Exam 1 Immune Response & Covid-19

Question 1

Innate Immunity components

Hint: what we possessive to defend against inflammation

Answer 1

Anatomic barriers; skin
Phagocytic cells; Neutrophils, monocytes
Processes within the GI tract; GI juices, Saliva (antibiotic properties )
Normal flora; reside in large intestines, good
Bodily secretions- tears, sweat, urine flushes micro organisms

Question 2

What happens when flora moves from its place of origin ?

Answer 2

Causes infection ex E. coli in gut is fine, if introduced to urethra this causes UTI

Question 3

Adaptive immunity in simple form

Answer 3

recognize an antigen, target the specific antigen, and develop memory for that antigen for future encounter.

Question 4

Explain human leukocyte antigen (HLA) and major
histocompatibility complexes (MHC)
Genetic coding

Answer 4

This allows the body to distinguish what is ”self” against “non-self” (antigens) from invaders.

Question 5

What are the 2 phases of antibody response and its functionality
What antibodies are found in each stage?

Answer 5

Primary phase- first time body meets microorganism There is ”lag time” between recognition and proliferation of immunoglobulins[ IgM] marks the primary response - > person can develop the disease. ex you’re exposed but body isnt aware yet

Secondary phase/Amnestic response
Second or succeeding exposure (to the same antigen) initiates secondary response.
[IgG] predominant antibody in re-exposure
Second or succeeding exposure (to the same antigen) initiates secondary response.
Ex had measles, got better, re-exposed, body initiates Amnestic response

Question 6

Explain B- Lymphocytes

Answer 6

Respond to and produce antibodies; B-cells
Produced and mature in the bone marrow -> then enters the circulation -> migrates to lymphoid tissues -> when exposed to antigen -> transformed into plasma cells and Memory B- cells (with the help of Helper T- cells) -> Plasma cells produce specific antibodies (or immunoglobulins); memory B-cells stay in the lymph nodes in preparation for subsequent antigen exposure.
• Immunoglobulins- Ig M;A;G;E; D

IgG- antiviral; antitoxin; antibacterial; can cross the placenta; provides protection for newborns; •
IgA- predominates in body secretions ( saliva, breast milk, etc.);
IgM- natural antibodies for blood antigen (ABO); prominent in early immune response;
IgD - aids in further maturation of B-cells
IgE- involves in parasitic infections; involves in allergic and hypersensitivity reaction

Question 7

Explain T Lymphocytes/ Tcells

Explain how it works against HIV

Answer 7

Arise from bone marrow cells then migrate to thymus for their maturation -> some become CD 4 (T helper cells) and CD 8 (cytotoxic T cells) • CD4 influences other immune-related cells (other T cells, B cells,
macrophages, NK cells);

Note: HIV targets these cells! especially CD4 • CD8 directly attacks the antigen • Antigen itself CANNOT activate T cells. Antigen-presenting cells (APCs) must ”process” the antigen first- (capture and attach themselves to the antigen, some release cytokines)-> T cells are activated - > attack the antigen-APC complex.

Question 8

What is Active Immunity? Explain Natural vs Artificial

Answer 8

body develops immunity by stimulating the B-cells and/or
T cells This lasts long
Natural Active- development of an illness you have memory cells

Artificial Active- vaccines (ex. MMR), stimulates body to make antibodies, works slowly; weeksPrevention

Question 9

What is Passive Immunity? Explain Natural vs Artificial

Answer 9

body receives antibodies (immunoglobulin)
• This does not last long •
Natural Passive- maternal transfer; obtained through breast milk, Vaccines that transfers to baby from mother

Artificial Passive- Immunoglobulin injection upon exposure to an illness (ex.- rabies immunoglobulin-tetanus shot) IgG injection for hepatitis A, measles, chickenpox, rubella; works rapidly** Treatment**

Question 10

Explain Type 1 Immediate Hypersensitivity

Answer 10

Sometimes called IgE- mediated hypersensitivity; most common type of allergies (to pollens, animal dander, etc.); requires repeated exposure (happens to individuals who are previously exposed).

Mast (Sneezing and coughing) cells are the culprit- they have cytoplasmic granules that contain histamine; these mast cells are widely distributed in respiratory, nasal, and conjunctival cells.
Big Concern: Systemic anaphylaxis
This is life threatening! Itching, urticaria, bronchoconstriction; laryngeal edema(wheezing), tongue swelling and angioedema

Angioedema- swelling of the lower layer of the skin or mucus membranes
Hive (urticaria)- swelling within the upper skin
Massive vasodilation (blood vessels dilate) may happen- > drop in blood pressure!
EpiPen!!

Question 11

Explain Type 2 (Cytotoxic Hypersensitivity)

Answer 11

This is characterized by a specific cell (with its specific antigen) being a target of the immune response; the antibodies target the cells coated with antigens – these antigens can be intrinsic or extrinsic.

Example: Blood transfusion reaction- the host’s Immunoglobulins react to the incompatible donor- > hemolysis of transfused blood- >renal failure (flank pain).this leads to fever and low BP

Question 12

Explain Type 3 (Immune Complex Hypersensitivity)

Answer 12

This happens when there is antibody binds with antigen creating complex (also called immune complex) • Main difference from Type 2: Type 2- the antibody binds with antigen on the cell surface; Type 3- antibody binds with soluble antigen that was released into the blood or body fluids (forming a complex)-> then deposited into tissues. •

Example: SLE- systemic lupus erythematosus- > complexes are deposited to
kidneys, blood vessels, lungs, skin; • Rheumatoid arthritis-> complexes are deposited in the joints- >joint
damage- > joint pain and disability • Can affect arteries- > damage to major organs (like: kidney ->
glomerulonephritis) • Treatment: anti-inflammatory; antihistamine; glucocorticoids;
immunosuppressants

Question 13

Explain Type 4 (Delayed Hypersensitivity/ Cell-mediated hypersensitivity)

Answer 13

• This is initiated by T-cells that have previous exposure to the antigen; (Sensitized) T- cells do not attack the antigen until days after the second exposure;
• Example: graft rejection/transplant rejection; allergic reaction from contact with poison ivy;
• This type of reaction can also be seen in autoimmune like T-cells attacking the collagen in joint tissues (rheumatoid arthritis); T-cells against thyroid cell antigens (autoimmune thyroiditis/Hashimoto’s disease)
• Note: reaction happens days after exposure- > can be difficult to diagnose the source.

Question 14

Explain Autoimmunity

Answer 14

Self antigens are usually in a state of tolerance with the host’s own immune system; • Autoimmunity happens when there is a breakdown of tolerance- the body’s
own immune system cannot recognize the “self” already and thinks that it is something “not self” or foreign. •

Remember: the purpose of the immune system is to protect the ”self” (body) from non-self invaders. • Thus, they begin to attack organ that is not recognized as part of the body and renders it dysfunctional. • Cause is poorly understood; one theory is molecular mimicry – part of infectious agent has similar amino acid sequence as some self antigen • Example: SLE; RA; scleroderma; RHD

Question 15

Give an example of molecular mimicry

Answer 15

Heart valve using molecular mimicry has similar amino acid sequence as microorganism GABH (strep throat) A small percentage- > attack the myocardial protein of the valvular tissues
(think of the molecular mimicry!)- > inflammation develops - > valves become stiff/harden- > heart murmurs- > RHD

Question 16

Immunodeficiency
Primary and Secondary
How does HIV work?

Answer 16

• This can be primary or secondary • Primary Immunodeficiency- congenital (born with it)

Secondary Immunodeficiency- developed after birth Radiation therapy
Human Immunodeficiency Virus (HIV) Infection
• HIV-> has affinity to CD4 and fuses itself to the CD4 surface receptor- > HIV inserts its RNA into the cell - > and the “RNA” virus is transformed into ”DNA” virus through its own enzyme called “reverse transcriptase”- > the HIV is now a DNA virus- > able to insert itself into the CD4 genome- > it now controls the CD4- > becomes the manufacturing site of HIV- > new HIVs begin infecting other CD4s (and CD4s could no longer do its job, thus, “ immuno-deficient”!) - > prone to develop infections; mild infections can become life-threatening; microorganisms that normally do not cause a disease (to a person with intact immune system) can cause severe infections; rare forms of malignancies can also develop.

Question 17

Life threatening cancers that affect HIV/AIDS pts

Answer 17

Kaposis Sarcoma

Hodgkins lymphoma

Question 18

Does DNA or RNA contain SARS virus?

Answer 18

RNA produces strands and readily mutates

Question 19

What is Covid-19 IP

and its MOT

Answer 19

IP: 5-6 days, up to 14 days; others: 2-14 days

CA binds with ciliated secretory cells in the nasal epithelium - > viral replication with limited immune response -> 1) containment of the virus - > no s/s.

-> 2) virus not contained- > migration of virus from nasal
epithelium to upper respiratory tract - > fever, malaise, dry cough; plus greater immune response - > a) virus is contained; majority of patients do not progress beyond this phase;

b) virus not contained - > invasion of pulmonary alveolar
epithelial cells via ACE-2* and undergo replication - > infected pneumocytes release cytokines and inflammatory markers ( a lot!!!!) (“cytokine storm”) LUNG CELLS - > attract more neutrophils, CD4 helper cells, CD8 T cells to the area- > further increase inflammation -> diffuse alveolar damage- > ARDS (severe respiratory issue!)- > severe dyspnea; CO2 retention; multiple organ failure

(These cells and inflammatory mediators are responsible for fighting off the virus but also responsible of severe inflammation and injury to the lungs!)

Question 20

Where is ACE-2 present?

What is the role of ACE-2 in the presence of COVID-19

Answer 20

ACE-2 is a protein present on the surface of cells; Found in the heart, lungs, mouth, blood vessels, GI tract, Nose

ACE-2 binds to the COVID-19 spike, acts a doorway for the receptor, When the virus binds w/ ACE-2 this prevents ACE-2 from performing its functions: Modulate/control inflammation.

When the SARS-CoV-2 virus binds to ACE2, it prevents ACE2 from performing its normal function to regulate ANG II signaling. Thus, ACE2 action is “inhibited,” removing the brakes from ANG II signaling and making more ANG II available to injure tissues

ANG II can increase inflammation and the death of cells in the alveoli which are critical for bringing oxygen into the body; these harmful effects of ANG II are reduced by ACE2.

Question 21

The quantity of ACE-2 varies amongst individuals,

Which group of individuals have an elevated amount of ACE-2?

Answer 21

HTN
Diabetes
Coronary artery disease
These are co-morbidities

Question 22

What is the primary role of ACE-2

Answer 22

Breaks down angiotensin 2, controls blood pressure, and blocks organ damage (by modulating inflammation)

Question 23

Which molecular test detects the viral RNA in COVID-19
What specimens are needed to complete this test?
How long for results?

Answer 23

NAAT (nucleic acid amplification test) Send it to lab; takes 1-3 days for results; expensive

Saliva
Sputum
Nasopharyngeal/Oropharyngeal

Question 24

Which molecular test uses the viral spike to identify the COVID-19 ?
What does it detect?
How long for results?

Answer 24

Antigen test
Necessary to confirm positive antigen test with NAAT
It detects specific viral antigen 
Less sensitive than NAAT 
15-30mins
It is advised to use this test first

Question 25

If its advised to use Antigen test over NAAT when should a person use NAAT?

Answer 25

Negative antigen test w/ symptoms

Positive Antigen test w/o symptoms

Question 26

When would a COVID-19 blood test be needed?

Answer 26

Admitted to the hospital 
Normal or decreased WBC
Increased level of lactate dehydrogenase (elevated lactic acid), c-reactive protein (inflammation)
Elevated d-dimer
Coagulation abnormalities

Question 27

Chest x-ray

Answer 27

Inconclusive in early stage if trying to detect pneumonia

Question 28

CT

Answer 28

Method of choice for diagnosing COVID-19 pneumonia even in initial stage of illness

Question 29

What are the Tx of COVID-19

Answer 29

Increase High flow oxygen
Mechanical Ventilation • ECMO- extracorporeal membrane oxygenation; Used when all medical options have been exhausted Patient’s blood - > flow into an artificial lung (machine)- > O2 is added and CO2 is removed - > sends back the (oxygenated) blood to the patient. entry to human cell (buying time)

Remdesivir; Only FDA-approved anti-viral drug •

Monoclonal antibody (blocks virus spikes from binding to ACE-2) – Tocilizumab; Sarilumab
Designed to act against the spike protein of Covid - > blocks the virus attachment and entry to human cell

Corticosteroid- Dexamethasone; Prevention: Vaccine (artificial, active)

Question 30

• Immunoglobulins- Ig M;A;G;E; D

Answer 30

IgG- antiviral; antitoxin; antibacterial; can cross the placenta; provides protection for newborns; •
IgA- predominates in body secretions ( saliva, breast milk, etc.);
IgM- natural antibodies for blood antigen (ABO); prominent in early immune response;
IgD - aids in further maturation of B-cells
IgE- involves in parasitic infections; involves in allergic and hypersensitivity reaction