Aspects of the Immune Response Flashcards
Functions ascribed to the various subsets of T cells
cooperation with B cells to enhance the production of antibodies (Th cells)
secretion of cytokines
lymphokines
cytokines released by lymphocytes
What happens once a T cell is activated (T helper)// Tdth
release cytokines that induce the migration and activation of monocytes and macrophages leading to the delayed hypersensitivity inflamaotry reactions
What happens once a CTL is activated
become killer cell that upon contact with their proper ligand=antigen, cytokines and co-stimulation kill the target
Th1
CD4+
intracellular mediated immune resposne
secrete IL-12, IFHg and TNFa
pro inflammatory
evoke cell-mediated immune responses
Th2
CD4+
extracellualr parasites
secrete IL-4, IL-5 and IL-10
anti inflammatory and evoke a humoral immune response
helminths
Th0 naive T cell
may differentiate into a helper Th cell when exposes to
proper nature of the antigen, does of antigen, the organ of initial antigen exposure and the cytokine milieu
teh cytokine milieu in whihc antigen presentation occurs is the most important determinant
IL-12 / IL-10 Th differentiation bias
early production of IL-12 in the immunological synapse between APC adn the Th0 cell has been shown to prime Th1 responses in response to to intracellualr microbial infections and the secretion of IL-10 to biase Th2 T cell responses
Mycobacteria
protective immunity mediaated by Th1 CD4+ T cells with the aid of other types of T cells
Th1 cells produce IFNg and TNFa in response to mycobacterial antigens
which are critical for macrophage activation and control of bacterial replicaiton
cell-to-cell contact between T cells and antigen-presentign cells is an importnat event for the induciton of the tcell mediated immune response
indeed interaction of co-stimulatory and co-inhibitory receprots like CD-028 and CTLA-4 expressed on T cells the the ligands B7-1 and B7-2 on APC influences the magnitude and duration of antigen-specific T-cell response
PC-1 expression
programmed cell death 1 (PD-1 = CD279) is a new member of the CD28/ CTLA-4 receptor family
PD-1 expression is induced on activated T cells and B cells and its constitutive
imbalance in costimulatory ligands
can results in an inefficient adaptive immune response to clear infection, and may contribute to pathological consequences
Brucella abortus
zoonotic Gram negative pathogen
in ruminants causes abortion and infertility
in humans causes undulant fever, characterized by malaise, aches and fevers
human brucellosis can be contraced by accidental contaminaiton form infected animals, handling infected tissues or sonsuming undercooked meat or unpasteurized dairy products from infected animals
Brucella facultative intracellualr bacterial pathogenesis
pathogensis and the nature of the protective immune response are closely related to this property
both antibody and cell mediated immune responses (CMI) can influence the course of infection with brucella
CMI essential for clearance of intracellualr bacteria
thus, IFNg plays a central role in aquired resistance agaisnt Brucells
upregulated macrophage microbial killing
Type I allergy
The mechanism of the pathogenesis of Type I allergy is initiated by phagocytosis of allergens by APCs
the balance between Th1 and Th2 dominant immunity is thought to be important here as well
Prominent systemic manifestations of inflammation
elevation of body temperature and variety of biochemical alterations known as the acute phase reaction which leads to the synthesis of acute phase protiens in the liver
The local infflammatory reaction is characterized by
an initial increase in blood flow to the site of injury
enhanced vascular permeability = more flow of WBCs
influc of antigen non-specific cells and highly destructive cells= neutrophils is one of the earliest stages of the inflammatory response
=> these cells mount a rapid, non-specific response
after, moncytes, macrophages and lymphocytes Bs and Ts appear at the site on injury
these cell types are associated with antigen-specific and more tightly regulated immune responses
inflammatory cells
express more cell-surface proteins and glycoproteins known as cell adhesion molecules
endothelial cells
are also activated during initial phase of the inflammatory response and then express, among other things, adhesion molecule counterreceptors
immune cell mediators
dound in the serum or tissu eof sluids, are released by degranulating cells upon activation , or activated endothelial cells in blood vessels at the site of inflammation
they serve as muscle-active and edema-promoting substances, chemotaxins, and cellular activators and inducers of all kinds of effector cells engaged in the inflammatory response
Types of inflammatory mediators
kinins of the coagualtion system
leukotrienes
prostaglandins
other lipid mediators
Acute phase proteins
a class of proteins whose plasma concentrations increase or decrease (positive or negative respectivly) in response to inflammation.
Secretion of cytokines in response injury
in response to injury, local inflammatory cells (neutrophils, granulocytes and macrophages) secrete a number of sytokines into the bloodstream, most notable of which are the interlukins
IL-1, IL-6, IL-8 and TNFa
positive acute phase proteins
some act to destroy or inhibit the growth of microbes (CRP, moonose binidn protein, complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin)
other give negative feedback on the inflammatory response (serpins, a 2-macroglobin and coagulation factors)
coagulation factors
negative acute phase protein
affect coagulation stimulating it
pro-coagulant effect may limit infection by trapping pathogens in local blood clots
also, some products of the coagulation system can contribute to the innate immune system by their abilibty to increase vascular permeability and act as chemotactic agents for phagocytic cells
Changes in C-reactive proteins
conditions that commoly lead to marked changes in CRP include infection, trauma, surgery, burns, inflammatory conditions, and advanced cancer.
moderate changes occur after strenuous exercise, heatstroke, and childbirth
small changes in CRP occur after psychological stress and in several psychiatric illnesses
CRP is a test of value. Marked rises in CRP reflect the presence and intensity of inflammation. An elevation in CRP, however, is not a tell tale sign pointing to just one disease
Pro-inflammatory cytokines
regulate inflammatory reactions either directly or by their ability to induce the synthesis of cellular adhesion moleucles or othe cytokines in certain cell types.
the major pro-inflammatory cytokines that are responsible for early responses are IL-1 a/b IL-6 and TNFa
activation of IL1-b by various caspases
proceeds in a large multiprotein complex that has been termed inflammasome
