IMMUNE SYSTEM IN HEALTH AND DISEASE Flashcards
WHAT IS INFLAMMATION?
A RESPONSE TO INFECTION OR INJURY OF VASCULARISED TISSUES TO ELIMINATE DYING CELLS AND FOREIGN BODIES
CLASSIC SIGNS OF INFLAMMATION?
- HEAT
- PAIN
- REDNESS
- SWELLING
- LOSS OF FUNCTION
WHICH ENDING IS USED IN NAMES OF INFLAMMATORY DISORDERS?
-ITIS
PATHOGENS THAT BECOME TOLERATED BY THE IMMUNE SYSTEM (LIKE THE EPSTEIN BARR VIRUS) ONLY CAUSE ISSUES IN WHICH PEOPLE?
IMMUNOCOMPROMISED
WHAT CAUSES INFLAMMATION?
INFLAMMATION WAS INITIALLY THOUGHT TO BE DIRECTLY CAUSED BY PATHOGEN BUT IT IS IN FACT A HOST INNATE RESPONSE TO CLEAR INFECTION
WHAT ARE PATHOGEN ASSOCIATED MOLECULAR PATTERNS (PAMPs)?
- MOLECULAR STRUCTURES SHARED BY MICROBES THAT ARE NOT PRESENT ON HOST CELLS
WHAT ARE DAMAGE ASSOCIATED MOLECULAR PATTERNS (DAMPs)?
- STRUCTURES FOUND IN/ON STRESSED, DYING OR DEAD HOST CELLS
GIVE SOME EXAMPLES OF PAMPs (PATHOGEN ASSOCIATED MOLECULAR PATTERNS):
- LIPIDATED OR GLYCOSYLATED MOLECULES (LIPOPROTEINS, LIPOPOLYSACCHARIDES..)
- ESSENTIAL MICROBIAL PROTEINS (FLAGELLIN, FORMYLATED PEPTIDES..)
- NUCLEIC ACIDS (DOUBLE STRANDED RNA, UNMETHYLATED CpG DNA..)
HOW CAN BACTERIA AVOID THEIR PAMPs GETTING RECOGNISED AND THEM GETTING DESTROYED?
- BACTERIAL SURFACE IS A POTENT SOURCE OF PAMPs, SO SOME BACTERIA DELIBERATELY MODIFY STRUCTURES TO AVOID BEING RECOGNISED OR CLOAK THEMSELVES IN SELF-PROTEINS (FIBRIN)
- BACTERIA CAN USE GENETIC VARIATION TO NOT DISPLAY CONSERVED PAMPs THAT COULD BE READILY DETECTED
- INTRACELLULAR BACTERIA (LIKE M. TUBERCULOSIS) CONTROL PHAGOCYTIC FUNCTION TO LIVE IN MACROPHAGES SO THEY LIVE IN CELLS THAT ARE SUPPOSED TO KILL THEM
- SOME BACTERIA (LIKE LISTERIA) CO-OPT ACTIN NETWORKS IN HOST CELLS TO LITERALLY PROPEL THEMSELVES OUT OF PHAGOSOMES AND INTO NEIGHBORING CELLS
ARE VIRUSES OR BACTERIA HARDER TO DETECT BY THE IMMUNE SYSTEM?
VIRUSES
INNATE RESPONSE TO VIRUSES:
- INNATE RECOGNITION OF VIRAL GENETIC MATERIAL LEADS TO THE PRODUCTION OF INTERFERON (IFN) PROTEINS
- IFN PROTEINS PUT THE SURROUNDING TISSUE ON A ‘WAR-FOOTING’ TO LIMIT THE SPREAD OF VIRUS
- THIS CAUSES CELLS TO EXPRESS PROTEINS THAT INHIBIT VIRAL RNA REPLICATION, AND BLOCK PROTEIN SYNTHESIS
WHAT ARE INTERFERON PROTEINS?
PROTEINS RELEASED BY HOST CELLS DURING INNATE RESPONSE TO VIRUSES; LEAD UNAFFECTED SURROUNDING CELLS TO PRODUCING PROTEINS THAT INHIBIT VIRAL REPLICATION
WHICH VIRUS TYPE HAS MORE MUTATIONS, DNA OR RNA AND WHY?
RNA VIRUSES
THEY REQUIRE REVERSE TRANSCRIPTION WHICH IS INHERENTLY MORE ERROR-PRONE BUT ALLOWS RAPID EVOLUTION OF NEW VARIANTS
WHAT IS ‘ANTIGENIC DRIFT’ IN VIRUSES?
POINT AMINO ACID MUTATIONS IN KEY VIRAL PROTEINS
WHAT IS THE DRIVER OF SEASONAL VARIATIONS IN FLU OUTBREAKS?
ANTIGENIC DRIFT (POINT AMINO ACID MUTATIONS IN KEY VIRAL PROTEINS)
WHAT ARE THE KEY VIRAL PROTEINS IN INFLUENZA WHICH MUTATE AND PRODUCE SEASONAL VARIATION?
- HAEMAGGLUTININ (H)
- NEURAMIDASE (N)
WHAT IS ANTIGENIC SHIFT IN VIRUSES?
SIGNIFICANT ALTERATION IN SEQUENCE, OFTEN BY CAPTURING GENETIC SEQUENCES FROM CLOSELY RELATED VIRUSES
- SUDDEN, RAPID CHANGE
- SEGMENTED GENOME HELPS THIS A LOT
DNA VS RNA VIRUSES, WHICH CAN SUPPORT LARGER GENOMES?
DNA
% OF THE DNA VIRUS SEQUENCE THAT IS DEDICATED TO IMMUNE EVASION (CONTROLLING THE HOST IMMUNE RESPONSE)?
> 50%
WHAT IS A LENTIVIRUS?
Virus causing chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species (e.g. HIV)
IS HIV RNA OR DNA VIRUS?
RNA
MAIN CONTRIBUTOR TO HIV-1/AIDS PATHOGENICITY?
INDUCTION OF SLOW DECLINE OF HOST CD4+ T CELLS NUMBERS ALLOWING LIFE THREATENING OPPORTUNISTIC INFECTIONS AND CANCERS TO THRIVE
WHAT IS AUTOIMMUNITY?
- IMMUNE RESPONSE AGAINST SELF (AUTO) ANTIGEN MISTAKENLY SEEN AS FOREIGN
- DRIVEN BY IMMUNE RESPONSE TO HOST PEPTIDES THAT BECOMES SELF-REINFORCING!!
- FAILURE OF TOLERANCE, LEADING TO AN ABERRANT IMMUNE RESPONSE
WHAT IS AUTOIMMUNITY?
- IMMUNE RESPONSE AGAINST SELF (AUTO) ANTIGEN MISTAKENLY SEEN AS FOREIGN
- DRIVEN BY IMMUNE RESPONSE TO HOST PEPTIDES THAT BECOMES SELF-REINFORCING!!
- FAILURE OF TOLERANCE, LEADING TO AN ABERRANT IMMUNE RESPONSE
GENETIC SCREENING FOR AUTOIMMUNE DISEASE?
- MULTIPLE GENES ASSOCIATED (E.G. MHC COMPLEX)
- EACH GENE INDIVIDUALLY MAKES A SMALL CONTRIBUTION
- THERE’S LITTLE PREDICTIVE VALUE IN GEN. SCREENING
- COMPLEX ENVIRONMENT AND GENE INTERACTIONS
- INITIATING TRIGGERS OFTEN UNKNOWN
GENETIC BASIS OF AUTOIMMUNITY/WHAT INITIATES IT?
- STRONG CONSENSUS THAT AUTOIMMUNITY IS INITIATED BY PATHOGENS OR CELLULAR DAMAGE
- THE IMMUNE RESPONSE TO THIS INSULT ‘CROSS-REACTS’ WITH SELF ANTIGENS THAT THEN DRIVE A SUSTAINED AND CHRONIC RESPONSE TO SELF
- AUTOIMMUNE RESPONSE IS SELF SUSTAINING
MECHANISMS THROUGH WHICH CHRONIC AUTOIMMUNE DISEASE DEVELOPS?
- POSITIVE FEEDBACK FROM INFLAMMATION
- INABILITY TO CLEAR THE SELF ANTIGEN
- BROADENING OF THE AUTOIMMUNE RESPONSE
EXAMPLE OF HOW PEOPLE CAN BE PREDISPOSED TO AUTOIMMUNITY?
CERTAIN MHC (HLA) ALLELES PREDISPOSE PEOPLE TO AUTOIMMUNITY THROUGH THEIR ENHANCED ABILITY TO BIND AND PRESENT SELF-ANTIGEN
WHAT IS THE ROLE OF REGULATORY T CELLS?
THEY MODULATE THE IMMUNE SYSTEM, MAINTAIN TOLERANCE TO SELF-ANTIGENS AND PREVENT AUTOIMMUNE DISEASE
WHAT IS THE FINAL CHECKPOINT THAT STOPS THE INITIATION OF AUTOIMMUNITY?
REGULATORY TOLERANCE (REGULATORY T CELLS ENSURING TOLERANCE TO SELF ANTIGENS)
CHARACTERISTICS OF TREATMENT FOR AUTOIMMUNITY:
- LIFELONG
- DOESN’T TARGET THE CAUSE, THE AIM IS TO CALM THE IMMUNE SYSTEM DOWN
EXAMPLES OF TREATMENTS FOR AUTOIMMUNITY?
- COSTIMULATORY BLOCKADE (TARGETS T CELLS)
- SMALL MOLECULE DRUGS (CORTICOSTEROIDS, IMMUNOSUPPRESSANTS..)
- MONOCLONAL ANTIBODIES (ANTI TNF ALPHA, ANTI IL6 AND IL12…)
WHAT ARE PRIMARY IMMUNODEFICIENCIES?
- CONGENITAL IMMUNODEFICIENCIES RESULTING FROM GENETIC MUTATIONS
IS SECONDARY IMMUNODEFICIENCY PRESENT AT BRITH?
NO, IT IS ACQUIRED
SEVERE COMBINED IMMUNODEFICIENCIES (SCIDs):
- A RANGE OF VERY SIGNIFICANT PIDs THAT CAUSE DEFECTS IN THE ADAPTIVE IMMUNE RESPONSE
- EXTREME ILLNESSES
- PATIENTS OFTEN COME FROM CONSANGUINEOUS FAMILIES (PARENTS WHO ARE CLOSELY RELATED), WHICH HIGHLIGHTS HOW RARE THESE MUTATIONS ARE
CASE OF DAVID VETTER:
- BORN WITH A SEVERE COMBINED IMMUNODEFICIENCY (SCID)
- LIVED FOR 12 YRS
- SPENT CCA 20 SECONDS OF HIS LIFE IN A NON STERILE ENVIRONMENT
WHY CAN NEWBORN SCID PATIENTS APPEAR HEALTHY/ APPEAR TO HAVE GOOD ANTIBODY PRODUCTION?
DUE TO MOTHER PROVIDING ANTIBODIES IN PLACENTA AND MILK
DESCRIBE TUMOR IMMUNOLOGY:
- TUMORS ARE MADE FROM OUR OWN CELLS, SO THE IMMUNE SYSTEM IS ABLE TO RECOGNISE THEM ONLY TO A CERTAIN EXTENT
- THE IMMUNE RESPONSE AGAINST TUMOURS IS OFTEN DOMINATED BY REGULATION OR TOLERANCE
- EVASION OF HOST IMMUNITY IS ONE OF THE HALLMARKS OF CANCER
- SOME IMMUNE RESPONSES PROMOTE CANCER GROWTH
- CANCERS CELLS HAVE LOST GENOME INTEGRITY AND ARE CAPABLE OF EVOLVING THEIR TRANSCRIPTOME TO AVOID DETECTION
