Clinical Immunology Flashcards
Cancer therapy
Antibodies against regulators of the immune response turn the immune system into overdrive
T cells with genetically engineered antigen receptors that target them to cancer cells
Autoinflammatory/autoimmune
Damage to self
Immunodeficiency
Greater susceptibility to infection/cancer
Two types of immunodeficiency
Primary
Secondary
Primary immunodeficiency
From birth
Due to genetic mutations
Secondary immunodeficiency
Generally not from birth
Due to environmental factors
-HIV/AIDS
-chemotherapy
-severe malnutrition
Primary immunodeficiency patients
Human gene knockouts
Studied to reveal role of individual components of immune system
Severe combined immunodeficiency
Bubble babies
No t or b cells
No adaptive immunity
One Cause is a loss of function muterions in RAG gene required for somatic recombination
Neutropenia
Common clinical presentation
Type of secondary immunodeficiency
Neutrophils produced in bone marrow
Circulate for 8-24 hours
Can occur due to diseases of bone marrow, radiation, chemo, caused by certain infections and autoimmune diseases
What is neutropenia associated with
Opportunistic infections
S. Aureus
E.coli
Pseudomonas aeruginosa
Aspergillus fumigatus
Clinical presentation of neutropenia
Rapid onset fever and sometimes sepsis
Abscesses
Dental infections
Peri-anal infection
Sinusitis
Tonsillitis/pharyngitis
Pneumonia
Mild fever
Acquired immunodeficiency syndrome
HIV hi jacks components of immune system in initial phase of infection
As it spreads, infection and destruction of CD4 T cell compartment contributed to persistence of infection and culminates in immunodeficiency
HIV infects host cell binding to CD4+ and CXCR4/CCR5 in mucosal tissue
Infected tissue dendritic cells and T cells migrate to lymph node where further viral replication and spread can occur
How are CD4 T cells central controllers of adaptive immunity
Loss of T cell help via th1 and th17 limits effectiveness of innate immune
Loss of b cell help and control causes failure of antibody responses
Loss of help for anti-viral and anti-tumour CD8+ T cells
Loss of T cell regulation can result in autoimmunity
Opportunistic infection presentation
Candida
CMV
Pneumocystis pneumonia
Toxoplasmosis
Cryptococcus
Cryptosporidiosis
Severe herpes zoster
Loss of b cell function presentation
Pneumonia
Salmonella
Loss of Th1 function
Mycobacterium
Loss of T cell anti tumour function
Non-hodgkins lymphoma
Kaposis sarcoma
Loss of T cell regulation presentation
Autoimmune disease e.g. ITP especially with HAART
High immunoglobulins
Over activity of the immune system causing disease
Inappropriate activation (autoimmunity and allergy)
Failure to switch off (chronic inflammatory diseases)
Autoimmune diseases
Adaptive targets self antigens leading to inflammation and tissue destruction of body’s tissues
Examples of autoimmune diseases
Multiple sclerosis
Type 1 diabetes
Polymorphisms and mutations in genes encoding components of innate immune systems link to disease
Failure of pattern recognition
Failure of early complement
Failure of pattern recognition
NOD2 receptor defects lead to susceptibility to Crohns diseases
Failure of early complement
Linked to systemic lupus erythrematosus and glomerulonephritis
Immune mediated inflammatory diseases IMID
tissues are chronically inflamed
The immune system damaged cells and Biomolecules
Example of IMID
Rheumatoid arthritis
Allergy
IgE antibodies are made against harmless antigens and then trigger acute response on re-exposure
Acute allergic reaction process
Allergen specific IgE is pre-bound to FceR1 receptor on mast cells
Circulating allergen binds IgE causing receptor cross linking and mast cell degranulation
Symptoms of acute allergic reaction
Wheezing
Urticaria
Sneezing
Rhinorrhea
Conjunctivitis
Chronic allergic reaction
Recruitment and activation of allergen specific T cells and other cells by mast cell derived mediators
Causes of systemic low grade inflammation
Physical inactivity
Chronic infections
Obesity
Dysbiosis
Diet
Isolation and chronic stress
Disturbed sleep
Xenobiotics
Consequences of low grade inflammation
Metabolic syndrome,type 2 diabetes and NAFLD
cardiovascular disease
Cancer
Depression
Auto-immune diseases
Neurodegenerative diseases
Sarcopenia and osteoporosis
Immunosenescence
Diagnosing in lab
Look for antibodies in blood serum
Antibodies against self
Autoimmunity
CD4 T cell count dropped below threshold
AIDS
Flow cytometry
Tag cells with fluorescent ly labelled antibodies and measure how many of each type there are
Whether they are functional based on their cytokine and surface marker profiles
Neutralising monoclonal antibody against COVID-19
Sotrovimab
Neutralises spike protein on SARS CoV 2 and blocks entry into host cells
For prevention and treatment of infection
Manipulating cytokines
INF alpha and hepatitis C
Interferons stimulate immune cells and turn on anti-viral mechanisms im infected cells
For Hep C treatment, synthetic IFN alpha is typically given in combination with anti-viral ribavirin
Manipulating cytokines
TNF alpha and rheumatoid arthritis
TNF alpha is key coordinator of inflammation
Blockade of TNF alpha signalling has revolutionised treatment of RA
blockade of TNF alpha is used for other diseases, IBD
What is given to some hospitalised covid patients
IL-6 inhibitor Tocilizumab
Manipulating antigen presentation to treat autoimmunity
Modification of dendritic cells and re-administration to patients to induce tolerance to self antigen
