11 - IMMUNE SYSTEM PATHOLOGY Flashcards
Pathologies of immune system
Hypersensitivity reactions
Autoimmune disorders
Immunodeficiencies
DESCRIPTION: antigen
substance triggering immune reaction
Description: antibodies
specific binding to antigen facilitate phagocytosis
Descripton: B cells
produces antibodies
Function macrophages
Phagocytosis
Description of cytotoxic T cells (CD8)
immune cell destroying infected cells (viruses) & cancer cells
Description: Helper T cells CD4
boost activity of B cells & macrophages
Description: Dendritic cells
antigen presentation
fct neutrophils
kill bacteria, do phagocytosis & degranulation
Description complement system
set of plasma protein: inflammation, kill cells, facilitate phagocytosis
Description mast cells
release histamine, trigger inflammation
Definition of hypersensitivity
disproportionate reactivity to antigen
Definition of hypersensitivity reactions
immune responses to harmless antigens causing symptoms upon re-exposure
Definition of hypersensitivity disease
persistent & recurrent reaction to innocuous antigen
Type 1 HS: features
Mediated by Ig E antibodies triggering mast cells
Immediate hypersensitivity: response within minutes
Many allergic reactions: reaction to common environmental allergens
Harmless substances that can be:
- Inhaled: pollen, dust misters
- Injected: venom from bees or wasps
- Contact allergies: metals, latex
- Eaten: nuts, shellfish
type 1 HS: 2 steps reactions
1) First exposure = sensitization
Dendritic cell bring allergen to lymph nodes & show it to T helper cells
IL-4: stimulate B cells to produce antibodies (IgE)
IgE antibodies binds to mast cells (airways, GI tract, dermis)
2) Subsequent exposure
Allergen bind to mast cells: degranulation
* Release of pro-inflammatory mediators (histamine)
* Bronchospasm
* Vasodilation & increase permeability
Type 1 hs: symptoms (mild & other)
Mild symptoms
Urticaria
Asthma
Eczema
Allergic rhinitis: most common 10-30% of population globally
Other symptoms
Runny or stuffy nose
Sneezing
Red, itchy & watery eyes
Swelling around eyes
Anaphylaxis: type of HS, def & causes
Type 1
Definition
= life-threatening emergency & requires immediate intervention with injected epinephrine to restore blood pressure, strengthen heartbeat & open airways
Exposure to large quantity of allergen
Wide spread release of histamine: increase vasodilation + airways constriction
Not enough oxygen to vital organs
Causes
Insect bites & stings (ants, bees)
Food ingestion (peanuts, seafood)
Medication (penicillin, aspirin)
Type 1 HS: treatment
Anti-histamines: counteract histamine effects
Corticosteroids: reduce inflammation
Epinephrine: induces vasoconstriction (prevent anaphylactic shock)
Type 2 HS: 2 types
Cytotoxic hypersensitivity
Myasthenia gravis
Cytotoxic hypersensitivity type 2 : def, features & steps
Definition
= antibody mediated destruction of healthy cells
Features
IgG antibodies recognize cell surface or matrix antigens
Tissue specific
Timing: 2-24h
Steps
1) Phagocytosis
2) Activation of complement system
- Recruitment of neutrophils & degranulation
- Lytic death of host cells
3) Cellular dysfunction
Myasthenia gravis: type of HS, def, symptoms & def of myasthenia crisis
Type 2
Definition
= antibody directed against nicotinic receptors
Nerve impulse of motor neuron fail to pass neuromuscular junction & stimulate contraction
Fluctuating weakness & fatiguability of skeletal muscle (cranial muscles = first affected)
85% of patients generalized weakness affecting muscles of limbs (later onset)
= slow progressive disease with daily & longer term fluctuations in symptoms
Infections can lead to exacerbation of symptoms
Symptoms
Double vision & dropping eyelid
Fatigue while chewing
Open jaw
Difficulty swallowing
Trouble talking & walking
Myasthenia crisis
= life-threatening medical emergency due to weakening of respiratory muscles & requiring ventilatory assistance
Type 3 HS: 2 types
Cytotoxic hypersensitivity
Systemic lupus erythematous
Cytotoxic hypersensitivity type 3: def, features, An-Ab complex
Definition
= antibody mediated destruction of healthy cells
Features
IgG antibodies recognize soluble antigens
—> Formation of antigen-antibody complexes
Systemic
Timing: hours, days or even weeks
Antigen-antibody complexes
Less immunogenicity, difficult to trigger phagocytosis
Deposit on basal lamina of blood vessel
Activation of complement system
—> Inflammation: edema
—> Recruit neutrophils: degranulation & tissue damage
Results: vascular is
Most happening in skin, kidneys, joints, pleura & pericardium
Systemic lupus erythematous: type of HS & def
Type 3
= defects in apoptotic clearance can be associated with onset of SLE
Type 4 HS: description & name 1
T-cell mediated hypersensitivity: damage to tissue through CD4 or CD8
Delayed type hypersensitivity: 24-72h from exposure
CD8+ mediated: directly kills target cells (perforin & granzymes)
(Example: type I diabetes)
CD4+ mediated: effector T helper cells activate macrophages
—> Secrete pro-inflammatory cytokines that damage tissues
Multiple sclerosis
Multiple sclerosis: def, symptoms, subtypes
Definition
= primary T-cell mediated inflammatory disorder
Inflammation
Demyelination: neurons more susceptible to apoptosis (lesions)
Irreversible axon loss & cell death (neurons & oligodendrocytes)
Brain atrophy
Symptoms
Fatigue
Pain
Weakness & balance problems
Sensory loss (paraesthesia or dysesthesia)
Visual dysfunction (optic neuritis)
Spasticity & spasms
Coordination issues (ataxia) & tremors
Depression
Bladder & bowel symptoms
Subtypes
Clinically isolated syndrome
Relapsing-remitting MS
Secondary progressive MS
Primary progressive MS
Autoimmune diseases: causes, treatment & etiology
Causes
Loss of tolerance towards self-antigens
Treatment
Corticosteroids & NSAIDs to reduce inflammation & suppress immune reaction
Physical therapy: if disease impacts bones, joints & muscles
Etiology
Often unknown
Mix genetic predisposition, hormonal factors & environmental factors
Immunodeficiency diseases: types & leads to
Primary immunodeficiency: congenital conditions
—> Mutation to genes affecting functioning of immune cells
Secondary immunodeficiency: acquired
—> Various factors reduce effectiveness of immune response in intrinsically normal immune system
Immunodeficiency lead to
Frequent & unusual complications of common infections (pneumonia)
Opportunistic infections (Candida, CMV)
Increase prevalence of tumors
Immunosuppressive drugs & adverse effects
Corticosteroids: to decrease inflammation
—> One of the most common used drugs
Adverse effects
Related to dosage & chronic use
=> Present in 90% of patients after 60 days
Osteoporosis & fracture: impairment of bone matrix mineralization
Adrenal suppression: inadequate cortisol production
Cushingoid features: weight gain & redistribution of adiposity
Diabetes & hyperglycaemia: most common cause of drug induced diabetes
Myopathy: muscle weakness & atrophy
Glaucoma: increase in intraocular pressure
Psychatric disturbances: psychosis, insomnia, euphoria, depression
Immunosuppression: predispose patients to fungal & viral infections
Infectious disease: name one
HIV infection
% of infected people & routes of transmission of HIV
- 0,7% of population infected with HIV
- Routes of transmission: unprotected sexual intercourse & sharing needles
HIV: life long infection: human immunodeficiency virus
Human immunodeficiency virus:
2 copies of ssRNA
Capside
Enzymes (retrotranscriptase, integrase)
Envelope
Envelope glycoprotein (gp120)
HIV = retrovirus —> genome integrated in DNA of CD4 T-cells
Infected T-cells will produce new HIV viruses
Killing CD4 T cell: cases of CD4 infected & non infected
CD4 helper cells infected by HIV can die:
- Integrase cause DNA damage => apoptosis
- Viral protease cleaves caspases => apoptosis
- CD8 cytotoxic T cells recognize viral protein on surface => apoptosis
- Antibodies recognizing viral protein on surface => apoptosis
Building up of viral RNA => Pyroptosis: highly inflammatory cell death
CD4 T helper cells not infected by HIV can also die:
- Exposure to HIV: move to lymph nodes
- Building up of viral RNA => pyroptosis: highly inflammatory cell death
- Release of inflammatory cytokines
- Death of non infected CD4 T cells through pyroptosis
Chronic inflammation & disease progression
HIV: clinical manifestations: types & description of each
1) Acute infection
- Initially high viral load
- Production of antibodies (3-6 weeks)
- Reduction of circulating virus
Symptoms:
Flu like symptoms
Lymphoadenopathy
2) Latent period: asymptomatic HIV disease (CD4 count > 500 cells/mm3)
- No clinical symptoms
- Positive antibody test for HIV
- Without treatment it can last anywhere between 1 to 20y
3) Early symptomatic HIV disease
- Persistent generalized lymphadenopathy
- Oral lesions (candida infections)
- Reactivation of varicella-zoster virus (shingles)
- Haematological disturbances (thrombocytopenia, anaemia)
4) Advanced HIV disease or AIDS (CD4 count < 200 cells/mm3)
- Neurological manifestations (AIDS encephalopathy)
- Weight loss
- Opportunistic infections (tuberculosis)
- Malignancies (lymphomas, kaposis’ sarcoma)
- Fatigue
- Dermatological conditions
HIV treatment
- Highly active antiviral therapy. (HAART): usually started in early symptomatic HIV disease
=> Suppress HIV replication
=> Undetectable levels of HIV in blood
HIV prognosis
- Manageable chronic illness for patients having access to treatment & adhere to treatment
- Leading cause of death is now kidney or liver failure, due to medications
HIV: standard precautions
- Use protective barriers (gloves, eye shields, gowns), when handling blood, body fluids & infectious fluids
- Wash hands, skin & mucous embraces immediately & thoroughly if contaminated by blood or other body fluids
- Prevent needle or scalpel sticks
- Any health care worker with open wounds or skin lesions should not treat clients or handle equipment until lesion heals
