The Immune Response Flashcards
first line of defence?
intrinsic barriers
second line of defence?
innate immunity
third line of defence?
adaptive immunity
confers protection against a broad spectrum of pathogens through use of surface receptors on phagocytic cells that recognize evolutionary conversed patterns unique to pathogens
the innate immune system (2nd line of defence)
do not phagocytose pathogens, rather they secrete toxic chemicals or induce apoptosis in target cells
natural killer cells
a localized response to infection involving vasodilation, increased vascular permeability and mobilization of phagocytes involving: leukocytosis, margination, diapedesis and chemotaxis
inflammation
It is initiated by release of pyrogens (pyro= fire) which include bacterial toxins and/or components, antigen-antibody complexes or substances released by phagocyte
a fever
The goal is to eliminate pathogens that may have circumvented or overwhelmed the first 2 lines of defence and to confer protection from new and emergent strains of pathogens
the adaptive immune response (3rd line of defence)
what are the hallmarks of the adaptive immune response?
- specificity (self vs non-self)
- memory
is the ability to mount a response to a particular pathogen or foreign substance while being able to discriminate between self vs non-self antigens
Specificity
represents the ability to recall past exposures to specific pathogens and provides the adaptive immune system with the ability to mount an even stronger response to a pathogen upon repeat exposure
Memory
- broad specificity
- limited repertoire
- lacks memory
innate immune system
- narrow specificity
- slow response
- memory
adaptive immune system
represents a loose aggregation of lymphoid tissue that is in a unique position to eliminate pathogens at mucosal surfaces before they spread to the underlying tissues
MALT (mucosal associated lymphoid tissue)
____ can only recognize antigens that have first been processed by specialized immune cells known as antigen presenting cells or APCs
T-cells
___ are capable of recognizing unprocessed (or native) antigens
B-cell receptors
DNA segments in T-cell and B-cell receptor genes are randomly combined to create a vast array of permutations
Somatic recombination
progressive neurodegenerative disorder involving demyelination of CNS axons
MS
an endocrine disorder resulting in hyperglycemia due to insulin insufficiency
T1DM
a neuromuscular disease resulting in progressive weakening or paralysis of skeletal muscle
Myasthenia Gravis (MG)
a thyroid disorder resulting in overproduction of thyroid hormone (thyroxine) leading to diffuse goitre and exophthalmos
Grave’s Disease
Auto-antibodies bind IgG, forming immune complexes in synovial joints resulting in synovitis with destruction of articular cartilage and bone
Rheumatoid Arthritis (RA)
impairment of renal function due to inflammation of glomerular basement membrane
Glomerulonephritis
Characterized by inflammation involving multiple body systems
Systemic Lupus Erythematosus (SLE)
___ are more prone to developing SLE
females
Inhibit the early events of antigen processing and cytokine production by macrophages, thereby reducing lymphocyte activation and subsequent autoantibody production
Anti-malarials
are a broad class of therapies that employ a wide variety of products from humans, animals, and microorganisms
Biologics
inhibits a cell survival factor called BLyS (or B-lymphocyte stimulator), which is necessary for B-cell survival.
One specific biologic (a monoclonal antibody preparation called belimumab)
is a cytokine that promotes the survival of regulatory T-helper cells
IL-2
T-cell development begins with a process known as ____
positive selection or MHC restriction
specialized thymic epithelial cells present self-antigens to developing T-cells in the context of MHC.
negative selection or clonal detection
both positive and negative selection occur within the ____
thymus
___ appears to be the main mechanism responsible for preventing B-cell mediated autoimmune responses should autoreactive B-cells make their way out of the bone marrow.
angery
For T-cells and B-cells to become fully activated antigen presenting cells must supply them with ___
additional co-stimulatory molecules
function to inhibit or suppress the activities of autoreactive lymphocytes, thereby contributing to peripheral tolerance and ensuring that autoimmune diseases do not arise.
Regulatory T-cells produced during thymic education
may result if self-antigens that were not present during T-cell and B-cell development suddenly become accessible
autoimmunity
Cytotoxic T-cells are responsible for mediating cellular immunity
CD8+
Helper T-cells aid in the induction of cellular and humoral responses by providing essential signals that drive T-cell and B-cell differentiation and clonal expansion
CD4+
largely secrete a chemical signal called interleukin-2 (IL-2) which helps to fully activate cytotoxic T-cells.
Th1 cells
largely secrete IL-4 which provides the co-stimulatory signal necessary to fully activate B-cells that have come into contact with foreign antigens
Th2 cells
cells secrete IL-17 which activates neutrophils and plays a major role in fighting fungal infections
Th17 cells
Their main function is to suppress adaptive immune responses
Regulatory T-cells
are largely found in the secondary lymphoid tissues
B-cells
when antibodies bind toxins, they often inactivate it through direct or allosteric inhibition of the toxin’s active site
Neutralization
each antibody possesses at least two antigen binding sites, hence they are capable of binding more than one antigen, resulting in clumping
agglutination
process of tagging antigens with antibodies to help improve phagocytosis
opsonization
__ on the surface of mast cells, basophils, and eosinophils are capable of binding the stem region of antibodies, which then act as a surface receptor
Fc-receptors
1st antibody produced during an adaptive response
IgM
- Activate compliment
- Enhance agglutination
- Neutralize toxins, bacteria and viruses
IgM Functions
- most abundant serum antibody (80-85%)
- Longest lasting antibody
IgG
- complement activation
- opsonization of pathogens
- neutralization of toxin, bacteria and viruses
IgG functions
found in mucosal secretions (milk, tears)
IgA
- confers protection to GI, resp, urinary, and reproductive tracts
- agglutination
- neutralization of pathogens
IgA functions
implicated in host response to parasites and involved in allergic reactions
IgE
- expressed on surface of B-cells (B-cell receptor)
- thought to participate in B-cell differentiation
IgD
largely reside in the skin and mucus membranes where they are most likely to encounter pathogens
dendritic cells
are considered professional since they are capable of processing extracellular antigens
antigen-presenting cells
are found on virtually all nucleated cells of the body
class I MHC molecules
only found on professional APCs
class II MHC molecules
involves processing of endogenous, cytoplasmic proteins which are then loaded onto MHC I within the endoplasmic reticulum
the MHC I pathway
Essentially, exogenous antigens are taken up by the cell through phagocytosis and processed by combining the resultant phagosome with a lysosome to create phagolysosome
MHC II pathway
Infected- and this is the key here - infected dendritic cells will present antigen via MHC I to cytotoxic T-cells
Step 1- antigen presentation
Cellular immunity
- involves helper T-cell differentiation
- For a helper T-cell to become activated, the dendritic cell must present antigen in the context of MHC II.
Step 2- involves helper T-cell differentiation
Cellular immunity
- requires both the coupling of MHC I with the T-cell receptor and IL-2 from activated helper T-cells
- Once activated, cytotoxic T-cells will proliferate to form identical clones that will either become memory T-cells or more cytotoxic T-cells
Step 3- involves clonal expansion of cytotoxic T-cells
Cellular immunity
As clonal expansion proceeds, many of the replicating cytotoxic T-cells will begin to secrete their own IL-2, thereby obviating any need for further dendritic or helper T-cell support
Step 4- involves self-stimulation
Cellular immunity
This response is initiated by cross-linking of more than one B-cell receptor by repeating epitopes contained on evolutionarily-conserved structures such as the capsule of the influenza virus, lipopolysaccharide expressed in the outer cell wall of gram-negative bacteria (as shown here), bacterial flagella, and other viral capsids
T-cell independent humoral activation
- the type of antibody produced will change
- involves an alteration in the stem or Fc region of an antibody
class switching
The hallmark of adaptive immunity is ___
immunologic memory
○ Sensitization to antigen (allergen) resulting in production of IgE which primes mast cells, basophils, and eosinophils
○ Subsequent binding of allergen to IgE-receptors of mast cells, basophils and eosinophils induces degranulation with release of histamine
○ Disorders- seasonal allergic rhinitis, conjunctivitis, asthma, acute anaphylaxis (shock)
Type I hypersensitivity reaction
○ Antibodies bind cells and fix complement resulting in cell lysis
○ Disorders- transfusion reaction, hemolytic disease of newborn, drug-induced cytotoxicity
Type II hypersensitivity reaction
○ Deposition of antigen-antibody complexes in joints, tissues, and vessel walls
○ Complement activation and inflammation damage tissues
○ Disorders- systemic lupus erythematosus, serum sickness, rheumatoid arthritis, glomerulonephritis, hypersensitivity pneumonitis
Type III hypersensitivity reaction
○ Host cells destroyed by cytotoxic T-cells
○ Delay reflects time required to initiate cellular response
○ Disorders- contact dermatitis, tuberculin response, graft rejection
Type IV hypersensitivity reaction
is largely due to increased vascular permeability in the mucus membranes of the lower airways
airway swelling
is a direct result of histamine-evoked airway smooth muscle contraction
bronchospasm
is characterized by system wide vasodilation and increased vascular permeability owing to massive combined release of histamine from tissue resident mast cells and basophils present in circulation
Anaphylactic shock
is a blood-borne pathogen that is also present in other bodily fluids including vaginal secretions, semen, and breast milk
HIV
HIV occurs in __ phases
3
usually occurs 1-3 months following infection and is characterized by detectable levels of anti-HIV antibodies
seroconversion
CD4+ T-cell counts gradually decline as the rate of T-cell death overcomes production
latency period
inhibit elongation of viral DNA by preventing addition of nucleosides
Nucleoside/nucleotide analogs (NRTI/NtRTI)
Bind RT active site to prevent transcription of viral RNA into DNA
Reverse Transcriptase inhibitors (NNRTIs)
Prevent cleavage of viral polypeptides necessary for viral assembly (virus rendered non-infectious)
Protease inhibitors
Block HIV fusion with CD4
Block CCR5 receptors
Entry inhibitors
Prevent viral DNA integration into host genome
Integrase inhibitors
