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PharmD Program Semester 2 > Pathophysiology Immune System > Flashcards

Pathophysiology Immune System Flashcards

1
Q

Benefits of the Immune System

A

Elimination of pathogens, toxins, and tumors

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2
Q

Detriments of the Immune System

A

Immediate/delayed hypersensitivities

Autoimmune diseases

Inherited and acquired immunodeficiency

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3
Q

Normal function of the Immune System

A

Discrimination: Self vs Non-self

Memory: Able to recall exposures to previous foreign antigens

Specificity: Ability to discern between different foreign antigens

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4
Q

Innate Immune System

A

1st line of defense

Nonspecific arm, pattern recognition of antigens

Controls/contains pathogen

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5
Q

Adaptive immune system

A

Antigen specific arm, focused recognition
- Discrimination, specificity, and memory

Less rapid, but more specific response

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6
Q

Physical barriers of the Innate Immune System

A

Skin, mucosal membranes, ciliary action in bronchi

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7
Q

Chemical barriers of the Innate Immune System

A

Intestinal and vaginal pH

Enzymes: Secretions, tears, and saliva

Complement: Alternative pathway

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8
Q

Cellular defense of the Innate Immune System

A

Dendritic cells

Monocytes/macrophages

Polymorphonuclear leukocytes

NK cells

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9
Q

Adaptive Immunity

A

Attacks specific pathogen after exposure to an antigen from a pathogen

Includes humoral and cell mediated immunity

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10
Q

Humoral immunity

A

B-lymphocytes and antibodies

Primarily extracellular pathogens

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11
Q

Cell-mediated immunity

A

T-lymphocytes

Primarily for intracellular antigens (Viruses)

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12
Q

Principle Adaptive Immunity Cells

A

Lymphocytes: B-cells, T helper (CD4), and Cytotoxic T (CD8) cells

Antigen presenting cells: Macrophages and dendritic cells

Effector cells: Activated cytotoxic T cells, B cells, and Leukocytes

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13
Q

Major Histocompatibility Complexes (MHC)

A

Two classes: MHC 1 and 2

Help with intracellular antigen recognition

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14
Q

MHC Class 1 antigens

A

On all nucleated cells of the body

Recognize intracellular antigens

Viral peptide complex with MHC-1 on surface, complex signal target for cytotoxic T-cell mediated death

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15
Q

MHC Class 2 antigens

A

On phagocytic cells

Engulfed fragments complex with MHC-2 on surface

T-helper cells recognize complex and become activated

Secrete cytokines

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15
Q

Typical Kinetics of an Immune Response

A

Innate Mostly: Phagocytes, inflammatory cytokines, interferons, and cytokines

Adaptive mostly: T cells and antibodies

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16
Q

Innate vs Adaptive Immunity

A

Innate: Physical barriers, phagocytes, complements, and NK cells

Adaptive immunity: B lymphocytes, T lymphocytes, and Effector T cells

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17
Q

Antibody Effector Functions

A

Neutralization

Opsonization

Antibody dependent cell-mediated cytotoxicity

Complement activation (fixation)

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18
Q

Antibody Neutralization Function

A

Toxins, viruses, bacteria

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19
Q

Antibody Opsonization Function

A

Coating of antigen by Ig increases efficiency of phagocytosis via Fc receptors on the phagocytic cells

20
Q

Antibody Cytotoxicity Function

A

Increases efficiency of NK lysis of target cell; IgE-mediated helminth destruction by eosinophils

21
Q

Complement Activation

A

Recruitment of inflammatory cells

Opsonization of pathogens

Killing of pathogens via membrane attack complex

22
Q

Lymphoid Tissue

A

Central organs: Bone marrow and thymus
- Cell production and maturation

Peripheral organs: Spleen, lymph nodes, tonsils, Peyer’s patches, appendix, and submucosal layers
- Trap and process antigens

23
Q

Human Immunoglobulins

A

IgA: Mucosal immunity, prevents antigens from entering

IgD: Found on B-cells, antigen receptor

IgE: Found on mast cells, immediate hypersensitivity, parasite immunity, inflammation reactions

IgG: Opsonization, neutralization, complement activation

IgM: Receptor - B cells, complement activation

24
Immune system regulation
Inadequate response: Immunodeficiency Excessive response: Hypersensitivity, autoimmune diseases Increased tolerance to foreign antigens: Infections Immune privileged tissues: Maternal-fetal tissues, brain, testes, ovaries, eyes
25
Type 1 Hypersensitivity
IgE mediated allergies Typical allergens: Pollen, dust mites, animal dander, foods, drugs Cells involved: Mast cells and CD4 T-helper cells Examples: Hay fever, asthma, and anaphylaxis reaction
26
Systemic Type 1 Hypersensitivity reactions
Anaphylactic shock: Can be stopped with epinephrine injection
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Local (Atopic) Type 1 Hypersensitivity reactions
Allergic rhinitis Hives Asthma Dermatitis GI distress
28
Type 2: Antibody-mediated
IgG or IgM mediated Directed against cell surface antigens - Endogenous: ABO/Rh mismatch - Exogenous: Drug=cell interaction
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Type 3: Immune-complex mediated
Insoluble Ag-AB complexes - Vessel wall = vasculitis - Glomeruli = Glomerulonephritis - Joint synovium Inflammation and tissue damage Systemic reactions - Lupus erythematosus - Serum sickness Local reactions - Arthus reaction --- Local skin necrosis and red, raised lesion with vasculitis
30
Type 4: Cell-mediated
Mediated with sensitized T-cells Direct cytotoxicity - Primed Th cells activate Tc cells - Self-antigen = autoimmunity Delayed type (DTH) - Activated Th secrete cytokines - Recruit, activate other cells - Cytokine synthesis = 24-74 hours
30
Mechanisms of Autoimmunity
Largely unknown - Genetic factors - but relatively few - Environmental factors: 1. Decreased anergy - Promotes responsiveness to self-antigens 1a. Anergy = Prolonged unresponsiveness to self-antigens 2. Release of normally sequestered antigens 2a. Sperm + ocular antigens via trauma 3. Molecular mimicry 3a. Mistaken identity 3b. Pathogens with same amino acid sequence as self antigens 4. Superantigens 4a. Exotoxins that inappropriately activate T-helper cells
31
Autoimmune diseases
Loss of self-tolerance - APC presents antigen + MHC-2 to CD4 cells Mechanisms of tolerance - Eliminate self-reactive B-cells in: --- Bone marrow --- Spleen + lymph nodes - Eliminate self-reactive T-cells in: --- Thymus gland Failure of tolerance results in: - Autoimmune diseases
32
Graves Disease
B-cells produce thyroid stimulating IgG 1. IgG mimics TSH; Greater T3/T4 from thyroid Symptoms: 1. Hyperthyroidism 2. Goiter
33
Myasthenia gravis disease
Auto-antibodies against nicotinic receptors in neuromuscular junction Symptoms: 1. Ptosis 2. Diplopia 3. Difficulty swallowing and chewing 4. Weakness in the extremities 5. Breathing difficulties
34
Rheumatoid arthritis
Pathogenesis: 1. Activated macrophages --> inflammation 2. Activated B-cells --> Complement activation --> damage 3. Pannus --> granulation tissue Results: 1. Immune-mediated inflammation: Synovitis 2. Destruction of articular cartilage and underlying bone Signs/Symptoms: Stiff achy joints, enlarged joints, extreme stiffness, ankylosis Variable progression 50% chronic remitting-relapsing course 25% stabilize 25% recover, near normal function Treatment: 1. NSAIDS 2. Immunosuppression (methotrexate) and steroids 3. Biologicals: anti-TNF's - recent advance in therapy
35
Systemic Lupus Erythematosus
Chronic, systemic inflammatory disease - Effects all organ systems Etiology: Largely unknown Pathogenesis: 1. B-cell hyperactivity - polyclonal autoantibodies a. Against RBCs, platelets b. Anti-nuclear (DNA) antibodies Factors: 1. Genetics: Class 2 HLA-DR, HLA-DQ, twins 2. Hormonal: Exacerbation during menses, pregnancy 3. Environmental: Some drugs, UV light
36
Systemic Lupus Symptoms and Treatment
Disease course (exacerbations and remissions): 1. Joints, kidney, musculoskeletal, CV/lungs, skin, RBCs, platelets Treatment: 1. Steroids 2. Immunosuppression
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Primary Immunodeficiency Disorders
Congenital or inherited a. Humoral deficiencies b. Cellular deficiencies c. Severe combined immunodeficiency syndrome
38
Humoral Disorder Examples
Genetically deceased/absent B-cell function and antibody production a. Prone to ---- pathogens Hypogammaglobulinemia or agammaglobulinemia (IgG, IgA, IgM, IgE, and IgD) or selective (IgA or IgG) a. Intracellular bacteria and viral pathogens ----
38
Secondary Immunodeficiency Disorders
Usually acquired later in life a. HIV/AIDS
39
Cellular Disorder Examples
DiGeorge syndrome: a. Chromosome 22 defect: Incomplete thymus development b. Decreased T-cell maturation c. Decreased T-helpers = No adaptive immune system d. Result: Prone to reinfection Treatment: Thymus transplant, bone marrow transplant Severe combined immunodeficiency syndrome: SCIDS a. Absence of all immune function b. Resembles AIDS: Cancers, disease, death by 2 years old c. Can be treated with bone marrow or stem cell transplants
40
Obligate Intracellular Bacteria
Chlamydia: Most common STD Rickettsia: Typhus Mycobacterium leprae: Leprosy
41
Facultative Bacteria
Bartonella henselae: Cat-scratch disease Salmonella typhi: Typhoid Legionella: Legionnaires' disease Mycobacterium: Tuberculosis Neisseria: Meningitis and gonorrhea S. aureus: Sinusitis, food poisoning
42
Acquired Immunodeficiency Syndrome (AIDS)
HIV infection Transmission: a. Unprotected sexual contact b. Blood-blood contact c. Occupational d. Breast feeding
43
AIDS Cellular Pathophysiology
Infects CD4 cells, macrophages, and dendritic cells Sequence of infection: 1. Binding/attachment to CD4 cells 2. Internalization and uncoating 3. DNA synthesis 4. Integration 5. Transcription 6. Translation 7. Cleavage 8. Assembly and release
44
AIDS Treatment Options
Reverse transcriptase inhibitors Protease inhibitors Attachment inhibitors Integrase inhibitors
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Diseases that are more common with HIV
Respiratory tract: Pneumonia, TB GI tract: Chronic gastroenteritis, esophagitis CNS infections: Dementia, lethargy, demyelination, and ataxia Malignancies: Kaposi's sarcoma, non-Hodgkin's Lymphoma General wasting syndrome

PharmD Program Semester 2 (14 decks)

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