Chapter 12 - I Flashcards
Mounting Immune response
For a successful immune response, 2 key events must occurs:
1. THe innate immune response must sense danger - dendritic cells recruits to the site of infection mature and move to lymph nodes
- TH cells must be activated - a dendritic cell must present a peptide complexed with MHC class 2 protein to TH cell
Intracellular Bacterial infections
Some bacteria are intracellular pathogens
These bacteria have special ability that most bacteria do not have - they can evade or shut down the innate immune responses
Appropriate response: cell-mediated response
Goal: activate the cell so that it can kill pathogen:
- only works with macrophages
- antibodies are useless as they can’t get into host cell
Cells that have an intracellular infection but are not capable of expressing MHC class 2 cannot be activated - these cells, the bacteria usually continue to grow until the cell dies and bacteria are released into the extracellular environment
Intracellular Bacterial infections
The immune response to intracellular bacterial pathogen starts off with the innate immune response
Macrophages can phagocytose repeatedly.
the first few bacteria that the macrophages engulf are killed, but the remaining bacteria start to express genes that encode virulence factors
However, remaining bacteria use their virulence factors to shut off the innate cell’s response - eg the macrophage loses the ability to kill the bacteria in the phagolysosome
so the macrophage did what it was supposed to do but the bacteria fought back and can grow inside of the macrophage
Strategies for survival
when the bacterium is phagocytosed by macrophage (1) or invades into the intestinal cell (2,3) the host cell will try to digest it
Immune response to Intracellular Bacterial infections - primary response
Pathogen enters body
- innate response to pathogen
- macrophages kills some bacteria but not ll
- bacteria start to grow in macrophage
- macrophage displays peptides from killed bacteria on MHC 2
at the same time, dendritic cells engulf pathogen and activate TH cells
Interaction of macrophage with TH cell
- activation of macrophage
- into angry macrophage and pathogen is killed
Intracellular Pathogens
Macrophage engulfs several bacteria - each bacteria in its own phagosome
some bacteria is digested in phgolysossome and peptide derived from it are loaded onto MHC class 2
Some bacteria manage to prevent the formation of phagolysosome and begin to replicate
End result: the macrophage displays a peptide from the bacterium in a new MHC class 2 but it still has bacteria replicating inside it
it up-regulates the expression of MHC class2 and B7 but it is stuck at the site of infection
Activating Macrophage
The infected macrophage is stuck at the site of infection. But dendritic cells come to rescue
Dendritic cells will engulf the bacterium and move to the lymph node to activate a TH cell and initiate the adaptive response
The activated TH cell then migrates back to the tissue to help the macrophage
The macrophage can be activated by 2 signals:
- secretion of IFN -y
- Binding of CD40L on the TH cell to CD40 on macrophage
End result: super activated macrophage
Super activated macrophage
A super activated macrophage activates transcription of different genes to induce the production of NO, oxygen radical and protease
They are more aggressive than normal macrophages
Result: Kill the bacteria but also the macrophage and the healthy tissue in the surrounding area
- Termed the primary response
The primary response
The primary response takes 7-10 days to develop
Most of the lag is accounted for by the changes in the gene expression and proliferation/differentiation of the naive TH cells
The effector TH cells migrate from the lymph node and to sites of inflammation, leave the blood vessel and enter into the tissue - (like neutrophils in innate response)- to activate the macrophage
Immune Response to intracellular pathogens
The downside to the primary response is that it can result in chronic inflammation
Chronic inflammation differs from acute in 3 ways:
- Duration - longer
- involvement of TH cells
- Damage to healthy tissue
The damage to healthy tissue results when the immune system tried to kill the pathogen at all costs
Examples of Immune Response to intracellular pathogens
TB is an infectious disease caused by MTB
MTB are spread from one person to another through respiratory droplets
TB generally affects the lungs but can also affect other parts of the body such as kidney, spine, and brain
TB has been known by names such as consumption and the white plague
Tuberculosis
2 TB related conditions:
Latent TB
- The bacteria are present in the body, but in an inactive state and cause no symptoms
- this form is not contagious, but can turn into active TB
Active TB
- the patient is ill with symptoms and can spread to other
- may occur in the first few weeks after initial infection with the TB bacteria, or it might occur years later
If not treated properly TB can be fatal
- treatment involved antibiotic therapy for months
Tuberculosis
Symptoms of active TB:
- Coughing that lasts 3+ weeks
- coughing blood
- chest pain, or pain with breathing/coughing
- unintentional weight loss
- fatigue
- fever
- night sweats
- chills
- loss of appetite
TB of spine might cause back pain and TB of kidneys might cause blood in urine
Progression of TB infection
- Inhalation of bacteria
- Bacteria are engulfed by macrophages in alveoli
some bacteria are killed by the macrophages but others survive and start to multiply
Macrophage may burst and bacteria spread to infect more macrophages
- Dendritic cells in the alveoli engulf the bacteria and move to the lymph node to activate CD4 T cells
Progression of TB infection
- CD4 T cells that are activated differentiated to effector TH cells
- Effector TH cells arrive at the infection site
They super activate the macrophages
They contributes to formation of tubercule or granuloma
Granuloma is an attempt to isolate the bacteria because the immune response has not been successful
Progression of TB: Granuloma
The granuloma consist of central core of infected macrophages
they are fused macrophages (multi nucleated cells) surrounding by large macrophages called epitheloid cells and foamy macrophages)macrophages that can’t break down lipids from bacterium)
These are surrounded by CD4 T cells that are still trying to super activate the macrophage
The granuloma may then be encased in collagen fibers
Progression of TB infection
Whem bacteria are inside the granuloma they are inactive –> the patient has latent TB
If the immune system is weakened the outer layer may break, bacteria are released and TB is re-activated
Sometimes the center of the granuloma liquifies and allows the bacteria to from very well
The tubercule can grow causing nearby lung tissue to die and rupture - forming a cavity
the tubercule might burst causing the release of more bacteria
Vaccines against TB
Bacille Calmette Geuren is a vaccine for TB
- live attenuated vaccine consisting of mycobacterium bovus cousin of MTB
The vaccine is widely used in many countries
most children scars after BCG vaccination
The intent of BCG vaccine is to generate memory TH cells and not an antibody or CTL response
The vaccine does not :
- Protect children from pulmonary disease caused by TB bacteria
- prevent latent TB infection from progressing to active disease
- prevent spread of disease
vaccine prevent some serious TB complications in children eg meningitis
TB vaccination
Primary response takes about 7-10 days to fully develop, most of the lag time is accounted for by the changes in gene expression and proliferation of CD4 T H cells
The secondary response takes only 2 days to develop as memory TH cells and are much easier to activate naive Cells
Testing for TB
Sometimes a Tuberculin skin test - a test that helps identify if a person might be infected with MTB
- a small volume of tuberculin is injected under the skin
the result of the test is not known immediately
Because: macrophage pick up protein, present to memory TH cel\ls and reactivate them
they differentiate into effectors cells thus take a few days
Effector TH cells tell macrophages to become super activated and make cytokines
TH cells overreact to harmless substances and the macrophages do what they are told to do
Testing for TB
The positive tuberculin skin test is a secondary reaction to a protein made by the bacilli - it indicates the presence of effector and memory TH cells to MTB
A positive test result can indicate possible infection - ned X ray to confirm
however a per vaccinated with BCG might also test positive because of the reactivation of memory TTH cells - it does not indicate disease or infection
Testing for TB
> 5 mm: Risk factors -HIV infection,contact with TB patient, organ transplant
> 10 mm: Risk factors -a recent arrival from the high-prevalence country, Mycobacteriology lab personnel, resident/employee of high-risk setting, certain medical conditions
> 15 mm: no known risk factors for TB
TB vaccine
This is the basis for BCG vaccine - a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened ) live bovine tuberculosis bacillus
- patient develops memory TH cells
the positive tuberculin skin test is a secondary reaction to a protein made by bacilli
This demonstrates the presence of memory TH cells in a vaccinated person - it does not indicate disease or infection
