The major histocompatibility complex (MHC) plays a key role in the immune system's response to transplants and infections. The MHC is a set of genes that encode MHC molecules which are expressed on nearly all cells and present antigen peptides. There are three main classes of MHC molecules - Class I presents antigens to CD8+ T cells, Class II presents antigens to CD4+ T cells, and Class III encodes proteins involved in immune processes. MHC molecules are important in transplant rejection, as mismatches can trigger an immune response against the donor tissue. Careful HLA typing and matching is done to minimize rejection.
Through this presentation you will be able to learn about the detailed knowledge of complement system and its functions along with the complement activation pathways [classical, alternative, lectin pathway ]
Through this presentation you will be able to learn about the detailed knowledge of complement system and its functions along with the complement activation pathways [classical, alternative, lectin pathway ]
introduction, history, classification of grafts, transplantation antigens, role of MHC in transplantation, immunology of allogenic transplantation, types of graft rejection, immunology of xenogeneic transplatation, organ trannsplantation.
Immunology of Transplantation and Rejection A. Rakha
This file gives info about transplantation and the immunological problem like tissue rejection. MHC role in transplantation, laws, and types of tissue transplantation. Explains all kinds of tissue rejection and source of tissue. Some immunological terms plus transplantation history, it also includes the genetic basis of Transplantation. Hope it's helpful
Transplantation : Introduction to immunology part of Major Histocompatability complex(MHC) that facilitates you to understand the basic principles or issues of graft rejection and How it occurs.
Description of various immunological mechanisms involved in the rejection of transplants. Lecture notes for medical, dental and allied health sciences undergraduate medical students.
Similar to Major Histocompatibility Complex & transplantation 3rd.pptx (20)
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. Major Histocompatibility Complex
• Major Histocompatibility Complex :
• The MHC is a collection (complex) of genes
arrayed within a long continuous stretch of
DNA on chromosome 6 in humans
MHC
Cell nucleus
3. These genes encode
Class I and class II
MHC molecules,
they are membrane
bound glycoproteins
that are closely
related in structure
and function.
Cell
membrane
MHC – I MHC- II
4. • Since the MHC was first defined in mice by
Gorer and Snell in 1937, the World Health
Organization (WHO) Nomenclature
Committee has named HLA (Human Leukocyte
Antigen) to the human MHC
5. Why the name
(Histocompatibility Antigen) ??
• Histocompatibility: (tissue compatibility in
transplantation)
• Antigens: Proteins on tissues and cells that
determine their rejection when grafted between two
genetically different individuals that cause a very
strong immune response and are most important in
rejection
6. • Expression of MHC antigens on cells:
MHC antigens are expressed on the cell
surface in a co-dominant manner: products of
both parental genes are found on the same
cells.
7. In all nucleated cell:
Muscles
Epithelial cells
Nerve cells
Blood cells
In Antigen presenting cells
(APC)
Monocytes, macrophages
Dendritic cells, B cells
Expression of MHC antigens on cells:
10. There are Three Classes of MHC:
• Class I genes
• encode glycoproteins expressed on the
surface of nearly all nucleated cells, where
they present antigens of altered self cells
necessary for the activation of Tc cells.
11.
12. • Class II genes
• encode glycoproteins expressed primarily on
APCs (dendritic, MO, B cells) where they
present processed Ag peptides to Th cells.
13.
14. • Class III genes
• encode somewhat different products, some of
which are also associated with the immune
process. These include a number of soluble
serum proteins such as some of the C'
components, TNF, and steroid enzymes.
15. Major Histocompatibility Complex
(MHC) in response to infections
• The major histocompatibility complex plays a
central role in the development of both:
• humoral
• and cell mediated immune responses
• and are the principal determinants of graft
rejection.
17. How can the MHC be involved in
Immune response??
• T cells only recognize antigen when it is
associated with an MHC molecule thus MHC
molecules play a critical role in Ag recognition
by T cells.
18.
19.
20. MHC or HLA in Organ Transplantation
• The clinical significance of the MHC is realized
in organ transplantation.
• Cells and tissues are routinely transplanted as
a treatment for a number of diseases.
21. • The transplant of organs is one of the greatest
therapeutic achievements of the twentieth
century. In organ transplantation, the adaptive
immunity is considered the main response
exerted to the transplanted tissue.
22. In transplantation, the principal target of the
immune response in recipient (patient) is the
MHC (major histocompatibility complex)or the
HLA (Human Leukocyte Antigen) molecules
expressed on the surface of donor cells, because
they vary between individuals.
24. • Types of grafts
• Xenograft
Grafts between members of different species
(also known as heterologous, xenogeneic or
heterografts)
• Allograft
Grafts between two members of the same
species (also known as allogeneic or homograft)
• Isograft
Grafts between members of the same species
with identical genetic makeup (identical twins)
25. • Because we get different HLA molecules, they
are regarded as foreign antigens on the
surface of the donor cells
• The process by which the immune system
recognizes pathogens, tumors, and
transplantation antigens involves the same
HLA antigen recognition molecules by the
immune system of the recipient.
26.
27. • The rejection response to grafted tissue is
caused by cell surface molecules (MHC or
HLA) that induce an antigenic stimulus.
29. Before Starting the Organ Transplantation :
• HLA Testing for compatibility
• To support the transplant programs, several
clinical laboratories perform various HLA tests,
including HLA typing of the recipient and the
donor, screening of HLA antibodies in the
recipient, and detection of antibodies in the
recipient that are reactive with lymphocytes
of a prospective donor (cross-matching)
30. • Historically, HLA typing was conducted by
serologic testing by using antiserum in
complement-dependent cytotoxic assays.
• Recently, more precise DNA-based HLA typing
methods using molecular techniques, such as
sequence-specific oligonucleotide probe
hybridization, sequence-specific primer
amplification, sequencing-based typing, and
reference strand-based conformation analysis,
have been developed and are frequently used
31. Survival rate of grafts
• There is a clear relationship between the
degree of HLA matching (compatibility) and
graft survival in transplants from living-related
donors.
• Simultaneous analysis of matched living-
related allografts HLA allografts showed 10-
year projected survival rates
32. • To avoid hyperacute rejection, it is very
important to identify recipient anti-HLA
antibodies to antigens expressed on donor
with blood cells.
33. ALLOGRAFT REJECTION
• However, reaction of the host immune system
against allo-antigens of the graft (HVG) results
in its rejection and is the major obstacle in
organ transplantation.
• The rejection time of a graft may vary with the
antigenic nature of the graft and the immune
status of the host and is determined by the
immune mechanisms involved
34. Types of Graft Rejection
• Hyper - acute rejection:
This occurs in instances when the recipient
has preformed high titer antibodies.
• A graft may show signs of rejection within
minutes to hours due to immediate reaction
of antibodies and complement system
activation that leads to lysis of the grafted
cells.
35. • Accelerated (2nd set; secondary) rejection
Transplantation of a second graft, which shares a
significant number of antigenic determinants
with the first one, results in a rapid (2 - 5 days)
rejection.
• It is due to presence of T-lymphocytes sensitized
during the first graft rejection.
• Accelerated rejection is mediated by immediate
production of lymphokines, activation of
monocytes and macrophages, and induction of
cytotoxic lymphocytes.
36. • Acute (1st set; primary) rejection
The normal reaction that follows the first grafting
of a foreign transplant takes 1 - 3 weeks.
• This is known as acute rejection and is mediated
by T lymphocytes sensitized to class I and class II
antigens of the allograft, elicitation of
lymphokines and activation of monocytes and
macrophages.
37. • Chronic rejection
Some grafts may survive for months or even
years, but suddenly exhibit symptoms of
rejection.
• This is referred to as chronic rejection, the
mechanism of which is not entirely clear.
• The hypotheses are that this may be due to:
- infection causes,
- loss of tolerance induced by the graft, etc.
38. Graft Versus Host Disease (Rejection)
(GVHD)
• Graft versus host disease (GVHD) is an
immune-mediated disease resulting from a
complex reaction of the donor adaptive
immunity against the recipient tissues.
39. • Most severely occurs with allogeneic
hematopoietic-cell transplantation (HCT)(Bone
marrow transplant).
40. • The acute GVHD develops within 100 days of
transplantation, describes a distinctive syndrome
of:
- Dermatitis (Pruritic painful rash (median onset,
day 19 post-transplantation; range, 5-47 days)
- Hepatitis (liver involvement, anorexia, weight
loss, followed rarely by hepatic coma
- Enteritis (Diarrhea, intestinal bleeding, cramping
abdominal pain)
44. • Chronic GVHD describes a more diverse
syndrome developing after day 100.
• In addition to allogeneic HCT, procedures
associated with high risk of GVHD include
transplantation of solid organs rich of
lymphoid tissue.
45. Immunologically privileged sites and
tissues
• There are certain locations in the body in which
allografts are not readily rejected. These include:
- the brain,
- anterior chamber of the eye,
- testis,
- renal tubule,
- uterus, etc.
• This stems from the fact that such sites may lack
of good lymphatic drainage.
46. • Similarly, corneal graft is an excellent example
that enjoys the highest success rate of any
form of organ transplantation.
47. PROCEDURES TO ENHANCE GRAFT SURVIVAL
• 1- Donor selection
Based on extensive experiences with renal
transplants, certain guidelines can be followed
in donor selection and recipient preparation
for most organ transplants. The most
important in donor selection is the MHC
identity with the recipient; an identical twin is
the ideal donor. Grafts from an HLA-matched
sibling have 95-100% chance of success.
48. • 2- Recipient preparation
The recipient must be infection-free and must
not be hypertensive. One to five transfusions
of 100-200 ml whole blood from the donor at
1-2 week intervals improves the graft survival
and is practiced when possible.
50. • Q- Why the fetus isn't rejected by the
maternal immune system during
pregnancy?????
51. • The researchers discovered that embryo
implantation sets off a process that ultimately
turns off a key pathway required for the
immune system to attack foreign bodies. As a
result, immune cells are never recruited to the
site of implantation and therefore cannot
harm the developing fetus.
52.
53. - The research team has discovered that the onset of
pregnancy causes the genes that are responsible for
recruiting immune cells to sites of inflammation to be
turned off within the decidua.
- As a result of these
changes, T cells are not
able to accumulate
inside the decidua and
therefore do not attack
the fetus and placenta.