BL Unit 2 Flashcards
6 types of T cells and functions
5 helper T cells with surface CD4, 1 killer T cell
Th0- undecided precursor; differentiate after dendritic cell presents antigen
Th1- hypersensitivity T cell
secretes INTERFERON GAMMA- pro-inflammatory; M1; chemotactic for monocytes/macrophages
Th17- makes IL-17; resembles Th1 (inflammation); particularly resistant to pathogens
Th2- make IL-4 and IL-3; macrophages are ALTERNATIVELY ACTIVATED or M2; more involved in healing; IL-4 also chemotactic for eosinophils (kill parasites/worms)
Thf- migrate to cortex follicles; help B cells activate into antibody-secreting plasma cells; switch B cells from IgM to IgG/A/E, depending on organ
Treg- suppress all other Th cells; produce TGFbeta and IL-10; very potent
CTL- kill infected cells; lethal hit- signals target to apoptosis
surface markers on T and B cells, and helper vs cytotoxic T cells
B cells: CD20
All T cells: CD3
All Th: CD4
CTL: CD8
cytokines, lymphokines, and chemokines
cytokines- short range mediators made by any cell; affect behavior of same or other cell
IL-1, IL-12
lymphokines- short range mediators made by lymphocytes; subset of cytokine
IFNgamma IL-2,4,5,10
chemokines- small short range mediators made by ay cell; primarily cause inflammation
IL-8, eotaxin
lymphokines made by Th and Treg cells
Th1- IFNgamma and IL-2; pro-inflammatory; attract/activate MI macrophages
Th17- IL-17; attract/activate MIs
Th2- IL-4; pro-inflammatory; attract/activate M2 macrophages
Treg- TGFbeta and IL-10; anti-inflammatory cytokine
describe how Thf and B cells get activated by antigen and switch immunoglobin class
B cell binds its specific epitope and enodcytoses it; the fragments bind to MHC class 2 molecs and move to surface
B cell displays new antigen and Class 2 MHC complex on surface
correct Thf binds and focuses surface interactions and helper lymphokines on B cell
define mitogen and uses for T and B cell mitogens in lab
a. Mitogen: protein that stimulates T cell division
examples of mitogens:
PHA: binds CD3, ConA to stimulate T cell division
PWM: nonspecifically stimulates B and T cell division
effects of mitogen vs antigen when added to normal blood lymphocyte
antigens are specific
mitogens are nonspecific
mitogen- binds CD3 domain to always keep signal on
antigen- binds to antigen-binding site on T cell
antigen receptors on T and B cells
B cells: bind antigen directly with surface antibodies; interact with free antigens
T cells: focus on cell surfaces; only see complexed antigens presented on surface of an identical cell
Antigen Presenting Cells APC
dendritic cells
chop up and display antigens on surface as MHC-antigen complex for recognition by another T cell
Class 2 MHC molecs- when antigens are endocytosed and presented
T cell helpers recognize Class 2
Class 1 MHC molecs- when proteins are synthesized within the cell (not endocytosed);
CTL recognize Class 1
role of T cells in ridding body of viral infection
CTL sees foreign cell (because MHC Class 1 will have it bound); activate target cell to commit suicide through CD95L or lytic granules
Th cells see antigen on dendritic cell, B cell, or macrophage via MHC Class 2; activate immune response and divide
characteristics of T independent antigens
T independent antigens usually have same epitope repeated over and over (common in carbs- streptococcus pneumoniae)
carb chains bind to B cell antibodies; cell activates/divides
response is almost all IgM, so a person deficient in T cells will still make carb antibodies
with protein antigen (rare)- NO IgM or IgG is made without T cell help
experiment where antibody response can be T-dependent
test two leukocyte populations’ ability to make antibodies to the same antigen- 1 with full complement of T and B cells, and 1 with T cells killed by radiation
define Human Major Histocompatibility Complex MHC
distinguish between HLA-A and HLA-B antigens and HLA-D
MHC- group of strongest histocompatibility antigens coded for by a family of genes on a single chromosome
Th- recognize MHC antigens on HLA-D loci (Class 2)
CTL- recognize MHC antigens on HLA-A and HLA-B loci (Class 1)
class 1 vs class 2 histocompatibility antigens
Class 1 antigens- found on all nucleated cells
Class 2 antigens- restricted to B cells, macrophages, dendritic cells, and a few others
define alloantigen and haplotype
alloantigen- part of animal’s self-recognition system (like MHCs)
when injected into another animal, they trigger an immune response aimed at eliminating them
present in some members of a species, but not common to all
haplotype: MHC gene set that you inherited from one parent
Given the HLA‐A, HLA‐B and HLA‐DR phenotypes of 2 parents and their child, work out the 4 haplotypes involved.
Typing at the HLA-A and HLA-B loci can be done by treating the patient’s leukocytes with allele-specific anti-HLA antisera and complement. The most sophisticated labs actually sequence the HLA genes themselves for typing.
D3, B7, A1, etc., are each individual’s haplotypes.
The cells show their phenotypes, the actual proteins expressed on the surface of their cells. Every cell expresses both alleles.
identify the best probable donors of tissues or bone marrow to an individual
good DR match is most important (Class 2)
for Class 1- HLA-A and HLA-B are most important
cells not identical will not stimulate Th1 cells and the huge response; they’ll activate everything else
cells identical at HLA-A and B will not stimulate CTL, but the Th1 cells will still be stimulated and won’t be great
identical twin or sibling is best chance for match
look for bone marrow matches at A, B, C, DR, and DQ
one-way mixed leukocyte reaction (MLR) and its use
cells from donor are treated to prevent their division (via DNA synthesis inhibitors/radiation)
observe recipient’s Th cells dividing in response to donor’s HLA-D (mostly DR)
a strong rxn may preclude doing the transplant
distinguish between HLA-D and DR, DP, DQ
HLA-D is general term for group of loci that give rise to MHC type 2 antigen-presenting proteins
DR, DP, DQ- individual loci within the D region of Chromosome 6
interaction of T cells recognizing antigen plus HLA-D and A/B in graft patient
Th are programmed to recognize HLA-D (class 2)
CTL recognize HLA-A and B (Class 1)
rejection: dendritic and macrophage cells from graft move to host lymph node; host Th1 cells recognize foreign HLA-D and synthesize lymphokines and up regulate cell-surface receptors for GFs like IL-2; Th1 also will secrete IFNgamma that attract M1 macrophage inflammation
CTL- recognize foreign HLA-A and B, but also require Th1-derived IL’s as a second signal for activation; once activated, highly cytotoxic and may proliferate
similar to virus, except:
normal response: peptide plus self-MHC recognition
rejection: foreign MHC recognition
cellular and molecular events of a graft rejection- normal and hyperacute
most important mech is via CTL and Th1 cells (via lymphokines and monocyte/macrophage inflammatory response)
normal rejection: Th1 cells are activated by “almost me” MHC type 2’s; activate Th2 cells, which activate B cells to produce antibody against graft; and CTL attach tissue directly once they bind to MHC type 1s
Th1 also brings other inflammatory cytokines, like TNF-alpha (tissue necrosis factor)
hyperacute rejection: graft tissue rejected immediately- stays white/bloodless even after reperfusion
- there was a circulating antibody against the graft from a previous/failed graft or against graft’s residual blood
- antibodies attach to endothelium, activate lots of complement, set off anaphylatoxin release (C3a, C4a, C5a) from mast cells; leads to vasospasm and tissue ischemia; can lead to systemic inflammation
- T-cell mediated rejection is slower than complement-mediated
- always cross-type the ABO blood antigens from donor and recipient
- immunosuppressants are typically given for a lifetime after a transplant
how T cells recognize “self + x” and foreign MHC (allorecognition)
receptors are selected to recognize “self + x”
recognition of foreign MHC is a “chance” cross-reaction
5% of T cells will bind a foreign MHC strong enough to cause activation
can’t give other people T-cells because MHCs are different and T cells are specifically selected for an MHC
example of disease whose incidence is tightly linked to a particular HLA allele and its mech
ankylosing sponditis- involves chronic inflammation and eventual calcification of the insertions of tendons into bones
95% of people w/ this have a specific HLA-B allele that will also disease rats
-price to pay for genetic variability in HLA region- eventually it’s going to look similar to an antigen and you’ll develop an autoimmune response to own tissues
also HLA-linked cases of diabetes, lupus, and kidney/lung degenerative disorder
basic structure and general movement of lymph and lymphocytes through a lymph node
lymph circulates to lymph node via afferent lymphatic vessels and drains into node just beneath capsule called sub scapular sinus
subcapscullar sinus drains into trabecular sinuses then to medullary sinuses
sinus space is criss-crossed by pseudopods of macrophages, which filter lymph
medullary sinuses converge at hilum and leave via efferent lymphatic vessel
ultimately drain to central venous subclavian blood vessel via post-capillary venules; cross wall via diapedesis
activated vs non-activated nodules
germinal center differentiates the two germinal centers- sites within lymph nodes/nodules in peripheral lymph where mature B cells proliferate and class switch
vasculature of lymph nodes
blood supply enters through small artery in hilum
branches repeatedly to entire node
specially lined with HIGH ENDOTHELIAL VENULE- site of diapedesis of lymphocytes from blood to lymph node
-allows you to populate all nearby lymph nodes rapidly during an infection
leaves via small vein
blood flow through thymus
small arteries enter thymus through outer capsule and penetrate into thymus
bifurcate within the CT septa between lobules
vessels’ cells have tight junctions, and surround by endothelioreticular cells- forms blood-thymus barrier for developing thymocytes
efferent lymphatics also travel in the septum
thymus blood flow and thymus lymph fluid flow
blood- everywhere, blood flow in via arteries, out via veins
pierce capsule; trebeculae; cortex; everywhere (incl medulla)
lymph flow- none coming in.
efferent lymphatic drain lymph fluid (and veins) outwards
NO afferent lymphatic to thymus
nuclei and cell bodies of reticuloendothelial cells in thymus and Hassall’s corpuscles
involved in selection process for thymocytes as they progress toward medulla; provide microenvironment to protect maturing thymocytes
Hassall’s corpuscles: cells that thickly populate medulla; produce lymphokines that promote thymocyte maturation into adult T cells
blood flow through spleen
open blood circulation through porous splenic sinuses
receives blood via splenic artery
branches into central arterioles into the red pulp
lined with discontinuous endothelial cells where RBCs, WBCs, and platelets exit to enter sinuses
Periarteriolar lymphoid sheath (PALS): sheath around central arterioles; WHITE PULP; germinal centers within these sheaths
drained via splenic vein
only has efferent lymph vessels (like thymus), which leave from hilum
cell components of red and white pulp
red pulp: 75% of spleen; RBC rich with loose sinuses; filters blood, antigens, microorganisms, and old RBCs
white pulp: organized lymph tissue
contains T cells, B cells, accessory cells; mount an immune response to antigens in blood; present in form of PALS, containing B cell follicles and T cells
regions of mucosal-associated lymphoid tissue
tonsils (palatine, lingual and pharyngeal (adenoids), esophageal nodules, appendix, bronchial nodules, large aggregation of lymphocytes in intestine,
colon: abundant nodules both in mucosa and submucosa known as Peyer’s patches
function and distribution of lymph system
cleanse blood and lymph and provide adaptive immunity
produces and stores agranular WBCs or lymphocytes
4 forms of lymph tissue: non-encapsulated aggregates of lymphocytes lymph nodes thymus spleen
these are composed of free lymphocytes and a supporting framework of reticular cells
types of lymphoid cells
helper T cells (5 kinds)
- help B cells
- express CD3 and CD4
- recognize MHC Class 2
CTL
- express CD3 and CD8
- recognize MHC Class 1
B cells
express CD20
structure of all major lymph organs
lymph nodes- small; found all over individually or clustered; non-specific filters of debris/microorganisms; site of antigen presentation in adaptive immunity
lymphocyte enters small lymphatic vessel; connects to afferent lymphatic vessel; enters node into sub capsular space
thymus gland- bilobed thymus with CT capsule where trabeculae divide organ into pseudo lobes, where all thymocytic cells develop to release mature T cells
-lymphocyte mass in thymus decreases through childhood
NO reticular fibers
stromal cells provide support
Hassall’s corpuscles: circular layer of reticular cells in medulla to suppress autoimmune events
CORTEX: densely packed developing thymocytes
MEDULLA: more mature thymocytes, less dense
thymocytes leave via lymphatics and blood vessels
spleen: multi purpose lymphoid organ; role in adaptive immunity
MALT: mucosal-associated lymphoid tissue
unencapsulated collections of lymph cells and associated support cells to encounter antigens passing through mucosa
-tonsils, appendix, nodules, Peyer’s patches in intestine
-M cells deliver antigen to underlying lymph tissue for adaptive immune response in intestine
primary vs secondary lymph organs
primary: bone marrow and thymus
major sites of development of B and T cells
secondary: seeded with cells from primary tissues (GALT, Peyers patches, etc)
encapsulated lymph organs
lymph nodes
spleen
thymus
humoral immunity and cell-mediated immunity
humoral immunity may prevent a viral illness, but T cell immunity is necessary for recovery
- antibody maybe prevent virus from establishing an infection
- once the infection takes place, you need to kill infected cells before virus multipilies
define local immunity
local immunity on the surface that is being invaded can prevent the invasion- secretory IgA
Sabin (attenuated, live, oral) polio vaccine was so effective- those immunized had high levels of IgA in their secretions and didn’t get colonized by real virus
organisms against which cell-mediated immunity is most effective
viruses, fungi, yeasts, intracellular bac
organisms against which humoral immunity is most effective
extracellular bac and pathogens
human and animal antitoxin
killed virus vaccine
live virus vaccine
longest immunity
human: IgG against tetanus
antimal: IgG against tetanus
practical difference: IgG solns tend to aggregate when they sit around
humans- causes lots of complement activation (pain, inflammation, etc) due to proximity of bound IgG antibodies
animal- less complement is activated due to inter-species antibodies not activating each other’s complement very well
killed vaccine: injected polio (Sabin) vaccine
live vaccine: oral polio (Sabin) vaccine
longest immunity tends to be live vaccines because body produces MHC Class 2 AND 1 responses from your own, infected cells
