Immune diseases Flashcards
what cells produce mucus?
goblet cells
what cells secrete antimicrobial peptides?
Paneth cells
what are the components of MAC?
C5b, C6, C7, C8, C9
which complement component is recognized by phagocytes? (opsin)
C3b
which complement components act as chemotactic agents?
C3a, C4a, C5a
what is the link of complement with antibodies?
they can form functional complexes with antibodies to facilitate the clearance of antigens by phagocytes
name the types of innate immune cells
mast cells, neutrophils, macrophages, DCs
what do Fc receptors recognize?
antibodies
what is special about PAMPs?
they are essential for the viability of the microbes and cant be mutated
what other than PAMPs can PRRs recognize?
flagella on bacteria, nucleic acid on viruses, GPI anchor on parasites
where can PRRs be found?
innate immune cells and epithelial cells
what does activation of PRRs lead to?
production of cytokines and chemokines that help recruit other immune cells
what do mast cells recognize? with what receptor? leads to what?
IgE antibodies with Fc receptors; activation
2 ways how mast cells help immune response?
- degranulation -> release histamine, proteases, chemotactic factors
- metabolism of membrane phospholipids (arachidonic acids -> prostaglandins + leukotrienes) -> sm contraction and vasodilation
what are mast cells involved in?
type I hypersensitivity (allergic) reaction, neutrophils extravasation, vasodilation
what process do neutrophils go through to participate in the immune response?
extravasation
where can we find neutrophils?
in circulation
what type of agents do neutrophils produce?
antimicrobial agents: ROS, cathepsin G, defensins
what happens if NETs are not cleared up rapidly?
they persist and result in cell damage through enhanced inflammatory processes
where are innate cell macrophages found?
in tissue
where are tissue-resident vs monocyte-derived macrophages from?
tissue-resident macrophages are derived from yold sac or fetal liver.
monocyte-derived macrophages are derived from bone marrow.
what 6 different tasks can macrophages perform?
antimicrobial actions through ROS.
antigen presentation.
antigen/antibody uptake.
wound healing through GF production.
phagocytosis.
bone resorption through osteoclasts.
what are DCs cell called in the skin?
Langerhans cells
what cells do DCs arise from?
monocytes
what is the most efficient APC?
dendritic cell
what are the structure of MHC class 1 and II molecules?
MHc class I = alpha chain + variant beta macroglobulin chain
MHC class II = alpha + beta chain
what are MHC called in humans? where is the gene located?
HLA;
chromosome 6
everyone has different HLA genes except?
except identical twins
what is the only cell that can activate naive T cells?
dendritic cell
where do innate lymphoid cells originate from?
hematopoietic stem cells in bone marrow
name the innate and adaptive immune cells from each lineage
innate myeloid lineage: neutrophil, eosinophil, basophil, monocyte, macrophage, dendritic cells, mast cells, platelets
adaptive lymphoid lineage: t cells and b cells
what is special about NK cells origin
derived from lymphoid progenitor but are innate immune cells
what are the 2 ways how NK cells kill?
- induce apoptosis by producing perforins and granzyme proteins.
- Fas ligand triggers cell death
what can tumor cells downregulate to evade immune regulation? what does this downregulation trigger regarding NK cells?
downregulate MHC class I. decreases the inhibitory signal that the NK cells recives -> activates NK cell -> kill
what does each of the 3 classes of innate lymphoid cells respond to?
ILC1: intracellular pathogens
ILC2: parasites
ILC3: extracellular bacteria and fungi
how is the variable regions of TCR generated? what does this allow for?
from VDJ recombination.
allows for specificity
where do t and b cells differentiate and mature?
both differentiate in bone marrow.
T cells mature in the thymus (become CD4/8 +)
B cells finishes maturation in lymph nodes
name the different subtypes into which CD4+ t cells can further differentiate in peripheral tissue, and their associated cytokine
TH2 cells: produce IL-4. involved in allergies
TH1 cells: produce IFNy
TH17 cells: produce IL-17 (TH1 and TH17 are involved in type IV hypersensitivity and autoimmune diseases)
Treg: TGFB
what happens in the lymph node to complete the maturation of B cells?
b cells enter through afferent lymphatic vessels, proliferate in primary follicles, become germinal centers when in contact with antigen. they fully mature and become plasma cells and exit through efferent lymphatic vessels
2 ways how B cell can activate
- T cell-independent: recognize antigen and BCRs aggregate
- T cell-dependent: through cytokines
antibody receptor produced by naive B cells
IgM receptors
what enzyme helps with variable region hypermutation of IgM receptors?
AID enzyme (activation-induced cytidine deaminase)
what antibodies do plasma cells secrete at a distance?
IgM or IgG
what are antibodies effector functions?
Neutralization of microbes and toxins.
Opsonization and phagocytosis of microbes recognized through Fc or C3b receptors.
Antibody-dependent cellular toxicity: activation of NK cells.
Complement activation to facilitate inflammation and lysis of microbes.
3 types of immune system failures
hypersensitivity, autoimmunity, immunodeficiency
what are the 4 types of hypersensitivity reactions? describe
type I: immediate T cell dependent allergic reaction
type II: antibody specifically recognizes a receptor on cell surface
type III: antibody driven: immune complexes trigger neutrophils activation and inflammation
type IV: delayed t cell dependent reaction involving TH1 and TH17
which cells and cytokines are involved in type I hypersensitivity?
Th2 cells and IL4, IL5, IL13, IGe production
what are the 2 steps of type I hypersensitivity reaction (during secondary exposure)?
- initial response within minutes & mast cells activation
- late phase reaction: cytokines infiltration other cell types
what do mast cells do after the second exposure to allergen (Type I hypersensitivity)
degranulate and release histamine
features of the secondary exposure of type I hypersensitivity?
mast cells, vasodilation, pain, eosinophils recruitment, hyperactive mucous production, platelets activation
what are the clinical manifestations of Type I reaction?
hay fever, food allergies
bronchial asthma
describe bronchial asthma
repeated exposure to antigen causing massive tissue remodeling. treated by bronchodilators
what can cause a systemic type I hypersensitivity reaction?
snake venom, food allergies
what do chemical mediators released during type I hypersensitivity reaction cause?
constriction of airways, GI tract dysfunction, diarrhea, massive drop in BP
what parasite did Th2 response evolve to deal with?
helminth
different mechanisms of type II hypersensitivity
phagocytosis, inflammation (complement system), blocking receptor function
what disease is associated with type II hypersensitivity blockage of receptor function?
Grave’s disease due to overproduction of hormones by thyroid epithelial cells
explain newborn hemolytic anemia
1st child has a different blood type than mother -> mother produces antibodies at birth -> second child also has different blood type -> attack the baby’s RBCs
what is the main feature of type III hypersensitivity reaction?
immune complex deposition made of antigens and antibodies aggregation
what do immune complexes cause in type III hypersensitivity?
complement activation, recruitment of granulocytes that cause release of proteases and oxygen free radicals = tissue damage
what is diphteria? what animal is naturally immune and can raise antibodies?
serum sickness; upper respiratory tract bacterial infection.
example of type III hypersensitivity.
Horse
what is glomerulonephritis?
immune complexes accumulate in glomerulus in kidneys + immune cell proliferation.
can cause renal failure.
type III hypersensitivity reaction.
differences between type II and II hypersensitivity?
type II: Antibody-Antigen interaction takes place on the cell surface of the target cell (bumpy immunofluorescence)
type III: Antibody-Antigen interaction forms free-floating complexes that can precipitate on tissues (linear immunofluorescence)
what 2 types of reactions are included in type IV hypersensitivity?
- delayed-type hypersensitivity: CD4+ T cells release cytokines
- CD8+ T cell-mediated cytotoxicity: CD8+ T cells directly kill their target cell
what cell type will naive CD4+ t cells differentiate into with type IV hypersensitivity? what do they release
Th1: releases IFN-y for macrophages differentiation
and Th17: recruit neutrophils via IL-6
what is a delayed-type hypersensitivity reactions? name an example and describe both phases
poison ivy.
Sensitization phase: hapten (in this case urushiol) gets absorbed by the dermis, picked up by langerhans cells, activation of CD4+ T cells -> IL-12 -> Th17 and Th1 differentiation
Effector phase: granulocytes secrete granules, causing tissue damage. Th1 releases INF-y and activates macrophages -> pro-inflammatory cytokines -> tissue damage
why is the tuberculin test necessary?
Tuberculosis is often present in the latent form, so need to test for past exposure
what can delayed type IV hypersensitivity create? why
granulomas; continual activation of macrophages
how do CD8+ t cells kill target cells?
release granzymes and perforin -> apoptosis of target cell
give 2 examples of CD8+ t cell-mediated toxicity type IV hypersensitivity
graft rejection and type I diabetes
what happens in type I diabetes?
autoimmune reaction against beta cells mediated by CD8+ T cellls
which cells delete the self-reactive t cells? where?
T reg in the thymus
what is anergy (related to lymphoid cells)
B and T cells failing to respond
name 4 autoimmune diseases
lupus, multiple sclerosis, Crohn’s disease, rheumatoid arthritis
genes encoding for what could be involved in autoimmune diseases
HLA, PTPN22 (immune cell activation), cytokine signaling, autophagy
what can microbe infection do to co-stimulation, causing autoimmune disease?
upregulation of co-stimulatory molecules on APCs, increasing self-reactive T cells
what is molecular mimicry?
APCs present microbial peptides that resemble self-antigen to T cells, which activates T cells against self-tissue
who is more affected by autoimmune diseases?
women because we have enhanced immunity & estrogen may be pro-inflammatory & X-linked genes encode immmunity
what is RA?
Rheumatoid Arthitis: chronic inflammation in the joints; symmetrical;
leads to joint deformity and disability
where other than joints can RA have effects?
nodules, lung, eyes, vasculitis
what are rheumatoid factors?
anti-IgG auto-antibodies (anti-citrullinated protein antibodies ACPC) & IgM antibodies that bind to self-IgG
what are the hypothesized causes of RA?
genetics (HLA subtype genes)
predisposing environmental triggers (smoking, infection) causing post translational modifications
what type of hypersensitivity is autoimmune disease?
type III
what are PAD and what do they do?
peptidylarginine deiminase: converts arginine to citrulline -> immune system now responds to protein
what other modifications can cause self-reaction?
carbamylation (irreversible), IgG antibody glycation
how can RA be detected?
presence of anti-citrullinated proteins aantibodies in blood.
X ray for erosion.
Rheumatoid factors.
what are characteristics of osteoarthritis joints?
vs of Rheumatoid joints?
osteoarthritis: bone erosion from rubbing leading to inflammation.
Rheumatoid: inflammation in synovial space
what causes synovial inflammation in RA?
macrophages, DCs, lymphocytes, plasma cells infiltrate synovial space and attack the cells causing hyperplastic synovium (pannus); fibroblast and myoblasts within the membrane because highly proliferative
name inflammatory mediators in RA
INF-y, IL-17, TNF, IL-1, RANKL (promotes osteoclasts)
what are symptoms of systemic lupus erythematosus?
butterfly rash, hair loss, swollen joints, light sensitivity
what causes SLE (systemic lupus erythematosus)
clearance failure of debris (ex NETs) by immune system -> autoimmunity
what is the main characteristic of SLE systemic lupus erythematosus
production of autoantibodies, triggering a type III OR type II hypersensitivity reaction
how does glomerulonephritis occur in SLE?
due to deposition of autoantibodies in the vasculature of the glomerulus
what cell types are affected by MS?
CNS: oligodendrocytes (attacks myelin sheaths)
what are characteristic of MS?
plaque formation & fibrosis, defects in conductivity
how does MS happen?
leaky blood-brain barrier & integrin expression -> T cells enter brain and interact with microglia -> cytokine release, macrophages activation -> myelin is attacked
what are the root causes of MS?
- genetics: class I and class II MHC genes (ex HLA-DR2)
- vitamin D deficiency
- viral infections: EBV latency antigen
describe the 4 types of MS (course of the disease)
relapsing-remitting: unpredictable attacks
primary progressive: steady increase
secondary progressive: attacks followed by steady increase
progressive-relapsing: steady increase with attacks
broadly describe the 2 types of IBD
Crohn’s disease: lesions (transmural inflammation, ulceration, fissures) in GI tract and granulomas formation
Ulcerative colitis: ulcers in distal colon causing pseudo-polyps
is Crohn’s disease an autoimmune disease?
no! immune-related process
what mutations and environmental factors can cause Crohn’s disease?
mutations = NOD2: innate immune receptor that senses GI tract microbiome
env = reduced microbial diversity
what can cause ulcerative colitis?
molecular mimicry/cross reactivity of perinuclear anti-neutrophil cytoplasmic antibodies pANCA
what can cause ulcerative colitis?
molecular mimicry/cross reactivity of perinuclear anti-neutrophil cytoplasmic antibodies pANCA
describe the 2 causes of graft rejection?
- mismatch MHC molecules: direct or indirect (involves MHC uptake by APC)
- mismatch MiHA genes: short segments that are very variable between people
describe the 3 types of host vs graft rejection
- hyperacute: immediate onset; caused by blood type incompatibility, preformed antibodies react to donor tissue and cause thrombosis and occlusion
- acute: weeks to months; T-cell mediated; leukocyte infiltration of graft vessels
- chronic: months to years; causes thickening and fibrosis of graft vessels
describe the 3 types of host vs graft rejection
- hyperacute: immediate onset; caused by blood type incompatibility, preformed antibodies react to donor tissue and cause thrombosis and occlusion
- acute: weeks to months; T-cell mediated; leukocyte infiltration of graft vessels
- chronic: months to years; causes thickening and fibrosis of graft vessels
where does graft vs host disease happen?
skin, liver, intestine
why does graft vs host disease happen?
immunocompetent tissue is transplanted into an immunocompromised host -> graft T cells recognize the host MHC molecules as non-self
what is upregulated in immunocompromised hosts?
costimulatory molecules because they are susceptible to infections
what is specific/adaptive immunodeficiency vs non-specific/innate?
specific/adaptive = B and/or T cells are affected
non-specific/innate = innate immunity is affected (Complement, neutrophil defect)
what is the origin of primary/congenital immunodeficiency? give an example
mutation in genes that allow differentiation of hematopoietic stem cells.
ex: ADA deficiency impairs b and t cell development
what is SCID?
X-linked Severe combined immunodeficiency: due to mutations in gamma chain of the IL-2 receptor (no T cells, B cells also affected) - thymus problem (primary immunodeficiency)
what is X-linked BTK?
immunodeficiency disease involved in transducing signals from BCR - bone marrow problem (can’t produce antibodies) (primary immunodeficiency)
what is DiGeorge syndrome?
thymus does not form, defect in T cell differentiation (primary immunodeficiency)
what is hyper-IgM
defect in CD40 ligand -> decreases expression of various Igs (primary immunodeficiency)
B vs T cell deficiency lead to susceptibility to what respectively?
B cells = bacteria
T cells = virus
what causes secondary immunodeficiency?
- infectious agents
- aging and malnutrition
- malignancy/other diseases/immunosuppressive drugs
what are HIV properties? what is the treatment for it?
retrovirus transmission through bodily fluids and blood.
anti-retroviral therapy
what cells do HIV infect? why?
cells with CD4 cell receptors: macrophages, DCs, T cells (main target).
because gp120 on virus recognizes CD4 receptor
what co-receptors are needed for HIV to enter cell?
CCR5 and CXCR4
what does HIV do once it enters the cell?
inject RNA genome & reverse transcriptase converts viral RNA genome into pro-viral DNA
what makes HIV hard to catch by the immune system?
it is highly mutagenic and very error-prone
in what cases can HIV stay dormant?
if the pro-viral DNA integrates the host genome of an unactivated T cell
how does HVC directly kills CD4+ T cells?
- creates membrane permeability & protein synthesis problems
- induces apoptosis
- expresses HIV peptides & gets killed by CTLs (cytotoxic T cells)
who are naturally immune to HIV infections?
people with the rare polymorphism of CCR5 co-receptor which prevents viral infection
what are the phases of HIV infection?
acute phase = immune system destroys most of the virus
chronic phase = immune response can’t get rid of the infection completely
