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CHAPTER 10 Infection and Immunity. Outline. 10.1 Infection 10.2 Non-specific immunity 10.3 Specific immunity 10.4 Medical Immunology. 10.1 Infection.

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Chapter 10 infection and immunity
CHAPTER 10Infection and Immunity


Outline
Outline

  • 10.1 Infection

  • 10.2 Non-specific immunity

  • 10.3 Specific immunity

  • 10.4 Medical Immunology


10 1 infection
10.1 Infection

  • Infection is the invasion of a host organism's bodily tissues by disease-causing organisms, their multiplication, and the reaction of host tissues to these organisms and the toxins they produce.


10 1 1 b acterial p athogenesis
10.1.1 Bacterial pathogenesis

  • Pathogen: A microorganism capable of causing disease.

  • Non-pathogen:A microorganism that does not cause disease. It may be part of the normal flora.

  • Opportunistic pathogen:An agent capable of causing disease only when the host’s resistance is impaired (e.g. the patient is immunocompromised).An agent capable of causing disease only when spread from the site with normal bacterial microflora to the sterile tissue or organ.


Pathogenicity and virulence
Pathogenicity and Virulence

  • Pathogenicity and virulence are terms that refer to an organism's ability to cause disease. Technically, pathogenicity is used with respect to differences between microbial species whereas virulence denotes differences between strains of the same species. In practice they are often used interchangeably.

  • Pathogenicity: The ability to cause disease; usually used to describe the difference in disease causing capability between two different species.

  • Virulence: The ability to cause disease; usually used to describe the difference in disease causing capability between two different strains of the same species.


To cause disease an organism must
To cause disease, an organism must:

  • 1. Maintain a reservoir before and after infection (humans, animals, environment, etc.),

  • 2. Leave the reservoir and gain access to the new host,

  • 3. Colonize the body, and

  • 4. Harm the body.

  • Whether or not a person actually contracts an infectious disease after exposure to a particular potentially pathogenic bacterium depends not only on the microorganism, but also on the number of bacteria that enter the body and the quality of the person's innate and adaptive immune defenses.


Quorum sensing
Quorum sensing

  • The production, release, and community-wide sensing of molecules called autoinducers that modulate gene expression in response to the density of a bacterial population.


Development of a biofilm by pseudomonas aeruginosa
Development of a Biofilm by Pseudomonas aeruginosa

  • Planktonic Pseudomonas aeruginosa use their polar flagella and chemotaxis to swim towards host mucous membranes. Pili then bind to host cell receptors for initial bacterial attachment.


Development of a biofilm by pseudomonas aeruginosa1
Development of a Biofilm by Pseudomonas aeruginosa

  • The pili retract and bacterial cell wall adhesins enable a more intimate attachment of the bacterium.


Development of a biofilm by pseudomonas aeruginosa2
Development of a Biofilm by Pseudomonas aeruginosa

  • As the bacteria replicate, quorum sensing genes trigger production of an extracellular polysaccharide called alginate to begin biofilm formation as well as exoenzymes and toxins that damage host cell membranes.


Development of a biofilm by pseudomonas aeruginosa3
Development of a Biofilm by Pseudomonas aeruginosa

  • Enzyme- and toxin-induced damage to host cell membranes supplies the bacteria within the biofilm with nutrients. The bacteria continue to replicate as the biofilm continues to develop and mushroom up.


Development of a biofilm by pseudomonas aeruginosa4
Development of a Biofilm by Pseudomonas aeruginosa

  • As the bacteria replicate, the biofilm continues to mushroom up. Water channels form within the biofilm to deliver water and nutrients to the growing population of P. aeruginosa.


Development of a biofilm by pseudomonas aeruginosa5
Development of a Biofilm by Pseudomonas aeruginosa

  • As the population begins to overgrow the area, quorum sensing genes trigger some of the P. aeruginosa in the biofilm to again produce flagella.


Development of a biofilm by pseudomonas aeruginosa6
Development of a Biofilm by Pseudomonas aeruginosa

  • Planktonic P. aeruginosa leave the biofilm and move to a new location to begin new biofilms.


Toxin
Toxin

  • Exotoxin: A soluble protein toxin usually secreted from a living bacterium. Not all exotoxins are necessarily produced to harm humans. Some may be designed to play a role in bacterial physiology, such as resisting bacteriophages, regulating cellular function, or quorum sensing. Other toxins may be produced primarily to target protozoa, insects, and smaller animals and harming human cells becomes an accidental side effect.

  • Endotoxin: A heat-stable toxin present in the intact bacterial cell but not in cell-free filtrates of cultures of intact bacteria. Endotoxins are lipopolysaccharide complexes that occur in the cell wall; they are pyrogenic and increase capillary permeability.



Detection of endotoxin
Detection of endotoxin

  • The Limulus lysate test


Toxoid
Toxoid

  • A toxoid is a bacterial toxin (usually an exotoxin) whose toxicity has been inactivated or suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained.


10 1 2 other microbial p athogenesis
10.1.2 Other microbial pathogenesis

  • Smallpoxwas an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. Transmission occurs through inhalation of airborne variola virus, usually droplets expressed from the oral, nasal, or pharyngeal mucosa of an infected person. In ordinary type smallpox the bumps are filled with a thick, opaque fluid and often have a depression or dimple in the center.

Girl infected with smallpox.

Bangladesh, 1973.


Smallpox
Smallpox

  • The smallpox virus, looking like an oil painting. The protein coat of each virus is coloured yellow; DNA genetic material is red. Magnification: ×28,500.


Smallpox1
Smallpox

  • Looking uncannily like a collection of sushi, in fact this is a closeup of Smallpox viruses. The virus consists of genetic material (red), DNA (deoxyribonucleic acid), enclosed by a protein capsid (coat, yellow).


Smallpox2
Smallpox

  • After vaccination campaigns throughout the 19th and 20th centuries, the WHO certified the eradication of smallpox in 1979. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest, which was declared eradicated in 2011.

The last known person in the world to have smallpox of any kind. Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia CDC.


10 1 2 other microbial p athogenesis1
10.1.2 Other microbial pathogenesis

  • Poliomyelitisoften called polio or infantile paralysis, is an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route.

Child with polio sequelae.


Poliomyelitis
Poliomyelitis

  • Polio viruses: RNA genetic material occurs in the core of each virus, surrounded by a protein coat (blue). There are three types of polio viruses, type 1 being the cause of most polio epidemics. Magnification: × 90,000.


10 1 2 other microbial p athogenesis2

Protozoan parasite

Plasmodium

10.1.2 Other microbial pathogenesis

  • Malaria isa mosquito-borne infectious disease of humans and other animals caused by protists of the genus Plasmodium. This disease is characterized by severe chills, fever, sweating, fatigue and great thirst.

  • One way to reduce human deaths (2.7 million annually) from Malaria is to control the mosquito populations. Without the mosquito host, the Plasmodium protozoan can not complete their life cycle. Malaria is usually cured with a drug derived from the Cinchona tree, which is called Quinine.



10 1 2 routes of pathogen transmission
10.1.2 Routes of pathogen transmission

  • intestinal infections, respiratory infections, wound infectons, contact infection, animal bites infections.


10 1 3 patterns of infection
10.1.3 Patterns of infection

  • Inapparent infection: subclinical infection that has no detectable clinical symptoms

  • Carrier state: The continued presence of an organism (bacteria, virus, or parasite) in the body that does not cause symptoms, but is able to be transmitted and infect other persons.

  • Apparent infection: When an infection causes pathological changes leading to disease, it is often accompanied by a variety of signs and symptoms. Infections that come on rapidly, with severe but short-lived effects, are called acute infections. The infection persists several months to several years called chronic infection.Localized infection stands for the case that the microbe enters the body and remains confined to a specific tissue.


Systemic infection
Systemic infection

  • Toxemia: the presence of microbial toxins in the blood.

  • Bacteremia: a transitory disease in which bacteria present in the blood are usually cleared from the vascular system with no harmful effects.

  • Septicemia: a disease in which the blood serves as a site of bacterial multiplication as well as a means of transfer of the infectious agent from one site to another.

  • Pyemia: the presence of pyogenic bacteria in the blood as they are being spread from one site to another in the body.


10 2 non specific immunity
10.2 Non-specific immunity

  • Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion.

  • The immune system is composed of two major subdivisions, the innate or non-specific immune system and the adaptive or specific immune system.

  • The innate immune system is our first line of defense against invading organisms while the adaptive immune system acts as a second line of defense and also affords protection against re-exposure to the same pathogen.


10 2 non specific immunity1
10.2 Non-specific immunity

  • Nonspecific immune response is the first and second line of defense when a foreign object tries to enter or enter the body.

  • This response will attack anything (specific immune response will only attack certain infections) that it comes in contact with.

  • Parts of nonspecific immune response are: Skin, Mucous membranes, Phagocytic (cells that eat foreign particles) cells, Antimicrobial proteins, and the inflammatory response.


10 2 1 a natomical barriers to infections
10.2.1 Anatomical barriers to infections

  • Anatomical barriers are tough, intact barriers that prevent the entry and colonization of many microbes.


Skin and mucous membranes
Skin and mucous membranes

  • The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents. Thus, the skin acts as our first line of defense against invading organisms.


Blood brain barrier and blood embryo barrier
Blood-brain barrier and blood-embryo barrier

  • The blood–brain barrier is a separation of circulating blood from the brain extracellular fluid in the central nervous system.


Normal microbiota of the human body
Normal microbiota of the human body

  • The mixture of microorganisms regularly found at any anatomical site is referred to as the normal microbiota, the indigenous microbial population, the microflora, or the normal flora.


10 2 2 humoral barriers to infection
10.2.2 Humoral barriers to infection

  • The anatomical barriers are very effective in preventing colonization of tissues by microorganisms. However, when there is damage to tissues, the anatomical barriers are breached and infection may occur.

  • Once infectious agents have penetrated tissues, another innate defense mechanism comes into play, namely acute inflammation.

  • Humoral factors play an important role in inflammation, which is characterized by edema and the recruitment of phagocytic cells. These humoral factors are found in serum or they are formed at the site of infection.


Interferon
Interferon

  • Interferons are proteins that can limit virus replication in cells.

Antiviral action of interferon


Lysozyme
Lysozyme

  • Lysozyme breaks down the cell wall of bacteria.

Streptococcus pneumoniae


10 2 3 cellular barriers to infection
10.2.3 Cellular barriers to infection

  • Part of the inflammatory response is the recruitment of polymorphonuclear eosinophiles and macrophages to sites of infection. These cells are the main line of defense in the non-specific immune system.


Defense cells in the blood the leukocytes

Basophil granulocyte

Neutrophil granulocyte

Eosinophil granulocyte

Monocyte agranulocyte

Lymphocyte agranulocyte

Defense Cells in the Blood: The Leukocytes


A macrophage with pseudopods
A Macrophage with Pseudopods

Defense Cells in the Tissue: Macrophages, Dendritic Cells and Mast Cells

A Macrophage Phagocytosis of E. coli

Dendritic Cell

Mast cell



10 2 4 inflammation
10.2.4 Inflammation

  • A process in which blood vessels dilate and become more permeable, thus enabling body defense cells and defense chemicals to leave the blood and enter the tissues. Acute inflammation is usually a localized, protective response to tissue injury. Excessive or chronic inflammation, however, may lead to tissue destruction.


Diapedesis during inflammation step 1
Diapedesis During InflammationStep-1

A normal capillary prior to inflammation.


Diapedesis during inflammation step 2
Diapedesis During InflammationStep-2

Integrins on the surface of the leukocyte bind to adhesion molecules

on the inner surface of the vascular endothelial cells.


Diapedesis during inflammation step 3
Diapedesis During InflammationStep-3

The leukocytes flatten out and squeeze between the endothelial cells to

leave the blood vessels and enter the tissue.

The increased capillary permeability also allows plasma to enter the tissue.


Diapedesis during inflammation step 4
Diapedesis During InflammationStep-4

External view of leukocytes squeezing between the endothelial cells,

leaving the blood vessels, and entering the tissue.



10 3 specific immunity
10.3 Specific immunity

  • The specific immune system of vertebrates has three major functions: to recognize anything that is foreign to the body (“nonself”), to respond to this foreign material, and to remember the foreign invader.

  • There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity.

  • Humoral immunity involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes.

  • Cell-mediated immunity involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen and is mediated by T-lymphocytes.


10 3 1 immune system immune organ immune cell and immune molecule
10.3.1 Immune system:immune organ, immune cell and immune molecule

Central immune organ: Thymus


Central immune organ bone marrow
Central immune organ: Bone marrow



Peripheral immune organ
Peripheral immune organ

  • Spleen

  • Lymphnode


Immune cells of the immune system
Immune cells of the immune System


T lymphocyte
T lymphocyte

  • T lymphocyte (thymus dependent lymphocyte): Lymphocytes are white blood cells that play key roles in humoral immunity, cell-mediated immunity,and innate immunity. They circulate back and forth between the blood and the lymphoid system ofthe body. They recognize antigens by way of their T-cell receptor (TCR).

Human T-lymphocyte attacking fibroblast tumor cells.


B lymphocyte
B lymphocyte

  • B lymphocytes (bone marrow dependent lymphocyte) are white blood cells that play a large role in humoral immunity. Their principal function is to make antibodies against antigens. They recognize antigens via B-cell receptors (BCRs).

B cells mature into plasma cells that produce antibodies.


Immune molecule
Immune molecule

  • Antigen

  • Antibody

  • Complement

  • Cytokine


10 3 2 antigen and antibody
10.3.2 Antigen and Antibody

Antigen

  • Substances, such as proteins, nucleoproteins, polysaccharides and some glycolipids that elicit an immune response and react with the products of that response.


Antigenic determinant or epitope
Antigenic determinant or Epitope

  • The part of an antigen that is recognized by the immune system, specifically by antibodies, B cells or T cells.

Polysaccharide

Protein



Antibody
Antibody

  • Specific protein configurations produced by B-lymphocytes and plasma cells in response to a specific antigen and capable of reacting with that antigen. Also known as immunoglobulins.


Antibody structure
Antibody Structure

  • The simplest antibodies, such as IgG, IgD, and IgE, are "Y"-shaped macromolecules called monomers. A monomer is composed of four glycoprotein chains: two identical heavy chains and two identical light chains. The two heavy chains have a high molecular weight that varies with the class of antibody. The light chains come in two varieties: kappa or lamda and have a lower molecular weight than the heavy chains. The four glycoprotein chains are connected to one another by disulfide (S-S) bonds and non-covalent bonds.


Folding domains of an antibody
Folding Domains of an Antibody

  • The Fab portion of the antibody, the first domain of the antibody shown in red has the complementarity-determining regions providing specificity for binding an epitope of an antigen. The Fc portion, shown in purple directs the biological activity of the antibody. (S-S = disulfide bond; N = amino terminal of glycoprotein; C = carboxy terminal of glycoprotein; CHO = carbohydrate.)


Epitope of an antigen binding to fab of an antibody
Epitope of an Antigen Binding to Fab of an Antibody

  • Fab: Antigen-binding fragment. The actual portions of an antibody molecule that have a shape corresponding to that of an epitope of an antigen. The amino acid sequences of the Fab portion of antibody molecules is hypervariable.


Ribbon drawing of the antibody molecule igg2a
Ribbon Drawing of the Antibody Molecule IgG2a

  • The Fab portion of the antibody has specificity for binding an epitope of an antigen. The Fc portion directs the biological activity of the antibody. Fc: Constant fragment. The portion of an antibody molecule that carries out the biological activities of that class of antibody. Biological activity includes binding to receptors on phagocytes and activating the classical complement pathway. The amino acid sequence of the Fc portion of an antibody is the same for every antibody in that class.


IgM

  • IgM is a pentamer and, therefore, has 10 Fab sites. IgM makes up approximately 13% of the serum antibodies and is the first antibody produced during an immune response.

  • IgM is found mainly in the bloodstream rather than in the intracellular spaces of tissues where it can control infections in the blood. IgM has a half-life of about 5 days.


IgA

  • Secretory IgA is a dimer and has 4 Fab sites. A secretory component helps protect it from digestion in body secretions. IgA makes up approximately 6% of the serum antibodies where it has a half-life of approximately 6 days. IgA is found mainly in body secretions (saliva, mucus, tears, colostrum and milk) as secretory IgA (sIgA) where it protects internal body surfaces exposed to the environment by blocking the attachment of bacteria and viruses to mucous membranes. While only 6% of the antibodies in the serum are IgA, secretory IgA is the most immunoglobulin produced.


10 3 3 h umoral immunity
10.3.3 Humoral immunity

  • There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity.

  • Humoral immunity involves the production of antibody molecules in response to an antigen and is mediated by B-lymphocytes.

  • Cell-mediated immunity involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen and is mediated by T-lymphocytes.


Anamnestic response
Anamnestic Response

  • As a result of B-lymphocytes recognizing T-dependent antigens (proteins) during humoral immunity, numerous circulating B-memory cells and T4-memory cells develop which possess anamnestic response or memory. The B-lymphocytes now differentiate into plasma cells that secrete large quantities of antibodies that "fit" the original epitope. Some B-lymphocytes differentiate into B-memory cells capable of anamnestic response.


Anamnestic response1
Anamnestic Response

  • After the primary exposure to an antigen, there is an inductive period of generally several days to a week when no measurable antibodies are detected in the serum. This is the period when the antigen is being exposed to immunocompetent cells, being processed by APCs, clonal selection and clonal expansion are taking place, and B-lymphocytes are differentiating into plasma cells and B-memory cells. Because of the memory cells, however, a second exposure to the same antigen results in more antibodies being made faster for a longer period of time, as shown in the secondary response.


10 3 4 cell mediated immunity
10.3.4 Cell-mediated immunity

  • Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells, the production of antigen-specific cytotoxic T-lymphocytes and the release of various cytokines in response to an antigen.


10 3 5 clonal selection clonal expansion
10.3.5 Clonal Selection & Clonal Expansion

  • Clonal selection: The selection and activation of specific B-lymphocytes and T-lymphocytes by the binding of epitopes to B-cell receptors or T-cell receptors with a corresponding fit.

  • Clonal Expansion:The proliferation of B-lymphocytes and T-lymphocytes activated by clonal selection in order to produce a clone of identical cells. This enables the body to have sufficient numbers of antigen-specific lymphocytes to mount an effective immune response.


Clonal selection step 1
Clonal Selection, Step-1

  • During its development, each B-lymphocyte becomes genetically programmed, through a process called gene translocation, to make a unique B-cell receptor. Molecules of that B-cell receptor are placed on its surface where it can react with epitopes of an antigen.


Clonal selection step 2
Clonal Selection, Step-2

  • A B-lymphocyte with an appropriately fitting B-cell receptor can now react with epitopes of an antigen having a corresponding shape. This activates the B-lymphocyte.


Clonal expansion
Clonal Expansion

  • Cytokines from an effector T4-lymphocyte now enable the activated B-lymphocyte to proliferate into a large clone of identical B-lymphocytes. During this time, "fine-tuning" of the B-cell receptor occurs through affinity maturation.


Differentiation of b lymphocytes into plasma cells and b memory cells
Differentiation of B-lymphocytes into Plasma Cells and B-Memory Cells

  • The B-lymphocytes now differentiate into antibody-secreting B-lymphocytes and plasma cells that secrete large quantities of antibodies that "fit" the original epitope. Some B-lymphocytes differentiate into B-memory cells capable of anamnestic response.



10 3 6 monoclonal antibody
10.3.6 B-Memory CellsMonoclonal antibody

  • Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different immune cells. Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope.





10 4 medical immunology
10.4 B-Memory CellsMedical Immunology

  • Vaccines and immunizations are among the most cost-effective weapons for microbial disease prevention.

  • Vaccines constitute one of the greatest achievements of modern medicine.


10 4 1 antigen antibody interactions in vitro
10.4.1 B-Memory CellsAntigen-Antibody Interactions In Vitro

  • Agglutination: The clumping of cells such as bacteria or red blood cells in the presence of an antibody.


10 4 1 antigen antibody interactions in vitro1
10.4.1 B-Memory CellsAntigen-Antibody Interactions In Vitro

  • Complement fixation: The complement fixation test is an immunological medical test that can be used to detect the presence of either specific antibody or specific antigen in a patient's serum.


10 4 2 immunolabelling technique
10.4.2 B-Memory CellsImmunolabelling technique

  • Immunolabeling is a process used in biological and medical analysis that allows localizing an antigen to a particular site in a cell, tissue, organ, or organism.

  • Immunofluorescence technique

  • Immunoenzymatic technique

  • Radioimmuno-assay

  • Immunoelectron microscopy

  • Luminescent immuno-assay


10 4 3 biologic products
10.4.3 Biologic products B-Memory Cells

  • Immunization is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease.


Artificial active immunization
Artificial active immunization B-Memory Cells

  • Artificial active immunization is where the microbe is injected into the person before they are able to take it in naturally. The microbe is treated, so that it will not harm the infected person. Depending on the type of disease, this technique also works with dead microbes, parts of the microbe, or treated toxins from the microbe.


Artificial passive immunization
Artificial passive immunization B-Memory Cells

  • Artificial passive immunity involves the introduction of antibodies through means such as injection.

  • In the treatment of some diseases, patients may be given a serum derived from patients who have recovered to help them fight the disease. This practice is sometimes seen when people are dealing with an outbreak of a new or extremely virulent disease for which no known treatment is available.


Summery
Summery B-Memory Cells

  • 10.1 Infection

  • 10.2 Non-specific immunity

  • 10.3 Specific immunity

  • 10.4 Medical Immunology


Further reading
Further reading B-Memory Cells

  • Microbiology (5th Edition):

  • Chapter 31 Normal Microbiota and Nonspecific Host Resistance

  • Chapter 32 Specific Immunity

  • Chapter 33 Medical Immunology


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