Chapter 17 Disease and Resistance: The wars within

Plague of Athens

Eyewitness account recorded by Thucydides

recognized that those who were infected and survived did not contract the disease again (immunity)

controversy as to the etiology of the disease

Infection

• entry, establishment and multiplication of pathogen in a host

• Host is the organism in which the infection occurs

Disease

• the change from a state of good health

• Virulence: associated with disease

• Avirulent: does not cause disease

Individual and Populations

Endemic

• constant low level in a particular geographic area

Epidemic

• an explosive increase in disease within a population

Outbreak

• a more confined epidemic

Pandemic

• a disease occurring worldwide

Transmission

• contact transmission 

  • direct contact

  • indirect contact

    • fomite

  • congenital

  • droplet

• Vector transmission

  • requires vector

  • mechanical

  • biological

• Vehicle transmission

  • airborne

  • waterborne

  • foodborne

Source of pathogens

• Human reservoirs

  • carriers may have inapparent infections or latent diseases

• Animal reservoirs

  • Zoonoses are diseases transmitted from animals to humans

• Nonliving reservoirs

  • Soil and water

Course of Disease

• symptoms

  • evidence of disease sensed by the patient

• Signs

  • evidence of disease detected by an observer

• Syndrome

  • specific group of signs and symptoms

• Diagnosis

  • based on signs and symptoms

Stages of Disease

• Incubation period (no signs or symptoms)

• prodromal period (mild signs or symptoms)

• period of illness (most severe signs and symptoms)

• period of decline (signs and symptoms)

• period of convalescence

Entry and invasion

• Portal of entry

  • respiratory tract

  • gastrointestinal

  • sexual transmission

  • nonoral (skin wound)

• Infectious dose

  • Infectious establishment depends on the number of cells or viruses transmitted

  • minimum number of microorganisms required to establish a disease 

The invasion of disease → process

• Portal of entry 

  • Microorganisms enter the sterile environment of the host’s tissues

• Infectious Dose

  • A sufficient number of microbes must penetrate the host’s defensive barrier

• Infection

  • They move into a specific target issue, such as an organ

• Disease

  • Here, they caused tissue damage, leading to disease

• Portal of exit

  • microorganisms leave the host, ready to infect other susceptible individuals

Microorg enter sterile envrmt of tissues → penetrates barrier → move into tissue → damage → leave host

Virulence

• The efficiency of invasion depends on many factors

• a wide array of structures and molecules that enhance the infective and disease-causing capabilities of a pathogen

• The ability of a pathogen to penetrate tissues and cause structural damage is called invasiveness

Virulence

• Surface virulence factors

  • glycocalyx

  • pili

• Enzyme virulence factors

  • tissue penetration or spread

Toxin virulence factors

• Exotoxins: proteins released by bacteria

• Endotoxins: part of the cell wall of gram-negative bacteria, released only upon disintegration 

The three tiers of protection 

• Immunity: ability of the body to resist infections 

Surface barriers to resistance

• Host resistance to microbes and other threats depends on many “umbrellas” of defense that must function well in the individual

• skin

• secretions

  • mucous membrane/mucus

  • lysozyme

• the cells

  • normal microbiome-competitive antagonism

Innate immunity

• host resistance may break down when 1 or more of the surface barriers fail or become inoperable. In other words, when surface barriers are damaged, some pathogens can penetrate the “umbrella” of surface resistance. Now innate immune defenses are critical.

Humoral, Adaptive Immunity and cell-mediated

• should innate defenses break down, or if they are overcome by a pathogen, disease may develop as the adaptive “umbrella” of defense is activated to fight infections in the body fluids (humoral immunity) and infected cells (cell-mediated)

Innate immunity (phagocytosis)

• Phagocytes: Macrophages, nuetrophils

• Lysosomes - site of digestion (low pH)

  • The macrophages attach to a bacterium

  • pseudopods then surround the bacterium

  • The pseudopods bring the bacterium into the cytoplasm of the macrophage, where union with lysosomes takes place

  • The lysosomal enzymes digest the bacterium

  • The process concludes with the elimination of bacterial debris

Innate immunity (inflammation) 

• response to tissue injury or traumatic event 

• redness and warmth are due to the dilation of the blood vessels bringing an increased flow of blood (and WBC) to the infection site

• swelling comes from the accumulation of fluid

Innate immunity (Inflammation)

• sets in motion the events leading to the repair of the damaged tissue

• Inflammation → hours

• Proliferation → days

• Remodeling → weeks 

• Pus, a mixture of blood fluid, dead WBC, and dead bacteria may accumulate at the site before complete repair or a scar is formed. 

Innate immunity (Fever) 

• fever

  • abnormally high body temperature

  • pyrogens (substances that cause fever) signal hypothalamus to increase body temperature 

  • low to moderate fever is a natural defensive response

  • high fever may damage host tissues 

Innate Immunity (interferon)

• interferon is a protein 

• warning signal to surrounding cells → signal thats like i got infected beware neighboring cells yall might get infected too

• induces protective antiviral protein production in adjacent cells and immune cells

• blocks viral nucleic acid production 

Adaptive immunity - Pathogen immunity

• Antigen

  • unique chemical groups on pathogens 

    • generally protein or carbs

  • like the little things that stick on the surface of a pathogen

  • recognized by T cells, B cells, and antibodies 

  • Examples: toxin, flagella, and pili, viral capsids

• Epitope

  • part of antigen recognized by immune cells 

  • the tip part of an antigen

  • an antibody or T cells usually binds to

Adaptive immunity (lymphocytes)

• lymphocytes

  • T cells and B cells 

  • arise from stem cells in bone marrow

  • acquire surface receptor

  • migrate to the lymph nodes, spleen, and tonsils after maturation

• T cells

  • mature in the thymus

  • acquire surface receptors

  • helper T cells, cytotoxic T cells

• B cells

  • mature in bone marrow

  • acquire surface receptors 

Adaptive Immunity (cell-mediated response) 

• T cell mediated

• viral infected cells destroyed by cytotoxic T cells

• formation of memory T cells

• An antigen-presenting cell (APC) such as a macrophage, processes antigen and then “presents” peptides from the processed antigens on the APC surface

• Cytotoxic T cells with the appropriate receptors recognize and bind to the peptide complex

• CTLS become active and divide and some become memory cell

• When CTLs recognize and bind to peptide displayed by infected cells, they release substance that destroy the infected cells 

Adaptive Immunity (Antibody-mediated response)

• B cell mediated → mainly responsible for making antibodies

• antibodies (proteins circulating in blood) → float around and search for specific invaders

• binds to the antigen → anything foreign, the antibody recognizes and sticks to the antigen, and this marks the pathogen  

• Helper T cells assist →  B cells can’t fully activate on their own, and they need helper T cells to confirm the threat, send chemical signals, and help B cells multiply and produce better antibodies 

• memory B cells → If the same pathogen shows up again, they respond much faster

• plasma cells (antibody producers) → most activated B cells become plasma cells → antibody factories, releasing thousands of antibodies, short-lived but powerful 

Adaptive immunity (antibody structure)

• consists of: 

  • 2 light chains

  • 2 heavy chains 

  • variable regions from antibody binding sites

Adaptive Immunity (Antibody classes)

• immunoglobins (Ig) = antibodies

• IgG 

  • up to 80% of circulating antibodies 

  • long-lasting

• IgM 

  • initial antibodies to be produced after B cell simulation 

Vaccine: Stimulating immune defenses

• taking up to two weeks for the adaptive immune response to become active 

• vaccination can generate immune response more quickly when infection is encountered because the immune system has already been primed (alr knows how to fight against this)

• Vaccines

  • composed of altered pathogen or part of a pathogen

  • stimulates adaptive immunity → B cells and T cells

  • does not trigger disease or illness

  • allows memory cells to be produced

• Immunization 

  • process by which an individual becomes protected from a pathogen 

• Whole agent vaccines

  • contain whole pathogen 

  • live attenuated vaccine or inactivated vaccines

• Genetically engineered vaccines

  • contain only a genetically fragment of pathogen

  • subunit vaccines, toxoid vaccines, mRNA vaccines, DNA vaccines, vector vaccines

Vaccines: Different type of vaccines

• Weaken the virus

  • virus are weakened so they reproduce poorly inside the body

• Inactivate the virus

  • viruses are completely inactivated with a chemical

• Use part of the pathogen

  • part of the virus or bacteria is used as the vaccine

• Inactivate the toxin

  • a harmful protein made by the bacteria (toxin) is inactivated with a chemical. The inactivated toxin is called a toxoid.

• Vector virus

  • the gene from the pathogen is put into a virus that can’t reproduce itself but can still enter cells and deliver the gene

• mRNA

  • mRNA that is the blueprint for a protein from the pathogen is used as the vaccine

• DNA

  • DNA, the genetic code from which mRNA is made, is used as the vaccine

Herd immunity

• in which most of the population is immune to an infectious disease, making its spread from person to person less likely

• provides indirect protection to the vulnerable and weak

Vaccine: need, safety and risk assessment

• Vaccine safety

  • FDA standards for safety

• Adverse Events

  • Vaccine Adverse effects reporting system

  • Vaccine Data safety datalink

  • Post Licensure Rapid Immunization Safety Monitoring System (PRISM)

  • Clinical Immunization Safety Assessment Project (CISA)