A1 1st Line of Defense Flashcards
Intro
Immunology:
deals with the ways in which the body protects itself from diseases and infections
Immunity = ability to recognise and eliminate or control abnormal foreign material.
Immunogen - induces immunity.
Antigen - provokes immune reaction and reacts with the products of the specific immune response.
Hapten - cannot provoke immune response unless conjugated with other molecule, e.g. protein, polysaccharidet etc.
Epitope/antigenic determinant - the part of the antigen that reacts with the products of specific immune response.
Antibody - specific protein that reacts with the atg. Produced by B cells.
TCR - specific protein that reacts with properly presented atg. Only on T cells.
• Immune system (IS):
the bodily system that protects the body from foreign substances by producing the immune response which includes the thymus, spleen, lymph nodes, special deposits of lymphoid tissue (GI & BM), macrophages, lymphocytes, B&T cells, & Abs
• Immune response:
bodily response to an Ag that occurs when lymphocytes identify the Ag molecule as foreign & induce the formation of Abs & lymphocytes capable of rendering it harmless — aka immune reaction.
Phases:
1 afferent (recognition, intake, processing),
2 central (targeted protection, activation)
3 efferent (elimination or neutralization)
Protection (4)
Immunity: the state of resistance to an infection. (Erlich) Meaning: protection, freedom (of illness)
Functions of the immune system
- Distinguish between self and non-self
- Prevent and minimize the effect of infections
- Ability to recognize and eliminate or control foreign or abnormal „self” materials
- Responsible for the integrity and genetic stability of the individual and the species
Foreign body
External substances can be taken from the environment via the mucosal membranes & skin.
– It is protected by physical, chemical and biological substances:
• hair/feather, mucus, movements, desquamation, rinsing
• lysozyme, defensin, proteolytic enzymes, pH, surfactants
• microbiome
• Internal substances are originated from within the body and the defense mechanisms mentioned above are ineffective
Microbiome
Microbiota:
gut flora composed of huge number of diverse microbial communities, our ”extended self”, a multicellular organ that consumes, stores and redistributes energy harvested from our food.
Microbiome:
collective genomic content of the gut microbiota (Joshua Lederberg)
The two concepts often merge together, so the community of bacteria is also called the microbiome.
- Maintain the immunohomeostasis
- 100x number of the cells
- Unique - Depend on species, localization, age Obesity
- Depression, schizophrenia
- Drug metabolism vs. Toxin elimination
- Enterotypes: Dominance of Prevotella, Bacteroides or Ruminococcusspecies (Type I. diabetes, Alzheimer’s disease)
Danger Model
- The foreign substance is not enough for the protection - Danger is also needed
- This is all together necessary to eliminate foreign materials
Antigen
Antigen (Atg): reacts with the products of the specific immune response, antigenicity
• Immunogen Atg: a molecule or structure which induces immunity; usually gets into the body from outside, but can be self-originated
• Hapten: a component with small molecular weight, which is not an immunogenic antigen
• Epitop or Atg determinant: the part of the antigen that reacts with the product of the specific immune response
Lymphoid Tissues
Primary lympoid tissues
• Bone marrow/ Bursa fabricii • Thymus
Secondary lymphoid tissues
• Lymph nodes • Spleen • MALT • SALT • BALT • Tonsilla • Peyer’s patch
Lymphocyte
• The populations of lymphocytes cannot be differentiated using light or electron microscopes
• T helper-, cytotoxic or regulator cells are separated by determination of CD (Cluster of Differentiation)
Lymphocyte
CD: the set of monoclonal antibodies that recognize a single protein on a cell surface
Antibody
- Antibody (Ab, immunoglobulin, Ig): a protein synthesized by an Atg exposure and produced by the immune system to recognise and eliminate that Atg.
- The Ab is produced by activated B-lymphocytes in the humoral immune response
- Plasma cells produce them in high amounts
- They consist of two heavy (H) and two light (L) chains, connected with S-S bridges through covalent bond
- The N-terminal of the chains is variable, it is capable to bind the antigen specifically
- The C-terminal takes part in an effector mechanism of the immune response
Lines of Defense
Non-specific immune response
• 1st Line
– Physical and chemical barriers – Skin and mucosa
– Enzymes, fatty acids, pH, etc.
• 2nd Line
– Phagocytosis (granulocytes, macrophages, etc.)
– PAMP recognition
– Antigen degradation and presentation
– Signals to the specific immune response
Specific immune response
T lymphocytes Cellular immune response Tc and Th
B lymphocytes Humoral immune response Antibodies, Th
• 3rd Line
– Systemic
– Local
First Line of Defense
Physical barrier
• Skin, mucous membranes, hair/feather, mucous
• Movements: palpebral reflex, (retro)peristaltic
• Desquamation: skin, intestine
• Flushing: saliva, tear, urine, sweating
Chemical barrier
• Acids: FA on the skin, lactic acid, gastric HCl
• Proteolytic enzymes (pepsin, trypsin etc.)
• Hydrolytic enzymes
• Lysozymes, cytokines and chemokines in cells
• Defensines: bind to foreign surfaces and damage the pathogen (eg. A-Def in crypt cells, B-Def in skin, respiratory tract) o Antibact., antiviral and antimicotic effect o Very imp. to protect newborns
• IFN – Interferon: signal of IC infection and is therefore produced by cells that are infected —> will activate other healthy cells which will change their cell membrane structure to a more rigid one to prevent infection. DNA/RNA production is altered.
• Complement system
• PAMP (pathogen-associated molecular pattern) this is the link between innate and specific immune
• response!
• Opsonines
• Acute phase proteins
• Inflammation: eg. Histamines from mast cells
• pH: skin: 5.5, stomach: 1.2-3, vagina 4.5, pus: 5.5-6, pancreatic fluid: 8
Biological protection
• Microbiome
Defensins: cysteine-rich, small (18-45 amino acids) proteins with positive charge
• conserved with antibacterial, antimicotic and antiviral effects
• usually connected with the membrane ”pierce” it
• very important to protect the newborns
• defensins can be α-, β-, and θ (and defensin 110-136)
Innate immunity
- present at birth and determined by genetic factors; aka natural or native immunity.
- Provides an early defence - responses are immediate (within minutes or hours) but there is no memory
- Invaders/foreign Atgs (eg. LPS or gram-negative bacteria) are recognised and destroyed in a general way without targeting specific individuals.
- The strategy or mechanism of defence of the innate immunity is the same regardless of pathogen type → nonspecific immune response
- 1st line of defence includes physical and chemical barriers to prevent the pathogen from entering the body. More than 90% of all pathogens are stopped here.
- 2nd line of defence is if the pathogen manage to enter the body and activate the cellular barrier. The phagocytic cells will be the most important in this process, especially macrophages and dendritic cells.
- 3rd line of defence consist of the activation of the B and T cells, the specific immune response.
