10% of CD4+ cells
express CD25 and FOXP3
what other types of cells are stimulated by Th1?
macrophages
what other types of cells are stimulated by Th2?
B cells
mast cells
what is meant by cross regulation of Th1 and Th2?
the cytokines produced by each type inhibits the production of the other type
i.e. IFN-gamma produced by Th1 inhibits the Th2 response
what enhances Tc (CD8+)activation?
Th1 cytokines
what is required for killing by Tc (CD8+) cells?
direct contact and conjugate formation
what are the two pathways of Tc cells?
1: cytoplasmic granules = perforin + granzymes > apoptosis
2: Fas-Fas ligand interactions > apoptosis
what is Fas?
a programmed cell death indicator
what types of cells are antigen presenting cells?
B cells
macrophages
dendritic cells
what is the function of an antigen presenting cells?
enzymatically process antigen
present digested fragments to Th cells
do this using MHC class 2 molecules
what is an epitope?
part of an antigen recognized by the lymphocyte receptor
small part of the actual antigen
which types of cells can recognize epitopes in isolation?
B cells
which cells require MHC to present an epitope?
T cells
what is MHC?
major histocompatibility complex
found on chromosome 6
controls T cells function as they cannot act in isolation
what are the 4 types of surface molecules responsible for antigen recognition?
B cell receptor
T cell receptor
MHC class 1
MHC class 2
where are MHC class 1 molecules found?
all cells
what types of cells do MHC class 1 present to?
CD8+ T cells
where are MHC class 2 molecules found?
only antigen presenting cells
what types of cells do MHC class 2 present to?
CD4+ T cells
what are the 3 components of an MHC class 1 molecules?
HLA-A
HLA-B
HLA-C
HLA= human leukocyte antigen
what are the 3 components of an MHC class 2 molecules?
HLA-DP
HLA-DQ
HLA-DR
what is the physical structure of an MHC class 1 molecule?
polymorphic heavy chain (a chain)
non-polymorphic light chain (B-2 macroglobulin) (not encoded within the MHC)
what types of antigens do MHC class 1 present?
endogenous
antigen formed inside a host cell (viruses, tumors)
what is the physical structure of an MHC class 2 molecule?
polymorphic a and b chains
both encoded within the MHC
what types of antigens do MHC class 2 present?
exogenous antigen
originate outside of presenting cells (bacteria, vaccines, viruses caught between cells)
describe the process of clonal selection
each lymphocyte coming into contact with specific antigen will be stimulated (becomes activated and proliferates)
clones of cells that are specific for the particular antigen will be made (larger population)
proliferation will take place at the expense of non-stimulated cells
what are the two types of lymphocytes that can form from clonal selection?
effector cells (majority) -T cells -plasma cells for B cells memory cells (fewer) -can be re-stimulated at a later date
what are the different types of lymphoid tissue?
primary: thymus (T) and bone marrow (B)
secondary: lymph nodes and tissues
tertiary: the remaining areas where lymphoid cells are found
describe the structure and function of the thymus
bilobed organ lying over the heart
contains T lymphocytes at various stages of development
committed T cells pass through the thymus where they undergo a selection process
describe the function of the bone marrow
site of lymphocyte origin
T and B cells both begin their existence here
T cells leave undeveloped for the thymus cells mature and undergo selection to remove potential autoreactive cells
what happens to foreign antigens which enter connective tissue?
carried by lymphatics to the nearest lymph node (draining lymph node)
how is lymph moved?
along vessels by contraction of the bodies’ muscles in a one way system
what would be the cause and result of lymph movement stopping?
lack of effective muscle contraction causes movement of lymph to cease
can cause edema in tissues
-legs and ankles swell after long journeys
-elephantiasis
where does antigen presentation take place?
lymph nodes
that are the 3 primary sections of the lymph node?
cortex
paracortex
medulla
what is located in the cortex of the lymph node?
mainly B cells in germinal centers
- primary follicles when resting
- secondary follicles when activated and dividing
what is located in the paracortex of the lymph node?
mainly Th cells
what is located in the medulla of the lymph node?
plasma cells
where are macrophages and dendritic cells found within the lymph node?
cortex and paracortex
describe the structure and function of the spleen
largest lymphoid organ
hilum containing the splenic artery and vein
no lymphatic vessels supplying this organ
plays a significant role in immune response to blood borne diseases
site of removal of damaged RBC and platelets
what are some other significant areas of lymphoid tissue throughout the body?
appendix
tonsils
adenoids
Peyer’s patches
gut associated lymphoid tissues (GALT)
appendix
Peyer’s patches
bronchial-associated lymphoid tissue (BALT)
similar system of tissues within the respiratory tract
GALT + BALT =
MALT
mucosal-associated lymphoid tissue
what types of cells transport antigens from mucosal surfaces to the lymphoid system?
microfold
membranous cells
referred to as M cells
describe the 3 steps in lymphocyte recirculation
- lymphocytes leave the blood and enter the lymphatic system at lymph nodes
- leave through venous system through specialized epithelial cells (high endothelial venules (HEV)) by diapedesis or extravasation
- re-enter the venous circulation via the thoracic duct which enters the left subclavian vein
what type of cells are part of the skin’s immune system?
Langerhans cells - dendritic cell of the cutaneous surface
intraepidermal lymphocytes
TCR gamma delta cells that are thought to be first response to infection
what is the definition of an antigen?
any molecule recognized by a BCR or TCR
what are haptens?
small molecules that by themselves cannot induce an immune response
antigens but not immunogenic
induce an immune response when attached to a larger protein (nickel, penicillin, poison ivy)
what is required by most isolated antigens to induce an immune response?
adjuvant
not all foreign proteins stimulate an immune response for this reason
what are adjuvants
third party compounds or substances which stimulate the immune system
what are some common functions of adjuvants
some non-specifically stimulate lymphocytes
some prolong antigen persistence
some induce receptors on accessory cells
what happens if an antigen contains many epitopes?
some more dominant than others
immunodominant
properties of T cell epitopes
much better defined than those of B cells 8-11 AAs for MHC class 1 13-17 AAs for MHC class 2 must interact with both MHC and TCR at the same time
what are 3 classes of T cell surface molecules?
CD40L
CD28
CTLA-4
describe CD40L
interacts with CD40 on APC important for antibody class switching lack of it leads to hyper IgM syndrome
describe CD28
interacts with B7.1 (CD80) and B7.2 (CD86) on APC
important in providing a second signal to activated naïve T cells
lack of interaction can lead to anergy (lack of immune response)
describe CTLA-4
constitutively expressed on Tregs and induced on activated T cells
interacts with B7.1 and B7.2
acts to switch off T cell function
describe the chains of the TCR in more detail
both anchored in cell membrane
consist of a V (variable) and C (constant) region
describe the process of generation of lymphocyte diversity
various V regions are encoded in a series of separate gene segments
when a functional gene is made, the appropriate gene segments are brought together in a unique physical rearrangement
prior to rearrangement, genes are in a germ line configuration
rearrangement called somatic recombination
other than gene rearrangement, what can contribute to antigen receptor diversity?
slight changes in DNA
induced during the cutting and splicing or gene segments
changes nucleotide sequence by the addition of extra nucleotides into the joints between gene segments
what is somatic hypermutation?
occurs in B cells (not T cells)
additional nucleotide substitutions take place during activation and division of cells
what do B cells require to function?
T cells
what do T cells require to function?
APCs to present antigen to them
what is hematopoiesis?
production of cells from bone marrow
what are the 2 primary genes which help regulate hematopoiesis?
BCL2 - inhibits apoptosis
Fas- when it interacts with FasL, apoptosis occurs
