Jim Hays final exam review Flashcards
What is type I hypersensitivity?
Allergic reaction
What is type II hypersensitivity?
Specific monoclonal antibodies produced against host tissue antigen. Examples of Type II: Good Pasture’s, Antibodies against platelets or RBCs
What is type III hypersensitivity?
An excess of antigen leads to immune complex accumulation that is not effectively cleared from the circulation leading to deposition. Examples of Type III: Lupus, Arthus reaction, serum sick syndrome
What is Type IV Hypersensitivity?
Delayed hypersensitivity, TMMI
Describe what is happening in an Arthus reaction
LOCAL reaction- Antibody accumulation due to previous infection/vaccination results in massive IC formation upon subsequent exposure to antigen, overwhelming RBC transport, causing massive neutrophil activation by IL-8 and complement components
IC recruits this leukocyte to site of infection
Neutrophil
What two inflammatory pathways does IC activate?
FcR-gamma crosslinking on macrophages and complement activation
Describe etiology of systemic immune complex disease, and what are its net effects on the body
IC binding to vascular C3b and Fc receptors, recruiting PMN via IL-8, activating inflammatory complement components
ITAM
Immunoreceptor tyrosine-based activation motif. FcgR present on phagocytes. very high affinity for IC. Induces phagoytosis
ITIM
FcgR on B cells. low affinity for IC. Inhibits B cells activation at high levels of Ag-Ab
Where are MCt mast cells predominantly found?
Mucosa
MCt = Mast cell tryptase
Where are MCtc mast cells predominantly found?
Epithelium (CT)
MCtc = tryptase and mast cell-specific
chymase
IgE class switching cytokines?
IL4 and IL13 Promotion of IgE class switching occurs by up regulation of CD-23 (FcεRII receptor) on mast cells and basophils that increase their production of IL-4 and IL-13. This is strongly influenced by gene influenced polymorphisms.
Name cytokine responsible for IgA class switching
TGF-beta, (IL5)
What is the cytokine profile in allergic reactions?
IL4, IL5, IL13
What is the onset of the early phase of Type I hypersensitivity after antigen exposure, and what is necessary for it to occur at all?
Occurs within 15 min antigen exposure. Dependent on previous exposure and sensitization. Inflammation due to complement activation and leukotriene/prostaglandin release
What is the onset of the late phase of Type I hypersensitivity after antigen exposure, and what does the reaction depend on?
Occurs within hours of antigen exposure. Dependent on Th2 activation and the presence of cytokines IL3, 4, 5, 13, TNF-_, GM-CSF and IL-10. Eosinophils present now.
List important eosinophil chemotactants
eotaxin, IL5 augments effect
Most important factor for allergy diagnosis
Careful history taking
What is the RAST assay?
Radioallergosorbent test- ELISA for serum IgE binding to solid allergen
List 3 ways superantigens differ from conventional antigens
- They can react with MHC class II in unprocessed form
- React with side of MHC class II and BCR/TCR
- Induce an immediate primary polyclonal response in T cells
What cells make up synapse I of the germinal center reaction, and where does it occur?
Naive CD4 T cell: Mature DC
Deep cortex of lymph node
What cells compose synapse II in the germinal center reaction, and where does the synapsing occur?
Antigen-primed B cell: Antigen-specific CD4 T cell
Near edge of follicle in lymph node
What cells will you find in synapse III of the germinal center reaction?
High affinity centrocyte: TFh (Follicular helper CD4 T cells)
List two CCR7 (commonly found on T cell) ligands
CCL19 and CCL21
What upregulates LFA-1 on lymphocytes in the HEPCV and what does LFA-1 bind to?
CCL21 upregulates LFA-1 on lymphocytes
Name a naive T cell receptor that binds endothelium and the naive T cell CD profile
L-selectin (binds CD34, promotes lymph node localization)
Name two effector T cell receptors that bind endothelium and the effector T cell CD profile
LFA-1 (binds ICAM-1) and VLA-4 (binds VCAM-1)
Why do DC’s migrate to lymph nodes after antigen TLR activation?
upregulation of CCR7, follow CCL19 and CCL21 gradient
Cytokine necessary for centrocyte differentiation, Class switching & Antibody secretion during the germinal center reaction
IL-21
IgG class switching cytokine?
IFN-gamma
List four IgA functions
- Barrier to pathogen invasion of mucosa
- Intracellular pathogen neutralization
- Excretion of invader from lamina propia into GI lumen
- Provides passive immunity to infant GI tract through breast milk
IgA deficiency: describe symptoms and associated diseases. Is IgA therapy a good idea in these patients?
Sx: often asymptomatic, but could present with FMH of IgA deficiency, high incidence of oral infection, frequent respiratory infection, chronic diarrhea
Assoc.: Lupus, rheumatoid arthritis, thyroiditis
Avoid IgA therapy! Host will produce anti-IgA antibodies
List two C3 convertases
C4b2a- Classical and Lectin pathway
C3bBb- Alternative pathway
Infection associated with MAC defect
Neisseria sp only
What history of illness may be seen in a patient with a defect in the Lectin complement activation pathway?
recurrent childhood bacterial infections
List two C5 convertases
C4b2a3b- Classical and Lectin pathways
C3bBbC3b- Alternative pathway
What does CD59 normally inhibit in the complement system, and what is the result of a CD59 defect?
Normal function is to prevent MAC formation
Defect results in RBC lysis- paroxysmal nocturnal hemologinurea
Describe the normal function of C1INH in the complement system, and the result of a C1INH defect.
Normal function is to inhibit C1 activity by decoupling C1q from C1r and s.
Deficit results in Hereditary Angioneurotic Edema- fluid accumulation, epiglottal swelling, abdominal attack
What is the consequence of a defect in the classical complement activation pathway?
IC disease
What is the consequence of a defect in the alternative complement activation pathway?
Infection with Neisseria spp and pyogenic bacteria
List one C3 convertase inhibitor (there are others, but he really only emphasized one)
DAF- delay accelerating factor
Name some C5 convertase inhibitors
Factor I, Factor H, CR1
What type of infections will you see in someone with a defect in C3b deposition?
Infection with pyogenic bacteria and Neisseria spp
Name 2 functions of C5a.
Leukocyte chemotaxis
Degranulation of Mast and Basophils along with C3a and C4a - anaphylatoxins, increases vascular permeability
Describe the mixed lymphocyte culture lab technique used in transplant immunology.
Mixing the serum of 2 patient’s together in a medium containing radioactive thymidine. One patient’s serum is inactivated so that their lymphocytes will not be able to proliferate. Any radioactive uptake by cells will be the result of responder lymphocytes from one host proliferating in response to the MHC of stimulator APC’s from the other host.
Why is the “direct” alloimmune response by the host to a transplanted organ a heresy?
Violates the dogma of MHC restriction. Donor APC’s migrate to secondary lymphoid tissue and activate naive CD4 T cells using their MHC II alone as the antigen- no antigen processing, and not recognized in the context of the HOST’S MHC
Hyperacute transplant rejection- time frame, why is the reaction so strong and fast?
Occurs within 48 hours of transplant.
Swift rejection due to presence of recipient alloantibody from previous exposure. Source of previous reaction against MHC could be multiple pregnancies, blood transfusions. Incorrect blood type matching can also precipitate rejection (type O getting a Type A or B organ- will have antibodies against A and B already)
Severe graft ischemia results from complement and coagulation mediated endothelial destruction, as well as leukocyte infiltration.
Acute onset transplant rejection- time frame and mechanism of rejection
Appearance of donor-specific immune effector cells within 3 weeks of transplant.
DTH- Type IV TMMI reaction. CD4 Th1 cells mediate the TMMI and activate CD8’s but TH17 and B cells are also involved.
Characteristic vascular changes seen in chronic rejection
Hallmark of chronic rejection is diffuse, widespread arteriolar narrowing caused by intimal thickening of the vessel- mechanism unknown
What epitope presents a barrier to xenotransplantation?
Alpha-GT. We lost this gene when we stopped being monkeys, have antibodies against it, all other animals have it
What HLA type does trophoblastic tissue display, and what does it do?
HLA-G, has an inhibitory motif for maternal NK’s
What’s different about maternal NK cells in the gravid uterus?
Stimulated by TGFb and progesterone to become inhibitory to other immune cells- produce anti-inflammatory cytokines, lack Fc receptor for ADCC (CD16)
Why is mom susceptible to viral infections during pregnancy?
High levels of circulating progesterone and IL-10 suppresses Th1 responses. Lack of TMMI, also Th17 and cytotoxic response
Name 3 proteins important in bone remodeling
RANK, RANKL, OPG
What immune responses are pro-clastogenic?
Th1 and Th17
Name the 4 adipocytokines
Leptin, adipoleptin, MIC-1, visfatin
List the anti-inflammatory adipocytokines
MIC-1 (macrophage inhibitory cytokine-1) and adiponectin
List the pro-inflammatory adipocytokines
Leptin and visfatin
Pro-inflammatory cytokine and strong m/m chemotactant
osteopontin
M2: pro or anti inflammatory?
Anti
M1: pro or anti inflammatory?
Pro
Net state of inflammation in non-obese WAT?
Slightly anti-inflammatory
What type of macrophages dominate WAT in obese people, and what is the net effect on health?
M1’s rule! Stuffing of adipocytes promotes pro-inflammatory signaling and recruitment of macrophages via osteopontin/CCL2, which recruit more.
Why is a fatty artery an example of local obesity?
Cholesterol in plaques recruit M1 macrophages, which recruit more M1’s via CCL2/osteopontin and prevent them from leaving
What type of cells mediate brain host defense, and why is inflammation bad in the brain?
Microglial cells- type M2, held in active suppression by TGF-B and IL10.
Activation by PAMPs (infection) or DAMPS (head injury) leads to M1 conversion, inflammatory response damages surrounding neurons.
What 3 highly polymorphic molecules determine the variations in the immune response between individuals?
MHC’s, TLR’s, cytokines (and their receptors)
What do you need to know about an infection before you make a vaccine for it?
What type of infection it is- do you need to promote a Th1, Th17, Th2?
Name 3 ways that tumor cells can “look different” immune effector cells
Mutation of self proteins displayed in their MHC
Over expression of self-protein in MHC
Modification of self-proteins in MHC
How do tumor cells evade destruction or detection?
Secrete CC21, recruit and convert to T cells to Tregs, which become trapped in the tumor tissue, setting up a immunosuppressive shield around it. LIKE A GIANT DEATH STAR OF IMPERIAL IMMUNOSUPPRESSION
Tumors upregulate PD-L1/2 on cell surface- induces death to all T cells with PD-1 receptor
Tumor cells have T regs protecting them. What is the only part of the immune system that is still capable of attacking the tumor?
“Save us NK Cell, you’re our only hope!”
Will only work if the tumor cell forgot to close its exhaust vent- the MHC-I displaying tumor specific antigen. Otherwise it should be just like shooting womp rats back home.
In response to stress, what neurotransmitters effect the release of CRH from the hypothalamus?
Epi, NE, GABA, Ach, SE
What lymphoid tissues are directly stimulated by the nervous system (as opposed to indirectly by the neuroendocrine system)?
Bone marrow- NE
Effect of cortisol on the immune system?
anti-inflammatory: reduced cytokine production, T and B cell reactivity, NK cell activity
Effect of epi and NE on the immune system?
Increase leukocyte mobilization to peripheral blood
Thymus- NE, Ach, peptidergic
Spleen- NE
Lymph- NE, peptidergic
Effect of beta endorphins and enkephalins on the immune system?
Increase T and NK cell reactivity
What triggers the acute mobilization/recruitment of lymphocytes to the blood in response to stress?
Epi, NE
What triggers the redistribution of lymphocytes to the lymph nodes 1-2 hours after exposure to stress?
Epi/NE in combination with cortisol
Effect of acute stress on DTH response?
Enhances it
Effect of chronic stress on DTH response?
Depresses it
Effect of low dose cortisol on DTH response?
Enhances it by increasing lymphocyte redistribution to the lymph nodes
Effect of high dose cortisol on DTH response?
Depresses it by suppressing immune function
In what direct and indirect ways (list 2) can the immune response affect the CNS?
Direct: IL-1, IL-6, TNF interaction with neurons after passing through the BBB
Indirect: stimulation of vagal afferents by IL-1
How does the nervous system attenuate the immune system to prevent excessive inflammation?
Splenic nerve: NE–> T lymphocyte in spleen: Ach–> macrophages inhibited from releasing inflammatory cytokines
What effector mechanisms of the immune system are involved in both bacterial and viral infections?
PMN, macrophages, Ab+complement opsonization, Ab+complement lysis, antibodies blocking absorption of pathogen into tissue
What effector mechanisms are specific to bacterial infection?
Neutralization of toxins by antibody
What effector mechanisms are specific to viral infection?
CTL and NK cytolysis of infected cells, IFN alpha and beta anti-viral protection
What 2 proteins do IFN alpha and beta upregulate?
Synthetase and protein kinase
A wild Candida albicans appeared! Name the type of pathogen and the immune response the body will choose.
Extracellular fungi. I choose you, cytokine activated phagocytes!
A wild Influenza virus appeared! Name the type of pathogen and the immune response the body will choose.
Obligate intracellular virus. I choose you, everything!
A wild Streptococcus pneumoniae appeared! Name the type of pathogen and the immune response the body will choose.
Extracellular bacteria. I choose you, antibodies, complement and phagocytes!
A wild Neisseria meningitidis appeared! Name the type of pathogen and the immune response the body will choose.
Extracellular bacteria. I choose you, antibodies, complement and phagocytes!
The toxin of a wild Clostridium tetani appeared! Name the type of pathogen and the immune response the body will choose.
Tetanus toxin. I choose you, antibody! Antibody used neutralization…. critical hit!
A wild Mycobacterium tuberculosis appeared! Name the type of pathogen and the immune response the body will choose.
Intracellular bacteria. I choose you, Th1 cells and activated macrophages!
A wild Schistosoma mansoni appeared! Name the type of pathogen and the immune response the body will choose.
Extracellular parasite. I choose you, antibody, complement and eosinophils! Eosinophil used ADCC…one hit KO!
