4 How the body responds to infection Flashcards
What is the human immune system?
The defensive mechanisms that identify and neutralise these threats
- it is able to distinguish ‘nonself’ organisms and molecules form ‘self’
What are some potential threats that may enter the body?
From the outside
- infectious organisms
toxic agents
Potentially harmful changes occurring within the body
- malignant transformation of a previously normal cell to cancer cell
What are the 3 layers of defence?
- Barriers
- Mechanical - skin
- Chemical (e.g. acidic environment in the stomach)
- Biological (microbes, flora) - Innate immune system
- Adaptive immune system
List the main properties of the innate immune system
- A limited number of hardwired pattern recognition receptors (PRR)
- Respond rapidly
- Common to all individuals
- No memory
- Class physical/chemical barriers here too
List the main properties of the adaptive immune system
- Enormous variety of somatically generated receptors, generated by gene rearrangement
- Response slowly on 1st contact (primary)
- Immunological memory specific to individuals
- Produces long-lived cells that persist in a dormant state
- But can re-express effector functions rapidly after another encounter with a specific antigen
What is the most common source of human infections?
- Human infections in infected humans
some:
- animal reservoirs
- soil organisms
Describe Major routes of infection and physical barriers
- Aerosol in the respiratory tract
- Direct mucosal contact - important in STIs
- Gut pathogens
> excreted in faeces, and enter the same way
> or via contamination of water or food (faecal-oral route) - Blood to blood
> exposure to blood, exposure to infected anthropoid (malaria)
How is infection prevented from an aerosol source?
barrier
Respiratory tract epithelium has:
- Mucus secreting cells
- and cilia
Cilia is are tiny hair-like structures that beat in a synchronous fashion
- to move particles up the respiratory tract
- mucociliary clearance
The mucus then traps particles and organisms
Describe the innate immunity in the eye?
and barriers?
The eye must be transparent
- and be able to transmit light without distortion
Eye’s defences include:
- nerve reflex to close the eyelids as danger approaches
- lacrimal gland to secrete teras to wash particles and pathogens away
The tears
- contain lysosomes
- an enzyme that can degrade the bacterial cell wall
Describe how infection is prevented from an ingested source
- HCl and enzymes in the stomach
- it secretions of the small intestine
Their main role is digestive (and can be harmful to many microorganisms)
The gut has a layer of protective mucosa
- IgA made specifically for the lining of the gut
- disables many bacteria and organisms
The gut is not sterile
- colonised by peaceful fauna that co-exists
- unless something upsets this balance
Describe the requirements for recognition and defence function in the immune system
And how it can achieve this
The requirement is to prevent morbidity and mortality from infection
Three general approached to prevent death and disease:
- Isolate organism (granuloma in TB)
- Disrupt organism (physically damaged membrane, or in cancer; activation of apoptosis; natural killer cells)
- Consume organism (phagocytosis of bacteria by macrophages)
The requirement is to clear pathogens or non-self cells
List the main cellular and secreted mediators of immunity
- Nitric Oxide - inflammation
- Cytokines (TNF, IL-1)
- Adhesion molecules for neutrophils and monocytes (selectin) - inflammation
- Reactive oxygen species (ROS, e.g. peroxide) - defence
- Antimicrobial peptides (defensins) - defence
- Chemokines (activate neutrophil and monocyte chemotaxis)
- Complement proteins and complement regulatory proteins
Describe cytokines
These are the small polypeptides released by a cell in order to change the function of the same or another cell
- these chemical messengers are found in many organs (especially the immune system)
The main immune cytokines:
- Interfererons (IFN)
- Interleukins (IL)
Describe chemokines
The defining feature of Chemokines
- is their function as chemotactic molecules
- i.e. they attract cells along a gradient of low to high chemical concentration, from the blood into tissues (and into lymphatics)
They also have the ability to activate immune cells
What does Interleukin-6 (IL-6) do?
Acts on the liver
- Production of acute-phase proteins (C-reactive proteins)
- elevated temperature
What does IL-8, a chemokine, do?
- Activation of the vascular endothelium
- Attraction/activation of neutrophils
What is Complement, or the complement system?
Complement
- an assortment of macromolecules circulating in the blood
- precipitates in a specific sequence and forms a Membrane Attack Complex on cell membranes of pathogens that enter the bloodstream
They act as opsonins
Neutrophils and macrophages
- possess C3b receptors
- that induce these cells to phagocytose microorganisms bearing C3b on their surface
Describe how complement proteins can act as chemotaxants?
Complement also attract immune cells to the site of infection and lead to the destruction of microbes
Describe the basic mode of action of complement and phagocytes function
A complement fragment binds to a microbe
This complement then facilitates the interaction with a complement receptor - C3b (which exists on a Phagocyte)
The receptor-complement complex is internalised into the cell
- by phagocytosis
Now contained within a vacuole, the ingested microbe may now be destroyed
Describe the main functions of complement activation:
- promote inflammation (through C3a, C4a, C5a)
- recruit cells (chemotaxis)
- kill targeted cells - MAC
- solubilise and remove from circulation the antigen-antibody complexes
(this protects unaffected tissues from these large, insoluble composites - could result in unwanted inflammation)
What are the 3 types of blood cells?
- Erythrocytes (RBCs)
- Thrombocytes (platelets)
- Leucocytes (WBCs)
Describe Leukocytes/WBCs
and state how they leave capillaries
Leukocytes (WBCs)
- involved in immune response (acquired)
- when they arrive at their destination
- they leave the capillaries via diapedesis (migration between endothelial cells), and enter the CT compartment, and do function
2 major categories:
- Granulocytes
- Agranulocytes
Describe the 2 types of WBCs
Agranulocytes: leukocytes that do not possess specific granules
- Lymphocytes
- Monocytes
Granulocytes: leukocytes that possess specific granules
- Neutrophils
- Eosinophils
- Basophils
Describe neutrophils
Neutrophils
- polymorphonuclear leukocytes - granulocyte
- 60-70% of WBC count
- nucleus has 3 lobes
- cell membrane of neutrophils display Fc receptor and complement receptor for C3b
> and L-selectins and integrins that facilitate adhesion to the endothelial lining in preparation for diapedesis
Neutrophils release enzymes from specific granules
- to kill bacteria
Neutrophils phagocytose bacteria
- using membrane-bound Fc and C3b receptors
Neutrophils accumulate in large quantities at sites of bacterial infection and tissue injury
- possess prominent phagocytic capabilities
