White blood cells (leukocytes)
– Granular
* myeloid lineage leading to basophils, eosinophils,
neutrophils, monocytes for example
– Agranular
* lymphoid lineage leading to B cells and T cells
(lymphocytes)
Tissue cells
– Mast cells, dendritic cells, macrophages
The immune system has
3 lines of defense
- Non-specific physical and chemical barriers surface barriers e.g. skin
- Non-specific inflammatory response and proteins/non-specific internal cellular and chemical defense
- A specific and adaptive or learned response from
the T and B cells/immune response
Summary of the inflammatory response
- Tissue damage
-Injured tissue releases chemical signals - Vasodilation
-Redness: blood flow carries defensive cells and chemicals to damaged tissue and removes toxins
-Heat: increases metabolic rate of cells in injured area to speed healing - Increased permeability of vessel
-Swelling: fluid w/ defensive chemicals, blood-clotting factors, oxygen, nutrients, and defensive cells seeps into injured area
-Pain: movement hampered, allowing injured area to heal - Phagocytosis - 2nd stage (macrophages, neutrophils)
-Complement destroys bacteria
-Phagocytes engulf bacteria - Stop inflammation (drugs + anti-inflammatory molecules)
-Clot formation prevents blood loss
-Sacar starts to heal
Third line of defense: the adaptive and specific response
of B and T cells
– Helps protect us against specific pathogens when
nonspecificc first and second lines of defense fail
– Helps protect us against cancer (renegade cells are found and destroyed)
– Relies on the recognition of an antigen:
* a molecule or part of molecule that can be recognized by an B cell receptor (antibody) or T cell receptor
* recall ABO blood group antigens and compatibility
– Has memory
– Provides immunity e.g. vaccine = adaptive immune system, body remembers
Phases of adaptive immunity:
3rd line of defense diagram
Immunity
- Is the ability to combat infectious diseases and cancer
- Primary exposure is shorter-lived and slower to respond while a secondary exposure is a rapid, strong response. It often indicates seroconversion, or the status where specific antibodies to an agent (antigen) are detected in the blood
- This type of immunity is usually long-lasting
- It depends on clonal selection and production of memory B and T cells
- Immunization can be brought about naturally through an infection or artificially through medical intervention (e.g. acquired by vaccination)
4 basic principles of clonal selection = makes immune system capable of specificity
- Each lymphocyte bears a single type of receptor with a unique specificity
- Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation
- The differentiated effector cells derived from an activated lymphocyte will bear receptors of identifcal specificity to those of the parental cell from which that lymphocyte was derived
- Lymphocytes bearing receptors specific for ubiquitous self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes
Self Tolerance
4 basic principles
of clonal selection
by diagram
Structure of antibodies
- Y-shaped protein assemblies
- Circulating antibodies are
known as a serum or sera - The end of the two arms are
the variable regions (VH and
VL) where specific antigens
bind - Antibody binding to an
an/gen helps to define it as
‘foreign’ and something to be
neutralized or destroyed
How to generate trillions (10^12) of
different antibodies
- In a B-cell, recombine up to ~100 possible variable (V) DNA segments to generate new coding sequences in the Ab genes
- Recombination is imprecise and creates unique sequences
- Combine heavy (5 classes) and light (2 classes) chain gene products into mature Ab
- The genes are subject to added mutation
- Heavy chains can switch classes
- Each immature B-cell does this as it matures and retains this gene & protein configuration
Infectious Agents
- Bacteria and viruses are the most common infectious microbes (microscopic organisms)
- Microbes that cause disease (note, not all do!) are called pathogens, and furthermore pathogens are not limited to microscopic organisms or even living things (think parasitic worms and viruses, respectively)
- When a microbe finds a tissue inside the body that will support its growth, it becomes infectious
- If a microbe can spread from one organism to another, then it is contagious
- New infectious diseases of humans can arise from animal reservoirs = zoonoses
Pictures of infectious agents
Sizes of infectious agents (10X)
A few bloodborne disease agents
– Hepatitis A, B, and C virus (HAV, HBV, HCV)
– HIV1 and 2 (AIDS) - attack CD4 T-cells
– HTLV-I and II
– West Nile virus (WNV) - mosquitos
– Cytomegalovirus (CMV)
– Treponema palladium bacteria (Syphilis)
– Trypanosoma cruzi protozoa (Chagas disease)
– Variant Cruetzfeld Jakob Disease (vCJD): prion, Prion = infectious protein - causes diseases
– Plasmodium protozoa (malaria)
– Leishmania protozoa (leishmaniasis)
– Schistosoma Oatworms (schistosomiasis)
– Babesia protozoa (babesiosis)
– Borellia burghdorfia bacteria (Lyme disease)
– Parvovirus
Transmission
- Insect and animal vectors
- Sexual contact
- Maternal to child (vertical)
- Respiratory (air)
- Gastrointestinal (food/drink) - hepatitis A
- Needle contamination, transfusions
– iatrogenic = medical procedure - HIV, hepatitis B + C
Transmission - The Fs
– Food
– Fluid
– Fingers
– Feces
– Flies
– Fornication
– Fomites
Bloodborne infection
- High levels of infections in the bloodstream
= viremia, bacteremia , fungemia, or parasitemia
– High levels of bacteria in the bloodstream deNnes septicemia or sepsis - Acute cases can turn fatal very quickly
– e.g. hemorrhagic fevers like Ebola Virus Disease and Lassa Fever - Latency and asymptomatic phases can make diagnosis
dincult in some cases - Creates threat of infection at tissues/organs throughout the body
– Especially heart, kidneys, lungs
Blood Donor Testing - CBS
What is HIV?
- Retrovirus family (HIV-1 most widely distributed)
- RNA-based genome copied into DNA inside infected cell, which integrates into host chromosomes = provirus, a form of latency
- Proviral form establishes latency and is essentially permanently retained
- Host cell preference: CD4+
T-cells, macrophages, and dendritic cells
– Uses CD4 for attachment and CCR5
or CXCR4 as co-receptors for virus-cell
membrane fusion to gain cell entry
– These markers define HIV tropism - As these helper T-cells are destroyed it disables the immune system
- Increases susceptibility to other infections and tumor formation
HIV progression to AIDS
- Primary infection
- Acute syndrome
- Immune response to HIV (generation of anti-HIV antibodies Seroconversion or seropositivity, HIV hiding outside the blood in lymphoid tisse = detection problem
- Clinical latency
- Loss of CD4+ T cells Lymphoid destruction
- AIDS = when CD4 < 200 cells per microlitre
HIV - treatment
- Primary testing is largely ELISA based, then followed up by PCR based
- ART: antiretroviral treatment
– Combination of 3 or more drugs that specifically target HIV proteins
– Suppressive therapy that significantly reduces virus levels and increases counts of functional CD4+
T-cells and improves immune function
– It is very effective (treatment as prevention strategy) - Natural resistance: CCR5 deletion mutation (CCR5D32)
– Timothy Brown, the ‘Berlin patient’, cured of AIDS by bone marrow (HSC) transplant to treat his leukemia from a matching donor who was also a CCR5D32 homozygote
What is hepatitis?
- inflammation of the liver
- A, B, C, D, and E forms of hepatitis viruses that are from different virus families
- B and C forms most concern for blood transmission and disease propagation; hepatitis, cirrhosis, and even liver cancer can result
- 75% of the US cases are from HepC (aka, HCV, an enveloped, ssRNA virus)
– Vaccines available for HepA and HepB
– New HCV antivirals drugs appear to be fairly effective cures (though $$$)
Hepatitis – HCV testing
- Liver function
- (protein & enzyme panels, biopsy)
- Viral load monitoring
- Genotyping
- Direct antiviral treatment
- Counseling
