Table of contents
Week 1................................................................................................................... 2
Lecture 1 – Introduction to the course.................................................................2
Lecture 2 – Chapter 5: Diseases of the Immune system and Chapter 22: Skin. . .2
Lecture 3 – Chapter 1: Cell injury, Cell death and Adaptations............................9
Week 2................................................................................................................. 16
Lecture 4 – Chapter 2: Inflammation and repair................................................16
Lecture 5 – Chapter 3: Hemodynamic Disorders, Thrombosis, and Shock.........22
Lecture 6 – Chapter 6: Neoplasia.......................................................................27
,Week 1
Lecture 1 – Introduction to the course
Lecture 2 – Chapter 5: Diseases of the Immune system and Chapter 22:
Skin
Introduction to the Immune System
The immune system protects the body against infections, but the same
mechanisms that defend us can also cause tissue injury. When immune
responses are excessive, misdirected, or uncontrolled, they lead to
hypersensitivity disorders. Then, the protection becomes the disease.
Conversely, insufficient immune activity results in immunodeficiency.
Understanding both the normal immune response and its pathological variants is
essential for recognizing immune-mediated diseases.
The immune system consists of innate and adaptive components. Innate
immunity provides immediate, non-specific defense through epithelial barriers,
phagocytes, dendritic cells, NK cells, and plasma proteins such as complement.
Adaptive immunity, mediated by lymphocytes and antibodies, is highly specific
but slower to develop, requiring several days to become fully active.
Innate Immunity
Innate immunity relies on cells and proteins that are always present (from
moment of birth) and ready to respond. Its key function is to recognize pathogens
or damaged cells through pattern-recognition receptors (PRRs), which
detect PAMPs (pathogen-associated molecular patterns – which do not exist in
human cells) and DAMPs (damage-associated molecular patterns). These
receptors are expressed by epithelial barriers, phagocytic cells and dendritic cells
and are located on the plasma membrane, in endosomes and in the cytosol. In
addition, the innate immune system also contains NK cells and the complement
system.
There are several classes of PRR Families:
Toll-like receptors (TLRs) detect microbial products and nucleic acids.
NOD-like receptors (NLRs) form inflammasomes, such as NLRP3, which
activate caspase-1 and promote IL-1β (alert molecule, causes fever) and
IL-18 secretion.
RIG-like receptors detect viral RNA.
C-type lectin receptors recognize fungal and bacterial carbohydrates.
,Innate immunity triggers two major reactions: inflammation, driven by
cytokines and lipid mediators, and antiviral defense, mediated by type I
interferons. These responses also provide signals that activate the adaptive
immune system.
, Adaptive Immunity
Adaptive immunity consists of humoral immunity, mediated by antibodies
produced by B cells, and cellular immunity, mediated by T cells. It provides
highly specific responses and immunological memory. This gets activated in 3 to
7 days, as it is usually in a dormant stage. The adaptive immune system gets
alerted by the dendritic cells: they digest the PRR and display peptides on their
outer surface. They form the bridge between the innate and adaptive immune
system.
Functions
Neutralization and elimination of microbes.
Killing of infected cells.
Regulation of immune responses.
Surveillance against abnormal or malignant cells.
Dysfunction
Hypersensitivity reactions (types I–IV).
Autoimmune diseases.
Transplant rejection.
Immunodeficiencies.
Cells of the Adaptive Immune System
T Lymphocytes recognize peptide antigens only when presented by MHC
molecules. There are two types of T cells:
1. CD4+ T cells (Helper T cells)
Recognize antigens presented by MHC class II. Activation requires both TCR
engagement and costimulation. Depending on cytokine signals, CD4+ T cells
differentiate into:
Th1 cells: produce IFN-γ, activate macrophages, defend against
intracellular pathogens; involved in autoimmunity and chronic
inflammation.
Th2 cells: produce IL-4, IL-5, IL-13; activate eosinophils; defend against
helminths (parasites, in this case worms); central in allergic disease. They
tell B cells to produce antibody IgE.
Th17 cells: produce IL-17 and IL-22; recruit neutrophils; defend against
extracellular bacteria and fungi; involved in autoimmunity. Call in for
massive reinforcement.
2. CD8+ T cells (Cytotoxic T lymphocytes)
Recognize antigens presented by MHC class I on nearly all nucleated cells. Once
activated, CTLs kill infected or abnormal cells through:
Perforin and granzymes (intracellular apoptosis).
Fas–FasL interactions (extrinsic apoptosis pathway).
B Lymphocytes produce antibodies and do not require MHC for antigen
recognition. After activation by an activated CD4-helper T cell, they differentiate
into plasma cells. Antibody diversity arises through:
Random Ig gene rearrangement in the bone marrow.
Affinity maturation and class switching in lymphoid follicles after
antigen exposure.
Major antibody classes include IgG, IgM (these two are the most abundant
opsonization), IgA (crucial for mucosal surfaces), IgE (fight parasites and causes
allergies), and IgD.
Antigen-Presenting Cells (APCs)