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PHAR 303 > 12. Immunotoxicology > Flashcards

12. Immunotoxicology Flashcards

1
Q

What is the main function of eosinophils?

A

Phagocytic
Parasitic infection
Allergy

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2
Q

What is the main function of neutrophils? What does it contain?

A
  • First responder
  • Recognize the enemy (IgG and C3b receptors-complement)
  • They go to the battle field (Chemotaxis)
  • Bacteria phagocytosis
  • Inflammation
  • Contain cytoplasmic granules that contain enzymes needed to kill the pathogen that it took up
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3
Q

What is the main function of basophils?

A

Allergy
Helminth (parasitic worm)
Infection

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4
Q

What is the main function of dendritic cells?

A

Presenting antigens to T cells to help its activation.

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5
Q

What is the main function of lymphocytes?

A

B cell: antibody production

T cell: helper/cytotoxicity

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6
Q

What is the main function of mast cells?

A

Inflammation
Infection/injury
Allergy

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7
Q

What is the main function of monocytes?

A

Phagocytic

Macrophage and dendritic cell precursor

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8
Q

What is the main function of natural killer cells?

A

Virus

Tumour cells

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9
Q

Order the WBCs by highest % of total WBCs to lowest.

A
  1. Neutrophils (50-70%)
  2. Lymphocytes (25-45%)
  3. Monocytes (3-8%)
  4. Eosinophils (2-4%)
  5. Basophils (0.5-1%)
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10
Q

What is innate immunity?

A

It is the first responder that fights against any foreign invader, non-specific, and has no memory. Works in 0-12 hours.
It is composed of:
- Barriers: skin, lungs, gut, mucus to protect airways
- Complement: Plasma proteins produced in the liver that help opsonize pathogens. Coats pathogens to target for destruction by other immune cells.
- Cells: Mast cells, phagocytes (macrophages), dendritic cells, and natural killer cells.

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11
Q

What is adaptive immunity?

A

It is a slow (1-2 weeks) and specific response to specific antigens by B and T cells. Has memory and helps confer longer protection.
Composed of:
B lymphocytes: produce antibodies and plasma cells
T lymphocytes
other immune cells

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12
Q

What are the different types of antibodies produced by B cells in order of most abundant to least abundant in serum? Give a characteristic of each.

A
  1. IgG: most abundant in serum
  2. IgA: The predominant antibody in secretions on and in mucosal surfaces, including the respiratory and GI tract
  3. IgM: First one produced in primary response
  4. IgD: Function isn’t completely clear but has same overall function of protecting against infection
  5. IgE: Mediates hypersensitivity reactions (ex: allergy, asthma)
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13
Q

What are the 2 types of adaptive immunity?

A

Humoral

Cell mediated

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14
Q

What is humoral immunity? What is the mechanism and what are its funtions?

A

A type of adaptive immunity.
Extracellular microbes get recognized by B cells which produce antibodies. These antibodies coat the pathogen to make it readily recognizable for the uptake by phagocytic cells. This prevents them from infecting cells.
• IgG coats microbes and targets them for phagocytosis by macrophages and neutrophils
• IgG and IgM activate complement system to promote phagocytosis of microbes
• IgA neutralizes microbes in the lumens of mucosal tissue (gut, lungs)
Functions: Block infections and eliminate extracellular microbes.

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15
Q

What is cell mediated immunity?

A

Where the Cytotoxic and helper T cells come into play:
- T helper (CD4+): they help activate other cells including macrophages. When the macrophage and T cell interact, the T cell can release cytokines to activate the macrophage making it more efficient at killing the pathogens it phagocytosed.

  • Cytotoxic T lymphocytes (CD8+): interact with infected cells themselves by the release of a number of different enzymes to directly kill that cell. This eliminates reservoirs of infection.
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16
Q

What is a regulatory T lymphocyte?

A

CD4+

Suppression immune response so that it doesn’t become chronic and ongoing.

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17
Q

What are the T helper (Th) subsets? For each of them provide their defining cytokines, target cells (to activate), Host defense contributions, and their role in disease.

A
  1. Th1
    Defining cytokines: Interferon-gamma (IFN-y)
    Target cells: macrophages
    Host defense contributions: Intracellular pathogens
    Role in disease: Autoimmunity, chronic inflammation
1. Th2
Defining cytokines: IL-4, IL-5, IL-13
Target cells: Eosinophils
Host defense contributions: Helminths
Role in disease: Allergy
1. Th17
Defining cytokines: IL-17, IL-22
Target cells: Neutrophils
Host defense contributions: Extracellular pathogens
Role in disease: Autoimmunity
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18
Q

What is immunotoxicity (immunotoxicology)? What is it caused by?

A

Any adverse effect on the structure or function of the immune system, or on other systems as a result of immune system dysfunction.
It is caused by immunomodulation:
1. Immunosupression: Impaired immunity leading to enhanced susceptibility to infection
2. Immunoenhancement: Autoimmunity, hypersensitivity, chronic inflammation

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19
Q

What is Azathioprine?

A

A halogenated aromatic hydrocarbon and an immunosupressive drug. It is used to treat diseases such as rheumatoid arthritis and inflammatory bowel disease (IBD).

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20
Q

Explain the mechanism of Azathioprine.

A
  1. Azathioprine is a prodrug that undergoes a non-enzymatic conversion in the liver to 6-mercaptopurine (6-MP). There are 3 pathways that this pathway stems off in from this point:
    2a. Xanthine oxidase (XO) creates oxidized metabolites from 6-MP that are cleared from the body
    2b. Thiopurine S-methyltransferase (TPMT) converts 6-MP to 6-Methyl mercaptopurine, an inactive metabolite that also gets cleared from the body. This is the rate limiting step to convert to inactive metabolites.
    2c. 6-MP is converted to 6-thioguanine nucleotides (6-TGN) by hypoxanthine phosphoribosyltransferase. These are the active metabolites and there are 2 different types:
    - 6-TGTP = 6-thioguanine 5’-triphosphate
    - 6-TGDP = 6-thioguanine 5’-diphosphate
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21
Q

What do the active 6-TGNs do?

A
  • The adverse effects of Azathioprine are dose dependent caused by elevated concentrations of 6-TGNs.
  • They cause the apoptosis of activated T cells and they have structural similarity to endogenous purine bases which allows them to be incorporated into DNA and RNA as “fraudulent” bases”.
    This leads to:
    ‣ Strand breaks, inhibition of DNA repair mechanisms, inhibition of replication
    ‣ Inhibition of B and T cell proliferation
    ‣ Induces apoptosis which leads to myelotoxicity (leukopenia and thrombocytopenia).
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22
Q

What happens if people with an inherited TPMT deficiency take Azathioprine?

A

TPMT is the rate limiting enzyme for the conversion of 6-MP to inactive metabolites. Having a deficiency leads to elevated concentrations of 6-TGNs leading to life threatening pancytopenia (combination of three different blood disorders: Anemia is when you have too few red blood cells. Leukopenia is when you have too few white blood cells. Thrombocytopenia is when you have too few platelets).

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23
Q

What is the drug drug interaction between Azathioprine and Allopurinol?

A

Allopurinol (used to treat gout) is a xanthine oxidase (XO) inhibitor. Therefore it also leads to elevated levels of 6-TGNs causing life threatening pancytopenia.

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24
Q

What is Clozapine? What are complications?

A

Anti-psychotic medication for schizophrenia used if it does not improve following use of other medications. Complications:
(normal neutrophil count= 1800-7500/ul)
- 3% of patients experience neutropenia (less than 1500 neutrophils/ul)
- 1% of patients experience agranulocytosis (less than 500 neutrophils/ul)

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25
Q

What are the mechanisms of the toxic effects on granulocytes (neutrophils) causing neutropenia?

A

Impaired proliferation due to:

  • Anti cancer drugs (cisplatin)
  • Vitamin B12 deficiency
  • Alcohol use disorder

Cell viability (direct cell cytotoxicity)

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26
Q

What is Idiosyncratic drug-induced

agranulocytosis (neutropenia)?

A
  • Failure of production of neutrophils in the bone marrow or peripheral destruction or both
  • Exact mechanisms largely unknown
  • Adverse reaction due to abnormal susceptibility
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27
Q

What is the mechanism of neutrophils and how does Clozapine affect it?

A

Neutrophils express myeloperoxidase (MPO) to generate ROS in the cell that the neutrophil can utilize a part of its killing strategy. One of the reactive species is HOCL (hypochlorous acid) which helps get rid of the intracellular pathogens taken up.

Clozapine reacts with HOCl to form a nitrenium ion which is highly reactive. This causes GSH and ATP depletion. This heightens the oxidative stress in the cell (remember last lecture) leading to apoptosis and neutrophil depletion (neutropenia).

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28
Q

What are the different kinds of tobacco smoke? How does it contribute to immunotoxicity?

A
  • Sidestream smoke: Comes off the end of the cigarette
  • Mainstream smoke: the smoke inhaled into the lungs
  • Environmental smoke/involuntary smoke/passive smoke/secondhand smoke: Exhaled smoke + smoke coming off the cigarette.
  • Contributes to immunotoxicity by immunosupression AND immunoenhancement.
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29
Q

What are the diseases attributed to cigarette smoke?

A
  • Many different cancers
  • Diabetes
  • Infections
  • Hypertension, Stroke, aortic aneurysm, heart disease
  • Chronic obstructive pulmonary disease (COPD)
  • Age-related macular degeneration (causes blindness)
  • Inflammatory bowel disease
30
Q

What is COPD?

A

A common lung disease characterized by worsening and irreversible (what differentiates it from asthma) airflow limitation
• Caused mostly by cigarette smoke exposure
• No medications to stop/slow this disease

31
Q

What are the traditional COPD classifications?

A

COPD can be split into:

  1. Chronic bronchitis: Inflammation in lungs and airways
  2. Emphysema: Destruction of alveoli
32
Q

How does cigarette smoke cause lung inflammation?

A
  1. Tobacco smoke can activate epithelial cells within the lungs and airways to cause a release of cytokines (including IL-8, IL-6, TNF-alpha) and other factors that recruit immune cells.
  2. Innate: The cytokines cause the recruitment of many different cells in the lungs including: neutrophils, macrophages, monocytes, dendritic cells, etc
  3. Adaptive: The recruitment of T helper cells 1 & 17 as well as CD8+ (cytotoxic T) cells.
  4. Tobacco smoke can also penetrate the epithelium to activate other cells such as fibroblasts (structural).
33
Q

How does Inflammation cause COPD?

A

Cigarette smoke activates epithelial cells and other cells in the lungs causing the secretion of cytokines and other factors. Leads to the recruitment of macrophages, neutrophils, monocytes that can ultimately lead to lung damage. Macrophages release TNF-alpha which causes apoptosis of alveoli, it also releases matrix metalloproteinases (MMPs) that produce proteases and oxidants (also produced by neutrophils) which damage the alveoli. The net effect of this is emphysema = destruction of alveoli.

34
Q

What are the functions of macrophages?

A
  • Detection, phagocytosis and destruction of bacteria and other harmful organisms
  • Present antigens to T cells
  • Release cytokines that recruit and activate other cells.
35
Q

What effect does cigarette smoke have on the function of these immune cells?

A
  • Alveolar macrophages have a reduced ability to phagocytose and/or kill bacteria
  • Reduced immunoglobin levels
  • Impaired T cell response (↓ proliferation)
  • Increased levels of auto-antibodies

All of this increases the risk of infections.

36
Q

What is efferocytosis? What is the mechanism?

A

The process by which apoptotic cells are removed by phagocytic cells. Literal translation: To carry the dead to the grave.
Mechanism:
1. Dead or dying cells (apoptotic) have “find me” signals that direct the macrophage to them.
2. Then there is an “eat me” signal so that the macrophages take them up.
3. Then engulfment and processing.
4. Then the macrophage releases other cytokines to tell everyone to stop coming to resolve the inflammation (anti-inflammatory response).

37
Q

What is the effect of smoke on efferocytosis?

A

In response to smoke and in COPD, efferocytosis by macrophages is impaired. The apoptotic cells don’t get taken up and the macrophages don’t send out an anti-inflammatory response, so this leads to increased inflammation and autoimmunity = COPD.

38
Q

Where are the phytochemicals of cannabis produced?

A

In the trichomes of the cannabis plant.

39
Q

What are the main cannabinoids of Cannabis sativa?

A

THC

CBD

40
Q

How is THC produced? Where does it bind?

A

Produced as THCA and converted by heat to THC. THC is psychoactive because it binds to CB1 in the CNS.

41
Q

What are the different cannabinoid receptors and what are their actions on the body?

A

CB1: (mostly in CNS) motor activity, thinking, motor co-ordination, appetite, short term memory, pain perception, immune cells.
CB2: (found in immune system) Gut, kidneys, pancreas, adipose tissue, skeletal muscle, bone, eye, tumours, reproductive system, immune system, respiratory tract, skin, CNS, CV system, liver.

42
Q

Place the immune cells in order from highest to lowest amount of CB2 receptors on their surface.

A 
Highest CB2: 
1. B cell
2. NK cells
3. Macrophage
4. Monocytes
5. PMN (Polymorphonuclear leukocytes are a type of WBC that include neutrophils, eosinophils, basophils, and mast cells)
6. T cell (CD4 and CD8)
The expression of CB2 receptors can be increased by activation of any of these cells.
43
Q

Explain what the function a cannabinoid can have on these cells when interacting with their receptor.

A

Suppresses the immune system:
1. Induction of apoptosis
2. Inhibition of proliferation
3. Suppression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1)
4. Induction of T regulatory (Treg) cells
This causes:
‣ Shut down T cell response
‣ Suppress autoreactive T cells (prevent pathologic autoreactivity)

44
Q

What are halogenated aromatic hydrocarbons also known as? What are the 3 main classes?

A

Also known as dioxin-like chemicals (DLCs) or dioxins.

  1. PCDD: TCDD, dioxin
  2. PCDFs
  3. PCBs (biphenyls)
45
Q

What is a PCDD: TCDD, dioxin? and what pathway does it act via?

A

Most toxic DLC
• Man-Made
• Unwanted contaminant of industrial processes
• Environmentally and biologically persistent
• Human exposures
- Acts via the Aryl hydrocarbon Receptor (AhR)

46
Q

What is the effect of TCDD (dioxin) on the immune system?

A

Immunotoxicity on primary lymphoid organs: Thymus and bone marrow.

47
Q

What is the thymus?

A

• Primary lymphoid organ
• Important for immune function
– Site of T cell maturation: Immature T cells (thymocytes) migrate from the bone marrow to the thymus
– Education process: helps make sure that the T cells don’t recognize self antigens
• Reaches maximum size at puberty
– 30-40g
– Declines thereafter (involution- 3g)

48
Q

Explain an experiment done on mice with TCDD.

A

TCDD induces thymic atrophy in mice who were treated on days 14&16 and evaluated on day 18: it decreases the size, weight and completely disrupts the organization (cellularity)

49
Q

Explain studies done on rats with TCDD.

A
  • TCDD administered by gastric intubation; thymus analyzed after 13 days
  • 5-10 rats (age 7-8 weeks) in each group
  • Results: increasing dioxin exposure decreased thymus weight.
50
Q

How does dioxin cause thymus atrophy? What does it depend on?

A

Via the AhR pathway. One of the end results is thymic atrophy. Dioxin decreases the thymus weight and the number of lymphocytes in an AhR dependent manner. No AhR=no thymus effect.

51
Q

What effect does TCDD (dioxin) have on immune cells in mice?

A

Because TCDD causes thymus atrophy, a primary lymphoid organ, it also reduces murine B cell proliferation and IgM production.

52
Q

What do we know about the effects of TCDD in humans? How do we know this?

A

In Seveso, Italy, there is a population of 17,000. They have an industrial plant where they manufactured 2,4,5-T (herbicide and a component of Agent Orange) which was used in the Vietnam war. In July 10, 1976 an exothermic reaction caused the contents of a vessel to be released into the atmosphere.
• Amount of TCDD released: Upwards of 34 kg
- Animals & vegetation died
- Health effects
- Acute- chloracne (193 cases; 88% children)
- Chronic- varied
- The people with the highest exposure to dioxin had the least amount of plasma IgG production

53
Q

What is autoimmunity?

A
  • When the immune system mistakenly recognizes self tissue as foreign- and then attacks
  • Causes chronic inflammation and tissue damage
54
Q

What are the different autoimmune diseases? does it affect men or women more?

A 
3 women : 1 man
Multiple Sclerosis
Graves' disease
Psoriasis
Inflammatory bowel disease
Guillain-Barre syndrome
Rheumatoid arthritis

Can be organ specific:
Type 1 diabetes

Can be systemic:
SLE (lupus)

55
Q

What is the fundamental cause of autoimmune diseases? explain.

A

Loss of self tolerance (lack of immune response to one’s own antigens):
– Autoreactive lymphocytes escape elimination by the body’s central tolerance mechanisms (mainly in thymus). They then travel to the periphery where these cells encounter specific autoantigens.

– Peripheral tolerance mechanisms (secondary lymphoid organs and/or sites of inflammation) also fail in stopping activation of autoreactive lymphocytes
• Specific response against autoantigen-bearing cells, leading to tissue damage.

56
Q

What are the mechanisms of immunologic tolerance?

A
  1. Central tolerance: Deletion (by apoptosis) of self-reactive T and B cells
    - During the education of the cells, if a T cell binds to a self antigen too strongly, usually there is a signal that causes the death of that cell so that it cant cause an issue.
    - Some of the autoimmune do escape into the periphery tho. This is regulated by:
  2. Peripheral Tolerance: the self reactive T and B cells that escape to the periphery undergo
    A. Anergy (failure to respond) = functional inactivation because co- stimulatory molecule on APC is not delivered
    B. Apoptosis by self-antigen recognition
    C. Suppression by T regulatory cells
57
Q

What is the cause of the symptoms of most autoimmune diseases? By what mechanism?

A

The symptoms are due to the responses of autoantibodies and autoreactive effector T cells against autoantigens:
– Activated effector T cells release proinflammatory cytokines
• Activate innate immune cells (such as macrophages and neutrophils) as well as nonhematopoietic cells (such as endothelial cells and fibroblasts) to induce the production of more cytokines.
• Autoreactive CD4+ cells, or helper T (Th) cells, also help autoreactive B cells in autoantibody production.
• In addition, these Th cells can activate autoreactive CD8+ cytotoxic T (Tc) cells.
–Inflammation and damage of the target as well as the surrounding cells.

58
Q

Explain the postulated mechanisms of autoimmunity.

A

► Genetic: Various genetic loci may confer susceptibility to autoimmunity, in part by influencing the maintenance of self-tolerance. The failure of self-tolerance due to the “susceptibility genes” cause the development of self reactive lymphocytes.
► Environment: Triggers from the environment may promote the influx of lymphocytes into tissues and the activation of self-reactive T cells, resulting in tissue injury..

59
Q

What is the etiology (reason) behind autoimmune diseases?

A

The etiology is unclear but they think it is a combination of:

  • Genetic predisposition: Tends to run in families but most autoimmune diseases cannot be explained by defects in single genes
  • Environmental factors: Xenobiotics (tobacco, drugs, UV, solvents, heavy metals), chemical-induced autoimmunity (Chemical modifies tissue/immune cells and generate antigens that the T and B cells become auto-reactive against)
  • Hormonal factors: More common in women (e.g. lupus female:male ratio is 9:1)
  • Lifestyle
  • Diet
  • Infection
60
Q

What are the Putative mechanisms of chemical-induced autoimmunity?

A
  1. Toxicant-induced aberrant cell death (hidden cellular material now available to APCs): for example, UV (sunlight) exacerbates lupus (SLE) flares
  2. Covalent binding of chemicals to tissue proteins
    (results in formation of neoantigens = newly formed antigens): for example, cigarette smoke risk factor for rheumatoid arthritis and SLE

Both of these cause inflammation and tissue injury.

61
Q

What is SLE?

A

Systemic Lupus Erythematosus:
• Genetic and environmental factors
– Familial association
– Environmental factors = cigarette smoking, drugs

• Pathogenesis not well understood
– Most is idiopathic (10% associated with specific drugs)

• Dysfunction of T cells, B cells and DC; production of anti-nuclear antibodies (auto antibodies that bind to the contents of the cell nucleus)

• Can involve any organ in the body but usually affects skin, kidneys, serosal membranes, joints and heart
– damage caused by immune complex deposition
– renal failure most common cause of death

• Female preponderance = 1/700 women of childbearing age

62
Q

What is DIL? What can it be caused by?

A

Drug-induced lupus (DIL)/lupus-like syndrome/SLE- like syndrome (SLE-ls). It is not exactly like lupus but causes many of the same symptoms. The mechanism is still unclear.
Can be caused by Isoniazid.

63
Q

What is Systemic sclerosis (Scleroderma)? What can it be caused by?

A

♦ An autoimmune disease of connective tissue that can be caused by Vinyl chloride (among other things).
♦ Characterized by fibrosis (thickening and scarring of connective tissue, usually as a result of injury)
♦ Localized (skin of hands, feet and face)
♦ Systemic: can have interstitial lung disease, PAH, muscoskeletal problems, renal crisis, GI complications.

64
Q

What is the mechanism of Systemic sclerosis (Scleroderma)?

A

Endothelial (structural cell) injury that leads to the activation B and T cells-> in this condition you will have the release of cytokines and growth factors (ex: TGF-b, IL13, PDGF) that promote fibrosis.

65
Q

How can Vinyl chloride cause Systemic sclerosis (Scleroderma)?

A

The mechanism for Vinyl chloride disease is not clear. It leads to an abnormal protein that is antigenic.

66
Q

What is hypersensitivity and what are the different types?

A

Hypersensitivity: Over-reaction of the immune system

  • Antibody-mediated hypersensitivity:
    Type 1– Immediate: Mast cell de-granulation leading to hay fever, asthma, anaphylaxis; allergy (involves histamine). IgE or Th2 response.
    Type 2– Antibody-dependent cytotoxic: leading to cell lysis; drug-induced hemolytic anemia. Involves IgG & IgM. Example: drug contributes to destruction by targeting neutrophils or macrophages to that cell.
    Type 3– Immune-complex mediated: Ag-Ab complexes leading to inflammation and tissue damage; SLE. Involves IgG and IgM.
  • T cell mediated:
    Type 4– Cell mediated: delayed-type/contact → memory T cell leading to erythema: T-cell mediated; contact dermatitis
67
Q

What is an example of type 1 hypersensitivity? Explain its symptoms and pathology.

A
  • Asthma: Wheezing, coughing, shortness of breath, tightness in chest.
  • Pathology: chronic disease caused by inflammation, airway remodelling, and bronchoconstriction.
68
Q

Explain the mechanism of a type 1 response.

A
  1. Exposure to allergen (or in the case of asthma its just an asthmatic trigger)
  2. Activation of T helper cells and B cells
    - T helper cells release:
    IL-4 = stimulates B cells specific for the antigen to produce IgE
    IL-5 = activates eosinophils which cause: AHR (airway hyperresponsiveness: the predisposition of the airways of patients to narrow excessively in response to stimuli that would produce little or no effect in healthy subjects), mucus production, remodeling
    IL-13 = stimulates mucus secretion by epithelial cells
  3. IgE binds to mast cells
  4. The next time the mast cell with IgE interacts with the allergen (repeat exposure) it causes degranulation of the mast cell and release of mediators:
    - Histamine = vasodilation, vascular permeability, smooth muscle contraction, mucus secretion
    - Adenosine = bronchoconstriction
    - Prostaglandins = bronchospasm
    - Cytokines (late phase: 2-8 hours after eexposure) = IL-4, IL-5, IL-13
69
Q

What is TDI? How is one exposed? What does it cause?

A

Toluene diisocyanate (TDI)
– High production volume chemical
Major use is production of polyurethane polymers: Adhesives, Pillows, Mattresses, Sealants

Cured TDI (foam) is inert and non-toxic

Occupational exposure
– Exposure is mostly by inhalation
– Isocyanate chemicals: common cause of occupational asthma in industrialized countries:
• After sensitization- subsequent exposure triggers severe asthma attacks
• 5-25% of exposed workers develop respiratory disorders

70
Q

What is the predicted mechanism for TDI-induced asthma? What is the threshold level?

A
  1. Damage lung epithelial cells
  2. Oxidative stress causing GSH to be exhausted
  3. Formation of neoantigen from airway proteins and recognition as non-self that dendritic cells can take up and present to T cells which release a number of cytokines.
  4. Hypersensitivity reaction (Th2 type 1 response)

Threshold level = pulmonary sensitization usually result of exposure to a spill; low level exposure to vapours no sensitization

71
Q

What is the mechanism for T-Cell mediated type 4 hypersensitivity?

A

2 Main categories:
A. Cytokine mediated inflammation:
- APC presents tissue antigen to F cell (CD4+)
- Th1 releases IFN-gamma
- Th17 releases IL17
- these cytokines recruit macrophages and neutrophils which leads to tissue damage. Ex: contact dermatitis by exposure to poison ivy.

B. T cell mediated cytolysis:
CD8+ CTLs interact with the tissue to cause cell killing and tissue injury.

PHAR 303 (21 decks)

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