Part 1 Flashcards by Arriane Cyrel (MTI)

Immunology

How well did you know this?

Not at all

Perfectly

Chinese developed a practice of inhaling powder made from smallpox scabs to induce protection.

1500

How well did you know this?

Not at all

Perfectly

practice of deliberately exposing an individual to material from smallpox lesions so that a
healthy individual when exposed to disease (small pox) the disease will be minimized

Variolation

How well did you know this?

Not at all

Perfectly

Edward Jenner discovered the relationship between exposure to cowpox and immunity to smallpox (explains the phenomenon of cross-immunity)

17005

How well did you know this?

Not at all

Perfectly

-from Latin word “vacca” which means “cow”
procedure of injecting cellular material. Edward Jenner injected individuals with material from a cowpox lesion and then exposed them from smallpox. This was based on his observation among milkmaids who were exposed to cowpox and eventually developed immunity to smallpox

Vaccination

How well did you know this?

Not at all

Perfectly

development of first attenuated vaccine

Louis Pasteur

How well did you know this?

Not at all

Perfectly

change of virulent to non-virulent by heat, aging or chemical means.

Attenuation

How well did you know this?

Not at all

Perfectly

Serum Antitoxins

Cellular Immunity in TB

Phagocytosis

Immunity

Anaphylaxis

Emil vin Behring

Robert Koch

Ellie Metchnikoff

Paul Ehrlich

Charles Richet

How well did you know this?

Not at all

Perfectly

Complement

Human Blood Group Ags

Immunologic Tolerance

Structure of Antibodies

Radioimmunosay

Major Histocompatibility Complex

Immunoregulation

Monoclonal Antibody

Antibody Diversity

Transplantation

Cytotoxic T cell -Recognition of virally infected cells
Theory of Cellular and Humoral Immunity

Jules Bordet

Karl Landsteiner

Macfariane Burnet ,Peter Medawar

Gerald Edelman Rodney Porter

Rosalyn Yallow

George Snell, Jean Dausset Baruj Benaceraf

Niels Jere .Georges Koehler

Cesar Milstein

Susumu Tonegawa

E.Donnall Thomas, Joseph Murray Peter Doherty ,Rolf

Zinkermagel Almoth Wright

How well did you know this?

Not at all

Perfectly

is the ability of the individual to resist infection by means of normally present body functions

is a type of resistance that is characterized by specificity for each individual pathogen and the ability to remember a prior exposure, which result in an increase response upon repeated exposure

Natural Immunity

Acquired Immunity

How well did you know this?

Not at all

Perfectly

First Line of Defense

Second Line of Defense

Third Line of Defense

How well did you know this?

Not at all

Perfectly

Mechanical barrier retard entry of microbes
Acidic environemtn (ph 3-5) retards growth of microbes.

1.Skin (unbroken)

How well did you know this?

Not at all

Perfectly

entraps foreign microorganisms
Cilia propel microorganisms out of the body

Mucous membrane

How well did you know this?

Not at all

Perfectly

Normal body temperature inhibits growth of some pathogens
Fever response inhibits growth of some pathogen

Temperature

How well did you know this?

Not at all

Perfectly

Secretions containing Lysozymes (which cleaves bacterial cell wall)

о Saliva
о Tears

How well did you know this?

Not at all

Perfectly

Phagocytic cells

Neutrophil
Monocytes
Macrophages

How well did you know this?

Not at all

Perfectly

Liver:
Lung:
Spleen:
Brain and CNS:

Kupffer cells

Alveolar Macrophage

Splenic Macrophage

Microglial

How well did you know this?

Not at all

Perfectly

Natural Antimicrobial Substances:

complement: lysis & facilitates phagocytosis
Independent Pathway

How well did you know this?

Not at all

Perfectly

Specialized Lymphocytes

a. T-cells
b. B-cells

How well did you know this?

Not at all

Perfectly

Antibodies:

Immunoglobulin G
Immunoglobulin A
Immunoglobulin M
Immunoglobulin E
Immunoglobulin D

How well did you know this?

Not at all

Perfectly

Natural Immune System

Cellular

Humoral

Mast cell
Neutrophil
Macrophages

Complement
Lysozyme
Interferon
C-Reactive protein

How well did you know this?

Not at all

Perfectly

(act as an opsonin and activate the classical complement pathway)

C-Reactive protein

How well did you know this?

Not at all

Perfectly

Adaptive Immune System

Cellular

Humoral

T-cell
B-cell
Plasma cell

Antibodies
Cytokines

How well did you know this?

Not at all

Perfectly

early responders to foreign particles, particularly bacteria and move through vessel walls by diapedesis to site of injury; response is phagocytosis and inflammation enhanced by cvtokines

NEUTROPHIL

How well did you know this?

Not at all

Perfectly

responder/effector cells in allergic and parasitic infections; can be involved in phagocytosis but not to large degree because the numbers of this WBC in response is low.

EOSINOPHIL

effector cells in immediate hypersensitivity reactions also can be involved in phagocytosis, but to a small degree because the number of circulating basophils is low. similar to basophils but have a longer life span, play a role in hypersensitivity reactions, binds immunoglobulin E (IgE).

BASOPHIL

Have long membranous extensions are antigen presenting cells and phagocytic, present to T cells in bloodstream or lymphoid tissue.

DENDRITIC CELL

large lobular phagocytic cells, in tissues are called macrophages.

MONOCYTE

important regulator of phagocytosis of bacteria and parasites. Secretes such as cytokines. • Tumoricidial effects • Antigen Presentation

MONOCYTE-MACROPHAGE

receptors recognize patterns in microbial cell walls or membranes and enance recognition by phagocytic neutrophils and monocytes

TOLL LIKE RECEPTORS PATHOGEN RECOGNITION RECEPTORS

Lipomannans (mycobacteria) Lipoproteins (diacy Iipopeptides; triacyl Iipopepides) Lipoteichoic acids (Gram-positive bacteria) Cel-wall B-glucans (bacteria and fungi) Zymosan (fungi) Monocytes, dendrite cels, mast cels. basophils, eosinophils

TLR-1:TLR-2 heterodimer TLR-2 TLR-6 heterodimer

Double-stranded RNA (viruses) NK cels

TLR-3

LPS (Gram-negatve bacteria) LIpoteichoic acids (Gram-positive bacteria) Macrophages, dendrite cels, mast cels, eosinophils

TLR4- (plus MD-2 and CD14)

Flagelin (bacteria) Intestinal epithelium

TLR-5

Single-stranded FNA (vises) Plasmacytoid dendritic cels, NK cells, eosinophis, B cells

TLR-7

Single-stranded RNA (viruses) NK cels

TLR-8

DNA with unmethylaled CpG (bacteria and herpesviruses) Plasmacytoid dendritic cells, eosinophis, B cells, basophils

TLR-9

Unknown Plasmacytoid dendritic cells, easinophils, B cells, basophils

TLR-10

Prollin and profin-like proteins (Toxoplasma gondi, uropathogenic bacteria) Macrophages, dendritic cells, Iiver, kidney, and bladder epithelial cells

TLR-11 (mouse only)

- process of engulfment of foreign bodies

Phagocytosis

- initiated as a result of tissue damage, either trauma or as a result of microorganism multiplication.

Phagocytosis

Phagocytosis Stages:

1. Initiation and Chemotaxis 2. Engulfment forming a Phagosome 3.Fusion of Cytoplasmic Granules and Phagosome to from Phagolysosome 4. Digestion 5. Excretion

Activated phagocyte has increased surface receptors that allow for adherence

1. Initiation and Chemotaxis

1. Initiation and Chemotaxis: 1. Physical contact starts when [?] roll along until they encounter the site of injury or infection. 2. They ADHERE to RECEPTORS on the endothelial cell wall of the blood vessel and penetrate the tissue by means of [?] which is aided by [?] (cells are attracted to the site of infection/inflammation by chemical substances such as soluble bacterial factors, complement components or C-reactive protein. 3. When neutrophil or monocyte come into contact with the foreign particle surface it is enhanced by [?] (greek word for " to prepare for eating") [?] are serum proteins that aids in the preparation of the foreign body for phagocytosis. - coating the particle with plasma factors to speed up phagocytosis ex. CRP, complements and antibodies, C3b

Neutrophils DIAPEDESIS; CHEMOTAXIS OPSONIN Opsonin

MECHANISM: opsonins neutralize the surface charge of foreign bodies making it easier cells to approach each other.

1. Initiation and Chemotaxis

Initiation and Chemotaxis NOTE: each phagocytic cells has a receptor for opsonins like Abs and complement.

a. CR3 b. Laminin receptor c. Leucyl formyl methionyl phenylalanine receptor

Phagocytic cell is attracted to the invading organism by chemical mediators secreted by other immune cells .

Initiation and Chemotaxis

Process by which cells tend to move in a certain direction under the stimulation of a chemical substance "chemotaxins"

Initiation and Chemotaxis

After attachment an increase in oxygen consumption respiratory or oxidative burst occurs within the cell) as pseudopodia enclose the particle within a vacuole forming PHAGOSOME Phagocytic cells engulf the particle

2. Engulfment forming a Phagosome

2. Engulfment forming a Phagosome • Possible by active

AMOEBOID MOTION

Final structure is known as

phagosome or phagocytic vacuole

= foreign particle + engulfment /outflowing of the cytoplasmin

PHAGOSOME

Inhibited by large capsule activity (H. influenzae, N, meningitidis and S. pneumoniae) Organism is enclosed in a vacuole.

PHAGOSOME

- coating of particles with plasma factors 10 hasten phagocytosis

OPSONIZATION

- antibodies and complement that interact with the surfaces of bacteria rendering them acceptable to the phagocyte

OPSONIN

Phagosome moves toward the center of the cell

3.Fusion of Cytoplasmic Granules and Phagosome to from Phagolysosome

4. Digestion Released is by

EXOCYTOSIS

The actual process of killing is oxygen dependent and results from the formation of bactericidal metabolites.

4. Digestion

* minute cell particle that contain Hydrolytic enzymes and peroxidase approach the phagosome , fuse with It, rupture and discharge contents to it. Cells become degranulated as foreign materials are digested.

4. Digestion

hydrolytic enzymes found in mucus secretions and tears cleaves the Peptidoglycan layer of the bacterial cell wall.

LYSOSOME

Cells become degranulated as foreign materials

4. Digestion

DIGESTION MECHANISM: • RESTING CELLS derived energy from [?] • IF PHAGOCYTOSIS is triggered: the respiratory burst produces energy via [?] • The [?] change NADP to NADPH (reduced for of NADP by adding Hydrogen) b. NADPH donates electron to oxygen in the presence of [?](a membrane-bound enzyme that is activated only when conformational change is triggered by the Microbes. c. The [?] is formed -this is highly toxic and converted more to lethal products d. 02 + Hydrogen ion in the presence of [?] - Hydrogen Peroxide or OH • [?] is a bactericidal agent and more stable compared to other free radicals. • The effect of Hydrogen Peroxide is potentiated by formation of Hypochlorite lons by action of [?] in the presence of Chloride ions

Anaerobic Glycolysis oxidative metabolism. HMP shunt NADPH oxidase radical 02 (superoxide) superoxide dismutase (SOD) Hydrogen peroxide Myeloperoxidse

2 MAJOR MECHANISM for the Killing of pathogen: a. [?] or Increase Oxygen consumption by activation of Hexose Monophospahte Shunt forming oxygen radicals. b. [?] across the membrane of Phagolysosome (NADPH oxidase depolarize the membrane allowing hydrogen and potassium lons enter the vacuole. When Hydrogen combines with Superoxides the pH increases which in tum activates proteases that kills the microbe.

Respiratory Burst Alteration of charge

is known to be central to the killing of microbes because or its dysfunction related to making an individual susceptible from recurrent and severe bacterial infections. (due to inability to phagocytose or kill ingested organism).

NADPH oxidase

By products of digestion are transported to cell membrane and released outside the cell.

5. Excretion

Destruction of the Antigen 1. Formation of the Phagolysosome leading to the release of lysosomal contents including [?] 2. [?] produced by activated macrophages which is toxic to micraorganisms such as bacteria 3. Activation of the NADPH oxidase which is present in the phagosome membrane leading to the production of reactive oxygen intermediates such as [?] which are cytotoxic for microorganisms (Respiratory Burst or Increase Oxygen consumption by activation of Hexose Monophospahte Shunt forming oxygen radicals or activation of NADPH oxidase present in the phagosome membrane producing reactive oxygen intermediates like superoxide anion, hydrôgen peroxide and hydroxyl radicals which are cytotoxic to microorganisms). 4. Alteration of charge across the membrane of Phagolysosome by activating [?] (increasing the pH activating protease)

defensins, lactoferrin, and lysozyme Nitric oxide superoxide anion, hydrogen peroxide and hydroxyl radicals NADPH oxidase

aids healing but can also cause damage to tissue around the site of inflammation.

Both cellular and humoral response

increased rate of blood flow towards site of injury transfer of internal heat to the surface site of injury brought about by increased blood content. due to pressure upon the sensory nerve by the exudate. increased capillary permeability, allowing extravasation of blood fluid due to pain interference with nerve supply and to destruction of the functioning units of the tissue.

RUBOR CALOR DOLOR TUMOR FUNTIO LAESA

Stages of Inflammation

1, Vascular response 2. Cellular response 3.Resolution and Repair

• first stage of inflammation

1. Vascular response

response of a Phagocytic cell / Effectors:

2. Cellular response NEUTROPHIL: ACUTE INFLAMMATION MACROPHAGES: TISSUE MONOCYTES

initiated by fibroblast proliferation as a result: a. affected area may be totally repaired b. injury may lead to the formation of an abscess with some loss of function

3. Resolution and Repair

- opsonization, complement activation - removal of cholesterol - protease inhibitor - clot formation - binds hemoglobin - binds copper and oxidized iron -opsonization, lysis

CRP Serum Amyloid A Alpha-1 antitrypsin Fibrinogen Haptoglobin Ceruloplasmin Complement C3

SOLUBLE SUBSTANCES Cytokines:

Interferon, Tumor Necrosis Factor, Interleukins, Chemokines, Transforming Growth Factor and Colony Stimulating Factor

Regulate growth and differentiation of immune system effector cells (chemical messengers)

Cytokines

Soluble proteins that regulate innate and adaptive immunity.

Cytokines

Cytokines - WITH MANY DIFFERENT EFFECTS - OVERLAPPING EFFECTS - COMBINED EFFECTS

Pleotropic Redundant Synergism

Example: gp 130 - shared by IL-6, IL-11, leukemia inhibitory factor, , oncostatin M, ciliary neurotrophic factor and cardiotrophin.

Redundant

- affects the same cell that secreted it - affects the target cell in proximity - systemic effect or direct in the bloodstream

Autoerine effects Paracrine effects Endocrine effects

Assist B-cell in commencing antibody production

Cytokines

Killing tumor and target cells

Cytokines

Rejecting grafts

Cytokines

Stimulating hematopoiesis in bone marrow

Cytokines

Initiating delayed hypersensitivity allergic reactions

Cytokines

• enhance motility and promote migration of many types of white blood cells toward the source of the chemokine (chemotaxis)

Chemokines

plays a key role on the initiation and development of inflammatory responses in numerous disease process.

Chemokines

are known to induce chemokine production in the inflammatory response.

IL-6 TNF-a

activates integrins or cell adhesion molecules, on leukocytes and leads to firm adhesion to endothelial cells.

Chemokines

Chemokines: classified according to the position of N-terminal cysteine residues.

Alpha or CXC Bete or CC C chemokines or CX3C

Has the ability to bind nearby cells and produce generalized anti-viral substances

Interferon

Family of glycoproteins produced by all animals cells that exert a virus-nonspecific but host specific antiviral activity.

Interferon

non-immune produced primarily in the initial innate response to viral infection

Type I Interferon

Produced by virus induced leukocyte culture

IFN- Alpha

IFN-Alpha Major producer:

NULL LYMPHOCYTE or NK CELLS

• Produced by double stranded RNA fibroblasts

IFN-Beta

IFN-Beta Major producer:

FIBROBLAST or ENDOTHELIAL CELL (FIBROENDOTHELIAL)

Immune, primarily produced as a component of the specific immune response to vira and other pathogens

Type Il Interferon

Produced by immunologically stimulated lymphocytes

IFN - Gamma

IFN - Gamma Major Producer:

T CELLS

- cytotoxic activity against tumor cells and virally infected cells

Tumor Necrosis Factor

produced by the macrophages called CATECHIN

TNF- Alpha

exist in both Membrane Bound and Soluble Forms

TNF- Alpha

- mediate all cytotoxic and inflammatory effect by TNF by cell to cell contact.

• Membrane Bound

causes VASODILATION AND INCREASED PERMEABILITY (RUBOR AND TUMOR)

TNF- Alpha

produced by ACTIVATED MACROPHAGE AND MONOCYTES

TNF- Alpha

Activate T-cells by inducing expression of MHC CLASS II MOLECULES

TNF- Alpha

-enhance Ag presentation and activate T cells.

Vascular Adhesion Molecules and Chemokines (similar with IL-1)

triggered by presence of LIPOPOLYSACCHARIDE FROM GRAM NEGATIVE BACTERIA

TNF- Alpha

produced by CD4 + and CD8 + cells called LYMPHOTOXIN

TNF- Beta

Cytokines produced mainly by T-cells for adaptive immune response.

Th1, Th2 and Treg (T-regulatory cells) Cytokines

responsible for cell-mediated immunity responsible for antibody-mediated immunity regulates activities of Th1 & Th2 from naive T cells

Th1 Th2 Treg

Clinical Assays for Cytokines

1. ELISA 2. PCR 3. Fluorescence 4. Microbead arrays

Cytokines of Innate Immunity Cytokines of Adaptive Immunity

IL-1 TNF-a IL-6 Chemokines TGF-B Th1 cytokines IFN-y IL-2 Th2 cytokines IL-4 IL-10

Acquired / Adaptive /Specific Immunity Basic principles:

Diversity, Memory, Specimpity, self/non-self recognition

Site of T and B cell maturation; CENTRAL LYMPHOID ORGAN Site of proliferation and differentiation of T and B cells; PERIPHERAL LYMPHOID ORGAN

Primary Lymphoid Organ Secondary Lymphoid Organs

Antigen trapping sites

Secondary Lymphoid Organs

CELL INVOLVED IN ADAPTIVE/ACQUIRED/SPECIFIC IMMUNITY

T- Lymphocytes Natural Killer (NK) cell

represent approximately 80% of the circulating lymphocytes in the peripheral bood

T- Lymphocytes

Most circulating T cells express three of the following CD markers: : SHEEP RBC RECEPTOR or CLASSICAL T-CELL SURFACE MARKER : PART OF T CELL AG RECEPTOR COMPLEX : RECEPTOR FOR MHC CLASS II MOLECULE : RECEPTOR FOR MHC MHC MHC CLASS I MOLECULE

CD2 CD3 CD4 CD8

- early precursor from bone marrow that enter the thymds.

Thymocyte

Development is by orderly rearrangement of genes coding for the antigen receptor.

Thymocyte

Thymic stromal cells (involved in T-cell development: epithelial cells, macrophages, fibroblasts and dendritic cells)

Thymocyte

Interaction of thymocytes with stromal cells is mediated by:

IL-7

Thymocyte With early surface:

CD44 and CD25

Considered a bridge between the innate and adaptive immune system because it is thought to have the same precursor as a lymphocyte but can respond to diseased cells without prior exposure to antigen.

Natural Killer (NK) cell

Thought to act by recognizing a lack of MHC class I proteins on diseased or cancerous cells

Natural Killer (NK) cell

Lack of these proteins along with signalers enhances the NK cell to cytolytic action against the damaged cell.

Natural Killer (NK) cell

Also act by way of ADCC or recognition and lysis of antibody coated infected cells.

Natural Killer (NK) cell

Important in transitional cell bridging innate and acquired response to pathogens.

Natural Killer Cells

Kill and initiate CYTOLYTIC REACTION without prior exposure to antigen

Natural Killer Cells

Natural Killer Cells Two subsets - produce higher level of cytokines INF-gamma and NF alpha) and support antibody production - higher cytotoxic activity

NK cell with high CD56 and low CD16 NK cell with low CD56 and high CD16

Note: NK cells are stimulated once exposed to cytokines which Includes

INF-gamma, TF-alpha

are able to distinguish a healthy cell from a infected or cancerous cell.

NK cells

Delivers inhibitory signal by recognizing MHC Class I

Inhibitory Receptor

Delivers signal to activate cytotoxic mechanism

Activating Receptor

Triggered by lack of MHC Class I protein Secretes PERFORIN and GRANZYMES

Activating Receptor

T- cell development B-cell Development

1. Double-Negative Thymocytes 2. Double-Positive Thymocytes 3. Mature T-cell / Single Positive 4. Activated T-cell 5. Sensitized T-cell 1. Pro-B-cell (progenitor C-cell stage) 2. Pre-B. cell (precursor) 3. Immature b-cell 4. Mature B cell 5. Activated B cell 6. Plasma cell 7. Memory cell

Part 1 Flashcards

(137 cards)