Pathological processes and mechanisms in the human body

What are the stages of infection?

1. Incubation→ period from exposure to pathogen until symptoms

2. Prodromal→ pathogen replicating, activation of immune response

3. Illness→ noticeable symptoms appear and worsen

4. Decline→ pathogen particles and symptoms decrease

5. Convalescence→ regaining of health

What is tuberculosis treated with?

Aminoglycosides which are antibiotics/otoxic drug that have a side effect of hearing loss

What causes inflammation? Classic signs?

Tissue injury caused by physical/chemical agent or pathogenic microorganism, damaged cells and immune cells release chemicals like cytokines, blood vessels widen, blood vessels become more permeable, white blood cells attack pathogens signs being→ heat, redness, swelling, tenderness, pain

What are cytokines and the 6 major cytokine families?

Cytokines are hormones of the immune system that mediate and regulate immunity, inflammation and haematopoiesis, the families are:

1. Interleukin 1 family

2. Hematopoetin family (class l cytokines)

3. Interferon family (class ll cytokines)

4. Tumor necrosis family

5. Interleukin 17 family

6. Chemokines

Distinguish the innate and adaptive immune system

Innate

• Physical barriers

• Chemical barriers

• Innate response→ mast cells, neutrophils, macrophages, natural killer cells

Linked by dendritic cells

Adaptive

• Cell mediated response→ humoral response so T lymphocytes and B lymphocytes

• T lymphocytes produce CD4+ and CD8+ T cells

• B lymphocytes produce antibodies

Name and define the innate immune cells

• Neutrophil→ first responder, phagocytic, releases toxins that kill/inhibit bacteria and fungi

• Monocyte→ differentiate into macrophage and dendritic cells

• Macrophage→ phagocytic cell, stimulates other immune cells

• Dendritic cell→ antigen presenting cell, triggers adaptive immune response

• Mast cell→ dilates blood vessels and induces inflammation (histamines/heparin), wound healing

• Natural killer cells→ kills tumour and virus infected cells

• Eosinophil→ releases toxins that kill bacteria and parasites, can cause tissue damage

• Basophil→ defends against parasites, releases histamines, allergies

What is the complement system?

Complements the ability of antibodies and phagocytic cells to clear microbes

State the 3 consequences of the complementary system

1. Increased phagocytosis

2. Increased level of inflammation

3. Increased cell lysis and activation

What is the NLRP3 inflammasome?

• A group of proteins inside immune cells that act like an alarm system for inflammation

• When signs of infection are detected or cell damage etc.

• Switches on to form NLRP3 inflammasome

• Activates enzyme caspase-1

• Causes inflammation helping body respond to danger

• Can contribute to hearing loss

What are DAMP and PAMP?

Damage associated molecular pattern

Pathogen associated molecular pattern

Which is what the immune cells recognise

Which MHC molecules go to which immune cells?

• Type l: surface of all uncleared cells, display peptide fragments to CD8+ cytotoxic T cells (kill cell)

• Type ll: surface of antigen-presenting cells (e.g. dendritic cells), initiate immune response so attach to CD4+ T cell

What are the 5 classes of antibodies, or immunoglobulins (lgs)?

• IgG antibodies

• IgE antibodies

• IgD antibodies

• IgM antibodies

• IgA antibodies

What are the different T cells types and what they do?

• Cytotoxic T cells→ produce toxic agents to kill their targets

• Helper T cells→ stimulate B cells to make antibodies and stimulate T cells to become active

• Regulatory T cells→ suppress immune responses

• Memory T cells→ remain after the threat is cleared in case the pathogen ever reenters in which the immune response will be much quicker

What are some different types of vaccines and for what infection?

• Inactivated vaccines (rabies)

• Life-attenuated vaccines (MMR)

• Messenger RNA vaccines (covid-19)

• Subunit, recombinant, polysaccharide, and conjugate vaccines (HPV)

• Toxoid (tetanus)

• Viral vector vaccines- adenovirus (covid-19)

What is an autoimmune disease?

• Immune system mistakenly attack tissues and organs

• Can’t be cured but can be treated with immunosuppressant medication

What are mechanisms that can lead to autoimmune diseases?

• Molecular mimicry→ pathogen has antigens that resemble the body’s own proteins

• Bystander activation→ infection can cause inflammation activating immune cells that can accidentally activate self-reactive immune cells that attack body’s own tissue

• Epitope spreading→ immune attack damages body’s tissues exposing new self antigens and immune response then expands to target additional parts of body’s own proteins

What are the types of multiple sclerosis?

• Clinically isolated syndrome

• Relapsing-remitting MS

• Secondary Progressive MS

• Primary Progressive MS

What type of cells does MS target?

Oligodendrocytes

Other examples of autoimmune disease?

Allergies

What is oxidative stress?

A phenomenon caused by an imbalance between production and accumulation of reactive oxygen species in cells and tissues and the ability of a biological system to detoxify these reactive products

What are reactive oxygen species?

An unstable molecule that contains oxygen and that easily reacts with other molecules in a cell

What are some extracellular and intracellular sources of ROS?

Extracellular

• Smoking

• Ionising radiation

• UV radiation

• Infection

• Pollution

Intracellular

• Major source is mitochondria

What are free radicals?

An atom or molecule containing one or more unpaired valance electrons

What is antioxidant?

Counteracts free radicals e.g. catalase

What is oxidative stress? (simplified)

An imbalance between antioxidants and free radicals

What are the different ways oxidative stress can lead to hearing loss?

• Cellular damage→ lipid peroxidation of cell membranes can compromise cell function and contribute to hearing loss

• Generation of oxidative stress by reactive oxygen and nitrogen species overproduced in the cochlea

• Inflammation→ triggers inflammatory response in cochlea, which can exacerbate tissue damage

• Apoptosis→ prolonged oxidative stress and inflammation lead to programmed cell death of sensory cells in cochlea

Noise exposure, aging and otoxic drugs all lead to oxidative stress

What is trauma what are the different types?

Any physical injury that could cause serious medical conditions or be life threatening

1. Blunt force trauma

2. Deceleration trauma

3. Penetrating traumatic injury

What is cancer and a brief timeline?

• A condition where cells in a specific part of the body grow and reproduce uncontrollably

• First identified 4,600 years ago

• First tumour removal in 440 BC- breast tumour

• 19th century various approaches devised by surgeons

• Chemotherapy developed mid 20th century from mustard gas

• Cisplatin chemotherapy approved 1978 which causes half a million cases of hearing loss annually

• Acoustic neuroma (vestibular schwannoma)- non cancerous tumour- can lead to hearing loss and tinnitus

Causes of cancer?

• Heredity

• Viruses

• Smoking

• UV radiation

• Chemicals

• Cells dividing

• DNA mutations leading to uncontrolled cell growth

What are the 2 main genes associated with cancer and what do they do?

• Oncogene→ mutated gene that has the potential to cause cancer so this one is activated, whilst a proto oncogene is an oncogene before it mutated

• Tumour suppressor gene→ gene that regulates cell division so this one is inactivated

What is cancer metastasis?

• Spread of cancer cells from the place where they first formed to another part of the body

• Cancer cells break away from the original (primary) tumour, travel through the blood or lymph system and form a new tumour in the other organs or tissues of the body. The new metastatic tumour is the same type of cancer as the primary tumour