Week 5: Immunology Flashcards
What cells make up the lymphocytes?
B Cells
T Cells
Natural Killer Cells
+ve selection of T cells occurs in ______
cortex of thymus
-ve selection of T cells occurs in _______
medulla of thymus
after -ve and +ve selection of T cells, approximately what percent are still remaining?
5%
3 ‘classical’ APCs
B Cells
Macrophages
DCs
What is different about how B cells and T cells recognize antigen
B cells recognize the 3D shape of peptide, whereas T cells recognize the sequence
Define hypersensitivity
immune responses that are capable of causing tissue injury
Type I Hypersensitivity
- Immediate
- IgE and Th2 cells
- Injury caused by mast cells, eosinophils, and their mediators
Type II hypersensitivity
- Ig mediated
- IgM, IgG against cell surface and EC matrix
Causes disease by (1) damaging cells with complement activating phagocytes (via FcR) or (2) disrupting cell signalling.
ex: hemolytic anemia, drug allergies, Graves Disease, Myasthenia Gravis
Type III hypersensitivity
- Immune complex-mediated
- Immune complexes of circulating antigens and IgM or IgG
- Immune complexes deposit in blood vessels, joints, and glomeruli
- Immune complexes trigger inflammation promoting tissue damage
Ex: Lupus, serum sickness, post-streptococcal glomerular nephritis
Type IV hypersensitivity
- T cell-mediated
Often called ‘delayed type hypersensitivity’ as the reaction takes two to three days to develop - (1) CD4 T cells (Th1 and Th17); (2) CD8 CTLs
- (1) cytokine-mediated inflammation; (2) direct target cell killing, cytokine-mediated inflammation
- Ex: contact dermatitis, Type 1 diabetes, MS, Tuberculin test
Clinical features (signs and symptoms) of Type I hypersensitivity reaction
- Conjunctivitis
- Angioedema (swelling)
- flushing
- urticaria
- Rhinitis
- laryngeal edema (Upper airway obstruction, stridor)
- voice change
- Shock
- Asthma (lower airway obstruction; wheezing)
- GI (diarrhea, vomiting)
Clinical sign vs clinical symptom
Sign = indication of a medical condition that can be objectively observed (i.e., vomiting)
Symptom = manifestation of a condition that is apparent to the patient (i.e., nausea)
Urticaria
raised, arythematous, central clearing, irregular border, often migratory
Angioedema
- swelling of soft tissues
- localized to subcutaneous or submucosal tissues: face, lips, mouth, eyelids, airway, bowel
- fast onset
3 diagnostic categories for anaphylaxis
simply put, it’s anaphylaxis if 2 or more body systems are involved.
1) acute onset of illness with skin/mucosal involvement and 1 of resp symptoms or reduced BP or signs of end-organ dysfunction.
2) Exposure to a likely allergen for that patient and 2 of: skin-mucosal involvement, resp compromise, reduced BP, persistent GI symptoms.
3) REduced BP after exposure to a known allergen for that patient.
How does epinephrine work for anaphylaxis?
- alpha 1 receptors - vasoconstriction and relief of airway obstruction
- Beta1 receptors - increased contractility and HR; prevent hypotension and shock
- Beta2 receptors - decrease mediator release from mast cells & basophils; increase bronchodilation
Second line treatments for anaphylaxis
H1 antihistamines (relieve itching, lushing, urticaria, angioedema, nasal/eye symptoms)
Glucocorticoids (turn off pro-inflam genes, take several hours to work)
Inhaled B-2 agonists (salbutamol to lower respiratory tract symptoms)
How are complement proteins generated?
Produced by the liver and mostly act as regulatory proteins. They are circulate as zymogens and become active when cleaved in response to contact with a pathogen or antibody.
Role of complement (4)
- Opsonize pathogen for phagocytosis
- Inflammation - bind mast cells and induce degranulation
- Promote a stronger immune response
- Direct attack through Membrane Attack Complex
what is the primary complement mediator for all complement pathways
c3 convertase and c5 convertase
Compare the complement pathways
Classical initiated by Ag-Ig complexes.
Alternative initiated by spontaneous cleavage of C3
Lectin initiated by Mannose-Binding Lectin bound to pathogen surface.
They all ultimately lead to formation of C3 convertase and C5 convertase
+ve selection (TCR)
Does the T cell receptor (TCR) bind MHC?
-ve selection (TCR)
Does the cell react to cell-peptides? If it binds them too strongly, that T cell will be removed.
Once T cells are activated, how do we control the degree and duration of response?
After T cell gets activated, it does its job and eventually upregulates its own inhibitory molecules, which, for example, bind to CD28’s receptor stronger than CD28 does itself.
Somatic Hypermutation (B cell)
a process that introduces random mutation in the variable region of the BCR Ig heavy and light chains at a high rate during B cell proliferation
Affinity maturation
the process that leads to increased affinity of Igs for a particular antigen as a T-dependent humoral response progresses and is the result of somatic hypermutations of Ig genes followed by selective survival of the B cells producing the Igs with the highest affinity.
primary vs secondary immunodeficiency
Primary immunodeficiencies are the result of genetic defects, and secondary immunodeficiencies are caused by environmental factors, such as HIV/AIDS or malnutrition
3 signals needed for adaptive immune activation
Innate Signal 1 (Ag presentation), Signal 2 (co-stimulation), & Signal 3 (cytokines) produced by the APC control adaptive immune activation
Response to T-independent antigen
- B cell can be activated directly by Ag that extensively crosslink BCR
- Because there is no T cell stimulation through CD40, there will be no class switching and B cell will only make IgM
- young children (<2) are relatively unable to produce strong T-independent immune responses.
primary immune response
first time infected
Correlates of Immunity
= measures that predict against infection
Ig levels in serum.
conjugate vaccine
○ Link a protein to the polysaccharide (antigen) to help T cell
○ Increases responses in young children (now T-dependent)
Adjuvants
- increase the immunogenicity of vaccine; reduced dose of antigen required for effectiveness.
- Broadens repertoire of antibody responses
- Modulate the phenotype of T cell responses
- Adjuvants induce signal 2 & 3 for non-live vaccines (co-stimulation & cytokines)
- Example adjuvants:
○ ALUM - oldest; used in many routine vaccines
○ Squalene solutions (oil in water)
natural passive immunity
the type passed from mother to fetus in the form of antibodies delivered from mother to fetus through placenta and breast milk. It is only in effect for a short period of time.
artificial active immunity
vaccination
exposure to antigen - mimicking a primary immune response - so your immune system can generate a response and memory for reinfection - a secondary immune response.
passive artificial immunity
- administration of antibodies to fight infection immediately.
- Only done when necessary
- no lasting immunity.
bioavailability
the amount of drug that reaches systemic circulation unchanged
How does anaphylaxis work?
- antigen binds IgE
- Mast cells degranulate
- Efflux of blood contents into periphery –> rapid decrease in BP and hypoxia
- inflammation of bronchi - trouble breathing
