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Immunology Lecturs 27
Immunology Lecturs 27
- César Milstein
NOTE:
There are videos in every lecture, for better understanding you should watch them
As Albert Einstein said:
“Imagination is more important than knowledge. For knowledge is limited to all we now
know and understand, while imagination embraces the entire world, and all there ever
will be to know and understand.”
Introduction to immunology
- Immunology: is the immune system and the host reaction when foreign body (Ag)
introduce to the body.
- Immune response: the reaction of an organism's body to foreign materials
(antigens), including the production of antibodies.
- Immunity: the ability of the body to defend itself against specific invading
agents such as bacteria, toxins, viruses and foreign tissues.
- Antibody: are protein that are formed in response to an antigen and that react
specifically with that antigen.
- Antigen: are substance that can stimulate an immune response.
- Intracellular pathogens: inter inside the human cells and multiply .
- Extracellular pathogens: exist outside the host cells they live in tissue and
body fluid.
INNATE DEFENSE:
§ Fever.
Introduction to immunology
- Granulocytes:
Þ Neutrophils: professional phagocytes and its increase during bacterial infection.
Þ Basophils: Involve in the allergic reactions and inflammation.
Þ Eosinophils: Produce toxic proteins against parasite.
- Mononuclear phagocytes:
Þ Monocytes: phagocytic cells circulate in the blood after leaving the BM.
Þ Macrophages (MÆ): when the monocytes migrate to the tissue they called MÆ.
Also considered professional phagocyte in spleen, liver, lungs and lymph nodes.
Þ Dendritic cells: phagocytic cells and more involve in adaptive immunity.
- Lymphocytes:
Þ B cells: produce antibodies.
Þ T cells: destroy infected and abnormal cells.
Þ Natural killer cells (NK): has the ability to kill tumor cells
Introduction to immunology
ADAPTIVE DEFENSE:
(Acquired immunity / Specific immunity)
- The adaptive immune response is specific to the pathogen presented. The adaptive immune
response is meant to attack non-self pathogens but can sometimes make errors and attack
itself. When this happens, autoimmune diseases can develop (e.g., lupus, rheumatoid
arthritis).
- Materials which induce specific immune reactions are called Antigens and The ways that the
immune system uses to perform this function fall into two categories:
• Cell mediated:
Is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the
activation of phagocytes, T-lymphocytes, and the release of various cytokines in response to antigen.
• Humoral:
Defense is accomplished by means of an antigen, antibody molecules. (Antibodies).
Also called antibody mediated immunity.
NATURAL IMMUNITY:
PASSIVE IMMUNITY:
Þ B cells: formed from the stem cells in the BM & mature in the BM.
- Are responsible for the humoral or antibody response.
- When B cells bind to a particular Ag they become activated and then divide and differentiate
into plasma cells, which produce and release Ab that circulate in the blood.
- Some B cells might divide without differentiation into plasma cells, and these
known as long-lived memory cells. On the second exposure to the same Ag these memory
cells responsible for the rapid, and long-lasting response.
Þ T cells: formed from the stem cells in the BM but mature in the thymus.
Ø Classes of T cells:
* T helper (TH): promote B cell and T cell response to Ag, secrete chemical signals (IL-2,
IFN- γ) that activate MÆ to destroy the invading microorganism.
* T suppressor (Ts): can suppress or block the inappropriate lymphocyte response to Ag.
* T cytotoxic (Tc): bring about cytolysis and cell death of target cell.
* Delayed -type hypersensitivity: regulate a variety of nonspecific blood cells and
macrophages in expression of delayed hypersensitivity (type IV) reactions.
* Memory T-cells: which recognise the original invading antigen. When the antigen returns
thousands of memory cells are available to initiate a far swifter reaction than occurred during
the first invasion.
Introduction to immunology
Humoral immunity:
https://www.youtube.com/watch?v=y0-BaWcU-SE
PHAGOCYTOSIS:
Phagocytosis, process by which certain living cells called phagocytes ingest or engulf other
cells or particles. The phagocyte may be a free-living one-celled organism, such as
an amoeba, or one of the body cells, such as a white blood cells.
Þ Many cells are capable of phagocytosis, but several types of immune cells are
particularly specialised in this role:
• Neutrophils: these are abundant in the blood and important in acute inflammation, as they are
the first immune cells to arrive at the site of infection.
• Macrophages: tissue resident cells that are key as a first defence mechanism and in initiating
the adaptive immune response.
• Dendritic cells: these cycle through the bloodstream, tissues and lymphoid organs, sampling
potential pathogens and acting as a major link between the innate and adaptive immune
systems.
• Chemotaxis:
Present of chemical stimuli from microorganisms, complement components or C-reactive protein attract
the phagocytes to the site of infection and this called opsonization.
• Recognition and attachment:
- Direct binding: occurs with surface receptors.
- Indirect binding: occurs when a particle has been opsonized.
• Engulfment:
Once attachment occurred, the cellular cytoplasm flows around the particle and eventually fuses with
it and forms vacuole called phagosome.
• Fusion with lysosome:
Within the phagocyte the phagosome fuses with a lysosome, and the vesicle filled with digestive
enzymes and this fusion result in the formation of a phagolysosome.
• Destruction and digestion:
Within the phagolysosome the microorganism is broken down with the aid of enzymes.
• Exocytosis:
The vesicle containing the digestive material joins with the plasma membrane and then the vesicle is
expelled to the external environment.
Phagocytosis
Phagocytosis
• Capital C followed by the number for the classic and common pathway (C1, C2, C3, …).
• Capital letter followed by number for the alternative pathway (B1).
• Fragments "which are derived from enzymatic cleavage of the parent molecules": small letter
suffix (C3a, Bb).
• Inactivated components: The letter i prefix (iC3b).
• The active state of isolated complement components: Bar over symbols (C4b 2a).
FUNCTIONS OF COMPLEMENT:
§ Production of opsonins: such as C3b and C4b which are coat the bacteria for opsonization.
§ Anaphylatoxins: C3a, C4a and C5a are known as anaphylatoxins (increase inflammation).
§ Lysis of cells (cytotoxic function): through the formation of membrane attack complex (MAC).
§ Remove of dead and dying cells.
§ Stimulation of leukocytes movement (Chemotaxis) and activation when bound to them.
1- Classical pathway.
2- Lectin pathway.
3- Alternative pathway.
Complement
CLASSICAL PATHWAY:
ALTIRNATIVE PATHWAY:
LICTEN PATHWAY:
Complement animation:
https://www.youtube.com/watch?v=mfCeCvkQbuI
Complement animation:
https://www.youtube.com/watch?v=DPNnZE4OtCM
Alternative pathway:
https://www.youtube.com/watch?v=qga3Wn76d9w
Lectin pathway:
https://www.youtube.com/watch?v=SJv9gDFgwtw
MAJOR HISTOCOMPATIBILITY COMPLEX
- Group of genes on the short arm of chromosome 6 code for proteins found on the
surface of cells that help the immune system to presenting peptide Ag to T cells.
- In human beings the complex is also called human leukocyte antigen (HLA).
- MHC molecules are glycoproteins expressed at the surface of almost all vertebrate
cells.
- Identical twins have same MHC molecules on their cells, so they accept transplant
tissue from each other.
- MHC molecules act as Ag when introduced into a different individual.
- MHC molecules are often called histocompatibility Ags or transplantation Ags.
Þ MHC Haplotype:
• The loci that make up the MHC are highly polymorphic.
• We inherit our alleles in sets, one from each parent.
• Each set of alleles is called a haplotype.
• Codominant expression: are MHC alleles expressed on cells of offspring from both
father and mother, so a person heterozygous for HLA-A, HLA-B, HLA-C express
6 different Class I proteins.
CLASS I CLASS II
Large chain (heavy chain) with three Slightly larger alpha chain (2 domains)
Peptide binding groove (8-10 a.a) Binding clefts face in opposite directions to form
Both on Chromosome 6
The peptide in the groove 2 α helices is The peptide in the groove between α and β is like a