The immune system is a collection of cells, tissues and molecules that protect our body against pathogenic microbes and toxins in our environment.
CONNECTED (NONSPECIFIC) IMMUNITY
Physical and chemical barrier (skin, mucous
membranes, stomach acid, mucus, cough reflex, enzymes in tears, sweat)
Phagocytic leukocytes
Dendritic cells
natural killer (NK) cells
Alternative complement pathway
ADAPTIVE (SPECIFIC) IMMUNITY
Humoral immunity: B cells, plasma cells and antibodies
Cellular immunity: T cells (helper T lymphocytes and cytotoxic T lymphocytes) and cytokines
classical complement pathway
MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)
While B cells recognize circulating
antigens, 95% of T cells only recognize peptides and antigens that have been
processed by the antigen-presenting cell and presented with the MHC molecule.
MHC 1
It is found in all healthy and
nucleated cells. It is responsible for the presentation of peptide antigens in
the cell cytoplasm. For example, if a virus invades a liver cell, the peptide
fragments of the virus are presented on the cell surface via the MHC I molecule
on the surface of this liver cell. These antigen or peptide fragments presented
by the MHC I molecule are recognized only by CD8-cytotoxic T lymphocytes.
MHC 2
It is not found everywhere. It is
found only on antigen presenting cells (dendritic cell, macrophage and B
lymphocyte). The antigen presented by MHC il is recognized only by CD4 T
lymphocytes.
IgG
1) Neutralizer for germs and toxins
2) Complement activation
3) Opsonization
IGA
Mucosal immunity: IgA is secreted into
the GI or respiratory system lumen in dimer form, neutralizing microbes and
toxins.
lgE
1) Response to helminths
2) Mast cell degranulation
lgM
1) Complement activation
2) Antigen receptor for naive B
lymphocyte
lgD
1) Antigen receptor for naive B
lymphocyte
When antigen-presenting cells
(macrophages, dendritic cells) encounter antigen, they break down antigens into
small peptides within their phagosomes.
MHC-I and MHC-2 molecules and peptides
synthesized in the endoplasmic reticulum in the antigen presenting cell (ASH)
combine with the processed peptides in the Golgi body and are expressed on the
cell surface, and these peptides are presented to T cells inside the MHC-1,
MHC-2 groove.
In lymph nodes, the receptor complex
of T-specific lymphocytes and the MHC complex associate with reciprocal
ligands.
Together with the T cell receptor
(THR) CD3 complex, it combines with the MHC-peptide complex, causing CD4
activation. This, in turn, stimulates IL-2, causing clonal proliferation of
antigen-specific T cells. IL-2 stimulates both CDS lymphocytes and CD4 cells.
When the T cell receptor is stimulated
by antigen, the CD3 molecule is responsible for the transmission of the
stimulation. The adhesion molecule found on helper T lymphocytes, which
combines with the B7 receptor on macrophages and B lymphocytes during antigen
presentation, is CD28. If this secondary peer connection does not exist, it is
called anergy. The B7 receptor in ASH and the CD28 molecule on the T cell
surface combine to stimulate IL-2 synthesis and increase T cell survival and
number. Causes activation of TH1 or TH2 trough by clonal proliferation of T
lymphocytes.
CD28 also binds with the B7 receptor
on the B lymphocyte surface, regulating CD40L: which plays a role in B cell
activation. With the activation of CD40L, antibodies are produced from B
lymphocytes.
If the stimulating peptide molecule is
allergen, an IgE type antibody is produced.
Two types of signals are required for
IgE synthesis:
1. IL-4-13 warning
2. Stimulation of T cells by CD40L to B lymphocytes
TYPE 1 (ANAPHYLACTOID TYPE) HYPERSENSITION REACTIONS
• In type-1 hypersensitivity reaction, allergens entering the body through the mucosa are presented to CD4 T helper (TH) cells with the effect of IL-1 released by local antigen presenting cells (macrophage and dendritic cells). TH cells differentiate in the TH2 direction in the presence of IL-4, and in the TH1 direction in the presence of IL-12 and 18.
• Formed TH2 cells stimulate B cell proliferation with the cytokines they secrete (IL 4-5-6-9-10-13). Specific IgEs are formed by B cells that return to plasma cells. Produced IgEs bind to receptors (FcR) on the surface of mast cells and basophils, thereby sensitizing these cells.
• If the allergen enters the body again, it binds to the specific IgEs on the mast cells to form a bridge and increases the amount of intracellular Ca, causing degranulation.
• As a result of degranulation, histamine and proinflammatory mediators (LTC4, D4, E4, PGD2, PAF) released into the environment increase vascular permeability. Vasodilation, contraction of bronchial smooth muscle, increase in mucus production.
• There are 2 phases of the allergic reaction:
- Early phase: Swelling and redness in the first 15-30 minutes in the skin prick test.
- Late phase: Inflammatory response in the prick test, which appears after 6-12 hours and disappears in 24-72 hours.
• TH2 cells play a role in type 1 allergic reaction.
- IL-5: Prolongs eosinophil lifespan.
- IL-4 13: Increases IgE production.
- IL-4-10-13: Inhibits TH1 cell production and some macrophage functions.
• Atopy: It is the predisposition to develop type 1 hypersensitivity reaction to general allergens.
Type 1 Hypersensitivity reactions
• Anaphylaxis
• Atopic dermatitis
• Allergic rhinitis
• Extrinsic asthma
• Allergic conjunctivitis
DIAGNOSIS IN ALLERGIC DISEASES
• Type 1 allergic reactions are diagnosed by showing sIgE.
• sigE can be demonstrated in blood or by skin prick test (DPT). The skin test is more sensitive.
• If the patient's clinic suggests allergic disease, but sIgE cannot be demonstrated, an intradermal test (ID) can be used (not recommended for food allergies due to the risk of anaphylaxis).
• Although intradermal tests are more sensitive than SPTs, SPT correlates more with symptoms.
