Immunology IM Flashcards
1
Q
Innate immunity
A
Is mediated by cells and proteins that are always present poised to react against infectious
pathogens
- Called into action immediately in response to infection Provide the first line of defense
- A major reaction of innate immunity is inflammation
2
Q
Adaptive immunity
A
Normally silent and responds(or adapts) to the presence of infectious agents by generating potent mechanisms for neutralizing and eliminating the pathogens
3
Q
Types of Innate immunity
A
-Dendiritic cells
-Complement
-Nk Cells
-Phagocytes
4
Q
Properties of Innate Immunity
A
● Innate immunity is resistance that exists prior to exposure to the microbe (antigen)
● Nonspecific
● Includes host defenses such as barriers to infectious agents (e.g., skin and mucous membranes), certain cells (e.g., natural killer cells), and certain proteins (e.g., the complement cascade and interferons)
● Involves processes such as phagocytosis and inflammation
● Does not improve after exposure to the organism, in contrast to acquired immunity
● Innate immune processes have no memory
● End Results is Inflammation
5
Q
Pattern recognition receptors
A
Are located in all the cellular compartments where pathogens may be present: plasma membrane receptors detect extracellular pathogens, endosomal receptors detect ingested microbes, and cytosolic receptors detect microbes in the cytoplasm
6
Q
T cell recognition of abnormal antigens on the surface leading to killing of infected cells
A
Cell-Mediated Immunity
7
Q
B cell production of antibodies that bind antigens resulting in either neutralization, lysis, or phagocytosis
A
Humoral Immunity
8
Q
Neutralization of microbe, phagocytosis, complement activation
A
B lymphocyte
9
Q
Helper T lymphocyte + Microbial antigen presented by APC
A
Cytokines
- Activation of macrophages
- Inflammation
- Activaation (proliferation and differentiation) of T and B lymphocytes
10
Q
Cytotoxic T lymphocytes (CTL) + Infected cell presenting microbial antigen
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Killing of infected cell
11
Q
Regulatory T lymphocyte
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Suppression of immune response
12
Q
express antigen receptors but have not responded to antigens and do not serve any functions
A
Naive lymphocytes
13
Q
induced by lymphocyte activation and perform the functions that eliminate microbes
A
Effector lymphocytes
14
Q
induced during activation, survive in a functionally silent state even after the antigen is eliminated and respond rapidly upon subsequent encounters with the antigen
A
Memory lymphocytes
15
Q
induced during activation, survive in a functionally silent state even after the antigen is eliminated and respond rapidly upon subsequent encounters with the antigen
A
Memory lymphocytes
16
Q
The process by which host defenses originate can be summarized by three actions:
A
- Recognition of the foreign organism by specific immune cells
- Activation of immune cells to produce a specific response (e.g., antibodies)
- Response that specifically targets the organism for destruction
17
Q
Major functions of T cells (Cell-Mediated Immunity)
A
- Host defense against infection (especially M. tuberculosis, fungi, and virus-infected cells)
- Allergy (hypersensitivity) - e.g poison oak
- Graft and tumor rejection
- Regulation of antibody response (help and suppression)
18
Q
Major functions of B cells (Antibody-Mediated Immunity)
A
- Host defense against infection (opsonize bacteria, neutralize toxins and viruses)
- Allergy (Hypersensitivity)- eg, hay fever, anaphylactic shock
- Autoimmunity
19
Q
Class I MHC
A
Molecules are expressed on all nucleated cells and are encoded by three closely linked loci, designated HLA-A, HLA-B, and HLA-C
20
Q
Class I MHC
A
Molecules are expressed on all nucleated cells and are encoded by three closely linked loci, designated HLA-A, HLA-B, and HLA-C
21
Q
Class II MHC
A
Molecules are encoded by genes in the HLA-D region, which contains three subregions: DP,DQ, and DR
Expression of class II MHC molecules is restricted to a few cell types, mainly APCs (notably, dendritic cells), macrophages, and B cells
22
Q
TH1 = IFN-y
A
Target Cells: Macrophages
Host defense: Intracellular pathogens
Role in disease: Autoimmunity; Chronic inflammation
23
Q
TH2 = IL-4, IL-5, IL-13
A
Target Cells: Eosinophils
Host defense: Helminths
Role in disease: Allergy
24
Q
TH17 = IL-17, IL-22
A
Target Cells: Neutrophils
Host defense: Extracellular pathogens
Role in disease: Autoimmunity
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IL-4
stimulates B cells to differentiate into IgE-secreting plasma cells
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IL-5
Activates eosinophils
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IL-13
activates mucosal epithelial cells to secrete mucus, and induces the “alternative” pathway of macrophage activation, which is associated with tissue repair and fibrosis
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Activated CD8+ T lymphocytes differentiate into CTLs that
kill cells harboring cytoplasmic microbes, thereby eliminating otherwise hidden reservoirs of infection
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Regulatory T cells (Tregs)
Are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and selftolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity.
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Primary T cell activation involves the integration of three distinct signals delivered in sequence:
1. antigen recognition
2. costimulation
3. cytokine- mediated differentiation and expansion
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IgA
-Found in mucus, saliva, tears, and breast milk
-Protects againts pathogens
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IgD
-Part of the B cell receptor: Activates basophils and mast cells
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IgE
-Protects against parasitic worms
-Responsible for allergric reactions
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IgG
-Secreted by plasma cells in the blood
-Able to cross the placenta into the fetus
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IgM
-May be attatched to the surface of a B cell or secreted into the blood
-Responsible for early stages of immunity (1st)
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NK cells are
lymphocytes that arise from the same common lymphoid progenitor that gives rise to T lymphocytes and B lymphocytes. However, NK cells are innate immune cells, as they are functional without prior activation and do not express highly variable and clonally distributed receptors for antigens
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NK cells 2 types of receptors
1. Inhibitory receptors - recognize self class I MHC molecules, which are expressed on all healthy cells, whereas
2. Activating receptors - recognize molecules that are expressed or upregulated on stressed or infected cells
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Innate Lymphoid Cells (ILCs)
● Population of lymphocytes that lack TCRs but produce cytokines similar to thosethat are made by T cells
● Classified into three groups, which produce IFN-γ, IL-5, or IL-17, cytokines that are characteristic of TH1, TH2, and TH17 subsets of T cells, respectively
● ILCs may be early participants against infections and in inflammatory diseases
● Because ILCs mostly reside in tissues, they are thought to provide early defense against infections in the tissues, before T cells are activated and can migrate into tissues.
39
Dendritic Cells (DCs)
● Are the most important antigen- presenting cells for initiating T-cell responses against protein antigens
● Located at the right place to capture antigens—under epithelia, the common site of entry of microbes and foreignantigens, and in the interstitial of all tissues, where antigens may be produced.
● Langerhans cells - DCs within the epidermis
● These cells have numerous cytoplasmic processes that resemble dendrites, from which they derive their name. Several features of DCs account for their key role in antigen capture and presentation.
● Express many receptors for capturing and responding to microbes (and other antigens)
● In response to microbes, DCs are recruited to the T-cell zones of lymphoid organs
● Express high levels of MHC and other molecules needed for antigen presentation and activation of T cell
● Increase MHC On there surface
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Active Immunity
● Resistance induced after contact with foreign antigens (e.g., microorganisms)
● Contact may consist of clinical or subclinical infection, immunization with live or killed infectious agents or their antigens, or exposure to microbial products (e.g., toxins and toxoids)
● Host actively produces an immune response consisting of antibodies and activated helper and cytotoxic T lymphocytes
● Main advantage: resistance is long-term
● Major disadvantage: slow onset, especially the primary response
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Active Immunity
● Resistance induced after contact with foreign antigens (e.g., microorganisms)
● Contact may consist of clinical or subclinical infection, immunization with live or killed infectious agents or their antigens, or exposure to microbial products (e.g., toxins and toxoids)
● Host actively produces an immune response consisting of antibodies and activated helper and cytotoxic T lymphocytes
● Main advantage: resistance is long-term
● Major disadvantage: slow onset, especially the primary response
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Passive Immunity
● Resistance is based on antibodies preformed in another host • Administration of antibody against diphtheria, tetanus, botulism, etc., makes large amounts of antitoxin immediately available to neutralize the toxins
● Preformed antibodies to certain viruses (e.g.,rabies and hepatitis A and B viruses) can be injected during the incubation period to limit viral multiplication.
● Other forms of passive immunity: IgG passed from mother to fetus during pregnancy and IgA passed from mother to newborn during breast feeding
● Main advantage: prompt availability of large amounts of antibody
● Disadvantages: short life span of these antibodies and possible hypersensitivity reactions if globulins from another species are used
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Classic activation pathway
Antigen/antibody immune complex
- C1q,C1r,C1s
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Mannose-binding lectin activation pathway
Microbes with terminal mannose groups
-MBL, MASP1, MASP2
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Alternative activation pathway
Bacteria, fungi, virus or tumor cells
-C3 (H2O)
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Type I - Immediate hypersensitivity
Immune mechanisms: Production of IgE antibody - immediate release of vasoactive amines and other mediators from mast cells; later recruitment of inflammatory cells
Histopathologic lesions: Vascular dilation, edema, smooth muscle contraction, mucus production, tissue injury, inflammation
Prototypical disorders: Anaphylaxis, allergies, bronchial asthma (atopic forms)
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Type II - Antibody-mediated Hypersensitivity
Immune mechanisms: Production of IgG, IgM - binds to antigen on target cell or tissue - phagocytosis or lysis of target cell by activated complement or Fc receptors; recruitment of leukocytes
Histopathologic lesions: Phagocytosis and lysis of cells; inflammation in some disease, functional derangements without cell or tissue injury
Prototypical disorders: Autoimmune hemolytic anemia; Goodpasture syndrome
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Type II
Immune mechanisms:
Histopathologic lesions:
Prototypical disorders:
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Type III - Immune Complex- Mediated Hypersensitivity
Immune mechanisms: Deposition of antigen-antibody complexes -> complement activation -> recruitment of leukocytes by compelement production and Fc receptors -> release of enzymes and other toxic molecules
Histopathologic lesions: Inflammation , necrotizing vasculitis (fibrinoid necrosis)
Prototypical disorders: SLE; some forms of Glomerulonephritis, Serum sickness, Arthus reaction
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Type IV - Cell- Mediated Hypersensitivity
Immune mechanisms: Activated T lymphocytes -> (1) release of cytokines, inflammation and macrophage activation; (2) T cell-mediated cytotoxicity
Histopathologic lesions: Perivascular cellular infiltrates, edema, granuloma formation, cell destruction
Prototypical disorders: Contact dermatitis, Multiple sclerosis, Type I diabetes, Tuberculosis
51
TH2 cells that are induced secrete several cytokines, including IL-4, IL-5, and IL-13 function :
• IL-4 stimulates B cells specific for the allergen to undergo heavy-chain class switching to IgE and to secrete this immunoglobulin isotype
• IL-5 activates eosinophils that are recruited to the reaction
• IL-13 acts on epithelial cells and stimulates mucus secretion.
• TH2 cells often are recruited to the site of allergic reactions in response to chemokines that are produced locally (eotaxin - recruits eosinophils to the same site)
52
Vasoactive amines
• released from granule stores
• granules of mast cells contain histamine released within seconds or minutes of activation.
• Histamine causes vasodilation, increased vascular permeability, smooth muscle contraction, and increased secretion of mucus.
• Other rapidly released mediators:
- chemotactic factors for neutrophils and eosinophils
- neutral proteases (e.g., tryptase), which may damage tissues and also generate kinins and cleave complement components to produce additional chemotactic and inflammatory factors (e.g., C5a)
53
Newly synthesized lipid mediators
• Prostaglandin D2 (PGD2) - most abundant mediator generated by the cyclooxygenase pathway in mast cells. (causes intense bronchospasm as well as increased mucus secretion)
• Leukotrienes LTC4 and LTD4 are the most potent vasoactive and spasmogenic agents known (several thousand times more active than histamine in increasing vascular permeability and in causing bronchial smooth muscle contraction)
• LTB4 is highly chemotactic for neutrophils, eosinophils, and monocytes
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Cytokines
• Important for the late-phase reaction
• TNF and chemokines, which recruit and activate leukocytes
• IL-4 and IL-5, which amplify the TH2initiated immune reaction
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The reactions of immediate hypersensitivity clearly did not evolve to cause human discomfort and disease by
• TH2 response plays an important protective role in combating parasitic infections.
• IgE antibodies target helminths for destruction by eosinophils and mast cells.
• Mast cells also are involved in defense against bacterial infections
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The immediate reaction
• stimulated by mast cell granule contents and lipid mediators
• characterized by vasodilation, vascular leakage, and smooth muscle spasm
• usually evident within 5 to 30 minutes after exposure to an allergen and subsiding by 60 minutes
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The immediate reaction
• stimulated by mast cell granule contents and lipid mediators
• characterized by vasodilation, vascular leakage, and smooth muscle spasm
• usually evident within 5 to 30 minutes after exposure to an allergen and subsiding by 60 minutes
58
Late- Phase Reaction
• Stimulated mainly by cytokines • Usually sets in 2 to 8 hours later, may last for several days
• Characterized by inflammation, tissue destruction, such as mucosal epithelial cell damage
• Dominant inflammatory cells are neutrophils, eosinophils, and lymphocytes, especially TH2 cells
- Neutrophils are recruited by various chemokines
- Eosinophils are recruited by eotaxin (produce major basic protein and eosinophil cationic protein, which are toxic to epithelial cells, and LTC4 and platelet-activating)
- TH2 cells produce cytokines (leukocytes can amplify and sustain the inflammatory response, even in the absence of continuous allergen exposure)
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Anaphylaxis (may be caysed by drugs, bee sting, food)
Clinical and Pathologic Manifestation: Fall in BP (shock) caused by vascular dilation; airway obstruction due to laryngeal edema
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Broncial asthma
Clinical and Pathologic Manifestation: Airway obstruction caused by bronchial smooth muscle hyperactivity; inflammation and tissue injury caused by LATE- PHASE REACTION
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Allergic rhinitis, sinusitis (hay fever)- local reaction
Clinical and Pathologic Manifestation: Increased mucus secretion; inflammation of upper airways; sinuses
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Food allergies
Clinical and Pathologic Manifestation: Increase peristalsis due to contraction of intestinal muscles -> Vomiting and Diarrhea
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Histamine
• Most tissue histamine is sequestered and bound in granules (vesicles) in mast cells or basophils; the histamine content of many tissues is directly related to their mast cell content.
• Non-mast cell histamine: brain, enterochromaffinlike (ECL) cells of the fundus of the stomach
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Histamine antagonists (Physiologic antagonists)
epinephrine–have smooth muscle actions opposite to those of histamine
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Histamine antagonists (Physiologic antagonists)
epinephrine–have smooth muscle actions opposite to those of histamine
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Histamine Antagonists (Release inhibitors)
Cromolyn and Nedocromil - reduce the degranulation of mast cells that results from immunologic triggering by antigen-IgE interaction
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Anaphylaxis
• Anaphylaxis is a potentially life-threatening systemic allergic reaction involving one or more organ systems that typically occurs within seconds to minutes of exposure to the anaphylactic trigger, most often a drug, food, or hymenoptera sting.
• 80–90% of anaphylactic episodes are uniphasic • 10–20% of cases are biphasic in which anaphylactic symptoms return about an hour or longer after resolution of initial symptoms
• Particularly dangerous when hypotension or hypoxia occurs, leading potentially to cardiovascular collapse or respiratory failure
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results in flushing, urticaria, pruritus, and, in high concentrations, hypotension and tachycardia
Histamine
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cause bronchoconstriction and increased microvascular permeability
Cysteinyl leukotrienes and prostaglandin D2
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cause bronchoconstriction and increased microvascular permeability
Cysteinyl leukotrienes and prostaglandin D2
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causes cutaneous flushing, and attracts eosinophils and basophils to the site of mast cell activation.
Prostaglandin D2
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Treatment of choice for anaphylaxis
Treatment of first choice is intramuscular administration of 0.3–0.5 mL of 1:1000 (1 mg/mL) epinephrine, with repeated doses at 5–20 min intervals as needed for a severe reaction
a- and β-adrenergic effects - resulting in vasoconstriction, bronchial smooth-muscle relaxation, and attenuation of enhanced venular permeability
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Type II Hypersensitivity (Antibody-Mediated Disorders)
• Caused by secreted IgG and IgM antibodies that bind to fixed tissue or cell surface antigens
• Antibodies injure cells by promoting their phagocytosis or lysis and injure tissues by inducing inflammation
• Antibodies also may interfere with cellular functions and cause disease without cell or tissue injury
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Type II - Opsonization and Phagocytosis
• When circulating cells, such as red blood cells or platelets, are coated (opsonized) with autoantibodies, with or without complement proteins, the cells become targets for phagocytosis by neutrophils and macrophages
• These phagocytes express receptors for the Fc tails of IgG antibodies and for breakdown products of the C3 complement protein, and use these receptors to bind and ingest opsonized particles
• Opsonized cells are usually eliminated in the spleen, and this is why splenectomy is of clinical benefit in some antibody-mediated diseases
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Type III (Immune Complex-Mediated Disorders)
• Antigen–antibody (immune) complexes that are formed in the circulation may deposit in blood vessels, leading to complement activation and acute inflammation
• The antigens that form immune complexes may be exogenous, such as a foreign protein that is injected or produced by an infectious microbe, or endogenous, if the individual produces antibody against self antigens (autoimmunity)
• Immune complex–mediated diseases tend be systemic, but often preferentially involve the kidney (glomerulonephritis), joints (arthritis), and small blood vessels (vasculitis)
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Type IV (Cell mediated disease)
Two types of T cell reactions are capable of causing tissue injury and disease:
1. cytokine-mediated inflammation, in which the cytokines are produced mainly by CD4+ T cells–
2. direct cell cytotoxicity, mediated by CD8+ T cells
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Tuberculin Reaction
• Classic example of DTH
• intracutaneous injection of purified protein derivative (PPD, also called tuberculin), a protein containing antigen of the Mycobacterium tuberculosis bacillus
• In a previously exposed individual, reddening and induration of the site appear in 8 to 12 hours, reach a peak in 24 to 72 hours, and thereafter slowly subside.
• characterized by the accumulation of mononuclear cells, mainly CD4+ T cells and macrophages, around venules, producing perivascular “cuffing”
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Granulomatous Inflammation
• Prolonged DTH reactions against persistent microbes or other stimuli
• initial perivascular CD4+ T cell infiltrate is progressively replaced by macrophages over a period of 2 to 3 weeks
CD4+ T Cell–Mediated Inflammation
• accumulated macrophages typically exhibit morphologic evidence of activation - become large, flat, and eosinophilic, and are called epithelioid cells.
• The epithelioid cells occasionally fuse under the influence of cytokines to form multinucleate giant cells
• An aggregate of epithelioid cells, typically surrounded by a collar of lymphocytes, is called a granuloma
