Chapter 5, Diseases of the immune system Flashcards
innate immunity definiton
(natural, or native immunity) mediated by cells and proteins that are always present, poised to react against infectious pathogens.
these cells are the 1st line of defense and the 1st to react.
they also have mechanisms to clear dead cell debris.
define hypersensitivity disorders?
the immune system causing tissue injury and disease
define adaptive, specific, acquired immunity
an immunity that is normally silent but responds to infectious agents. Since many pathogens have evolved to resist innate immunity and thus protection from the requires the specialized and powerful adaptive immunity/acquired or specific immunity.
what are recognized by the innate immunity?
phagocytes, dendritic cells and many other cells, such as epithelial cells, express receptors that sense the presence of infectious agents and substances released from dead cells.
these are called PAMP (pathogen-associataed molecular patterns)
what are the components of the innate immunity called that are responsible for pathogen recognition?
- pathogen-associated molecular patterns (shared among microbes of the same type)
- damage-associated molecular patterns (released from injured and necrotic cells.
- pattern recognition receptors (cellular receptors that recognize these molecules) 100 different receptors are used to recognize 1000 molecular patterns.
where are receptors of the innate immunity located?
everywhere; in the cell membrane for extracellular recognition, in endosoms for ingested substance detection and cytoplasm.
types of innate immunity receptors? best known receptors?
-toll-like receptors (these activate transcripton factors that stimulate the production of several membrane proteins to mediate inflammation, anti-viral cytokines (interferons). proteins promote lymphocyte activation, even more potent adaptive immune response.) TLR recognize, LPS (lipopolysaccharide) endosomal TLRs recognize viral and bacterial RNA and DNA
NOD-like receptors and inflammasome. activation of which form the cytokine interleukin-1 (IL-1) which recruits leukocytes and induces fever.
NODS recognize: uric acid and ATP and ion distrubances (K concentration)
-C-type lectin receptors (CLRs) in macrophages membrane
-RIG-I recognize RNA
-DNA sensors recognizes DNA
They (NOD) signal via a protein complex called the “inflammasome” which activates Caspase-1 which cleaves interleukine-1 to generate IL-1 which causes acute inflammation when secreted.
what are the 2 mechanisms by which the innate immunity provides defense.
- inflammation: complement activation trigger components of inflammation.
- anti-viral defense: type I interferons produced in response to viruses act on infected and infected cells and act to prevent replication and digest viral nucleis acids. They also serve to activate he more powerful adaptive immune response.
name the 2 type of adaptive immunity?
-humoral immunity: antibodies made by B-lymphocytes
-cell-mediated (cellular) immunity mediated by T-lymphoctes.
Antibodies protect from extracellular pathogens in blood and mucosal surfaces.
T-cells directly kill via cytotoxic T-cells or activate phagocytes.
where do T and B lymphocytes mature from?
-T lymphocytes mature in thymus
-B lymphocytes mature in bone marrow
each T or B cell expresses only one type of receptor
what are the receptors on B and T cells called?
B-cell (antibody)
T-cell (T-cell receptors)
there is massive diversity in the structure of these receptors.
define Clonal selection?
a process proposed to explain how a single B or T cell that recognizes an antigen that enters the body. The antigen is selected from the pre-existing cell pool of differing antigen specificities and then reproduced to generate a clonal cell population that eliminates the antigen. (the cell that recognizes it is replicated)
phases of lymphocytes?
- naive lymphocytes (antigen receptors expression but no function)
- effector lymphocytes (eliminate microbes)
- memory lymphocytes (rapid response upon subsequent encounter with antigen)
function of T lymphocytes.
they help B-cells make anibodies for foreign antigens.
they recognize protein fragments on MHC displayed by cells via the TCR (T-cell receptor)
what is the TCR (T cell receptor) made of?
heterodimer of disulfide linked a- and b- chains that have a variable and constant region.
CD3 and ζ-chain do not bind antigen but initiate intracellular mechanisms upon antigen recognition.
what does CD4 and CD8 on T-cells bind to?
class II MHC = CH4 CD4+ cells help B cells produce antibodies by secrete soluble cytokines. help macrophages destroy what they ingested. class I MHC = CH8 (called cytotoxic T lymphocytes (CTLs) because they kill infected cells, and tumor cells.)
function of T-cells with CD28?
function as receptors for molecules called costimulators. control the migration of the T cells to different tissues.
what suppresses immune response.
regulatory T lymphocytes
what is MHC restriction?
T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.
Class I MHC
expressed on all cells surfaces that are nucleated expressed in 3 closely linked loci; HLA-A, HLA-B, HLA-C
has a conserved region for CD8+ binding.
has polymorphic a-chain noncovalently associated with invariable B2- microglobulin polypeptide.
binds moslty intracellular elements.
Class II MHC
encoded by HLA-D. class 2 are heterodimers with a- and b-chains. expression restricted to APC's (antigen presenting cells) dendritic cells, macrophages and B-cells binds extracellular elements. (has domain for CD4+)
How to B-lymphocytes recognize antigens?
via membrane bound antibody of the immunoglobulin M (IgM) class, expressed on the surface together with signaling molecules to form the B-cell receptor (BCR) complex.
IgM has large diversity due to rearrangement and assembly of a multitude of immunoglobulin gene segments.
what can B-cells respond to?
unlike T-cells that respond to MHC only, B-cells can respond to more chemical structure; soluble or cell-associated proteins, lipids, polysaccharides, nucleic acids, without the requirement of MHC.
when B cells are activated they secrete what?
they turn into plasma cells to secrete immunoglobulins: (5 classes)
IgG, IgM, IgA, which make up 95% of circulating antibodies
IgA: (mucosal secretions)
IgE, IgD.
what receptors do natural killer cells express?
2 types of receptors:
Inhibitory, which recognize self/MHC 1 which is on all cells
Activating receptors which are on infected and stressed cells (stressed cells have fewer MHC I, thus NK cells are activated via their activating receptors and kill the stressed cells.
what do natural killer cells secrete upon activation?
cytokines: interferon-y (gamma) which activates macrophages.
Function of ILC’s (innate lymphoid cells)
these cells lack TCR (T-cell receptors), but produce cytokines similar to those made by T-cells.
these cells mostly reside withing tissues, so they provide early defense before T-cell activation.
which cells function as antigen presenting cells?
macrophages also engulf and present proteins
dendritic cells that display protein antigens to naive T-cells. (they have spines branching off of them, hence the name)
Dendritic cells properties?
1: they are located right under the skin (called langerhans cells)
2: they display many receptors for capturing microbes (TCR’s and C-type).
3: they go to T-cells zones upon activation to present antigen
4: express high levels of MHC.
name the lymphoid tissues?
generative/primary/central lymphoid organs: T and B-cells mature here to become competent to respond to antigens (thymus, bone marrow)
Peripheral/secondary lymphoid organs: in which adaptive immune responses to microbes are initiated.
where are the peripheral lymphoid organs located?
- lymph nodes:
- spleen
- cutaneous and mucosal lymph systems: under epithelia and GI tract. (peyers patches, tonsils)
location of B and T cells in lymphoid organs (lymph)?
B-cell = follicle
T-cell = parafollicle cortex
activated B cells from germinal center. FDC (follicle dendritic cells) which present antigens
location of B and T cells in the spleen?
T = around periarteriolar lymphoid, and B cells inside follicles.
cytokines of the innate immune system function?
induce inflammation and inhibit virus replication; TNF, IL-1, IL-12, type I IFNs, IFN-y
made by macrophages, DC, ILC, and NK cells
cytokines of the adaptive immune system function?
made by CD4+ T-cells activated by antigen and other signals to promote lymphocyte proliferation and differentiation, and activate effector cells.
TGF-b and IL-10 limit immune response to prevent damage.
function of colony stimulating factors?
they function to produce more WBC from bone marrow in response to infection. Examples: GM-CSF and IL-7.
Adapative immune system steps?
- antigen recognition
- activation
- proliferation
- differentiation (into effector and memory cells)
- elimination of antigen and decline of response
what do APCs secrete during innate immune responses to antigens?
APCs express molecules called costimulators and secrete cytokines that stimulate the proliferation and differentiation of T lymphocytes. principle costimulators of T-cells are CD80 and CD86 (b7 proteins) expressed on APC’s and recognized by CD28 on T-cells.
what happens to T-cells activated by antigen and costimulators?
CD4+ helper T-cells is secretion of the cytokine IL-2 and expression of IL-2 receptors. This stimulates the growth of T-cells with a specific antigen.
their actions is mediated by CD40 (activate macrophages).
what do CD4+ T-cells of the TH1 subset secrete?
IFN-y (gamma) along with CD40 they activate macrophages
what do CD4+ T-cells of the TH2 subset secrete?
IL-4 sitmulates B cels differentiation into IgE-secreting plasma cells
IL-5 = activates eosinophils
IL-13 activates mucosal epithelial cells to secrete mucus + “alternative pathway” macrophage activation for tissue repair.
what do CD4+ T-cells of the TH17 cells do?
IL-17 is the signature cytokine to recruit neurophils and monocytes to destroy some extracellular bacteria and fungi.
what happens of activated B-cells?
CD8+ T-lymphocytes differentiate into CTL’s (cytotoxic T-lymphocytes) which kill infected cells via the perforin and granzymes (perforin makes a hole in membrane, granzymes activate cellular caspases to induce apoptosis.
how are T-cells regulated?
by a balance of costimulatory (CH28 recognizing B7 ligands on APCs)
and inhibitory receptors (CTLA-4 and PD-1, which block signals from the TCR and from CD28).
2 pathways of B-cell activation?
- T-cell independent: long polysaccarides have long sequences that may bind to IGD and IGM receptors, the clustering of the receptors creates a strong signal.
- T-cell dependent: B-cell cleaves up protein and presents them on MHC II which if T cells recognize will activate B-cells via CD40 secretion.
what do B-cells do upon activation?
expanded B-cell clones differentiate into antibody-secreting plasma cells which secrete antibodies with the same specificity as the cell surface antibodies that recognized the antigen. polysaccarides = IgM.
define affinity maturation?
Helper T cells stimulate the production of antibodies with higher affinity for the antigen.
define follicular helper T cells (Tfh)?
helper T cells that stimulate these processes in B lymphocytes also migrate to and reside in the germinal centers along with B-cells.
the follicles are a major sites of isotype switching and affinity maturation.
humoral immune response function?
- antibodies bind to microbes to prevent them infecting cells
- IgG antibodies (opsonize) microbes for neutrophils and macrophages
- IgG and IgM activate the complement system via classic path
- IgA secreted in mucosal tissues and neutralizes microbes in respiratory and GI tract.
- passive immunity for newborn as IgG goes across placenta
- IgE coats helminthic parasites (eosinophils kill them)
