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Hematology > Innate Immune System > Flashcards

Flashcards in Innate Immune System Deck (72):


An antigen is a molecule capable of inducing an immune response on the part of the host organism, though sometimes antigens can be part of the host itself. In other words, an antigen is any substance that causes an immune system to produce antibodies against it.



Autoimmunity is the immune response against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease. Prominent examples include celiac disease, diabetes mellitus type 1.



Allergies are caused by hypersensitivity of the immune system to something in the environment that usually causes little or no problem in most people.


Barrier immunity

Barriers to infection, including skin, tears, mucous, antimicrobials, peristalsis, acidity, and antimicrobial enzymes/peptides.


Adaptive immunity

The adaptive immune system is highly specific to a particular pathogen. It has a delayed response as antibodies are generated. Characteristics are self-recognition, specificity, diversity and memory. Includes B cells (antibodies) and T cells (helper and cytotoxic).


Innate immune system

The innate immune system is fast acting and generic. It broadly identifies foreign bodies, removes them, and then activates the adaptive system, and triggers inflammation.

Includes phagocytosis, cytokines, inflammation, antigen presentation, and complement.



Innate system. Engulf bacteria into a phagosome and kill it via lysosomes (hydrolase and NADPH oxidase). Includes neutrophils, dendrites, and macrophages. Phagocytes then release cytokines and present bacterial residues on surface for T-cell recognition.



Monocytes travel in the blood and can differentiate into macrophages or dendritic cells.



Macrophages are type of phagocytotic WBC that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the types of proteins specific of healthy body cells on its surface. They, along with dendritic cells, are progeny of monocytes.


Dendritic cells

They, along with macrophages, are progeny of monocytes. Dendritic cells are phagocytes whose main function is to process antigen material and carry it to the secondary lymphocyte organs to be processed by the innate immune system.



Neutrophils are the most abundant white blood cell and often the first line of defense. They are phagocytes but also activate other immune cells with danger signals.


Mast Cells

Very similar in appearance and function to basophils. Mast cells may be implicated in the pathology associated with autoimmunities, inflammation disorders and allergies. They release histamine.



Very similar to mast cells. Basophils are responsible for inflammatory reactions, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They can perform phagocytosis.



Eosinophils are responsible for combating multicellular parasites. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma.



An antibody (Ab), aka immunoglobulin (Ig), is a Y-shaped protein produced by B-cells. The antibody recognizes a unique antigen on a pathogen and binds to it, essentially tagging it for destruction by other immune cells.


Immunoglobulin (Ig)

Aka antibody (Ab).


Primary lymphocyte organs

Thymus and bone morrow-provides environment for maturation of B and T lymphocytes.


Secondary lymphocyte organs

Secondary lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes and initiate an adaptive immune response.


Lymph nodes

Small organs that trap antigen-bearing dendritic cells for processing by B and T lymphocytes as well as macrophages.

They are composed of a cortex (which houses B Cells), a paracortex (which houses T cells) and a medulla, which contains the dendritic cells.



Cytokines are signaling proteins produced by immune cells and include chemokines, interferons, interleukins, lymphokines (think kines). They determine cell population size and turn the immune cells on or off. Their work by binding to specific receptors on immune cells and triggering gene expression.

They are like hormones, but are not produced in a specific tissue. They act locally and systemically.


Signs of inflammation (4)

Redness (rubor), heat (calor), swelling (tumor), loss of function.


Danger model

The Danger model is the idea that the immune system does not distinguish between self and non-self, but rather between things that might cause damage and things that will not. Self molecules recognize danger and trigger cytokines and chemokines.


Stages of inflammation (3)

1. Cell activation: bacteria in damaged cells trigger the release of cytokines and chemokines. Resident mast cells release histamine and prostaglandins for stage 2.
2. Increased vasodilation and cell permeability causes heat and swelling.
3. Cells migrate to infected tissue (neutrophils first, then monocytes). Neutrophils phagocytose. Monocytes differentiate. Inflammatory mediators are released that cause pain.


Vasodilators in inflammation (stage 2)

Nitric oxide and prostaglandins increase diameter of vessels.


Membrane permeabilisers in inflammation (stage 2)

Prostaglandin, histamine, and cytokines (IL-1 and TNF) cause cells near infection to become leaky, allowing immune cells and proteins to come to the rescue.


Cell activators in inflammation (stage 1)

Cytokines (IL-1 and TNF) and chemokine IL8 signal the immune response, turning it on.


Cell recruiters in inflammation (stage 1)

Chemokine (IL-8) brings immune cells to the site of infection.


IL-1 and TNF

Inflammatory cytokines that signal the activation of the immune response (stage 1).

TNF (tumor necrosis factor) refers to cytokines that can cause cell death (apoptosis)



Inflammatory chemokine that recruits other immune cells (chemoattractant) in stage 1 of inflammation activation.



Extravasation is the movement of white blood cells from the capillaries to the tissues surrounding them.

Immediately after infection, cytokines signal expression of cell surface molecules that slow down, bind, and help passing immune cells migrate inside.



Another term for extravasation, the process by which immune cells leave circulation and enter infected tissue cells.



Phagocytes (neutrophils and monocytes [dendritic cells/macrophages]) are in the blood stream and upon infection are recruited by epithelial chemokines (IL-8). They enter the cell by diapedesis (aka extravasation). Then recognize bacteria with their pattern recognition receptors and engulf the bacteria into phagosomes which fuse with lysosomes where they are digested by hydrolase and NADPH oxidase. Finally the decomposed byproducts, as well as more cytokines are released into the cytoplasm. Peptides from the bacteria are presented on the phagocyte's surfaces for T-cell activation.



Interleukins (ILs) are a group of cyto/chemokines that help activate and inhibit the immune response, and drive inflammation.

IL-1 triggers activation
IL-2 stimulates T cells
IL-8 recruits phagocytes to sites of infection
IL-10 turn immune system off.


Chronic Granulomatous disease

A disease caused by defective NADPH oxidase within the lysosomes of phagocytes.

Leads to severe infection of protective immune barriers (mucous, skin, mouth, intestines).


Resolution of inflammation and chronic inflammation

-Neutrophils have short lives and are ingested by macrophages.
-Inhibitory cytokines are released (IL10).
-Growth factors promote repair.
-Mediators de-permeabilize and vasodilate.

Chronic inflammation-immune response never turns off causing constant release of inflammatory mediators. Results in fibrosis (scar tissue).


Rheumatoid Arthritis

Chronic autoimmune disease characterized by inflammation that destroys bone cartilage and thickens synovial membrane.

Joints have elevated macrophages, dendritic cells, and cytokines.


NSAIDs in inflammation

NSAID's prevent production of lipid prostaglandins which has the downstream effect of restricting vasodilation and permeabilization.


Anti-permeabilisation drugs

IL-1 and TNF are the main cytokines responsible for permeabilization.

Anti-TNF therapy:
Anti-IL1 therapy:


Obesity and inflammation

As fat cells get large they begin to produce adipokines, some of which are inflammatory mediators.


Pattern recognition receptor

Receptors on the cell surface of phagocytes that identify non-self bacteria prior to ingestion.


Antigen processing

The pattern-associated molecular pattern on a microbe is recognized by the 'pattern recognition receptor' on a phagocyte. Bacteria are engulfed into phagosomes. The phagosome fuses with a lysosome, making a phagolysosome, which breaks the microbe into peptides. MHC class 2 then enters the scene from the ER, binds to a peptide residue and displays it on the cell surface, to be presented to T cells for recognition. This phagocyte is now an antigen presenting cell (APC).


Antigen presenting cell (APC)

Cells that endocytose and digest bacteria and present decomposed peptide residues on their surface for T-Cell presentation.

APC's include B-Cells, some endothelial cells, and some macrophages (dendritic cells and macrophages). It does NOT include neutrophils, as they die soon after phagocytosis.


MHC class II pathway (aka endogenous pathway)

Bacteria undergoes endocytosis via phagocytosis into antigen presenting cell and is engulfed by lysosome where it is degraded by hydrolase and NADPH oxidase. MHC class II molecule interacts with phagolysosome and attaches bacterium peptide fragments to it. MCH II molecules then travel to the cell surface where they present the fragment for T helper cell recognition.

Occurs in antigen presenting cells.

MHC class II presents only peptide fragments.


MHC class II (molecule)

MHC class II is a cell surface receptor that specializes in antigen presentation to T helper cells. MHC class II molecules travel from the endoplasmic reticulum to the lysosome where they adhere bacterial peptide residues, and then to the cell's surface where the MHC II peptide complex is presented for T helper cell recognition.


MHC class I pathway (aka endogenous pathway)

MHC class I molecules are found on all cell surfaces (except RBCs). Invaders (usually viruses) cross the cell membrane and degraded by proteasomes. The peptide residues are transported to the ER when MHC class 1 molecules rest. They attach and the MHC class I molecule leaves for the cell surface to display the antigen for recognition by Cytotoxic T cells, triggering immune response.

MCH class I also marks cells as self to prevent self-destruction.

Deficiency in MHC class 1 leads to viral susceptibility.


Differences between MCH class I and II pathways

Class II:
-pathogen is phagocytosed
-MCH class II molecule travels to phagolysosome
-only occurs in phagocytic cells
-mostly bacteria
-antigen recruits T helpers cells.

Class I:
-pathogen invades cell on its own (not via phagocytosis)
-virus fragments taken MCH class I molecule on ER
-it occurs in most cells of the body
-mostly viruses
-antigen recruits cytotoxic T-cells.


MHC genes

MHC class I and II are encoded by the Human leukocyte antigen genes. The complexes are the most polygenic in our genome. Each class is composed of three types and each type has thousands of variants. This makes the HLA genes highly polymorphic and is why each person has unique self recognition. Yet we each have a different range of antigen recognition but this helps us as a species avoid extinction.

Class I: types A, B, C
Class 2: types DP, DQ, DR


Immunosuppressant drugs

Used to prevent T-cells from destroying transplanted organs due to MCH class I differences.


Complement system

Part of the innate immune system. It is non-specific and acts rapidly. Consists of 20+ inactive C proteins that are produced in the liver and travel in the plasma. C proteins will undergo either the classical or alternative pathway upon contact with an antigen or pathogen. Both pathways result in a cascade that leads to the activation and fragmentation of C3 into pieces, which go on to cause localized inflammation and pathogen destruction.


Classical complement pathway

Triggered by contact with an antigen-antibody complex. Upon contact with an antigen, the C protein will form an antibody-antigen complex. A cascade will follow, leading to activation and fragmentation of C3 into C3a and C3b, which go on to cause localized inflammation and pathogen destruction.


Alternative complement pathway

The alternative pathway occurs when a C protein comes into contact with the surface of a pathogen. A cascade will follow, leading to activation and fragmentation of C3 into C3a and C3b, which go on to cause localized inflammation and pathogen destruction.


C3a (complement system)

A small fragment of protein C3 that plays an important role in the inflammatory activation, including vasodilation, permeability, and chemoattraction. C3 triggers mast cells to release histamine.


C3b (complement system)

A larger fragment of protein C3 that has two effects:

1. It is secures itself on the surface of the pathogen and acts as an opsonin (tag) for phagocytosis.

2. Secured to the surface of the pathogen, C3b invites other C proteins the scene (C5-9). Together they assemble on the surface and make a pore, which allows extracellular fluid to enter the pathogen and destroy the the cells integrity.



Any molecule that enhances phagocytosis. Eg, C3b.



B and T cells. Each cell recognizes only one antigen. Once recognized, they proliferate. Response is delayed. May generate memory cells.


B cells

Each B cell recognizes a specific antigen via an antigen receptor. While T cells can only recognize the peptide form of an antigen, B cells are able to recognize the antigen in any form. Once activated they function to make antibodies that will recognize the antigen.



Made by B cells to fight infection. The antibody recognizes and binds to a specific antigen. upon binding it promotes neutralization, aggregation, and the uptake of the pathogen by macrophages.


T Cells

Each cell recognizes a specific antigen via an antigen receptor.

There are 2 types of T cells with different functions.
-T helper cells, which help to activate B cells and produce cytokines.
-Cytotoxic T cells (Killer T cell) kill virally infected or tumor altered cells.



Act as chemoattractants that bring immune cells to the site of infection (IL-8).



Cytokines important in oral responce.

Type 1: limits spread and growth of viruses
Type 2: activate phagocytes.


Activation of inflammation

Inflammation occurs when a barrier is breaches and microbes infect. Microbes have regular molecular patterns that are recognizable by innate immune cells. These are called 'pattern-associated molecular patterns' (PAMP). Macrophages, dendritic cells and neutrophils express receptor that recognize PAMPs called Pattern recognition receptors (PRR). Upon recognition they trigger the production of cyto/chemokines, which initiate inflammation.



Pantern-associated recognition patterns on microbes are recognized by Pattern recognition receptors on macrophages, dendritic cells, and neutrophils. This triggers inflammation.



TNF (tumor necrosis factor) refers to cytokines that can cause cell death (apoptosis). It also causes permeabilization.

Anti-TNF therapy:


Cancer and inflammation

There are links between chronic inflammation and cancer growth/metastasis because chronic inflammation supports the tumor environment.


Arachidonic Acid metabolism

Arachidonic acid is derived from omega 3/6. It has to hydrocarbon tails.

It is metabolized into to different families; Leukotrienes (IL) and Prostaglandins (PG).

The synthesis of prostaglandins occurs via COX1,2. Prostaglandin may the be converted to:
1. prostacyclins - promotes vasodilation and inhibits platelet aggregation.
2. thromboxane - promotes vasoconstriction and promotes platelet aggregation.



cyclooxygenase- membrane enzyme that converts arachidonic acid to prostaglandins. The specific enzyme is expressed differently depending on the tissue.


Roles of prostaglandins

Induce uterus contraction.
Regulate inflammation.
Protect stomach mucosa.
Sensitize spinal neurons to pain.
Constrict/dilate vascular smooth muscle.
Produce fever
Increase glomerular filtration rate.


Omega 3 vs 6 in regards to prostaglandins

Omega 3, derived from fish, produces prostaglandins that are less inflammatory and less thrombotic.


Types of NSAIDS

Aspirin - non specific. Irreversible
Ibuprofen - non specific. competitive
Paracetamol - We aren't sure. Maybe inhibits COX 3?


COX 1,2,3

COX 1: expressed in all tissues
COX 2: Not detectable in most tissues. Expression increases during inflammation.
COX 3: Found in heart and CNS. A splice variant of COX 1.


Explain the genes coding for MHC class 1/2.

Human leukocyte antigen (HLA) genes on part of the Major Histocompatibility Complex (MHC). Highly polygenic, therefore highly diverse. Immense gene variability creates thousands of different MHC class possibilities.


Natural killer cells (NK)

NK cells are a type of cytotoxic lymphocyte critical to the innate immune system. They have the ability to recognize stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction.

NK cells are cytotoxic; small granules in their cytoplasm contain proteins such as perforin and proteases known as granzymes.

Cytokine can be activated by opsinization by antibodies or chemokines signaling.

What makes NK cells unique is that they do no require MHC Class 1 representation. Instead, they are able to recognize cells that have down regulated expression of MCH11 due to pathogenic infection. Such cells would otherwise be disregarded by cytotoxic T cells.