Immune System Pt 1 Flashcards
Innate immunity - non specific
Physical barrier
Chemical barrier
Cellular response
Acquired (adaptive) immunity - specific
Active- Natural (getting cold), Artificial (vaccs)
Passive-Natural (maternal), Artificial (Tetanus antitox)
Immune system: main components
Roles: Response to external antigens (protection) and avoid self-damage
White blood cells, bone marrow and antibodies
The complement system
The lymphatic system
Barriers that are part of innate immune response
Myeloid cells:
Granulocytes* (neutrophils, eosinophils, basophils) and agranulocytes (monocytes** and macrophages)
Lymphoid cells
T cells, B cells, Natural Killer cells (NK cells) and NK T cells
Adaptative immune response
cytotoxic T cells, T helper cells, B cells, and natural killer (NK) cells
T cells mature thymus
B cells mature in spleen and LN
NK are also part of the innate cellular immune response
technically agranulocytes but derived from a lymphoid cell
Mast cells
– not truly the regular haematopoiesis but they are defence cells
Part of innate immune response (non-specific)
Produce histamine (vasodilation) and other inflammatory mediators (IL-4, IL-13, TNF-⍺, leucotriens and prostaglandins)
Live in tissues (gut, lungs, skin, blood vessel)
Important in parasite infections and allergic reactions
WBC can be generally divided as
granulocytes and agranulocytes (monocytes, macrophages and lymphocytes of all kinds) regardless of the way they are produced, and this is a useful classification when checking blood smears and cytologies
monocytes can turn into
dendritic cells
haematopoiesis:
Defence cells, white blood cells (WBC), are generated in the bone marrow from a haematopoietic stem cell through a process called haematopoiesis
Granulocytes
Granular cytoplasm and multilobed nucleus
Predominant cells in blood
Made in myeloid tissue in the bone marrow
Types:
Neutrophil
Basophil
Eosinophil
Neutrophils
Make up pus! Short life span in blood, longer in tissues
40-60% of white cells in blood
High numbers in bacterial infection
Phagocytic i.e. engulf micro organisms and foreign particles.
Granules contain myeloperoxidase, lysozymes, acid hydrolases, proteasas and defensins, lysozymes, lactoferrin and collagenases [Klein, Bradley G.. Cunningham’s Textbook of Veterinary Physiology - E-Book]
Neutrophils come to the site through diapedesis guided by chemokines and chemical messengers, they adhere to the bad guy, eat it (phagocytosis) and digest it.
steps of phagocytosis
Step 1: Activation/ actuation
This step of phagocytosis occurs when the cell comes in close proximity to given objects/particles. For instance, when phagocytes are near such cells as bacteria, this activates the phagocytes and stimulates binding.
- The first step also involves chemotaxis. Here, the cells move towards the area with a high concentration of the foreign particles/cells or molecules. Cells are chemically stimulated by the presence of the foreign molecules/ particles etc.
Step 2: Binding
Here, surface receptors on the phagocyte bind/adhere to the surface of the particle. This step of phagocytosis is necessary for the molecule to be ingested.
Depending on the cell, there are different types of surface receptors that play an important role in phagocytosis (binding).
These include:
Scavenger receptors- Bind to various types of molecules on the surface of bacteria
Opsonin receptors- Opsonin receptors are some of the most studied surface receptors. They bind to molecules that possess immunoglobulin G on their surface
Antibodies- Some of the cells are capable of producing antibodies that make it possible to attach to certain antigens
Toll-like receptors- These receptors bind to specific molecules on the surface of bacteria, fungi, and viruses
* Receptor binding is an important step in phagocytosis allowing the cell to identify the object/particle/bacteria etc and thus elicit the appropriate reaction.
Step 3: Ingestion
The cell (phagocyte) starts expanding as it surrounds the molecule. This process also involves formation of a vacuole or vesicle around the molecule as it is completely ingested.
Step 4: Digestion
In some cells, enzymes in the vesicle (e.g. lysosome) break down the molecule into simpler components. Waste materials that cannot be used are then removed from the cell through a process known as exocytosis. However, for phagocytes involved in immunity, special structures are known as peroxisomes are created to trap and remove toxic molecules.
Neutrophil mechanisms
Phagocytic
Respiratory burst- basically they create a reaction that frees up H2O2 (a disinfectant) and increase O2 locally which is toxic for some bacteria
NETosis- they release sticky substances (a bit like spiderman!) in response to LPS from bacterial wall, TNFalfa or IL8. They trap cells
Release “insides” and act as markers (martyrs of the immune system)
Basophils
Contain histamine (inflammation and allergic reaction) Contain heparin (anti coagulant) Stained purple (basic, haematoxylin)
Eosinophils
Stain acidophilic (eosin) contains enzymes Allergic responses (hypersensitivity type I)and parasite infections
Agranulocytes
Made up of monocytes, macrophages and lymphocytes (separate section)
Made in bone marrow, spleen and lymph nodes
Lymphocytes - most common agranulocyte in blood (80% of agranulocytes)
Macrophages and monocytes produce chemicals that trigger fever
Monocytes
Early macrophages that are in blood. When migrated to tissues: macrophages (and different names, see next slide)
Macrophages
Express MHC I and II in surface
Biggest WBC
Can express Toll-like receptors (TLR) which serve for pattern recognition to trigger innate immune response
There are 13 TLRs in mammals that mainly are produced by macrophages. They can be on the surface or intracellular.
describe the maturation of Lymphoid cells
T cells (adaptative immune response)
Lymphoid stem cells generated in the bone marrow go to the thymus (thymocytes)
Added markers CD4+ and CD8+,T cell receptor and CD28 (naïve T cells)
Specialisation:
Loose CD8+ turns into a CD4+ Lymphocyte T helper (Th) produce cytokines
Loose CD4+ turns into a CD8+ Cytotoxic T cell
Any T cells that respond to inner antigens or cannot bind antigens are eliminated by apoptosis.
>90% of the naïve T cells die in the thymus (selective!)
T cells (adaptative immune response)
Lymphoid stem cells generated in the bone marrow go to the thymus (thymocytes)
Added markers CD4+ and CD8+,T cell receptor and CD28 (naïve T cells)
Specialisation:
Loose CD4+ turns into a CD8+ Cytotoxic T cell
Loose CD8+ turns into a CD4+ Lymphocyte T helper (Th) produce cytokines
Any T cells that respond to inner antigens or cannot bind antigens are eliminated by apoptosis.
>90% of the naïve T cells die in the thymus (selective!)
Cytotoxic (CD8+) and helper (CD4+)
Helper are divided in Th1 and Th2
Th1 produce IFN-ɣ and are involved in delayed hypersensitivity
Th2 activate B cells (IgE)
There is sometimes cross immunity against different pathogens
B cells (adaptative immune response)
Antibodies on surface specific to antigens
B cells act as antigen presenting cells like macrophages or neutrophils (they engulf pathogens and present the antigen through a MHC II receptor to CD4+ T helper)
T helpers activate B cells to either “memorise” the pathogen (memory B cell) or plasma cells
Activated B cells turn into:
Plasma cells - the ”army”, produce antibodies
Memory cells prepare for long term immunity
Natural killer cells (innate immune response)
They can kill external (bacteria) or internal cells (defective cells such as cancerous cells) by apoptosis
They recognise lower or lack of MHC I as a signal
Release IFN-ɣ, which activates naïve T cells
Antigens
Antigens are substances that trigger an immune response (immunogens)
Infections (virus, bacteria, fungus, parasite) or non-infectious (plant, animal protein), external (wall of a bacteria) or internal (inside of a bacteria)
“hooking” points for antibodies – epitopes
The degree of immune response that an antigen elicits is called antigenicity, which is used in the design of vaccines
Antibodies recognise and attach to antigens
Foreign, big, complex (lipids or CH) and stable are the worst combo!
Example: Spike protein COVID19
Used in vaccines to stimulate immune response
Antigens - antibodies
Antibodies are produced specifically from B cells. There are 5 types of antibodies (IgM, IgE, IgG, IgA,IgD)
Ab-Ag reactions are used in tests such as canine parvo(Ag), FeLV(Ag)/FIV(Ab) and in therapy (tetanus antitoxin)
Present in the colostrum (adaptative passive immunity)
Ab and Ag tests are also used for COVID testing
Innate immune response is faster and not long lasting whereas adaptative takes a while to build up and once B memory cells are created it is long lasting. The time to get to B cell formation and the duration of the immunity after exposure varies with different pathogens and also immune system (very very variable!)
The complement system
Actions:
Opsonization: C3b activates phagocytic cells which engulf and destroy pathogens
Cell lysis: membrane attack complex or C5b6789 breaks cellular walls
Chemotaxis: C5a attracts phagocytic cells
Activation of mast cells: C3a, 4a, 5a activate basophils and mast cells driving inflammation
Lymphatic system: components
Tonsils Thymus Spleen Peyer patches Lymph nodes Lymph
Physical and chemical barriers
Physical: Skin* and mucous membranes, respiratory ciliary system
Chemical: pH sebaceous glands (skin), pH stomach, mucus, saliva, tears, “good flora” in skin, gut and reproductive tract
