Week 5: Immunology

Question 1

What cells make up the lymphocytes?

Answer 1

B Cells
T Cells
Natural Killer Cells

Question 2

+ve selection of T cells occurs in ______

Answer 2

cortex of thymus

Question 3

-ve selection of T cells occurs in _______

Answer 3

medulla of thymus

Question 4

after -ve and +ve selection of T cells, approximately what percent are still remaining?

Answer 4

5%

Question 5

3 ‘classical’ APCs

Answer 5

B Cells
Macrophages
DCs

Question 6

What is different about how B cells and T cells recognize antigen

Answer 6

B cells recognize the 3D shape of peptide, whereas T cells recognize the sequence

Question 7

Define hypersensitivity

Answer 7

immune responses that are capable of causing tissue injury

Question 8

Type I Hypersensitivity

Answer 8

• Immediate
• IgE and Th2 cells
• Injury caused by mast cells, eosinophils, and their mediators

Question 9

Type II hypersensitivity

Answer 9

• 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

Question 10

Type III hypersensitivity

Answer 10

• 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

Question 11

Type IV hypersensitivity

Answer 11

• 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

Question 12

Clinical features (signs and symptoms) of Type I hypersensitivity reaction

Answer 12

• Conjunctivitis
• Angioedema (swelling)
• flushing
• urticaria
• Rhinitis
• laryngeal edema (Upper airway obstruction, stridor)
• voice change
• Shock
• Asthma (lower airway obstruction; wheezing)
• GI (diarrhea, vomiting)

Question 13

Clinical sign vs clinical symptom

Answer 13

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)

Question 14

Urticaria

Answer 14

raised, arythematous, central clearing, irregular border, often migratory

Question 15

Angioedema

Answer 15

• swelling of soft tissues
• localized to subcutaneous or submucosal tissues: face, lips, mouth, eyelids, airway, bowel
• fast onset

Question 16

3 diagnostic categories for anaphylaxis

Answer 16

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.

Question 17

How does epinephrine work for anaphylaxis?

Answer 17

• 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

Question 18

Second line treatments for anaphylaxis

Answer 18

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)

Question 19

How are complement proteins generated?

Answer 19

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.

Question 20

Role of complement (4)

Answer 20

1. Opsonize pathogen for phagocytosis
2. Inflammation - bind mast cells and induce degranulation
3. Promote a stronger immune response
4. Direct attack through Membrane Attack Complex

Question 21

what is the primary complement mediator for all complement pathways

Answer 21

c3 convertase and c5 convertase

Question 22

Compare the complement pathways

Answer 22

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

Question 23

+ve selection (TCR)

Answer 23

Does the T cell receptor (TCR) bind MHC?

Question 24

-ve selection (TCR)

Answer 24

Does the cell react to cell-peptides? If it binds them too strongly, that T cell will be removed.

Question 25

Once T cells are activated, how do we control the degree and duration of response?

Answer 25

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.

Question 26

Somatic Hypermutation (B cell)

Answer 26

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

Question 27

Affinity maturation

Answer 27

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.

Question 28

primary vs secondary immunodeficiency

Answer 28

Primary immunodeficiencies are the result of genetic defects, and secondary immunodeficiencies are caused by environmental factors, such as HIV/AIDS or malnutrition

Question 29

3 signals needed for adaptive immune activation

Answer 29

Innate Signal 1 (Ag presentation), Signal 2 (co-stimulation), & Signal 3 (cytokines) produced by the APC control adaptive immune activation

Question 30

Response to T-independent antigen

Answer 30

- 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.

Question 31

primary immune response

Answer 31

first time infected

Question 32

Correlates of Immunity

Answer 32

= measures that predict against infection | Ig levels in serum.

Question 33

conjugate vaccine

Answer 33

○ Link a protein to the polysaccharide (antigen) to help T cell ○ Increases responses in young children (now T-dependent)

Question 34

Adjuvants

Answer 34

- 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)

Question 35

natural passive immunity

Answer 35

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.

Question 36

artificial active immunity

Answer 36

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.

Question 37

passive artificial immunity

Answer 37

- administration of antibodies to fight infection immediately. - Only done when necessary - no lasting immunity.

Question 38

bioavailability

Answer 38

the amount of drug that reaches systemic circulation unchanged

Question 39

How does anaphylaxis work?

Answer 39

- antigen binds IgE - Mast cells degranulate - Efflux of blood contents into periphery --> rapid decrease in BP and hypoxia - inflammation of bronchi - trouble breathing